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08 October 2023, Volume 27 Issue 28 Previous Issue    Next Issue

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Size of the borehole affects rabbit tibial osteomyelitis models Qiu Xiaoming, Li Jidong, Kang Guan, Qiao Yongjie, Li Wenbo, Feng Qiangsheng, Zhen Ping, Lan Xu 2023, 27 (28):  4429-4434.  doi: 10.12307/2023.693 Abstract ( 280 )   PDF (1342KB) ( 119 )   Save BACKGROUND: Osteomyelitis remains a challenge for clinical orthopedic surgeons to address until now, and the development of ideal models of osteomyelitis was very important for the evaluation of new treatments. OBJECTIVE: To stably and effectively establish a rabbit tibia model of osteomyelitis, suitable for different experimental requirements.  METHODS: A total of 25 New Zealand white rabbits were randomly divided into three animal model groups: pore group (n=10), macropore group (n=10) and sham operation group (n=5). In the pore group, a 1 mm drill was used to drill holes in the tibia and the 100 μL Staphylococcus aureus (2×106 cfu) was injected. In the macropore group, the same method was used but the drill holes were 5 mm. The sham operation group was cut and sutured without drilling or injecting bacteria. The general state, body temperature, X-ray, CT, histopathological observation, serum C-reactive protein and procalcitonin mass concentration were measured within 1 month after surgery. RESULTS AND CONCLUSION: Compared with the sham operation group, the body temperature and serum C-reactive protein mass concentration of rabbits in the pore group and the macropore group increased in varying degrees. Molybdenum target X-ray film and CT examination: The imaging manifestations of the pore group were whole marrow cavity infection, while the macropore group was local bone defect infection. It is suggested that in the preparation of rabbit models of tibial osteomyelitis, the size of the borehole may lead to different consequences of tibial infection. The 5 mm borehole model may be suitable for the study of the efficacy of local anti-infection materials, and the 1 mm borehole model may be suitable for the evaluation of the efficacy of systemic antibiotic drug treatment of osteomyelitis. Figures and Tables | References | Related Articles | Metrics

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Establishment and validation of a clinical prediction model for severe loss of cervical lordosis after posterior cervical surgery Ma Sheng, Miao Jiahang, Yu Huilin, Li Qupeng, Qu Zhe, Pan Bin, Feng Hu 2023, 27 (28):  4435-4440.  doi: 10.12307/2023.691 Abstract ( 308 )   PDF (1035KB) ( 54 )   Save BACKGROUND: Current studies only predict the loss of cervical lordosis after cervical surgery through imaging measurement indicators and other indicators at present. There are a few articles summarizing these prediction indicators. This paper establishes a prediction model to summarize these prediction indicators. OBJECTIVE: To investigate the risk variables for severe loss of cervical lordosis following posterior cervical spondylotic myelopathy surgery, as well as to develop and validate the prediction model.  METHODS: Retrospective analysis was performed on the cervical spondylotic myelopathy patients who underwent posterior approach of cervical surgery in the Affiliated Hospital of Xuzhou Medical University from January 2015 to January 2020 and met the inclusion criteria. The observation indexes included age, sex, body mass index, surgical technique chosen, the number of operation segments, accumulation of C2 or C7, C2-7 Cobb angle prior to operation, Cobb angle of operation segment, C7 slope angle, sagittal vertical angle of the cervical spine, C2-C7 curvature, extension range of motion, and flexion range of motion. The difference between the cervical spine’s C2-7 Cobb angle before and after surgery (ΔCL) was used to calculate the change in cervical lordosis. Those with ΔCL≤-10° had significant loss of cervical lordosis, while those with ΔCL > -10° had less severe loss of cervical lordosis. Prediction models were created and validated by doing single-factor and multi-factor analyses on these parameters to identify pertinent risk factors.  RESULTS AND CONCLUSION: 117 patients in all, 48 females and 69 males, met the inclusion criteria. The follow-up time ranged from 12 to 26 months. Among these patients, 30 experienced a severe loss of cervical lordosis following surgery, while 87 patients did not have a severe loss of cervical lordosis. Statistical analysis showed that the choice of procedure, whether it involved the C2 or C7 vertebral bodies, the C2-7 Cobb angle, the C7 slope angle, the C2-C7 curvature, and flexion range of motion prior to the procedure were independent risk factors linked to serious loss of cervical lordosis following posterior cervical surgery. Most obviously, whether the surgical segment involved the C2 or C7 segment (OR=3.524, 95% CI:1.127-11.013), and the surgical approach chosen (OR=3.165, 95% CI: 1.013-9.889) were the factors that enhanced the probability of significant postoperative curvature loss. Further foundations were laid for the clinical prediction model (nomogram) and its validation. The model has an excellent capacity for prediction, as evidenced by the C-index of internal validation, which was 0.91, and the C-index of external validation in the validation group, which was 0.87. It is indicated that after posterior cervical surgery, the choice of operation method, whether the operation segment involves the C2 or C7 segment, the preoperative C2-7 Cobb angle, the C7 slope angle, and flexion mobility all are high risks of severe loss of cervical lordosis.  Figures and Tables | References | Related Articles | Metrics

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Effects of Yiqi Tongmai Fang on serum amino acid metabolism of atherosclerotic mice Wang Shurui, Zhang Yilei, Jiao Weijie, Liu Zhihua, Zhang Kuiming, Cui Yinglin 2023, 27 (28):  4441-4447.  doi: 10.12307/2023.523 Abstract ( 245 )   PDF (1616KB) ( 130 )   Save BACKGROUND: Atherosclerosis is the pathological basis of many cardiovascular and cerebrovascular diseases. Yiqi Tongmai Fang can significantly improve atherosclerosis in patients, but the metabolic spectrum and mechanism underlying the intervention of atherosclerosis using Yiqi Tongmai Fang are still incomplete. OBJECTIVE: To explore the possible mechanism of Yiqi Tongmai Fang in the treatment of atherosclerosis.  METHODS: Thirty-six male C57/B6J mice were selected, 6 of which were used as normal controls and given normal diet for 12 weeks. The remaining 30 ApoE-/- mice were randomly divided into model group, low-, medium- and high-dose Yiqi Tongmai Fang groups and atorvastatin group, with 6 mice in each group, and then were fed with high fat diet combine with intragastrical administration of sodium chloride, low-, medium- and high-dose Yiqi Tongmai Fang (0.39, 0.78, 1.56 g/kg per day) and atorvastatin (2.6 mg/kg per day), respectively. Serum and aortic tissue were collected after 12 weeks. The pathological changes of the aorta and vascular stenosis were observed by vascular histopathological section. The serum samples were analyzed by ultrahigh performance liquid chromatography-mass spectrometer for high-throughput target metabolomics, to screen different amino acids between groups.  RESULTS AND CONCLUSION: In terms of morphology, vascular pathological injury and stenosis were significantly improved in the Yiqi Tongmai Fang groups compared with the model group. In terms of serum amino acid metabolism, the levels of seven amino acids were significantly changed in the Yiqi Tongmai Fang group compared with the normal control group, including the increased levels of L-Glutamic acid, L-Tyrosine, L-Aspartate, L-Lysine and L-Valine, and the decreased levels of L-Arginine and 3-methyl-L-histidine. Yiqi Tongmai Fang could regulate the levels of different amino acids and high-dose Yiqi Tongmai Fang could regulate the most metabolites. Overall, these findings indicate that Yiqi Tongmai Fang can delay the progression of atherosclerosis and its mechanism may be related to the regulation of amino acid metabolism. Moreover, high-dose Yiqi Tongmai Fang has the most significant effect. Figures and Tables | References | Related Articles | Metrics

