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18 April 2026, Volume 30 Issue 11 Previous Issue    Next Issue

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Three-dimensional culture of stromal vascular fraction self-assembles into complex vascularized osteogenic organoids Wu Jiazhou, Qian Tao, Liu Zexian, Wu Yanbin, He Ying, Li Yazhou, Peng Jiang 2026, 30 (11):  2681-2690.  doi: 10.12307/2026.112 Abstract ( 33 )   PDF (3186KB) ( 4 )   Save BACKGROUND: Compared with two-dimensional culture techniques, three-dimensional culture technology can more accurately simulate the in vivo environment of natural cell growth, which becomes a key focus in the fields of basic scientific research and translational medicine. OBJECTIVE: To construct prevascularized osteogenic organoids through three-dimensional culturing techniques. METHODS: Stromal vascular fraction (SVF) and adipose mesenchymal stem cells were isolated and extracted from the same human adipose tissue, and the cell components were identified by flow cytometry. The SVF and adipose mesenchymal stem cells were inoculated into 96-well U-plates. After 3 days of culture, the SVF was self-assembled and the adipose mesenchymal stem cells were formed into spheres. On the 14th day of culture, the internal structure of the spheres and cell morphology were observed by hematoxylin-eosin staining and cytoskeletal staining. Viability of the cells was detected by Presto Blue assay on days 0, 7, 14, and 21 of culture. Osteogenic, chondrogenic, and lipogenic differentiation were induced after 3 days of culture. After 14 days of induction, alizarin red staining was used to observe osteogenic differentiation; alizarin blue staining to observe chondrogenic differentiation; oil red O staining to observe lipogenic differentiation; immunofluorescence staining to co-localize CD31 (endothelial cell marker), RUNX2 (early osteogenic marker), CD44 (mesenchymal stem cell marker), type I collagen (late-stage osteogenic marker), and peroxisome proliferator-activated receptor γ (lipogenic markers); and qRT-PCR to detect the mRNA expression of RUNX2, osteopontin, type I collagen, Sp7 transcription factor, CD31, and vascular endothelial growth factor. RESULTS AND CONCLUSION: (1) Flow cytometry results revealed that the SVF contained various cell types including adipose mesenchymal stem cells and endothelial cells, whereas adipose mesenchymal stem cell spheroids were primarily composed of adipose mesenchymal stem cells. (2) Hematoxylin-eosin staining with cytoskeleton staining indicated that compared with adipose mesenchymal stem cell spheroids, SVF organoids more closely mimicked natural tissue structures with orderly arranged cells and richer extracellular matrix. Cell viability tests showed that adipose mesenchymal stem cell spheroids had higher activity on day 7, but SVF organoids surpassed the cells by day 21 (P < 0.05), exhibiting longer-lasting cell viability. (3) In tri-lineage differentiation experiments, SVF organoids demonstrated superior osteogenic and chondrogenic potential compared with adipose mesenchymal stem cell spheroids. Multicolor immunofluorescence colocalization revealed rich vascular networks and pronounced osteogenic marker expression in SVF organoids, with complex cell-to-cell and cell-to-matrix interactions, whereas adipose mesenchymal stem cell spheroids showed a simpler structure with a lack of endothelial gene expression. qRT-PCR results indicated significantly higher expression of RUNX2, osteopontin, type I collagen, Sp7 transcription factor, CD31, and vascular endothelial growth factor in SVF organoids compared with adipose mesenchymal stem cell spheroids (P < 0.05). Overall, the findings suggest that SVF organoids possess complex physiological structures with enhanced capabilities in vascular and bone formation, as well as sustained cell viability. Figures and Tables | References | Related Articles | Metrics

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Isoliquiritigenin inhibits wear particle-induced formation and differentiation of osteoblasts in vitro and in vivo Tan Fei, Zeng Jiankang, Wang Jing, Liu Jian, Li Jiahuan, Li Peijie, Qiao Yongjie, Zhou Shenghu 2026, 30 (11):  2691-2701.  doi: 10.12307/2026.129 Abstract ( 26 )   PDF (2303KB) ( 0 )   Save BACKGROUND: The differentiation of osteoclasts caused by wear particles is one of the main causes of periprosthesis osteolysis. Inhibiting the differentiation and absorption of osteoclasts is an important research direction in the treatment of periprosthesis osteolysis. Studies have shown that isoliquiritigenin can promote the maturation of osteoblasts and inhibit the bone resorption of osteoclasts. OBJECTIVE: To investigate the effect of isoliquiritigenin on osteoclast formation and differentiation induced by wear particles. METHODS: (1) Cell experiment: Passage 3 RAW264.7 cells were divided into five different groups. The control group was not treated with any treatment. The titanium particle group was added with titanium particles. The osteoclast induction group was added with nuclear factor κB receptor activating factor ligand to induce osteoclast differentiation. The osteoclast induction+titanium particle group was added with nuclear factor κB receptor activating factor ligand and titanium particles at the same time, and the isoliquiritigenin group was added with nuclear factor κB receptor activating factor ligand and titanium particles. On the 2nd day of treatment, 20 μmol/L isoliquiritigenin was added. After 5 days of induction with receptor activator of nuclear factor-κB ligand, tartrate-resistant acid phosphatase and F-actin staining were used to evaluate osteoclast formation and bone resorption. Western blot assay was used to detect the effect of isoliquiritigenin on the phosphorylation of IκBα and p-65 in the nuclear factor-κB pathway. Enzyme-linked immunosorbent assay was used to detect the levels of inflammatory factors (tumor necrosis factor-α, interleukin-6, and matrix metalloproteinase-9) in the cell supernatant. Reverse transcription polymerase chain reaction was used to detect the expressions of osteoclast-related genes (cathepsin K, nuclear factor of activated T cells 1, proto-oncogene protein, and tartrate-resistant acid phosphatase). (2) Animal experiment: Totally 32 BALB/c mice were used to construct dorsal airbag bone graft models and randomly divided into four intervention groups: the blank group (n=8) was injected with PBS into the airbag, and the model group (n=8), solvent group (n=8), and isoliquiritigenin group (n=8) were injected with titanium particle suspension into the airbag. On the second day after the titanium particle suspension was injected, the blank group, model group, solvent group, and isoliquiritigenin group were intraperitoneally injected with phosphate buffered saline, phosphate buffered saline, dimethyl sulfoxide+corn oil, and 40 mg/kg isoliquiritigenin, respectively, once every other day for 2 consecutive weeks. After the intervention, tartrate-resistant acid phosphatase staining was used to detect the number of osteoclasts in the airbag. Enzyme-linked immunosorbent assay was used to detect the level of inflammatory factors in the grinding fluid of the airbag. Reverse transcription polymerase chain reaction was used to detect the expression of osteoclast-related genes in the grinding fluid of the airbag. RESULTS AND CONCLUSION: (1) Cell experiment: Compared with the control group, the number of osteoclasts formed in the other four groups increased, and the bone resorption capacity was enhanced. Among them, the osteoclast induction+titanium particle group had the largest number of osteoclasts formed and the strongest bone resorption capacity. Compared with the osteoclast induction+titanium particle group, the number of osteoclasts formed in the isoliquiritigenin group decreased, and the bone resorption capacity decreased. Compared with the control group, the phosphorylation of IκBα and p65 in the other four groups increased, indicating that the number of osteoclasts increased. Among them, the phosphorylation of IκBα and p65 in the osteoclast induction+titanium particle group was the highest, and it was significantly reduced after isoliquiritigenin treatment. Compared with the control group, the levels of inflammatory factors and the expression of osteoclast-related genes in the other four groups increased, among which the osteoclast induction+titanium particle group was the highest. Compared with the osteoclast induction+titanium particle group, the levels of inflammatory factors and the expression of osteoclast-related genes were reduced in the isoliquiritigenin group. (2) Animal experiment: Compared with the blank group, the number of osteoclasts, the level of inflammatory factors and the expression of osteoclast-related genes increased in the other three groups. Compared with the model group, the number of osteoclasts, the level of inflammatory factors and the expression of osteoclast-related genes decreased in the isoliquiritigenin group. These findings indicate that isoliquiritigenin could suppress the formation and differentiation of osteoclasts in vivo and in vitro induced by wear particles.  Figures and Tables | References | Related Articles | Metrics

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Network pharmacological analysis and experimental verification of semen cuscutae in treating postmenopausal osteoporosis Xu Sheng, Zhang Wenwen, Zhang Weiwei, Wang Hongtao, Zhang Jun, Yang Ruisheng, Yuan Yuan, Wang Li, Hao Haihu 2026, 30 (11):  2702-2711.  doi: 10.12307/2026.095 Abstract ( 11 )   PDF (3385KB) ( 1 )   Save BACKGROUND: Semen cuscutae, a traditional Chinese medicine, has gradually shown its potential in anti-postmenopausal osteoporosis because of its relatively small side effects, which provides new ideas and possibilities for the treatment of this disease. OBJECTIVE: To explore the mechanism of anti-postmenopausal osteoporosis of semen cuscutae based on network pharmacological analysis and molecular docking and to validate it with animal experiments.  METHODS: The main active components and corresponding targets of semen cuscutae were screened in TCMSP database, and the disease targets of postmenopausal osteoporosis were collected in GeneCards, OMIM and PharmGKB databases. After identification of common targets, a series of analyses were carried out, and core targets were selected. The core targets were analyzed by GO function and their role was verified by molecular docking. The corresponding active components were selected for animal experiments. RESULTS AND CONCLUSION: (1) Eleven main active components of semen cuscutae and 110 common targets of semen cuscutae and postmenopausal osteoporosis were screened out, and 10 core targets were identified. (2) GO function analysis showed that the core targets were closely related to oxidative stress and estrogen. (3) The top two ranked core target proteins, interleukin-6 and activated T-cell nuclear factor 1, were molecularly docked, and the top two ranked affinities, picloram and interleukin-6 as well as picloram and activated T-cell nuclear factor 1, were selected for validation in animal experiments. (4) Animal experimental results showed that matrine could inhibit the levels of interleukin-6 and activated T-cell nuclear factor 1 and improve trabecular bone structure of rats with postmenopausal osteoporosis. To conclude, low-dose matrine may affect the steady state of interleukin-6/soluble interleukin-6 receptor system by decreasing the level of interleukin-6, and inhibit the expression of nuclear factor 1 in downstream transcription factor-activated T cells in combination with nuclear factor-κB and mitogen-activated protein kinase signaling pathway to inhibit osteoclast differentiation, reduce bone resorption, repair trabecular structure and treat postmenopausal osteoporosis. Figures and Tables | References | Related Articles | Metrics

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Neuroprotective regulation of the IRF9 gene after spinal cord injury: bioinformatics analysis combined with experimental validation Tian Minghao, Liao Yehui, Zhou Wenyang, He Baoqiang, Leng Yebo, Xu Shicai, Zhou Jiajun, Li Yang, Tang Chao, Tang Qiang, Zhong Dejun 2026, 30 (11):  2712-2726.  doi: 10.12307/2026.119 Abstract ( 33 )   PDF (5509KB) ( 0 )   Save BACKGROUND: The precise regulatory mechanisms of inflammation following spinal cord injury remain unclear. In recent years, studies have shown that interferon regulatory factor 9 (IRF9) plays a key role in various inflammation-related diseases, but its specific role in spinal cord injury has not been systematically studied. OBJECTIVE: To systematically investigate the role of IRF9 in the inflammatory response after spinal cord injury and its potential molecular mechanisms by integrating bioinformatics analysis and in vitro experiments.   METHODS: (1) Gene microarray data from the GEO database were integrated and analyzed using differential gene expression analysis, GO and KEGG functional enrichment analyses, gene set enrichment analysis, and protein-protein interaction network analysis to explore the functions and pathways of differentially expressed genes after spinal cord injury and identify the key genes related to inflammation. (2) The 3rd generation PC12 cells were cultured in four groups: blank control group without any treatment, injury control group with lipopolysaccharide intervention for 24 hours, IRF9 overexpression group transfected with IRF9 overexpression lentivirus for 72 hours followed by lipopolysaccharide intervention for 24 hours, and IRF9 knockdown group transfected with IRF9 knockdown expression lentivirus for 72 hours followed by lipopolysaccharide intervention for 24 hours. After the end of lipopolysaccharide intervention, cell proliferation was detected by cell counting kit-8 assay, brain-derived nerve growth factor and neurotrophic factor 3 levels in cell culture medium were detected by Elisa, intracellular Bcl-2, Bax, Cleaved-Caspase3 protein expression was detected by western blot, and cell migration ability was detected by cell scratch assay.  RESULTS AND CONCLUSION: (1) Bioinformatics analysis demonstrated that spinal cord injury significantly activated inflammation- and immune-related pathways, identifying IRF9 as a potential core regulator. High IRF9 expression was found to potentially upregulate Toll-like receptor and nuclear factor-κB signaling pathways while suppressing cyclic adenosine monophosphate and calcium signaling pathways and glutamatergic synaptic function, contributing to the regulation of inflammation and neurological dysfunction. (2) The results of cellular experiments showed that compared with the blank control group, the injury control group had lower cell proliferation, migration ability and Bcl-2 protein expression, lower levels of brain-derived nerve growth factor and neurotrophic factor 3, and higher expression of Bax and Cleaved-Caspase-3 proteins. Compared with the injury control group, the IRF9 knockdown group showed higher cell proliferation, migration ability and Bcl-2 protein expression, higher levels of brain-derived nerve growth factor and neurotrophic factor 3, and lower expression of Bax and Cleaved-Caspase-3 proteins. To conclude, IRF9 may serve as an important regulator of secondary injury and a potential therapeutic target for spinal cord injury. Figures and Tables | References | Related Articles | Metrics

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Influencing factors of spine deformity progression in adolescent idiopathic scoliosis and construction of a joint prediction model and nomogram Li Jie, Zhao Xiaofeng, Zeng Qi, Zhou Runtian, Chen Rong, Hu Xijian, Zhao Bin 2026, 30 (11):  2727-2735.  doi: 10.12307/2026.102 Abstract ( 27 )   PDF (2383KB) ( 0 )   Save BACKGROUND: To establish a model for predicting the progression of scoliosis at different time points after the first diagnosis of adolescent idiopathic scoliosis contributes to accurately identify and predict the risks of progression in the early stage of disease development. OBJECTIVE: To explore the factors influencing the progression of scoliosis in patients with adolescent idiopathic scoliosis after first diagnosis, and to construct a nomogram risk prediction model.   METHODS: The clinical data of patients with adolescent idiopathic scoliosis who were first diagnosed at the Second Hospital of Shanxi Medical University from January 2019 to June 2023 were retrospectively analyzed and followed up to the progress of lateral bending, that is, the progress of main bend Cobb angle ≥ 6°, the last visit or cutoff date (June 2023). The patients were randomly divided at the rate of 8:2 into training set and verification set, and the patients were divided into progressive group and non-progressive group according to whether the patients had lateral bending progress or not. Least Absolute Shrinkage and Selection Operator (LASSO)-Cox regression analyses were used to investigate the independent influences on the occurrence of scoliosis progression in adolescent idiopathic scoliosis and to construct a Cox regression algorithm-based risk prediction model for column-line diagrams based on the area under the curve (AUC) of the receiver operating characteristic curve of the subjects, calibration curve, and decision curve were used to validate and evaluate the differentiation, accuracy, and clinical application value of the model.   RESULTS AND CONCLUSION: (1) A total of 294 patients with adolescent idiopathic scoliosis were included in this study, with a progression rate of 41.84%. (2) The results of LASSO-Cox regression analysis showed that age at first diagnosis ≥ 14.5 years, brace treatment, Risser’s sign ≥ 1 grade, parietal cone offset > 1.6 cm, and thoracic 1 cone tilt angle > 1.2° were protective factors for scoliosis progression, whereas age at first diagnosis Cobb’s angle > 16.5°, parietal cone rotation ≥ 2 degrees, and spinal growth rate > 4.5 cm/year were risk factors for scoliosis progression. (3) The nomogram model constructed according to the above factors had excellent predictive ability and clinical significance. The AUC values of 6, 12, 18 and 24 months in the training set and verification set were 0.731, 0.852, 0.855, 0.843 and 0.766, 0.850, 0.850 and 0.830, respectively, and the C-index of the model was 0.795 and 0.771 respectively, indicating that the model has good discrimination. The calibration curve showed that the actual observation results fitted well with the predicted results, and the accuracy of the model was high. In addition, the decision curve showed that the use of the model to make clinical decisions could bring net benefits to patients. Therefore, the adolescent idiopathic scoliosis progression risk prediction nomogram model constructed in this study can use simple variables to judge the risk probability of patients' progression at different time points in the future, and then guide clinicians to choose a more reasonable treatment. Figures and Tables | References | Related Articles | Metrics