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Role and mechanism of Rongjin Niantong Fang for extracellular matrix metabolism of chondrocytes Zhao Zhongsheng, Chen Zhenyuan, Huang Yunmei, Zhang Ling, Wu Guangwen, Chen Jun 2023, 27 (28):  4448-4455.  doi: 10.12307/2023.522 Abstract ( 252 )   PDF (1378KB) ( 56 )   Save BACKGROUND: Our previous animal experiments have shown that Rongjin Niantong Fang can affect the decomposition and anabolism of cartilage matrix through long non-coding RNA (LncRNA) growth arrest-specific transcript 5 (GAS5)/miR-21, thereby preventing and treating knee osteoarthritis. Whether LncRNA GAS5/miR-21 can be used as a target for the prevention and treatment of knee osteoarthritis still needs to be verified at the cellular level. OBJECTIVE: To explore the mechanism of Rongjin Niantong Fang in the treatment of knee osteoarthritis at the cellular level.  METHODS: (1) Forty 8-week-old SPF male Sprague-Dawley rats were randomly divided into blank serum group, Rongjin Niantong Fang-containing serum group, and glucosamine hydrochloride capsule-containing serum group. 0.9% normal saline, Rongjin Niantong Fang (0.45 g/mL), and glucosamine hydrochloride capsule (0.015 g/mL) were intragastrically given to the rats in the corresponding groups to collect drug containing serum. (2) Cells were treated with interleukin-1β to induce degenerative chondrocyte model. (3) Chondrocytes from the knee joint of Sprague-Dawley rats were isolated and cultured. Passage 2 chondrocytes were obtained and divided into blank group (blank serum), and model group (interleukin-1β+blank serum), treatment group (interleukin-1β+Rongjin Niantong Fang-containing serum), and control group (interleukin-1β+glucosamine hydrochloride capsule-containing serum). After 48 hours of intervention, the gene and protein expressions of LncRNA GAS5, miR-21, tissue inhibitor of metalloproteinases 3 (TIMP-3), matrix metalloproteinase (MMP)-3, MMP-9, MMP-13, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-5) were detected by real-time PCR and western blot, respectively. (4) Chondrocytes were transfected with LncRNA GAS5 overexpression lentiviral vector. Then, the transfected cells were divided into LncRNA GAS5 empty vector + blank serum group, LncRNA GAS5 empty vector + Rongjin Niantong Fang-containing serum group, LncRNA GAS5 overexpression + blank serum group, and LncRNA GAS5 overexpression + Rongjin Niantong Fang-containing serum group. The gene expressions of LncRNA GAS5, miR-21, TIMP-3, MMP-9, MMP-13, and ADAMTS-5 were detected using real-time PCR.  RESULTS AND CONCLUSION: Culture with the serum containing 10% Rongjin Niantong Fang and 15% glucosamine hydrochloride capsule for 48 hours significantly increased the activity of chondrocytes. Compared with the model group, Rongjin Niantong Fang-containing serum and glucosamine hydrochloride capsule-containing serum could inhibit the gene expression of LncRNA GAS5, MMP-3, MMP-9, MMP-13, and ADAMTS-5 (P < 0.05) and promote the gene and protein expression of miR-21 and TIMP-3 (P < 0.05). Compared with the blank group, the gene expression of LncRNA GAS5, MMP-3, MMP-9, MMP-13, and ADAMTS-5 in the LncRNA GAS5 overexpression group increased significantly (P < 0.05), while the gene expression of miR-21 and TIMP-3 decreased significantly (P < 0.05). Compared with the LncRNA GAS5 overexpression+blank serum group, the gene expression of MMP-9, MMP-13, and ADAMTS-5 was significantly decreased in the LncRNA GAS5 overexpression+Rongjin Niantong Fang-containing serum group (P < 0.05), while the gene expression of miR-21 and TIMP-3 were significantly increased (P < 0.05). To conclude, Rongjin Niantong Fang could delay the degradation of cartilage extracellular matrix by promoting TIMP-3 expression and inhibiting the expression of MMP-3, MMP-9, MMP-13 and ADAMTS-5 through regulating LncRNA GAS5/miR-21, thereby preventing and treating knee osteoarthritis. Figures and Tables | References | Related Articles | Metrics

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Expression of intercellular cell adhesion molecule 1 and matrix metalloproteinase 9 in endometrium of pregnant mice with long-term exposure to low concentration of sevoflurane Shu Rui, Zhang Chengming, Zhang Ruyi, Liu Jinqian, Song Lijuan, Jing Guangjian, Yu Fei 2023, 27 (28):  4456-4461.  doi: 10.12307/2023.515 Abstract ( 255 )   PDF (1343KB) ( 78 )   Save BACKGROUND: Epidemiological studies have found that female workers who are exposed to waste sevoflurane for a long time have reduced fertility and increased incidence of abortion and fetal deformity. OBJECTIVE: To imitate the working environment of long-term exposure to waste sevoflurane and investigate the mechanism of embryo implantation disorder induced by low-concentration sevoflurane exposure by observing the expression of intercellular adhesion molecule 1, integrin β1, P-selectin, and matrix metalloproteinase 9 in endometrium of pregnant mice exposed to low concentrations of sevoflurane, attempting to provide a basis for clinical safe drug use and occupational protection and to lay a foundation for further research on the mechanism of inhalation anesthetics on embryo implantation at gene and molecular levels. METHODS: Forty female Kunming mice and sixteen male Kunming mice, aged 6 weeks, weighting (20±2) g, were caged separately. Forty female mice were randomly divided into experimental group and control group. Mice in the experimental group were exposed to 0.1% sevoflurane, 6 hours per day, while those in the control group were exposed to the air. Thirty days later, the female mice in estrus were caged with mature male mice at a rate of 2:1. Whether the female mice were pregnant was observed at 7:00 am on the second day after mating. The pregnant mice were kept independently in the original condition  (n ≥ 8 pregnant mice in each group). Mouse uterus on day 4.5 of gestation was removed and sliced for histological observation. The expression of intercellular adhesion molecule 1, integrin β1, P-selectin, and matrix metalloproteinase 9 in endometrial tissue was detected by immunohistochemistry and statistically analyzed. The average integrated absorbance value of positive reactants was calculated. RESULTS AND CONCLUSION: In the experimental and control groups, 17 and 15 female mice were respectively found in estrus; 12 and 10 female mice respectively were found vaginal plugs after mating. Five and two female mice were found pseudopregnant on day 4.5 of gestation in the experimental and control groups, respectively. Therefore, there were 7 and 8 pregnant mice in the experimental and control groups, respectively, and the vacant value in the experimental group was replaced by the average value obtained in the same group, which would be subsequently used in the controlled trial. Immunohistochemical results showed that the endometrium (glandular epithelial cells, luminal epithelial cells and stromal cells) of all pregnant mice were positively stained brownish yellow, but the expressions of intercellular adhesion molecule 1, integrin β1, P-selectin, and matrix metalloproteinase 9 (0.019±0.007, 0.017±0.007, 0.015±0.005, 0.012±0.005) in the experimental group were significantly lower than those in the control group (0.032±0.014, 0.025±0.008, 0.021±0.007, 0.023±0.005) (P < 0.05). All these findings indicate that long-term exposure to 0.1% sevoflurane may affect the adhesion of mouse embryos to endometrium and the embryo implantation, which may be related to the inhibitory effects of sevoflurane on the expressions of intercellular adhesion molecule 1, integrin β1, P-selectin, and matrix metalloproteinase 9, causing the imbalance in endometrial immunoregulation, the invasion of trophoblast cells into the endometrium and the inhibition of endometrial decidualization, and miscarriage and bleeding due to damaged vascular endothelium. Figures and Tables | References | Related Articles | Metrics