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Abdominal electrical stimulation combined with core stabilization training improves balance and cough function in patients with stroke pseudobulbar palsy Gao Shiai, Chen Jinhui, Cao Xinyan, Leng Xiaoxuan, Liu Xihua 2026, 30 (11):  2736-2744.  doi: 10.12307/2026.076 Abstract ( 27 )   PDF (1251KB) ( 2 )   Save BACKGROUND: Pseudobulbar palsy is a common complication in stroke patients. Additionally, patients often experience reduced trunk core muscle control and weakened voluntary cough reflexes. Current clinical treatments for pseudobulbar palsy predominantly focus on speech and swallowing rehabilitation, often neglecting systematic interventions for balance, motor function, and cough expectoration. OBJECTIVE: To investigate the effects of abdominal electrical stimulation combined with core stability training on balance, motor function, and cough ability in stroke patients with pseudobulbar palsy. METHODS: Sixty patients with post-stroke pseudobulbar palsy from the Rehabilitation Center of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine were randomly divided into a control group and an experimental group, with 30 patients in each group. Both groups received basic treatment and conventional rehabilitation training. The control group additionally underwent core stability training (30 minutes as a session, once a day, six sessions per week, for 2 weeks), while the experimental group received abdominal electrical stimulation (30 minutes as a session, once a day, six sessions per week, for 2 weeks) in addition to the control group’s treatment. Before and after 2 weeks of treatment, the Berg Balance Scale, Fugl-Meyer Assessment for Lower Extremity, Modified Barthel Index, and Semiquantitative Cough Strength Score were evaluated. Abdominal muscle thickness ratio of the external oblique, internal oblique and transversus abdominis muscles was assessed using ultrasound, and cough peak flow was measured via pulmonary function testing. RESULTS AND CONCLUSION: After 2 weeks of treatment, both groups showed improvements in the Berg Balance Scale, Fugl-Meyer Assessment for Lower Extremity, Modified Barthel Index, and Semiquantitative Cough Strength scores, and abdominal muscle thickness ratio compared with pre-treatment levels, with the experimental group demonstrating significantly greater improvements than the control group (P < 0.05). These findings indicate that abdominal electrical stimulation combined with core stability training is superior to the control group in improving patients' balance function, lower limb motor function, activities of daily living, cough ability, and core muscle activation, demonstrating significant clinical efficacy. This combined intervention provides effective support for the overall rehabilitation of patients with pseudobulbar palsy. Figures and Tables | References | Related Articles | Metrics

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Optimal finite element analysis of arch expansion in patients with cleft palate with bracketless invisible appliance during dental replacement Yu Miao, Shao Tianyang, Zhuang Yan, Luan Chunyang, Zhao Yue 2026, 30 (11):  2745-2751.  doi: 10.12307/2026.075 Abstract ( 26 )   PDF (1102KB) ( 1 )   Save BACKGROUND: The advantages of bracketless invisible orthodontic technology in patients with cleft palate are gaining attention, but there are fewer studies on its control of teeth and the effect of bracketless invisible orthodontic appliance on arch expansion in patients with cleft palate during dental replacement. OBJECTIVE: Through three-dimensional finite element analysis, to evaluate the effect of arch expansion on tooth displacement pattern and root control efficiency in unilateral cleft lip and palate prosthesis repair with invisible appliance without groove, and to reduce the buccal tilt of teeth and improve the arch expansion effect of appliance through optimization design.  METHODS: CT scan data of a 10-year-old male with unilateral complete cleft palate were selected to establish the finite element model of maxillary arch expansion in patients with unilateral complete palate cleft with bracketless invisible orthodontics. The model was imported into the finite element solver ANSYS workbench software to analyze the first premolar, first molar displacement and periodontal membrane stress distribution after arch expansion under various working conditions. Condition 1: Only the arch expansion of the invisible appliance was simulated; Condition 2: To simulate the arch expansion of the invisible appliance without brackets, and add 1° root buccal torque of the first molar and the first premolar; Condition 3: On the basis of Condition 2, the first premolar and the pressure point of the first molar were added by computer CAD and CAE combined optimization design; Condition 4: On the basis of Condition 2, the first premolar and a pair of pressure point sets of the first molar were added through optimal design.  RESULTS AND CONCLUSION: The total displacements of the first premolars and first molars moved slightly to the middle in the four conditions. The root displacements of the first premolars and first molars were the largest in Condition 4, the difference of displacements was the smallest in Condition 4, and the periodontal membrane stress was the smallest in Condition 4. The expansion with bracketless invisible orthodontic appliance can effectively reduce the mesial inclination of the first premolar and first molar, improve the overall movement effect, and optimize the internal stress of periodontal ligament to achieve a more balanced and orderly distribution of stress, reducing the situation of excessive local stress concentration. Figures and Tables | References | Related Articles | Metrics

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Impact and mechanism of low-dose hexafluoropropylene oxide dimer acid exposure during pregnancy on renal toxicity in offspring mice Hong Runyang, Zhou Qiyue, Fan Zhencheng, Shi Yujie, Chen Hao, Pan Chun 2026, 30 (11):  2752-2763.  doi: 10.12307/2026.099 Abstract ( 27 )   PDF (5223KB) ( 0 )   Save BACKGROUND: Hexafluoropropylene oxide dimer acid (also known as GenX) is widely used as a novel substitute for perfluorooctanoic acid in coatings, inks, antioxidants, and other fields. However, GenX exhibits multi-organ toxicity, and exposure to GenX can lead to elevated blood urea nitrogen levels and renal pathological damage in rats.  OBJECTIVE: To investigate the toxic effects and mechanism of low-dose GenX exposure during pregnancy on the kidney of offspring mice. METHODS: (1) Animal experiment: Sexually mature 8-week-old female BALB/c mice were randomly divided into normal control group and GenX group after mating with male mice and showing vaginal plug, with six mice in each group. The control group was gavaged with ddH2O, while the GenX group was gavaged with GenX (2 mg/kg/d) until birth. Kidney tissues of male and female offspring mice were collected at 3 and 8 weeks after birth. Hematoxylin-eosin staining and Masson staining were used to explore the effects of GenX on the pathological structure and fibrosis of the kidney in offspring mice of different sexes. Immunohistochemical staining was used to detect the expression of inflammatory factors (tumor necrosis factor α and interleukin 6) in renal tissues. β-galactosidase staining was used to detect renal aging. Immunofluorescence staining of calcineurin E and vimentin expression was used to detect renal epithelial-mesenchymal transition, and immunofluorescence staining was used to detect transforming growth factor β1 expression. (2) Cell experiment: Renal tubular epithelial cells HK-2 were divided into three groups: control group with no treatment, GenX group treated with 600 μmol/L GenX for 72 hours, and GenX+rapamycin group with 10 nmol/L rapamycin pretreatment for 1 hour followed by addition of 600 μmol/L GenX for 72 hours. Cell supernatant was taken for use in the following experiment. Kidney fibroblasts NRK-49F were treated in three groups, and the culture supernatants of the above three groups were added and treated for 48 hours. Immunofluorescence staining was performed to detect the expression of fibroblast activation markers α-smooth muscle actin and fibronectin. RESULTS AND CONCLUSION: (1) Animal experiment: Exposure to low-dose GenX during pregnancy could cause structural damage and tissue fibrosis in the kidneys of female and male offspring mice, trigger inflammatory responses and renal senescence in female and male offspring mice, induce the development of epithelial-mesenchymal transition in the kidneys of female and male offspring mice, and increase the expression of transforming growth factor β1 in the kidneys of female and male offspring mice. (2) Cell experiment: Immunofluorescence staining showed that hexafluoropropylene oxide dimer acid-treated HK-2 cell culture supernatants significantly increased α-smooth muscle actin and fibronectin expression in NRK-49F cells, but this effect was inhibited by the senescence inhibitor rapamycin. To conclude, GenX exposure during pregnancy is toxic to the kidneys of offspring mice, causing the development of renal inflammation and fibrosis, mainly through accelerating the senescence of renal tubular epithelial cells, promoting epithelial-mesenchymal transition, and promoting the proliferation and activation of fibroblasts, and ultimately leading to the development of renal fibrosis. Figures and Tables | References | Related Articles | Metrics

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Moxibustion improves endothelial function in atherosclerotic mice by regulating fatty acid oxidation through mediating mitochondrial autophagy Pan Li, Zhu Zhou, Yan Zhaobo, Zhang Ning, Yang Zhihong, Xiong Jiaojiao, Yang Xiaofang 2026, 30 (11):  2764-2773.  doi: 10.12307/2026.317 Abstract ( 26 )   PDF (1638KB) ( 0 )   Save BACKGROUND: Atherosclerosis serves as the core pathological basis for cardiovascular diseases, closely linked to lipid metabolism disorders and endothelial dysfunction. Previous studies have indicated that moxibustion effectively protects mitochondrial morphology and function, inhibiting cell apoptosis.  OBJECTIVE: To explore the potential mechanism of moxibustion in regulating fatty acid oxidation via mitochondrial autophagy for anti-atherosclerosis effects. METHODS: Thirty male ApoE−/− mice were randomly divided into a model group, a moxibustion group, and a moxibustion+mitochondrial division inhibitor 1 (Mdivi-1) group, with 10 mice in each group. They were fed a high-fat diet for 12 weeks to replicate the atherosclerosis model. Ten male C57BL/6J mice served as the control group, receiving a regular diet. All groups received interventions on the first day of modeling. The control and model groups underwent only grasping and fixation, while the moxibustion group received moxibustion at “Danzhong,” “Shenque,” and bilateral “Neiguan” and “Xuehai” acupoints for 30 minutes, 5 times a week continuously. The moxibustion+Mdivi-1 group was administered Mdivi-1 (1.2 mg/kg/d) via intraperitoneal injection 30 minutes before moxibustion, also 5 times a week continuously. Both groups were treated for 12 weeks and samples were then collected. Enzyme determination was used to measure serum triglyceride and total cholesterol levels, while colorimetry determined low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels. Hematoxylin-eosin staining was used to observe the pathological morphology of the mouse thoracic aorta and liver. Oil red O staining was performed to assess liver lipid changes. Enzyme-linked immunosorbent assay was used to detect carnitine palmitoyl transferase-1α (CPT1α) and medium-chain acyl-CoA dehydrogenase (MCAD) levels in the liver and endothelin-1 levels in the serum. The nitric acid reductase method was conducted to measure serum nitric oxide levels. Western blot assay was adopted to analyze BCL2/adenovirus E1B 19kDa interacting protein 3 (BNIP3), becline-1, thylakoid outer membrane translocase 20 (TOMM20) protein expression in liver tissue, as well as endothelial nitric oxide synthase and phosphorylated endothelial nitric oxide synthase in the thoracic aorta. RESUITS AND CONCLUSION: (1) Compared with the control group, mice in the model group showed significantly increased levels of serum triglyceride, total cholesterol, and low-density lipoprotein cholesterol (P < 0.01), while high-density lipoprotein cholesterol levels were significantly reduced (P < 0.05). The inner wall of the thoracic aorta was irregular, with intimal thickening and matrix dissolution. Hepatic tissue cells were swollen and rounded, showing spotty necrosis of hepatocytes, neutrophil infiltration, numerous fat vacuoles, and steatosis. Oil red O staining of the mouse liver also revealed a large accumulation of lipid droplets. The contents of CPT1α and MCAD and the expression levels of BNIP3 and Becline-1 proteins in liver tissue were significantly reduced (P < 0.05, P < 0.01), while the expression of TOMM20 protein was significantly increased (P < 0.05). The nitric oxide content in mouse serum was significantly reduced (P < 0.01), while the endothelin-1 concentration was significantly increased (P < 0.01). The expression of endothelial nitric oxide synthase and phosphorylated endothelial nitric oxide synthase proteins in the thoracic aorta tissue decreased (P < 0.05, P < 0.01). (2) Compared with the model group, the serum triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels in the moxibustion group were significantly reduced (P < 0.01). The thoracic aortic lumen was more regular, and the media was more neatly arranged. The swelling of liver tissue cells was significantly reduced, the texture was clear, and lipid droplet deposition was reduced. Oil red O staining showed a significant reduction in lipid droplet accumulation. The contents of CPT1α and MCAD and the expression levels of BNIP3 and Becline-1 proteins in liver tissue were significantly increased (P < 0.05, P < 0.01), while the expression of TOMM20 protein was significantly decreased (P < 0.05). The nitric oxide content in mouse serum was significantly increased (P < 0.01), while the endothelin-1 content was significantly decreased (P < 0.01). The expression of endothelial nitric oxide synthase and phosphorylated endothelial nitric oxide synthase proteins in the thoracic aorta tissue increased (P < 0.01). (3) Compared with the moxibustion group, the serum total cholesterol and low-density lipoprotein cholesterol levels in the moxibustion + Mdivi-1 group were significantly increased (P < 0.05, P < 0.01). The inner wall of the thoracic aorta was slightly irregular, with intimal thickening and a small number of foam cells. The swelling of liver tissue cells was aggravated. Oil red O staining of liver tissue showed increased lipid droplet accumulation. The contents of CPT1α and MCAD and the expression levels of BNIP3 and Becline-1 proteins in liver tissue were significantly reduced (P < 0.05, P < 0.01). The nitric oxide content in mouse serum decreased (P < 0.05), while the endothelin-1 content significantly increased (P < 0.01). The expression of endothelial nitric oxide synthase and phosphorylated endothelial nitric oxide synthase proteins in the thoracic aorta tissue decreased (P < 0.01). To conclude, moxibustion can improve lipid levels, fatty acid oxidation, lipid accumulation, restore endothelial damage, and reduce symptoms of atherosclerosis in ApoE−/− mice. The mechanism may be related to regulating mitochondrial autophagy, which affects fatty acid oxidation, reduces lipid accumulation in liver tissue, and improves endothelial dysfunction. Figures and Tables | References | Related Articles | Metrics

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Huidouba inhibits ferroptosis in high glucose-cultured HK-2 cells to attenuate cell fibrosis Yao Shunhua, Huang Caiding, Zhang Mengyu, Zhang Kexin, Yin Changjiang, Yang Kunbao 2026, 30 (11):  2774-2783.  doi: 10.12307/2026.124 Abstract ( 30 )   PDF (1712KB) ( 0 )   Save BACKGROUND: Diabetic nephropathy is closely related to ferroptosis. Previous studies have found that Huidouba has a significant hypoglycemic effect, protects against diabetic nephropathy-induced renal oxidative stress injury and fibrosis, and also reduces the level of fibrosis in high glucose-induced HK-2 cells.  OBJECTIVE: To investigate the role of Huidouba in regulating glutathione peroxidase 4 (GPX4) to inhibit ferroptosis and attenuate cellular fibrosis in human renal cortical proximal tubular epithelial cells (HK-2) cultured in high glucose conditions. METHODS: (1) In order to investigate the interventional effect of Huidouba on ferroptosis and fibrosis in high glucose-cultured HK-2 cells, the cells were divided into six groups: control group, model group, low-, medium-, high-dose Huidouba groups, and rosiglitazone group. The morphology of HK-2 cells was observed. Cell viability, levels of oxidative stress-related indicators (malondialdehyde and glutathione), and protein and mRNA expression levels of ferroptosis-related indicators (GPX4, ferritin heavy chain 1, nuclear factor-E2-associated factor 2, transferrin receptor) and fibrosis-related indicators (transformed growth factor-β1 and kidney injury molecule 1), were detected. (2) To observe the effect of siRNA interfering with GPX4 expression in HK-2 cells, the cells were divided into negative control group and si-GPX4 group. The expression of GPX4 at protein and mRNA levels was detected. (3) In order to observe the effect of siRNA interference with GPX4 on the effect of Huidouba on the inhibition of ferroptosis and mitigation of cellular fibrosis in high glucose-cultured HK-2 cells, the cells were divided into negative control group, high glucose group (treated with 30 mmol/L glucose), high glucose+Huidouba group (treated with 30 mmol/L glucose+400 μg/mL Huidouba water extract), and high glucose+Huidouba+si-GPX4 group (treated with GPX4-siRNA followed by intervention with 30 mmol/L glucose+400 μg/mL Huidouba water extract). The levels of malondialdehyde and glutathione, and the protein and mRNA expression of GPX4, ferritin heavy chain 1, nuclear factor-E2-associated factor 2, transferrin receptor, transformed growth factor-β1, and kidney injury molecule 1 were detected.  RESULTS AND CONCLUSION: (1) Compared with the control group, the cell viability, glutathione level, the protein and mRNA expression of GPX4, ferritin heavy chain 1, and nuclear factor-E2-associated factor 2 were significantly reduced in the model group, while the malondialdehyde level and protein and mRNA expression of transferrin receptor, transformed growth factor-β1, and kidney injury molecule 1 were significantly increased. Compared with the model group, the above indicators were improved to varying degrees in different dose groups of Huidouba and rosiglitazone group. (2) The protein and mRNA expression of GPX4 was significantly lower in the si-GPX4 group compared with the negative control group. Compared with the high glucose+Huidouba group, the glutathione level, the protein and mRNA expression of GPX4, ferritin heavy chain 1, and nuclear factor-E2-associated factor 2 were significantly reduced in the high glucose+Huidouba+si-GPX4 group, while the malondialdehyde level and protein and mRNA expression of transferrin receptor, transformed growth factor-β1, and kidney injury molecule 1 were significantly increased. To conclude, Huidouba attenuates cell fibrosis by inhibiting ferroptosis in high glucose-cultured HK-2 cells through the upregulation of GPX4. Figures and Tables | References | Related Articles | Metrics