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Effect of Ratnasampil on pia microcirculation and glial scar in a rat model of cerebral infarction Ma Hui, Sun Zhengqi, Li Yansong 2023, 27 (28):  4462-4467.  doi: 10.12307/2023.576 Abstract ( 396 )   PDF (1397KB) ( 98 )   Save BACKGROUND: Improving cerebral infarction micromeningeal circulation and inhibiting scar formation can effectively treat cerebral infarction. Therefore, it is very important to develop safe and effective drugs to improve cerebral microcirculation and scar formation. OBJECTIVE: To investigate the effects of Ratnasampil on pia meningeal microcirculation, Janus kinase 2/signal transducer and activator transcription 3 protein expression and glial scar in rats with cerebral infarction. METHODS: The 15 of 95 male Sprague-Dawley rats were randomly selected as healthy group and the remaining rats used to establish cerebral infarction models. Five rats died accidentally during the modeling process and the remaining rats were successfully modeled. Model rats were divided into model group, low-dose, medium-dose and high-dose groups of Traditional Chinese medicine and nimodipine group with 15 rats in each group. Low-, medium-and high-dose groups were given 16.67, 33.34 and 66.68 g/kg Ratnasampil suspension once by intragastric administration respectively at 25 minutes before modeling. The nimodipine group was given 30 mg/kg nimodipine tablet once by intragastric administration at 25 minutes before modeling. MCIP microcirculation image processing system was used to detect cerebral blood flow velocity. Hematoxylin-eosin staining was used to observe brain histopathological morphology. Real-time fluorescence quantitative PCR was used to detect gene levels of Janus kinase 2, signal transducer and activator transcription 3, neurocan and glial fibrillary acidic protein. In situ terminal transferase labeling technique was used to measure cell apoptosis. Western blot was used to detect the protein expression of Janus kinase 2, signal transducer and activator transcription 3, phosphorylated signal transducer and activator transcription 3, neurocan and glial fibrillary acidic protein. RESULTS AND CONCLUSION: Compared with the healthy group, the nimodipine group showed reduced cerebral blood flow velocity, increased expression of Janus kinase 2, signal transducer and activator transcription 3, phosphorylated signal transducer and activator transcription 3, neurocan and glial fibrillary acidic protein, and increased neuronal apoptosis rate at different time points (P < 0.05). Compared with the nimodipine group, the low-dose group showed an increase in cerebral blood flow velocity and a reduction in neuronal apoptosis rate and the expression of Janus kinase 2, signal transducer and activator transcription 3, phosphorylated signal transducer and activator transcription 3, neurocan and glial fibrillary acidic protein (P < 0.05). Compared with the medium-dose group, the high-dose and nimodipine groups showed an increase in cerebral blood flow velocity and a reduction in neuronal apoptosis rate and the expression of Janus kinase 2, signal transducer and activator transcription 3, phosphorylated signal transducer and activator transcription 3, neurocan and glial fibrillary acidic protein (P < 0.05). Compared with the high-dose group, the nimodipine group showed decreased cerebral blood flow velocity, increased neuronal apoptosis rate and elevated expression of Janus kinase 2, signal transducer and activator transcription 3, phosphorylated signal transducer and activator transcription 3, neurocan and glial fibrillary acidic protein at different time points (P < 0.05). The histological structure of the cerebral cortex was normal in the healthy group. In the model group, the number of neurons in the cortex was decreased, some living neurons were pyknotic, and a large number of inflammatory cells were infiltrated. Compared with the model group, these changes were all improved in the low-, medium- and high-dose groups and the nimodipine group, and the high-dose group had a remarkable effect. Overall, these findings suggest that Ratnasampil may affect the formation of glial scar by inhibiting the levels of glial scar marker proteins, including neurocan and glial fibrillary acidic protein, improve the pia meningeal microcirculation, and reduce the apoptosis of brain tissue cells by inhibiting the activation of Janus kinase 2/signal transducer and activator transcription 3 pathway in rats with cerebral infarction, thus playing a role in brain protection. Figures and Tables | References | Related Articles | Metrics

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Effect of blood viscosity on computational fluid dynamics in vascular network Zheng Liqin, Lai Hourong, Dai Yuexing, He Xingpeng, Wu Minhui, Zheng Desheng, Lin Ziling 2023, 27 (28):  4468-4472.  doi: 10.12307/2023.439 Abstract ( 295 )   PDF (1599KB) ( 115 )   Save BACKGROUND: Patients with osteoporosis patients often present with increased blood viscosity, which belongs to the category of “blood stasis” in traditional Chinese medicine. How, the effects of increased blood viscosity on microvascular fluid properties remain to be elucidated. OBJECTIVE: To investigate the effect of blood viscosity on the hydrodynamics of vascular network by computational fluid dynamics.  METHODS: The three-dimensional model of vascular network was constructed based on the Geometry module of ANSYS 19.0 software, and the vascular network was then meshed to tetrahedral elements in Mesh module. The vascular network was assumed to rigid wall without slip, and the blood was assumed to laminar, viscous, and incompressible Newtonian fluid. Blood density, velocity, and a series of blood viscosity coefficients were also established. The Navier-Stokes equation was adopted for simulation. The effects of blood viscosity on the hydrodynamics of different parts of vascular network were analyzed.  RESULTS AND CONCLUSION: The streamline, velocity, mass flow, and wall shear stress in the vascular network demonstrated a “U” shaped distribution, that is, these contents in outlet and inlet were higher than those in the junction of the vascular network. With the increase of blood viscosity, the streamline, velocity, and mass flow in each part of vascular network became sparse and decreased slightly; however, the wall shear stress increased significantly. The largest percentage change in wall shear stress was observed at the intersection of vascular network. To conclude, blood viscosity will change the hydrodynamics of the vascular network, especially in term of wall shear stress. Computational fluid dynamics can provide a good insight into the influence of blood viscosity alteration on the hydrodynamic performance of the blood, thereby providing a new research tool for the study of osteoporosis based on the coupling of angiogenesis and osteogenesis by tonifying the kidney and activating the blood circulation. Figures and Tables | References | Related Articles | Metrics

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Tetrandrine inhibits osteoclast differentiation by inducing autophagy Zhang Bowen, Li Mei, Zhang Jinning, Yang Tianxiang, Cheng Mengqi, Chen Desheng 2023, 27 (28):  4473-4479.  doi: 10.12307/2023.531 Abstract ( 332 )   PDF (1486KB) ( 44 )   Save BACKGROUND: Previous studies have shown that tetrandrine can inhibit the proliferation of tumor cells by activating AMPK signaling pathway to induce autophagy. However, there are few studies on tetrandrine induced autophagy and differentiation of osteoclasts.   OBJECTIVE: To explore the effect of tetrandrine at different concentrations on autophagy during osteoclast differentiation, and analyze whether inducing autophagy of osteoclasts can inhibit their differentiation.   METHODS: Part one: Recombinant mouse macrophage colony-stimulating factor and receptor activator of nuclear factor-κB ligand cytokines were used to induce mouse RAW264.7 macrophages into osteoclasts. Mouse RAW264.7 macrophages were divided into five groups: blank group (complete medium), positive control group (treated by two cytokines), and low-, medium-, and high-concentration drug groups (treated by two cytokines and added 0.1, 0.5, and 1.0 μmol/L tetrandrine, respectively). Tartrate resistant acid phosphatase staining method was used to detect the number of mature osteoclasts. Western blot assay and RT-PCR were utilized to detect the relative expression levels of proteins of Cathepsin K, autophagy microtubule-associated protein 1 light chain 3-II, and autophagy substrate ubiquitin-binding protein (p62) at protein and mRNA levels, respectively. Monodansyl cadaverine staining was used to detect the number of autophagosomes in osteoclasts. Part two: The concentration of tetrandrine (1.0 μmol/L) with the best inhibitory effect on osteoclast differentiation was selected for regression verification. Cells were divided into positive control group (treated by two cytokines), autophagy inhibitor group (bafloamycin), drug intervention group (tetrandrine), and drug intervention+authophage inhibitor group. Tartrate resistant acid phosphatase staining was used to detect the number of mature osteoclasts. Western blot assay was utilized to detect the relative protein expression level of Cathepsin K.  RESULTS AND CONCLUSION: Tetrandrine at a certain concentration inhibited the differentiation of osteoclasts and the inhibitory effect increased with the increase of drug concentration. Tetrandrine at a certain concentration could stimulate the expression of autophagy markers, reduce the accumulation of autophagy specific substrates during osteoclast differentiation, and stimulate the formation of autophagosomes during osteoclast differentiation. After using autophagy inhibitor, the effect of tetrandrine on inhibiting osteoclast differentiation was significantly affected. In conclusion, tetrandrine at a certain concentration can inhibit the differentiation of osteoclasts by activating autophagy. Figures and Tables | References | Related Articles | Metrics