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Mechanism of Shixiang plaster to promote healing of infectious wounds Liu Man, Zhang Kaiwei, Zhu Xu, Ruan Jinghua, Chen Jiunyi, Fei Ji 2026, 30 (11):  2784-2794.  doi: 10.12307/2026.085 Abstract ( 20 )   PDF (1880KB) ( 0 )   Save BACKGROUND: Previous experiments have shown that Shixiang plaster can regulate the Nrf2-ARE signaling pathway and inhibit the glycosylation end product/nuclear factor κB pathway, effectively reducing oxidative stress and inflammation, and promoting wound repair, but the mechanism remains unclear. OBJECTIVE: To study the therapeutic effect and mechanism of Shixiang plaster in a rat model of infectious wounds, with a particular focus on the changes in the content of growth factors and M2 macrophages in the wounds. METHODS: Thirty-six male Sprague-Dawley rats, SPF grade, were selected. A rat model of infectious wounds was established using the skin lesion+bacteria implantation method. Model rats were randomized into model group (the wound was applied wetly with normal saline and then covered with a sterile dressing), the Befuji group (the wound was treated with Befuji, with recombinant bovine basic fibroblast growth factor as the main ingredient), and the Shixiang plaster group (the wound was treated with Shixiang plaster). Gross observations of the wound were performed and samples were taken at 3, 7, and 14 days after modeling. Hematoxylin-eosin staining and Masson staining were used to observe the histopathological changes, ELISA was used to detect the levels of platelet-derived growth factor, transforming growth factor β, and basic fibroblast growth factor in the wound tissues; flow cytometry and immunofluorescence were used to detect the content and localization of macrophages in wound tissues; and histological changes and the role of immune cells during the wound healing were analyzed. RESULTS AND CONCLUSION: (1) On the 3rd, 7th, and 14th days after modeling, wound healing was fastest after intervention with Shixiang plaster, which was significantly better than the other two groups in both the early healing rate and the late healing rate. The healing effect in the Befuji group ranked second. (2) Treatment with Shixiang plaster in the early stage of inflammation (3 days) downregulated the levels of basic fibroblast growth factor and platelet-derived growth factor, inhibited the over-activation of M1-type macrophage, reduced the secretion of pro-inflammatory cytokines, and maintained the moderate inflammatory environment, which was compatible with the inflammatory response dominated by M1-type macrophage. At 7 days after the formation of wounds, Shixiang plaster upregulated the levels of basic fibroblast growth factor and platelet-derived growth factor, at which time M2-type macrophages gradually increased and transforming growth factor β levels were decreased. To conclude, Shixiang plaster alleviates inflammatory responses and promotes the formation of granulation tissue by regulating growth factors in a time-dependent manner. Combining with previous experimental studies, it is speculated that Shixiang plaster can activate the Nrf2-ARE signaling pathway to promote the polarization of M2 macrophages, achieving the effects of anti-inflammation and accelerating wound healing. Figures and Tables | References | Related Articles | Metrics

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Protective effect and mechanism of Zhigancao Decoction on doxorubicin-induced myocardial injury Yu Manya, Cui Xing 2026, 30 (11):  2795-2805.  doi: 10.12307/2026.069 Abstract ( 15 )   PDF (2658KB) ( 0 )   Save BACKGROUND: Clinical observations have shown that Zhigancao Decoction can effectively improve the symptoms and signs of doxorubicin-induced cardiotoxicity and protect cardiac function. Nevertheless, its exact mechanism of action remains unclear. OBJECTIVE: To explore the protective effect and mechanism of Zhigancao Decoction on myocardial injury induced by doxorubicin.  METHODS: (1) The targets of Zhigancao Decoction were obtained from PharmMapper, TCMSP, PubChem and BATMAN-TCM databases, and mitochondria-related genes were obtained from MitoCarta 3.0. Intersection genes were screened for myocardial injury-related targets by GEO database. (2) Cell experiment: Thirty Sprague-Dawley rats were given 12.15 g/kg/d Zhigancao Decoction by gavage (in two doses) for 3 consecutive days. Blood samples were collected from the abdominal aorta 2 hours after the last dose, and the serum was separated to obtain the drug-containing serum. Passage 10 rat cardiomyocytes (H9C2 cells) were divided into five groups: the control group without any intervention, the model group treated with adriamycin for 48 hours, the low, medium, and high dose drug-containing serum group treated with 5%, 10%, and 20% drug-containing serum for 6 hours, and then treated with adriamycin for 48 hours. At the end of the interventions, the levels of lactate dehydrogenase and creatine kinase in the cell supernatant were measured, and the protein expression of Caspase-7, cellular mitochondrial ultrastructure, cell apoptosis, reactive oxygen species level, and the localization and distribution of α-actinin were detected. (3) Animal experiment: Thirty C57BL/6 mice were randomly divided into five groups with six mice in each group: the control group was subcutaneously injected with saline, the model group and the low, medium and high dose Zhigancao Decoction groups were injected intraperitoneally with adriamycin (once a week for 4 weeks) to establish the myocardial injury model. Meanwhile, the low-, medium- and high-dose Zhigancao Decoction groups were given 8.775, 17.55 and 35.12 g/kg Zhigancao Decoction by gavage respectively (once a day for 4 weeks), and the control and model groups were given saline by gavage. After the final administration, left ventricular ejection fraction, serum lactate dehydrogenase and creatine kinase levels, structural changes in myocardial tissue, cardiomyocyte apoptosis and Caspase-7 protein expression in myocardial tissue were detected.  RESULTS AND CONCLUSION: (1) Venn plots of Zhigancao Decoction targets, myocardial injury targets, and mitochondria-related genes showed that Caspase-7 was an intersection gene. (2) Cell animal: Compared with the model group, the levels of supernatant lactate dehydrogenase and creatine kinase, reactive oxygen species, apoptosis and the protein expression of Caspase-7 and α-actinin were significantly reduced in the medium- and high-dose drug-containing serum groups. Damage to the ultrastructure of cellular mitochondria was significantly reduced. (3) Animal experiment: Compared with the model group, serum lactate dehydrogenase and creatine kinase levels, cardiomyocyte apoptosis and Caspase-7 protein expression were significantly reduced, left ventricular ejection fraction increased, and myocardial tissue structure was significantly improved in the medium- and high-dose Zhigancao Decoction groups. To conclude, Zhigancao Decoction can prevent and treat doxorubicin-induced myocardial injury primarily to a certain extent by reducing oxidative stress and mitochondrial damage, inhibiting myocardial cell apoptosis, protecting cardiac function, and improving the damaged structure of myocardial tissue. In terms of inhibiting the endogenous apoptosis pathway, Caspase-7 may be a key target. Figures and Tables | References | Related Articles | Metrics

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Endoplasmic reticulum stress promotes ferroptosis and aggravates cerebral ischemia-reperfusion injury#br# #br# Zhang Yueting, Li Jinglin, Fu Zhenyi, Yan Fei, Gao Yu, Liu Jiaxin 2026, 30 (11):  2806-2813.  doi: 10.12307/2026.038 Abstract ( 17 )   PDF (2278KB) ( 0 )   Save BACKGROUND: Embolization of cerebral arteries leads to cerebral tissue ischemia and hypoxia. Restoration of blood flow and reoxygenation usually results in cerebral ischemia-reperfusion injury. However, current research on the interaction between ferroptosis and endoplasmic reticulum stress in cerebral ischemia-reperfusion injury is relatively limited. OBJECTIVE: To investigate the roles and mechanisms of endoplasmic reticulum stress and ferroptosis in cerebral ischemia-reperfusion injury. METHODS: The HT-22 cell line was used and divided into four groups. An oxygen glucose deprivation/reperfusion (OGD/R) model was established in the model group. Cells were treated with 1.25 mmol/L 4-PBA (an endoplasmic reticulum stress inhibitor) for 2 hours prior to OGD/R, forming the 4-PBA group. Cells were treated with 1.25 mmol/L 4-PBA and 5 μmol/L CCT020312 (a protein kinase RNA-like ER kinase activator) for 2 hours before OGD/R, forming the 4-PBA+CCT group. Cell viability was detected by cell counting kit-8 experiment; western blot was used to detect the expression of ferroptosis-, endoplasmic reticulum stress, and protein kinase RNA-like ER kinase/transcription activating factor 4-related proteins; flow cytometry was used to detect cell apoptosis; and a reagent kit was used to detect the concentration of Fe2+. RESULTS AND CONCLUSION: Compared with the control group, OGD/R treatment significantly suppressed neuronal cell proliferation activity by inducing ferroptosis, endoplasmic reticulum stress and apoptosis mechanisms. Treatment with the endoplasmic reticulum stress inhibitor 4-PBA effectively alleviated ferroptosis, apoptosis and inhibition of cell viability caused by OGD/R. In addition, 4-PBA significantly reduced the expression levels of protein kinase RNA-like ER kinase and transcription activating factor 4 induced by OGD/R. The protein kinase RNA-like ER kinase activator CCT020312 reversed the inhibitory effects of 4-PBA on endoplasmic reticulum stress, ferroptosis, apoptosis and cell activity in the OGD/R model. To conclude, endoplasmic reticulum stress promotes ferroptosis through the protein kinase RNA-like ER kinase/transcription activating factor 4 signaling pathway, thereby exacerbating cerebral ischemia-reperfusion injury.  Figures and Tables | References | Related Articles | Metrics

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Effects of nocturnal sleep duration on new-onset cardiovascular and cerebrovascular diseases in middle-aged and elderly patients with chronic comorbidities Wang Degang, , Chen Guohua, , Mei Junhua, Wang Junli, Zheng Li 2026, 30 (11):  2814-2822.  doi: 10.12307/2026.092 Abstract ( 13 )   PDF (1284KB) ( 0 )   Save BACKGROUND: Existing studies have clearly demonstrated a strong association between nocturnal sleep duration and the incidence of cardiovascular and cerebrovascular diseases in the general population. However, in the specific group of patients with chronic comorbidities, the role of nocturnal sleep duration warrants further in-depth exploration. OBJECTIVE: To comprehensively analyze the intricate relationship between nocturnal sleep duration and cardiovascular and cerebrovascular diseases among elderly Chinese patients with chronic comorbidities and to precisely investigate whether body mass index plays a potential mediating role in this relationship. METHODS: This study enrolled middle-aged and elderly individuals aged 45 years and above from the China Health and Retirement Longitudinal Study (CHARLS) in 2011 and 2020 as the research subjects. The Logistic regression model was employed to meticulously analyze the potential impact of nocturnal sleep duration on cardiovascular and cerebrovascular diseases (including heart diseases, strokes, emotional and mental disorders, and memory-related diseases). Furthermore, a mediation analysis was conducted to accurately evaluate the role of body mass index in the relationship between nocturnal sleep duration and cardiovascular and cerebrovascular events. RESULTS AND CONCLUSION: (1) There was a significant association between age, body mass index, and the incidence of new-onset cardiovascular and cerebrovascular diseases among patients with chronic comorbidities (all P < 0.05). Moreover, there were highly significant differences in factors such as sex, marital status, educational level, and region among different sleep duration groups (all P < 0.001). Specifically, in individuals with chronic comorbidities, being female, married, having an educational level of primary school or below, and living in urban areas were all identified as risk factors for new-onset cardiovascular and cerebrovascular diseases. (2) Further analyses indicated that when the sleep duration reached 6.9 hours, the risk of developing cardiovascular and cerebrovascular diseases was significantly reduced (P < 0.05). Additionally, as the nocturnal sleep duration increased by one interquartile range, the risk of new-onset cardiovascular and cerebrovascular events gradually decreased, with a statistically significant difference (P < 0.05). (3) Moreover, the impact of nocturnal sleep duration on cardiovascular and cerebrovascular diseases was mainly mediated by body mass index, and this mediating effect was highly significant (P < 0.001). Meanwhile, nocturnal sleep duration also had a direct negative effect on cardiovascular and cerebrovascular diseases, and this effect was also statistically significant (P < 0.05). In conclusion, an appropriate amount of sleep can significantly reduce the incidence of cardiovascular and cerebrovascular diseases in this population, and body mass index plays a crucial partial mediating role.   Figures and Tables | References | Related Articles | Metrics

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Critical role of lysosomal enzymes in metabolic diseases Zou Yuxi, Chen Yanyan, Jiang Peng, Chen Ting, Ding Lingling 2026, 30 (11):  2823-2833.  doi: 10.12307/2026.101 Abstract ( 12 )   PDF (1443KB) ( 0 )   Save BACKGROUND: Individuals with metabolic syndrome are at increased risk of developing chronic diseases, particularly type 2 diabetes mellitus, non-alcoholic fatty liver disease, and cardiovascular diseases. Lysosomes are linked to various metabolic disorders, but their specific roles have not been fully elucidated. OBJECTIVE: To explore the research progress on lysosomes in metabolic syndrome through a literature search, providing insights into the mechanisms by which lysosomes and their enzymes influence metabolic syndrome. METHODS: The first author conducted a computerized search of PubMed and Web of Science from database inception to October 2024 using the keywords of “metabolic syndrome, glucose metabolism, lipid metabolism, type 2 diabetes mellitus, non-alcoholic fatty liver disease, lysosomes, lysosomal enzymes.” A total of 90 relevant articles were identified and analyzed. RESULTS AND CONCLUSION: (1) Metabolic disturbances are associated with metabolic syndrome and other metabolism-related diseases. These disturbances include glucose and lipid metabolism disorders. Disrupted glucose metabolism can lead to diabetes, causing severe complications and contributing to the development of metabolic syndrome. Abnormal lipid metabolism may result in dyslipidemia and fatty liver disease. (2) Lysosomal enzymes play a crucial role in metabolism, and their dysfunction can lead to various metabolic disorders. (3) Abnormalities in several lysosomal cathepsins are linked to insulin resistance, further contributing to the development of type 2 diabetes. (4) Deficiency in lysosomal acid lipase activity is one of the triggers for the progression of non-alcoholic fatty liver disease. Figures and Tables | References | Related Articles | Metrics

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The roles and mechanisms of axon guidance molecules in alpha-synuclein-related neurodegenerative diseases Zhang Yingbi, Li Minghui, Zhang Xiaorui, Yin Jihong, Wang Peng 2026, 30 (11):  2834-2845.  doi: 10.12307/2026.083 Abstract ( 13 )   PDF (1200KB) ( 0 )   Save BACKGROUND: Axon guidance molecules may play a critical role in alpha-synuclein-related neurodegenerative diseases. OBJECTIVE: To explore the roles and mechanisms of axon guidance molecules in alpha-synuclein-related neurodegenerative diseases. METHODS: The first author conducted a comprehensive search of databases including CNKI, WanFang Data, PubMed, Nature, Embase, Web of Science, JAMA, and BMJ. We systematically collected and organized literature on axon guidance factors and α-synuclein-related neurodegenerative diseases in recent years. The search terms were “Parkinson’s disease, axon guidance molecules, dementia with Lewy bodies, multiple system atrophy, pure autonomic failure” in Chinese and “Parkinson’s disease, axon guidance molecules,  Netrin, Ephrin, Semaphorin, Slit, dementia with Lewy bodies, multiple system atrophy, pure autonomic failure” in English. After screening, 89 articles were ultimately included for review and analysis. RESULTS AND CONCLUSION: The axon guidance factor protein family includes Netrins, Ephrins, Semaphorins, and Slits. Netrins modulate the activity of dopaminergic neurons by influencing intestinal factors and through DCC receptors, thereby impacting the progression of neurodegenerative diseases. Within the Ephrins family, EphrinA/EphA is involved in mediating neuronal regeneration signals. EphA1 regulates inflammation and neuropathology via the CXC chemokine ligand 12/CXC chemokine receptor 4 pathway, affecting disease development. Semaphorins-3 within the Semaphorins family can improve behavioral symptoms of neurodegenerative diseases by guiding the growth of axons from the substantia nigra to the striatum in dopaminergic neurons. On the axonal conduction pathway of dopaminergic neurons, Slits regulate the localization and pathfinding process through the Slit-Robo signaling, ensuring the accuracy of neuronal signal transmission pathways, which is crucial for maintaining and repairing neuronal connections. Figures and Tables | References | Related Articles | Metrics

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Pathogenesis of diabetic periodontitis and its local drug delivery treatment strategies Yang Xirui, He Jinfeng 2026, 30 (11):  2846-2857.  doi: 10.12307/2026.109 Abstract ( 12 )   PDF (1825KB) ( 1 )   Save BACKGROUND: Periodontitis is the sixth most common complication of diabetes. The complex two-way relationship between diabetes and periodontitis poses a challenge to the treatment of diabetic periodontitis. OBJECTIVE: To systematically summarize the types of drugs and carriers that can be used for the topical treatment of diabetic periodontitis from the perspective of the pathogenesis of diabetic periodontitis and the special pathological microenvironment. METHODS: We searched the databases of PubMed, Web of Science, and CNKI from database inception to February 2025 with the search terms of “periodontitis, diabetes, hydrogel, fiber, film, microparticle, nanoparticle, microneedle” in both Chinese and English, and 119 articles were finally included for review and analysis. RESULTS AND CONCLUSION: Diabetic periodontitis involves a complex pathological microenvironment of hyperglycemia, bacterial infection, inflammatory microenvironment, oxidative stress, immune dysregulation, and bone loss. For the unique pathological microenvironment of diabetic periodontitis, a variety of drugs such as blood glucose control drugs, antibacterial and anti-infection drugs, anti-inflammatory and immunomodulatory drugs, anti-oxidative stress drugs, and periodontal tissue regeneration drugs are available for the local treatment of diabetic periodontitis from multiple perspectives. Among them, hydrogel plays an important role in the treatment of diabetic periodontitis with its advantages of good biocompatibility, highly adjustability, and diversity of functions. Safer, smarter, and more controllable local drug delivery systems adapted to the pathological microenvironment of diabetic periodontitis are expected to play a significant role in the future treatment of diabetic periodontitis. Figures and Tables | References | Related Articles | Metrics