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Expression and effect of microRNA-2116-3p in human hypertrophic scar Tian Wenrong, Zuo Jun, Yu Yang, Qi Yusong, Ai Jiang, Bu Panpan, Zhao Jiaojun, Ma Zhiwei, Li Peipei, Ma Shaolin 2023, 27 (28):  4480-4486.  doi: 10.12307/2023.562 Abstract ( 242 )   PDF (1257KB) ( 42 )   Save BACKGROUND: A wide range of studies have demonstrated that microRNA (miR) plays a crucial role in hypertrophic scars development, and type I collagen is closely related to hypertrophic scar fibroblasts. There might be a relationship between miR-2116-3p and occurrence and development of hypertrophic scars. OBJECTIVE: To investigate the expression and role of miR-2116-3p on human hypertrophic scar fibroblasts. METHODS: Hypertrophic scar tissues were collected from six patients from the First Affiliated Hospital of Xinjiang Medical University and normal skin tissues were collected from another six patients after blepharoplasty in the same unit at the same time. The expression of miR-2116-3p and type I collagen was detected by qRT-PCR. Hypertrophic scar tissues were taken and primary cells were cultured to passages 3 to 6. Hypertrophic scar fibroblasts were divided into negative control group, miR-2116-3p mimic group, and miR-2116-3p inhibitor group, and transfected with corresponding sequences. Cell proliferation was detected by cell counting kit-8 and EdU kit. Cell migration was detected by cell scratch assay, and apoptosis was detected by flow cytometry. Expression of type I collagen, type III collagen and α-smooth muscle actin was detected by western blot and qRT-PCR at protein and mRNA levels, respectively. Dual luciferase reporter assay system was used to carry out targeting assays. RESULTS AND CONCLUSION: The mRNA expression of miR-2116-3p and type I collagen in hypertrophic scar tissues was significantly lower than that in normal skin tissues (P < 0.01). After 24, 48, and 72 hours of transfection, the cell viability of the miR-2116-3p mimic group was significantly lower than that of the negative control group (P < 0.05 or P < 0.01), while the cell viability of miR-2116-3p inhibitor group was significantly higher than that of the negative control group (P < 0.05 or P < 0.01). At 48 hours after transfection, the number of EdU positive cells in the miR-2116-3p mimic group was significantly lower than that in the negative control group, while the number of EdU positive cells in the miR-2116-3p inhibitor group was significantly higher than that in the negative control group (P < 0.05). At 24 hours after transfection, the cell scratch area and apoptotic rate of the miR-2116-3p mimic group were significantly higher than those of the negative control group (P < 0.01), and while the cell scratch area and apoptotic rate of the miR-2116-3p inhibitor group werer significantly lower than those of the negative control group (P < 0.01 or P < 0.05). At 24 hours after transfection, the mRMA and protein expression levels of type I collagen, type II collagen and α-smooth muscle actin were significantly decreased in the miR-2116-3p mimic group (P < 0.05 or P < 0.01) and significantly increased in the miR-2116-3p inhibitor group (P < 0.01) compared with the negative control group. Results from the dual luciferase assay showed that miR-2116-3p could bind to type I collagen. To conclude, the expression of miR-2116-3p is down-regulated in human hypertrophic scar. miR-2116-3p may inhibit the proliferation and migration of human hypertrophic scar fibroblasts and promote their apoptosis by targeting the expression of type I collagen. Figures and Tables | References | Related Articles | Metrics

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Effect of ginsenoside Rg1 on learning and memory ability of brain aging mice induced by D-galactose Yang Yazhu, Du Juan, Qu Haifeng, Li Jianmin, Zhang Yuxin, Liu Junjie 2023, 27 (28):  4487-4493.  doi: 10.12307/2023.556 Abstract ( 226 )   PDF (1320KB) ( 43 )   Save BACKGROUND: Brain aging can decline learning and memory functions, and the mechanism is not clear. Recent studies have found that ginsenoside Rb1 can improve the learning and memory ability of Alzheimer’s disease model mice, and its mechanism may be related to the improvement of postsynaptic density protein 95 expression. OBJECTIVE: To investigate whether ginsenoside Rg1 can improve the learning and memory function and postsynaptic density protein 95 expression in the hippocampus of D-galactose-induced aging mice through brain-derived neurotrophic factor/TrkB signaling pathway.  METHODS: Fifty male SPF Kunlun mice were randomly divided into five groups, A, B, C, D, and E, with 10 mice in each group. Group A: normal blank control group with no treatment; group B: brain aging model was established through subcutaneous injection of D-galactose solution 300 mg/kg per day; group C: at 1 hour after modeling, donepezil hydrochloride was intragastrically administered daily; group D: at 1 hour after modeling, ginsenoside Rg1 was intragastrically given; group E: at 1 hour after modeling, ginsenoside Rg1 (30 mg/kg per day) was intragastrically given and selective TrkB blocker ANA-12 was intraperitoneally injected every 2 days. Mice in each group were administered according to the corresponding dose and frequency for 6 weeks. The following contents were observed: learning and memory ability (open field test, novel object recognition test, and Morris water maze test); morphological observation of brain tissue using hematoxylin-eosin staining and Nissl staining; and western blot detection of postsynaptic density protein 95 and brain-derived neurotrophic factor protein expression in mouse hippocampus.  RESULTS AND CONCLUSION: Compared with group A, the learning and memory abilities of mice in group B were significantly decreased (P < 0.05); compared with group B, the learning and memory abilities of mice were significantly improved in groups C and D (P < 0.05); compared with group D, the learning and memory abilities of mice were significantly decreased in group E (P < 0.05). Results of hematoxylin-eosin staining and Nissl staining showed that: compared with group A, the number of normal neurons in the hippocampal CA1 region was reduced and the expression of Nissl bodies was significantly reduced in group B; compared with group B, the number of normal neurons increased and the number of Nissl corpuscle granules increased significantly in groups C and D; compared with group D, the number of normal neurons was reduced and the expression of Nissl bodies were significantly reduced in group E. Western blot results indicated that compared with group A, the expressions of postsynaptic density protein 95 and brain-derived neurotrophic factor in the hippocampus of mice were significantly decreased in group B (P < 0.05); compared with group B, the expressions of postsynaptic density protein 95 and brain-derived neurotrophic factor were significantly increased in groups C and D (P < 0.05); compared with group D, the expression of postsynaptic density protein 95 was significantly decreased in group E (P < 0.05), while the expression of brain-derived neurotrophic factor had no statistical difference (P > 0.05). To conclude, ginsenoside Rg1 can improve D-galactose-induced neuronal damage and learning and memory abilities in brain aging mice and promote the expression of postsynaptic density protein 95 in the hippocampus. The brain-derived neurotrophic factor/TrKB signaling pathway may be one of its mechanisms. Figures and Tables | References | Related Articles | Metrics

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Zoledronic acid promotes alveolar bone formation in ovariectomized rats Song Na, Liu Guanjuan, Cheng Yuting, Xiong Yue, Luo Shanshan, Hong Wei, Liao Jian 2023, 27 (28):  4494-4501.  doi: 10.12307/2023.518 Abstract ( 311 )   PDF (1335KB) ( 64 )   Save BACKGROUND: Zoledronic acid mainly acts on the formation of osteoclasts and also inhibits osteoblast apoptosis, proliferation, and differentiation. However, the effect and mechanism of zoledronic acid on alveolar bone formation in ovariectomized rats are still controversial. OBJECTIVE: To explore the osteogenic effect of zoledronic acid on alveolar bone of ovariectomized rats via alveolar nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/cysteinyl-aspartate protease-1 (Caspase-1)/interleukin-1β pathway. METHODS: Totally 36 female Sprague-Dawley rats were randomly divided into control group, model group, and zoledronic acid group, with 12 rats in each group. Bilateral oophorectomy was used to establish an animal model of osteoporosis in the latter two groups. The zoledronic acid group was subcutaneously given 20 μg/kg zoledronic acid at 12 weeks after modeling, while the control and model groups were injected with the same dose of normal saline. All animals were anesthetized after 4-week drug intervention to collect serum samples from the abdominal aorta and alveolar bone samples. Serum alkaline phosphatase, osteocalcin and interleukin-1β levels were detected by ELISA. Hematoxylin-eosin staining was used to observe the pathological changes of rat alveolar bone. TUNEL staining was used to detect the apoptosis of osteoblasts in rat alveolar bone. The formation of alveolar bone was detected by calcein fluorescent labeling. Western blot assay was used to detect the levels of NLPR3, Caspase-1 and interleukin-1β in alveolar bone tissue as well the protein expression of Runt related transcription factor 2, alkaline phosphatase, and osteocalcin. RESULTS AND CONCLUSION: Compared with the model group, the expression level of alkaline phosphatase in rat serum decreased in the zoledronic acid group (P < 0.01), while the expression level of osteocalcin increased significantly (P < 0.05). Compared with the model group, the pathological structure of alveolar bone in the zoledronic acid group was improved. The number of TUNEL positive cells in the zoledronic acid group was significantly lower than that in the model group (P < 0.001). The mineralization deposition rate and new bone formation rate of trabecular bone in the zoledronic acid group were higher than those in the model group (P < 0.05). (5) Western blot results showed that compared with the control group, NLRP3, Caspase-1, interleukin-1β proteins was highly expressed in the model group (P < 0.05), while the expressions of Runt related transcription factor 2, alkaline phosphatase, and osteocalcin proteins were decreased (P < 0.05). However, treatment with zoledronic acid decreased the protein expression of NLRP3, Caspase-1, and interleukin-1β (P < 0.05), but increased the protein expression of Runt related transcription factor 2, alkaline phosphatase, and osteocalcin (P < 0.05). The above results show that zoledronic acid can affect the expression of osteogenic related factors and inflammatory factors in serum to improve bone metabolism and inflammatory response, enhance the differentiation function of osteoblasts, and delay the formation of osteoporosis. Zoledronic acid can improve alveolar bone structure, reduce alveolar bone osteoblast apoptosis and the protein expression of NLRP3, Caspase-1, and interleukin-1β, increase the mineralization deposition rate and new bone formation rate of alveolar bone trabecula and the protein expression of Runt related transcription factor 2, alkaline phosphatase, and osteocalcin, which may be related to the inhibition of NLRP3/Caspase-1/interleukin-1β signaling pathway. Figures and Tables | References | Related Articles | Metrics

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Effects of Gushukang on transforming growth factor beta1 and beta-catenin during molar intrusion in Beagle dogs Wan Zhe, Du Jun, Hu Yang 2023, 27 (28):  4502-4506.  doi: 10.12307/2023.511 Abstract ( 195 )   PDF (1641KB) ( 54 )   Save BACKGROUND: Gushukang can effectively promote apoptosis of osteoclasts, increase bone mineral density and bone mineral content, and inhibit bone resorption. However, studies on root resorption are scarce and its regulatory mechanism remains unclear.   OBJECTIVE: To investigate the effect of Gushukang on root resorption and expression of transforming growth factor-β1 and β-catenin in Beagle dogs.   METHODS: Sixteen Beagle dogs were randomly divided into normal control group (n=4), distilled water group (n=6), and Gushukang group (n=6). Normal control group did not do any treatment. Distilled water group and Gushukang group established Maxillary first molar intrusion models were established in the distilled water and Gushukang groups. After modeling, distilled water and Gushukang groups were intragastrically given distilled water and Gushukang at a dose of 2.1 g/kg body mass respectively. After 6, 9, and 12 weeks of intervention, Beagle dogs were anesthetized to collect root and periodontal tissues of the maxillary first molars. The pathological changes were observed by hematoxylin-eosin staining and the expression levels of transforming growth factor-β1 and β-catenin were detected by immunohistochemistry.   RESULTS AND CONCLUSION: The maxillary first molars were obviously intruded over time, especially at the 12th week. The results of hematoxylin-eosin staining revealed that the number of osteoclasts in molar tissue increased in the distilled water group with the prolongation of loading, accompanied by aggravated bone resorption. The Gushukang group had less resorption of molar root and better ability of bone repair and periodontal tissue remodeling than the distilled water group. The expression levels of transforming growth factor-β1 and β-catenin in the distilled water group were significantly lower than those in the normal control group (P < 0.05), while the expression levels of transforming growth factor-β1 and β-catenin in molar tissue of the Gushukang group increased with time, which were significantly higher than those in the distilled water group at the 9th and 12th weeks (P < 0.05).  To conclude, Gushukang could regulate transforming growth factor-β1 and β-catenin and promote osteogenic differentiation of molar bone tissue in Beagle dogs.   Figures and Tables | References | Related Articles | Metrics

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Effect of Bushen Zhuanggu Fang on bone metabolism and bone mineral density in rats with ovariectomized osteoporosis Su Hui, Yan Binghan, Wang Ruochong, Xue Haipeng, Tan Guoqing, Xu Zhanwang 2023, 27 (28):  4507-4512.  doi: 10.12307/2023.538 Abstract ( 260 )   PDF (1818KB) ( 36 )   Save BACKGROUND: Chinese medicine with its good treatment effect and safety is increasingly applied to the treatment of osteoporosis. Bushen Zhuanggu Fang is currently widely used in clinical practice as an agreement of the Affiliated Hospital of Shandong University of Chinese Medicine, and has obtained excellent treatment results.  OBJECTIVE: To evaluate the effects of Bushen Zhuanggu Fang on bone metabolism and bone density in a rat model of ovariectomized osteoporosis. METHODS: Sixty Sprague-Dawley rats were randomly grouped into sham group, model group, alendronate sodium group, high-, middle-, and low-dose Bushen Zhuanggu Fang groups (n=10 per group). Rat models of ovariectomized osteoporosis were made in the latter five groups. The sham group received no intervention except for the removal of periovarian adipose tissue. After 8 weeks of modeling, high-, middle- and low-dose Bushen Zhuanggu Fang groups were given 2.34, 1.17, 0.58 g/kg per day, respectively, the alendronate sodium group was given 1 mg/kg per day, and sham operation group and model group were intragastrically given the same volume of normal saline, once a day. The serum levels of alkaline phosphatase, RUNT-related transcription factor 2 and receptor activator of nuclear factor-κB ligand were detected after 12 weeks of continuous gavage. The bone mineral density and microstructure of the right femur were observed. Hematoxylin-eosin staining was used to observe histopathological changes. The expressions of Wnt1 and bone morphogenetic protein 2 were immunohistochemically detected. RESULTS AND CONCLUSION: Compared with the sham group, the bone mineral density and bone trabecular number of the model group were significantly reduced at 8 weeks after modeling (P < 0.05), indicating the successful modeling. Compared with the model group, the bone mineral density, bone volume ratio, bone surface area/tissue volume ratio, and the number of bone trabeculae were significantly increased, while trabecular separation was significantly reduced in the low-, middle-, and high-dose Bushen Zhuanggu Fang groups and the alendronate sodium group (P < 0.01). Moreover, the alendronate sodium group showed better improvements than the three Bushen Zhuanggu Fang groups. Hematoxylin-eosin staining results showed that compared with the model group, the number and continuity of bone trabeculae were increased in the low-, middle- and high-dose Bushen Zhuanggu Fang groups and alendronate sodium group, indicating that Bushen Zhuanggu Fang could significantly improve the bone microstructure of ovariectomized rats. The serum levels of RUNT-related transcription factor 2 in the low-, middle- and high-dose Bushen Zhuanggu Fang groups and the alendronate sodium group were higher than those in the model group (P < 0.01), while the levels of alkaline phosphatase and receptor activator of nuclear factor-κB ligand were significantly lower than those in the model group (P < 0.01). The alendronate sodium group showed better improvement effects than the three Bushen Zhuanggu Fang groups. Immunohistochemistry results showed that the relative expressions of Wnt1 and bone morphogenetic protein 2 in the femur of rats were significantly increased in the low-, middle- and high-dose Bushen Zhuanggu Fang groups and the alendronate sodium group. To conclude, Bushen Zhuanggu Fang can partially improve bone metabolism imbalance in rats, improve the levels of bone formation-related factors, and thereby improve the imbalance between bone resorption and bone formation. Figures and Tables | References | Related Articles | Metrics

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Effects of long non-coding RNA H19 on apoptosis of osteoblasts induced by dexamethasone Yang Huixia, Bai Zhigang, Chi Hongyang, Ma Tianlong, Ma Shengchao, Jiang Yideng 2023, 27 (28):  4513-4518.  doi: 10.12307/2023.500 Abstract ( 206 )   PDF (2469KB) ( 59 )   Save BACKGROUND: The pathogenesis of steroid-induced osteonecrosis of femoral head is still unclear, which is closely related to osteoblast apoptosis. OBJECTIVE: To investigate the role of long non-coding RNA H19 (lncRNA H19) in dexamethasone-induced osteoblast apoptosis. METHODS: Mouse osteoblasts (MC3T3-E1) were cultured and divided into control group (no treatment) and dexamethasone group (treated with 1 μmol/L dexamethasone for 24 hours). Western blot was used to detect the protein expression levels of Bax, Bcl-2, and p-ERK1/2/ERK1/2. Flow cytometry and cell viability staining were used to detected cell apoptosis. qRT-PCR was performed to detect the expression of lncRNA H19. lncRNA H19 negative control plasmid (ad-NC) and lncRNA H19 overexpression plasmid (ad-lncRNA H19) were transfected into MC3T3-E1 cells, followed by 24 hours of dexamethasone intervention. Cell apoptosis of MC3T3-E1 was detected using cell viability staining, western blot assay, and flow cytometry. MC3T3-E1 cells were treated with MAPK-ERK pathway inhibitor (PD98059) for 24 hours and western blot was used to detect the protein expression levels of Bax and Bcl-2.   RESULTS AND CONCLUSION: Compared with the control group, the apoptotic rate of MC3T3-E1 cells was increased in the dexamethasone group (P < 0.01), while the expression of lncRNA H19 was decreased (P < 0.01) and the MAPK/ERK signaling pathway was inhibited. Up-regulation of lncRNA H19 in MC3T3-E1 cells reduced the apoptosis of cells (P < 0.01) and activated the MAPK/ERK signaling pathway. MC3T3-E1 cells treated with dexamethasone+ad-lncRNA H19+PD98059 showed an increase in the expression of Bax (P < 0.01) and a decrease in the expression of Bcl-2 (P < 0.01) compared with the cells treated with dexamethasone+ad-lncRNA H19. These findings indicate that overexpression of lncRNA H19 can inhibit dexamethasone-induced apoptosis in MC3T3-E1 cells by activating the MAPK-ERK signaling pathway. Figures and Tables | References | Related Articles | Metrics