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Effects of long-term exercise interventions on appetite-regulating hormones in overweight and obese populations: a meta-analysis Xin Xianyang, Liu Longyan, Guo Yongqing, Wang Hai, Xie Jun 2026, 30 (11):  2858-2869.  doi: 10.12307/2026.123 Abstract ( 9 )   PDF (2872KB) ( 0 )   Save OBJECTIVE: Long-term exercise is recommended as a weight loss strategy, but its specific effects on appetite-regulating hormones in overweight and obese individuals remain unclear. This study aims to evaluate the effect of long-term exercise on appetite-regulating hormones in this population through a meta-analysis.  METHODS: A systematic search was conducted in PubMed, EBSCO, Cochrane Library, Web of Science, and Embase for randomized controlled trials from database inception to December 2024. Overweight or obese individuals were included, and the outcome indicators were appetite-regulating hormones (ghrelin, acylated ghrelin, peptide YY, and glucagon-like peptide 1). Meta-analysis was performed using Review Manager 5.4 and Stata 16. RESULTS: Long-term exercise interventions significantly increased ghrelin [standardized mean difference (SMD)=0.46, P=0.007] and glucagon-like peptide 1 levels (SMD=0.43, P=0.04). However, their effects on acylated ghrelin (SMD=-0.18, P=0.39) and peptide YY (SMD=0.23, P=0.39) were not significant. Substantial heterogeneity was relatively high, suggesting potential influences of individual differences and intervention protocols. High-intensity interval training showed the most pronounced effects on appetite-regulating hormone modulation, followed by resistance training. The mechanisms underlying these effects remain unclear. Short-term training exhibited more notable effects on peptide YY and glucagon-like peptide 1 levels, but these effects diminished with extended training duration.  CONCLUSION: Long-term exercise can modulate appetite-regulating hormones and suppress appetite in overweight or obese individuals, with high-intensity interval training and resistance training demonstrating significant potential for appetite reduction, which deserves further in-depth research. Figures and Tables | References | Related Articles | Metrics

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Carboxypeptidase M: unveiling a new therapeutic target for osteonecrosis based on eQTL Database and Finnish Genetic Big Data Gao Xinhai, Tan Huangsheng, He Shenghua 2026, 30 (11):  2870-2876.  doi: 10.12307/2026.037 Abstract ( 16 )   PDF (1371KB) ( 0 )   Save BACKGROUND: Osteonecrosis is a chronic orthopedic disease characterized by ischemic necrosis of bone tissue. Current treatment methods can delay the disease progression, but cannot completely cure it. There is an urgent need to explore new therapeutic targets. Against this backdrop, the development of omics technologies has provided effective tools for analyzing the genetic mechanisms of complex diseases. Among them, expression quantitative trait locus (eQTL) and genome-wide association studies (GWAS) data can reveal the impact of genetic variations on gene expression.  OBJECTIVE: To explore the potential protective role of the Carboxypeptidase M gene in osteonecrosis, evaluate its possibility as a new therapeutic target, and provide a theoretical basis for the precision treatment of osteonecrosis. METHODS: Two-sample Mendelian randomization analysis was adopted, integrating two international databases: eQTLGen and FinnGen GWAS. eQTLGen was jointly established by the University of Groningen in the Netherlands and the University of Tartu in Estonia, covering 31 684 European populations, which focuses on revealing the regulatory effect of genetic variations on gene expression. The FinnGen GWAS database was constructed by the Finnish Biobank in collaboration with multiple research institutions, containing 1 788 osteonecrosis patients and 429 826 controls, dedicated to in-depth research on the association between disease phenotypes and genotypes. This study systematically screened 2 534 druggable genes in the eQTL database and found that the eQTL signal of the Carboxypeptidase M gene shared causal variations with the GWAS signal of osteonecrosis. Sensitivity analyses (including heterogeneity detection, horizontal pleiotropy assessment, and leave-one-out analysis) and colocalization analysis were carried out to ensure the robustness and reliability of the results. RESULTS AND CONCLUSION: The study found that the Carboxypeptidase M gene was significantly associated with osteonecrosis, and its high expression could significantly reduce the risk of osteonecrosis (odds ratio < 1, false discovery rate < 0.05). Colocalization analysis confirmed that the eQTL signal of the Carboxypeptidase M gene shared causal variations with the GWAS signal of osteonecrosis (PP.H4=98.03%). This study is the first to reveal the protective role of the Carboxypeptidase M gene in osteonecrosis, clarifying its value as a potential therapeutic target and providing a solid basis for the precision treatment of osteonecrosis. It has important implications for basic and clinical medical research in China. Figures and Tables | References | Related Articles | Metrics

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Daily diet and structural damage of the knee joint: a large-scale genetic analysis based on UK and FinnGen databases Yan Wenjian, Li Yinghui, Zhang Yong 2026, 30 (11):  2877-2885.  doi: 10.12307/2026.094 Abstract ( 17 )   PDF (2368KB) ( 0 )   Save BACKGROUND:  Structural damage of the knee joint is a common musculoskeletal disorder, including meniscus injury and internal derangement of the knee, which severely impact the quality of life in athletes and elderly populations. Existing studies have shown that daily diet may influence the occurrence and progression of structural knee joint damage, but the causal relationship remains unclear.  OBJECTIVE: To explore the causal relationship between daily diet and structural damage of the knee joint based on a genetic approach and to identify potential risk and protective factors.  METHODS: Two-sample Mendelian randomization was conducted to explore the causal relationship between daily diet and structural damage of the knee joint. Outcome datasets for meniscus injury and internal derangement of the knee were obtained from the FinnGen database, while exposure datasets involving 20 dietary factors were derived from the OpenGWAS and GWAS Catalog databases. The inverse variance weighted method served as the primary analytical approach, supplemented by MR-Egger regression, weighted median, simple mode, and weighted mode method for validation. Sensitivity analyses were conducted to test the robustness of the results.  RESULTS AND CONCLUSION: The inverse variance weighted method showed that 13 dietary factors were potentially causally associated with meniscus injury, while 12 dietary factors showed potential causal relationships with internal derangement of the knee. Notably, vegetable was a significant risk factor for meniscal injury (odds ratio [OR] = 2.59, P < 0.001). Similarly, psychoactive drink was a significant risk factor for internal derangement of the knee (OR = 1.26, P < 0.001). In contrast, fruit was a significant protective factor for internal derangement of the knee (OR = 0.68, P < 0.001). Based on the large-scale European population data, these findings provide a potential causal relationship between dietary structure and knee joint damage, which may offer a useful reference for disease prevention and nutritional intervention strategies in China. Figures and Tables | References | Related Articles | Metrics

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Visualization analysis of piriformis syndrome: research trends and hotspots Li Kanglin, Jiang Yongdong, Wu Yufeng 2026, 30 (11):  2886-2895.  doi: 10.12307/2026.081 Abstract ( 16 )   PDF (3514KB) ( 0 )   Save BACKGROUND: Piriformis syndrome is a common clinical disorder characterized by sciatic nerve compression due to piriformis muscle pathology, resulting in lower limb pain. Currently, no standardized diagnostic criteria or therapeutic consensus exist in clinical practice. OBJECTIVE: To comprehensively investigate the research status, trends, and hotspots in the field of piriformis syndrome. METHODS: On November 13, 2024, subject headings (MeSH terms) and free-text keywords were searched in PubMed. A tailored search strategy was applied to the Web of Science Core Collection. After language and document type restrictions followed by manual screening, bibliometric visualization analysis was performed using Excel, VOSviewer, CiteSpace, and SciExplorer. RESULTS AND CONCLUSION: A total of 238 articles were included, covering 128 journals and 478 institutions, with a total of 1 033 authors from 57 countries or regions contributing valuable research to the field of pyriformis syndrome, including a total of 5 742 citations, with an average of 24 citations per article and an H-index of 42. From 1994 to 2024, global research output on piriformis syndrome exhibits an upward trend. The United States contributed the highest number of publications. The most prolific author was Fishman L.M., while Harvard University (USA) ranked as the leading institution. The Archives of Physical Medicine and Rehabilitation was identified as the most influential journal. Current research focuses predominantly on the diagnosis, anatomy, etiology, and treatment management of piriformis syndrome. Future directions are anticipated to emphasize advancements in “anatomy,” “deep gluteal syndrome,” and “management.” Figures and Tables | References | Related Articles | Metrics

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Visualization analysis of whole-body vibration training: research progress, hotspots, and future trends Xiao Meina, Jiang Chuanyin 2026, 30 (11):  2896-2908.  doi: 10.12307/2026.062 Abstract ( 13 )   PDF (2599KB) ( 1 )   Save BACKGROUND: Whole-body vibration training has been widely applied in various fields, including sports performance, rehabilitation medicine, and health management.  OBJECTIVE: To conduct a visual analysis of domestic and international research on whole-body vibration training methods using CiteSpace software, in order to reveal the research progress, key issues, and future development trends in this field. METHODS: Literature regarding whole-body vibration was selected from the CNKI and Web of Science databases from 2000 to 2024. CiteSpace V (6.2.R6) software was used to visualize the trends in publication, collaboration networks, keyword clustering, and research hotspots. RESULTS AND CONCLUSION: A total of 661 Chinese articles and 1 005 English articles were included. Both domestic and international whole-body vibration research has shown a yearly growth trend. Domestic studies primarily focus on the effects of vibration training on sports performance and rehabilitation, especially for the elderly, athletes, and patients with specific diseases. International studies, on the other hand, emphasize the effects of whole-body vibration on neuromuscular function, metabolic syndrome, and the rehabilitation of chronic disease patients. The key research topics in domestic studies center around vibration frequency, vibration training, and vibration therapy, while international studies focus more on postural control, muscle strength, and the comprehensive effects of whole-body vibration. Finally, future research on whole-body vibration should strengthen international collaboration, optimize training parameters, and explore personalized applications for different populations, in order to promote the widespread application of whole-body vibration technology in sports, rehabilitation, and health management. Figures and Tables | References | Related Articles | Metrics