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Relaxin protects myocardial microvascular endothelial cells from hypoxia-reoxygenation injury Wei Qin, Amanguli·Ruze, Chen Bingxin, Zhao Ling, Zhao Banghao, Jiang Tao, Zhang Chun, Li Zhiqiang, Gao Xiaoming, Duan Mingjun 2023, 27 (28):  4519-4524.  doi: 10.12307/2023.568 Abstract ( 308 )   PDF (956KB) ( 53 )   Save BACKGROUND: Relaxin can significantly improve cardiac and renal dysfuction caused by pathological factors, inhibit myocardial hypertrophy, have an anti-fibrosis effect, and improve ischemia-reperfusion injury. However, its protective mechanism against hypoxia-reoxygenation injury of endothelial cells remains unclear. OBJECTIVE: To investigate the protective mechanism of relaxin against hypoxia-reoxygenation injury of myocardial microvascular endothelial cells. METHODS: Mouse myocardial microvascular endothelial cell line (H5V cells) was used for the experiment. Cells were treated by three different interventions: in control group, cells were normally cultured for 33 hours; in model group, cells were treated by 6-hour hypoxia followed by 3-hour reoxygenation); and in relaxin group, 24 hours of routine culture (180 ng/mL relaxin), 6 hours of hypoxia and 3 hours of reoxygenation (180 ng/mL relaxin) were given to simulate myocardial hypoxia-reperfusion injury. Cell permeability and Caspase-3 activity were then detected. Levels of tumor necrosis factor-α, interleukin-1β and interleukin-6 in cell supernatants were detected by ELISA. Expressions of VE-cadherin, Akt, and GSK-3β at mRNA and protein levels were detected by RT-PCR and western blot, respectively. RESULTS AND CONCLUSION: Compared with the control group, the cell permeability and expression of caspase-3 increased significantly in the model group (P < 0.05). Compared with the model group, the cell permeability and expression of caspase-3 decreased in the relaxin group (P < 0.05). Moreover, the levels of tumor necrosis factor-α, interleukin-1β and interleukin-6 were elevated in the model group, while the levels were significantly decreased after relaxin treatment (all P < 0.05). There were no significantly changes in the mRNA and protein expressions of VE-cadherin, Akt1, and GSK-3β mRNA among three groups (all P > 0.05). Compared with the control group, the expression of phosphorylated VE-cadherin, Akt1 and GSK-3β were decreased in the model group (P < 0.05), and relaxin treatment reversed these changes to the control levels (P < 0.05). To conclude, relaxin treatment could enhance VE-cadherin expression, reduce hypoxia-reoxygenation-induced microvascular endothelial cell damage, inhibit inflammatory cytokine release, and reduce cell apoptosis, which may be related to the activation of the Akt/GSK-3β signaling pathway. Figures and Tables | References | Related Articles | Metrics

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Screening and identification of Hub genes in osteoarthritis based on bioinformatics Wu Suwen, Chen Zheng, Jiang Yuankang, Chen Leilei 2023, 27 (28):  4525-4532.  doi: 10.12307/2023.567 Abstract ( 404 )   PDF (1999KB) ( 68 )   Save BACKGROUND: Osteoarthritis is a degenerative disease characterized by joint pain, stiffness and swelling. At present, the pathogenesis of osteoarthritis is not clear. OBJECTIVE: To screen out Hub genes in osteoarthritis-related data sets based on bioinformatics and then identify them using cell experiments to screen the key biomarkers of osteoarthritis. METHODS: Osteoarthritis-related data sets were searched from GEO database and differentially expressed genes were identified by GEO2R analysis. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed for differentially expressed genes. Meanwhile, a gene set enrichment analysis was performed for all genes in the data set. Protein-protein network was constructed by inputting differentially expressed genes on String website. The functional modules of the protein-protein network were analyzed by MCODE plug-in in Cytoscape software and the top 10 Hub genes were identified by CytoHubba plug-in. The knee meniscus cells of Sprague-Dawley rats were extracted. In the experimental group, interleukin-1β (10 ng/mL) was used to intervene the cells for 24 hours. Cells with no intervention were used as controls. The expression of Hub genes was detected by RT-qPCR. RESULTS AND CONCLUSION: A total of 147 differentially expressed genes were up-regulated and 212 down-regulated. Gene ontology, Kyoto Encyclopedia of Genes and Genomes enrichment and gene set enrichment analyses showed that the enriched pathways and biological processes mainly involved collagen fiber organization, extracellular matrix interaction, Th17 cell differentiation and interleukin-17. CytoHubba, a plug-in in Cytoscape software, was used to identify the top 10 Hub genes in MCC algorithm, including COL1A1, COL3A1, COL5A1, COL5A2, COL6A3, LOX, LOXL1, LOXL2, POSTN, and PLOD1. RT-qPCR results showed that compared with the control group, the mRNA expression of COL1A1, COL3A1, COL5A1, COL5A2, COL6A3, LOXL1, and LOXL2 decreased (P < 0.000 1), while the mRNA expression of LOX and POSTN increased (P < 0.000 1). However, there was no significant difference in the PLOD1 expression between the two groups (P > 0.05). To conclude, differentially expressed Hub genes in osteoarthritis may provide new insights into the development of osteoarthritis in the future.    Figures and Tables | References | Related Articles | Metrics

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Comparison of two kinds of tendon fixation in arthroscopy for treating proximal lesions of long head of biceps tendons Gong Li, Zhou Ming, Fan Shaoyong, Hou Huiming, Zou Wen, Hu Liangshen 2023, 27 (28):  4533-4538.  doi: 10.12307/2023.696 Abstract ( 254 )   PDF (1020KB) ( 45 )   Save BACKGROUND: For young patients with proximal lesions of long head of biceps tendons with high requirements for upper limb movement, the commonly tendon fixation includes interface extrusion screw fixation and suture anchor ligation fixation. At present, there are few clinical reports and no conclusion on the comparison of the clinical efficacy of the two. OBJECTIVE: To compare the clinical efficacy of proximal lesions of long head of biceps tendons by interface extrusion screw fixation and suture anchor ligation fixation in arthroscopy.  METHODS: Totally 52 patients with proximal lesions of long head of biceps tendons treated in Nanchang Hongdu Hospital of TCM from January 2019 to December 2020 were enrolled and randomly divided into interface extrusion screw group (n=29) and suture screw group (n=23). The patients in both groups were subjected to interface extrusion screw fixation and suture anchor ligation fixation in arthroscopy, respectively. Before, 1, 3, 6, and 12 months after operation, and during last follow-up, shoulder visual analog scale score, the American shoulder and elbow surgeons score, and range of motion in anterior flexion of shoulder and internal and external rotation at elbow flexion 90° were compared between the two groups. Elbow flexion muscle strength, reoperation rate and complication rate (Popeye sign) were compared between the two groups at the last follow-up. RESULTS AND CONCLUSION: The visual analog scale scores, the American shoulder and elbow surgeons score and shoulder range of motion in anterior flexion of shoulder and internal and external rotation at elbow flexion 90° were significantly improved after operation compared with those before operation in both groups (P < 0.05). There were no significant differences in visual analog scale scores, the American shoulder and elbow surgeons score and shoulder range of motion in anterior flexion of shoulder and internal and external rotation at elbow flexion 90° between the two groups before and at various time points after operation (P > 0.05). At the last follow-up, the elbow flexion muscle strength of the two groups reached above grade IV, and the results showed no significant difference. Popeye syndrome occurred in the interface extrusion screw group (14%) and reoperation was performed (7%). In the suture screw group, the incidence of Popeye sign was 4.3% and the reoperation rate was 0%. The incidence of Popeye sign and the reoperation rate were not significantly different between the two groups (P > 0.05). For the proximal lesion of long head of biceps tendons, both the interface extrusion screw fixation and the suture anchor ligation fixation in the arthroscopy can effectively relieve shoulder pain and improve shoulder function within one year and the clinical effects of the two methods are equivalent. Figures and Tables | References | Related Articles | Metrics

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Construction of a risk model of steroid-induced necrosis of the femoral head and prediction of potential Chinese medicine treatments Zhang Xiaoyun, Gao Zhengang, Chen Feng, Zeng Hao, Liu Hua, Su Yunyu 2023, 27 (28):  4539-4545.  doi: 10.12307/2023.519 Abstract ( 279 )   PDF (2576KB) ( 60 )   Save BACKGROUND: With the change of disease treatment mode, people have realized the importance of traditional Chinese medicine in the treatment of steroid-induced necrosis of the femoral head (SANFH). Therefore, bioinformatics is used to analyze the pathogenesis of SANFH at the molecular level, build a disease risk model, and predict the potential therapeutic effects of traditional Chinese medicine, so as to provide a theoretical basis for the treatment of SANFH by traditional Chinese medicine in the future. OBJECTIVE: To mine the competing endogenous RNA regulatory network of SANFH based on bioinformatics, analyze its molecular regulatory mechanism in SANFH, predict relevant disease targets, build disease risk models, and predict Chinese herbal medicines with potential therapeutic effects. METHODS: The GEO database was searched to download the SANFH matrix file GSE123568 and gene annotation file GPL15207. The differentially expressed long non-coding RNAs and mRNAs were obtained by software analysis such as R language, and the miRNA-mRNAs associated with the differentially expressed long non-coding RNAs were predicted through the public database. Then, predicted and differentially expressed mRNAs were intersected and integrated to obtain the competing endogenous RNA network. STRING database and Cytoscape software were used to screen key genes and R language was used to analyze the functions and related pathways of key genes and mine the key competing endogenous RNA network. Finally, the risk model of SANFH was constructed according to the key genes and the prediction of traditional Chinese medicine was carried out. RESULTS AND CONCLUSION: Compared with healthy controls, a total of 7 long non-coding RNAs and 1763 mRNAs were differentially expressed in SANFH patients. Six key genes including STAT3, KAT2B, AGO4, JAK2, JAK1, and PTGS2 were identified. The enriched functions of key genes include biological processes such as response to peptide hormones, interleukin-6-mediated signaling pathways, and cell responses to interleukin-6, and are involved in signaling pathways such as JAK-STAT, adipocytokines, and prolactin. Four miRNAs (miR- 135a-5p, miR-137, miR-17-5p, miR-20b-5p) and two long non-coding RNAs (SNHG11, C20orf197) may play a key role in the occurrence and development of SANFH. KAT2B is most likely to be a risk factor for SANFH. Turmeric, Epimedium, and Astragalus have the potential to treat SANFH. Through the analysis of the competing endogenous RNA network mediated by SANFH-related long non-coding RNAs, potential disease targets, signaling pathways, and potential therapeutic traditional Chinese medicines can be identified, providing a reference for further clarifying its pathogenesis in subsequent experimental research. Figures and Tables | References | Related Articles | Metrics

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Icariin improves pituitary development in hypothyroidism model rats Bai Gaigai, Zhao Yujuan, Wei Jiakai, Huang Wendi, An Yao, Wang Zhi 2023, 27 (28):  4546-4553.  doi: 10.12307/2023.151 Abstract ( 295 )   PDF (1352KB) ( 71 )   Save BACKGROUND: Hypothyroidism is often accompanied by inadequate secretion of pituitary synthetic secretory hormones. Some studies have shown that icariin has an exact effect on pituitary hormone secretion deficiency caused by hypothyroidism, but the mechanism is still unclear. OBJECTIVE: To investigate the effect and mechanism of icariin on pituitary hormone synthesis and secretion after hypothyroidism in rats.  METHODS: (1) Forty newborn female Sprague-Dawley rats were randomized into control, model, 75, 150, 300 mg/kg icariin groups with 8 rats in each group. The rats in the latter four groups were intragastrically treated with propylthiouracil (1.5 mg/kg/day) to construct a hypothyroid rat model, and treated with different doses (0, 75, 150, and 300 mg/kg) of icariin. The expression of miR-17-5p, LIM homeobox 4 (LHX4), prop paired end homology 1 protein (PROP1), and HESX1 was detected, as well as hormone content synthetized and secreted by the pituitary gland. (2) Co-cultured rat thyrocytes and anterior pituitary cells were treated with lithium salt, and different concentrations of icariin (10, 30, 50, 70, 100 μmol/L) were administered. Anterior pituitary cell viability was assessed by cell counting kit-8. Follicle-stimulating hormone, growth hormone, and thyroid-stimulating hormone levels were detected by ELISA kits. miR-17-5p expression was detected by real-time fluorescence quantitative PCR. PROP1 and HESX1 protein levels were measured by western blot assay. The binding relationship between miR-17-5p and LHX4 was examined by RNA binding protein immunoprecipitation and dual luciferin reporter assays.  RESULTS AND CONCLUSION: In vivo results showed that the treatment with 150 mg/kg icariin decreased the contents of thyroid-stimulating hormone and significantly increased the contents of growth hormone and follicle-stimulating hormone compared with the model group. In addition, the hormone secretion levels of serum free triiodothyronine, serum free thyroxine, serum triiodothyronine, and serum thyroxine were increased in the 150 mg/kg icariin group compared with the model group. Intervention with 50, 70 and 100 μmol/L icariin could enhance the cell viability of rat anterior pituitary cells (P < 0.01), among which 70 μmol/L icariin had the best effect (P < 0.01). Icariin treatment inhibited the increased expression of miR-17-5p and upregulated the expression of PROP1 and HESX1 in lithium salt-treated rat anterior pituitary cells (P < 0.05). The contents of growth hormone and follicle-stimulating hormone in the cell supernatant of the lithium salt treated group were obviously decreased, and the content of thyrotropin was significantly increased compared with the control (P < 0.01). When the cells were intervened with different doses of icariin, the contents of growth hormone (P < 0.01) and follicle stimulating hormone (P < 0.01) increased, the level of thyroid-stimulating hormone (P < 0.01) decreased significantly, and the best intervention effect was achieved at 70 μmol/L, with a significant difference (P < 0.01). Compared with the control group, transfection with miR-17-5p mimic inhibited cell viability of anterior pituitary cells (P < 0.05), downregulated the protein expression of PROP1 and HESX1 in the cells, increased thyrotropin content (P < 0.05), and decreased growth hormone (P < 0.01) and follicle-stimulating hormone (P < 0.01) contents in the cells (P < 0.01), whereas transfection with miR-17-5p inhibitor had the opposite effect as transfection with miR-17-5p mimic. LHX4 is a target gene of miR-17-5p. Overexpression of LHX4 increased cell viability, promoted PROP1 and HESX1 protein expression (P < 0.01), reduced thyrotropin content (P < 0.05), and increased growth hormone (P < 0.01) and follicle-stimulating hormone (P < 0.05) contents. To conclude, icariin may restore the level of secretory hormones synthesized by dysregulated pituitary gland through the miR-17-5p/LHX4 axis. Figures and Tables | References | Related Articles | Metrics

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Key pathways and hub genes of osteoarthritis based on transcriptome data of sports injury synovial tissue Fu Dongge, He Jingzi 2023, 27 (28):  4554-4558.  doi: 10.12307/2023.683 Abstract ( 289 )   PDF (1421KB) ( 59 )   Save BACKGROUND: Osteoarthritis is inseparable from synovitis, so it has important clinical significance to explore osteoarthritis pathogenesis based on synovial tissue.  OBJECTIVE: To explore the diagnosis and therapeutic targets of osteoarthritis from the perspective of synovium through analyzing the transcriptome data of synovial tissues between patients with osteoarthritis and healthy controls based on bioinformatics methods, as well as to provide follow-up research ideas for osteoarthritis.  METHODS: Datasets containing normal and osteoarthritis synovial tissues were screened from Gene Expression Omnibus (GEO) database. GSE55457 and GSE55235 were selected, both of which contained 10 synovial tissue samples of osteoarthritis and 10 synovial tissue samples of healthy controls. GEO2R was utilized to perform differential gene expression analysis of GSE55457 and GSE55235 datasets, and genes with adjusted P values (adj.P) < 0.05 were collected. The online tool Xiantao Academy was used to obtained common up-regulated and down-regulated differentially expressed genes in the two datasets. GO functional annotation and KEGG pathway enrichment analysis for differentially expressed genes were performed. The STRING database was used to perform protein-protein interaction analysis. The results were visualized in Cytoscape software through CytoHubba App by 7 algorithms (BottleNeck, Clossness, Degree, DNNC, EPC, NNC and MCC). The top 10 genes with the highest scores were picked out for each algorithm, and the intersected genes of 7 algorithms were selected as the hub genes of osteoarthritis.  RESULTS AND CONCLUSION: 200 common up-regulated differential genes and 124 common down-regulated differential genes were gained from the above two datasets. The results of GO analysis for the 324 differential genes showed that these genes were mainly associated with the DNA-binding transcription factor binding, RNA polymerase II specific DNA-binding transcription factor binding, poly(A) binding, platelets-derived growth factor receptor binding, glucocorticoid receptor binding, etc. KEGG analysis showed that the differential genes were mainly enriched in MAPK signaling pathway, insulin signaling pathway, osteoclast differentiation as well as parathyroid hormone synthesis, secretion and action pathways. Protein-protein interaction network analysis screened two hub genes of osteoarthritis, namely heat shock protein 90α class A member 1 (HSP90AA1) and suppressors of cytokine signaling 3 (SOCS3). These findings confirm that HSP90AA1 and SOCS3 are differentially expressed in synovial tissue of patients with osteoarthritis and healthy subjects, and may serve as surveillance markers and therapeutic target, which provide sound ideas for further study of molecular mechanisms of osteoarthritis.  Figures and Tables | References | Related Articles | Metrics