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Insulin-like growth factors and ischemic stroke: a genome-wide association analysis in European populations Zhou Xinying, Sun Xinyue, Zhu Wenhao 2026, 30 (11):  2909-2919.  doi: 10.12307/2026.093 Abstract ( 14 )   PDF (3332KB) ( 0 )   Save BACKGROUND: In recent years, increasing evidence has shown that insulin-like growth factors may be associated with ischemic stroke. However, the causal association between insulin-like growth factors and ischemic stroke and its subtypes remain unclear. OBJECTIVE: To explore the causal association between insulin-like growth factors and ischemic stroke and its subtypes by Mendelian randomization. METHODS: We obtained genome-wide association study (GWAS) data for insulin-like growth factor from the IEU OpenGWAS database (developed by the MRC Integrative Epidemiology Unit at the University of Bristol, UK, which focuses on integrating data from epidemiology, genetics, and biostatistics), and acquired GWAS data for ischemic stroke and its subtypes (large artery stroke, cardioembolic stroke, and small vessel stroke) from the MEGASTROKE database (a collaborative initiative by the International Stroke Genetics Consortium aimed at meta-analyzing GWAS data for stroke and its subtypes). We performed two-way Mendelian randomization analysis to explore the causal association between 14 insulin-like growth factors and ischemic stroke and its subtypes. The inverse variance weighted method was used as the main statistical method. Cochran’s Q test and MR-Egger regression were used to evaluate the pleiotropy and heterogeneity. RESULTS AND CONCLUSION: (1) Results of the forward Mendelian randomization analysis showed no significant causal association between any insulin-like growth factors and the risk of ischemic stroke, large artery stroke, or small vessel stroke (all P > 0.05). However, insulin-like growth factor-binding protein 7 exhibited a negative causal relationship with cardioembolic stroke (odds ratio=0.82, 95% confidence interval=0.74–0.91, P=0.006), indicating that insulin-like growth factor-binding protein 7 is a protective factor against cardioembolic stroke. Results of the reverse Mendelian randomization analysis revealed no reverse causal relationship between ischemic stroke, large artery stroke, cardioembolic stroke, or small vessel stroke and insulin-like growth factors. (2) The findings provide epidemiological evidence on the association between insulin-like growth factors and ischemic stroke and its subtypes, highlighting the potential role of insulin-like growth factors in the pathogenesis and progression of different stroke subtypes. This study offers valuable insights for research on insulin-like growth factors and ischemic stroke in Chinese populations, contributing to a deeper understanding of the pathological mechanisms underlying ischemic stroke and suggesting novel perspectives for its prevention and treatment. Figures and Tables | References | Related Articles | Metrics

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Global research status, trends and hotspots of anxiety/depression in chronic obstructive pulmonary disease Wang Jiaying, Xu Chun, Mayila · Abudukelimu 2026, 30 (11):  2920-2932.  doi: 10.12307/2026.074 Abstract ( 17 )   PDF (6775KB) ( 1 )   Save BACKGROUND: Anxiety and depression are among the common and significant comorbidities in patients with chronic obstructive pulmonary disease, associated with poor health status and prognosis. Research on chronic obstructive pulmonary disease combined with anxiety and depression has garnered increasing attention. OBJECTIVE: From a bibliometric perspective, to analyze the global research landscape of chronic obstructive pulmonary disease with comorbid anxiety and depression, and to investigate the research hotspots and emerging trends in this field. METHODS: Relevant literature published from January 1, 2015 to November 1, 2024 was retrieved from the Web of Science Core Collection database using the search query: TS=(“Chronic obstructive pulmonary disease” AND “anxiety”) OR TS=(“Chronic obstructive pulmonary disease” AND “depression”). CiteSpace and VOSviewer were utilized to analyze and visualize the data, including annual publication trends, contributions by countries, institutions, authors, and journals. RESULTS AND CONCLUSION: During the 2014–2024 period, a total of 1 763 publications were identified in the research domain of chronic obstructive pulmonary disease comorbid with anxiety or depression. These works were authored by 9 616 authors from 83 countries and disseminated across 623 journals, demonstrating global collaborative engagement. The United States emerged as the most productive country, followed by China. The International Journal of Chronic Obstructive Pulmonary Disease was recognized as the highest-impact journal. M.A. Spruit and Maastricht University were identified as the most prolific individual author and institution, respectively. However, bibliometric analysis revealed that researcher clusters have not yet reached critical mass, indicating suboptimal interdisciplinary collaboration requiring strategic enhancement. Global research efforts concentrated on 10 thematic clusters: palliative car, chronic obstructive pulmonary disease, mental health, cardiovascular interactions, systemic inflammation, chronic disease, chronic pain, heart failure, pulmonary rehabilitation, chronic obstruction. The field has shifted through three evolutionary phases: clinical phenotyping-molecular mechanism elucidation-systemic intervention frameworks. Future research should prioritize multi-omics integration, digital biomarker discovery, and precision pharmacotherapy. Such advancements will optimize holistic management strategies for chronic obstructive pulmonary disease with comorbid anxiety and depression. Figures and Tables | References | Related Articles | Metrics

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Causal relationship between diabetes mellitus and hypertrophic cardiomyopathy: information analysis based on the GWAS database Zhao Yingxin, Lang Tong, Meng Lingbing, Gao Yuxia 2026, 30 (11):  2933-2948.  doi: 10.12307/2026.305 Abstract ( 11 )   PDF (4691KB) ( 0 )   Save BACKGROUND: Diabetes mellitus and hypertrophic cardiomyopathy influence each other, with diabetic patients exhibiting a significantly increased risk of cardiovascular complications. However, the causal relationship and underlying molecular mechanisms between these conditions remain unclear.  OBJECTIVE: To assess the causal effect of diabetes mellitus on hypertrophic cardiomyopathy using a Mendelian randomization approach combined with data from genome-wide association studies (GWAS) and Gene Expression Omnibus (GEO) databases, and to screen for key regulatory factors by bioinformatics analysis. METHODS: From the latest GWAS database (a collaboration between the U.S. National Human Genome Research Institute and the European Bioinformatics Institute), we obtained 162 single nucleotide polymorphisms associated with diabetes, which were identified from 24 659 diabetic cases and 459 939 control participants, and harvested data on hypertrophic cardiomyopathy, which were from 507 cases of hypertrophic cardiomyopathy and 489 220 control participants. A two-sample Mendelian randomization analysis was then conducted. The inverse variance weighted method was utilized to estimate the causal relationship between diabetes and hypertrophic cardiomyopathy. The diabetes dataset GSE184050 and the hypertrophic cardiomyopathy dataset GSE160997 profiles were downloaded from the GEO database. Weighted gene co-expression network analysis (WGCNA) was employed to investigate the important modules and core genes associated with diabetes and hypertrophic cardiomyopathy. Gene set enrichment analysis (GSEA) was utilized to explore enriched terms and pathways related to core genes. Core genes were inputted into the comparative toxicogenomics database (CTD) website to identify diseases most relevant to core genes. Various algorithms were applied to explore the role of HSF1 in diabetes and hypertrophic cardiomyopathy. RESULTS AND CONCLUSION: (1) We used diabetes as the exposure factor and extracted results from 160 single nucleotide polymorphisms. The inverse variance weighted method, MR-Egger, and weighted median regression methods were employed to estimate the causal relationship between genetically predicted diabetes and hypertrophic cardiomyopathy. The MR-Egger method demonstrated a significant causal association between diabetes and hypertrophic cardiomyopathy, with HSF1 identified as a core biomarker for the causal relationship between diabetes and hypertrophic cardiomyopathy (P=0.018 028 98). The weighted median and inverse variance weighted algorithms also provided consistent trends. Furthermore, validation through datasets from the GEO database confirmed HSF1 as a potential core biomarker influencing both diabetes and hypertrophic cardiomyopathy. HSF1 exhibited high expression in diabetes and low expression in hypertrophic cardiomyopathy. According to the analysis results, systematically removing individual single nucleotide polymorphisms and repeating Mendelian randomization analysis did not significantly alter the causal relationship between diabetes and hypertrophic cardiomyopathy. This suggests that no single single nucleotide polymorphisms significantly influence the causal estimate. In this study, we input HSF1 into the CTD website to identify diseases associated with core genes. Core gene HSF1 was found to be associated with diabetes, type 2 diabetes, hypertrophic cardiomyopathy, heart disease, hypertension, metabolic disorders, and inflammation. (2) This study is primarily based on large international databases, including GWAS and GEO expression profiles from European populations, and employs genetic instrumental variables for causal inference, ensuring high scientific rigor. For biomedical research in China, the findings highlight the need to strengthen the collection and integration of local multi-omics data and to apply similar approaches to identify precision prevention and treatment targets suitable for the Chinese population. Figures and Tables | References | Related Articles | Metrics