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Competing endogenous RNA regulates the development of osteoarthritis Liu Xingyu, Liu Riguang, Li Guangdi, Wang Jian, Li Long, Shi Hao, Deng Keqi 2023, 27 (28):  4559-4565.  doi: 10.12307/2023.700 Abstract ( 292 )   PDF (1469KB) ( 83 )   Save BACKGROUND: Osteoarthritis is one of the most common joint diseases. With the increasing global incidence and prevalence of osteoarthritis, effective early diagnosis and treatment of osteoarthritis have become an urgent problem.   OBJECTIVE: To elucidate the important biological functions of long non-coding RNAs, circular RNAs and pseudogenes and their regulatory roles as competing endogenous RNAs in osteoarthritis pathogenesis to gain a comprehensive, in-depth and new understanding of the involvement of competing endogenous RNAs in osteoarthritis progression and to provide new clues for early diagnosis and treatment of osteoarthritis. METHODS: CNKI, PubMed, VIP and WanFang databases were searched for articles published before 2022. The search terms were “osteoarthritis, competing endogenous RNA, circular RNA, long non-coding RNAs, pseudogenes” in Chinese and English.   RESULTS AND CONCLUSION: Non-coding RNAs with the same microRNA response elements, including long non-coding RNAs, cyclic RNAs and pseudogenes, are involved in the construction of a regulatory network of competing endogenous RNAs centered on microRNAs. Non-coding RNAs, cyclic RNAs and pseudogenes can act as competing endogenous RNAs to adsorb microRNAs through “sponge” so as to regulate gene expression. Long non-coding RNAs, cyclic RNAs and pseudogenes can act as competing endogenous RNAs to regulate the proliferation, apoptosis and autophagy of osteoarthritic chondrocytes, the synthesis and degradation of extracellular matrix and the occurrence of inflammatory events. The practical application of the regulatory network of competing endogenous RNA to the clinical setting still faces many challenges and problems. The research on competing endogenous RNA as diagnostic markers or therapeutic targets for osteoarthritis is still at an early stage, and the current research on competing endogenous RNA regulatory network is still focused on the identification and validation of individual competing endogenous RNAs, and this regulatory network needs to be further supplemented and improved. However, with the development of advanced technologies, competing endogenous RNAs are expected to become early diagnostic markers and therapeutic targets for osteoarthritis diseases. Figures and Tables | References | Related Articles | Metrics

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Roles of N6-methyladenosine methyltransferase-like 3 in regulating bone metabolism and related diseases Xiong Bo, Zeng Ping, Liu Jinfu, Lu Guanyu, Chen Cai, Huang Yue, Chen Lihua 2023, 27 (28):  4566-4570.  doi: 10.12307/2023.431 Abstract ( 270 )   PDF (1135KB) ( 40 )   Save BACKGROUND: As one of the most prevalent types of RNA modification, N6-methyladenosine (m6A) methylation has emerged as a bright spot for regulating various diseases by interfering with RNA splicing, translation, nuclear export and decay. However, studies of methyltransferase-like 3 (METTL3)-mediated epigenetic modification of m6A methylation on bone metabolism have not been summarized. OBJECTIVE: To summarize the potential molecular mechanism of m6A core methyltransferase METTL3 in bone metabolism and its latest progress and future prospects in regulating osteogenic differentiation, osteoclastic differentiation, cartilage apoptosis, extracellular matrix degeneration, and bone metabolism-related diseases, thereby offering new insights into the study of the pathological mechanism of bone metabolism-related diseases and then providing a theoretical reference for the early diagnosis, clinical treatment, and prognosis of the diseases. METHODS: The CNKI database was searched with the Chinese keywords of “N6-methyladenine, methyltransferase-like 3, osteoblasts, osteoclasts, chondrocytes, mesenchymal stem cells, bone metabolism, osteoporosis, osteoarthritis, orthopedic diseases, treatment.” The PubMed database was searched with the English keywords of “m6A, METTL3, Osteoblast, osteoclasts, chondrocyte, mesenchymal stem cells, bone metabolism, osteoporosis, osteoarthritis, orthopedic disease, therapy.” Literature on METTL3/m6A-mediated RNA methylation in orthopedic diseases was retrieved from database establishment to March 2022. As per the inclusion and exclusion criteria, 35 articles were finally selected for review. RESULTS AND CONCLUSION: The role of METTL3 in osteogenesis is controversial and remains to be further studied in depth. METTL3/m6A-mediated RNA methylation can regulate osteogenic and adipogenic differentiation of bone marrow mesenchymal stem cells through a variety of mechanisms, but the specific mechanism is not clear. METT3 regulation of osteoclast differentiation function is essential for maintaining bone homeostasis as well as maintaining bone integrity. METTL3 plays an important role in the development of bone metabolism-related diseases; therefore, METTL3 overexpression may become a new alternative therapy for the treatment of human bone metabolism-related diseases such as osteoporosis. Figures and Tables | References | Related Articles | Metrics

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Novel programmed cell death of chondrocytes in osteoarthritis Lu Xiaojun, Xiong Bohan, Yang Tengyun, Wang Xu, Zhang Yaozhang, Zhong Ruiying, Li Yanlin 2023, 27 (28):  4571-4576.  doi: 10.12307/2023.585 Abstract ( 317 )   PDF (851KB) ( 33 )   Save BACKGROUND: Osteoarthritis is a common degenerative joint disease. Its pathogenesis is complex and has not been elucidated. However, studies have shown that the occurrence and development of osteoarthritis is related to the programmed death of chondrocytes.  OBJECTIVE: To summarize the research progress in new programmed cell death in osteoarthritis chondrocytes.   METHODS: “Osteoarthritis, Pyroptosis, Necroptosis, Ferroptosis, ROS, L-ROS, iron-overload” were used as English and Chinese search terms. Relevant articles on programmed cell death were searched in CNKI, WanFang, VIP, and PubMed. The search time was from July 2012 to July 2022. All included articles were summarized, concluded, and analyzed. RESULTS AND CONCLUSION: The relationship between pyroptosis and osteoarthritis has attracted much attention in recent years, and current research still focuses on NLRP3 inflammasome and lipopolysaccharides. The development of osteoarthritis has also been shown to be closely associated with receptor-interacting protein kinase 1 in studies concerning necroptosis, and receptor-interacting protein kinase 1 could be a potential target for the treatment of osteoarthritis. Ferroptosis is a recently discovered mode of cell death, which has been found to mediate chondrocyte death through iron overload and lipid peroxidation, but ferroptosis involves the expression and regulation of multiple genes via complex signaling pathways and mechanisms that are not yet fully elucidated. Pyroptosis, necroptosis, and ferroptosis have important roles in the occurrence and development of osteoarthritis, but their related pathways, genes, and miRNAs still need further study. Figures and Tables | References | Related Articles | Metrics

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Improvement of cognitive function by blood flow restriction training: mechanisms and applications Bai Xing, Wang Guojun, Wang Shaokun 2023, 27 (28):  4577-4585.  doi: 10.12307/2023.813 Abstract ( 346 )   PDF (1105KB) ( 212 )   Save BACKGROUND: Blood flow restriction training is a new resistance training. Blood flow restriction training can not only influence muscle strength, mass and physical ability, but also induce and activate related signaling pathways such as neural plasticity and cognitive function. However, current studies have not systematically evaluated the effects of blood flow restriction training on the cognitive ability of different populations, and the neurobiological mechanism by which blood flow restriction training improves cognitive function is not fully understood. Moreover, the application solutions of blood flow restriction training are still not fully understood. OBJECTIVE: To review the existing experimental studies on the influence of blood flow restriction training on cognitive function of different populations, deeply analyze the potential neurobiological mechanisms, and summarize the previous rational programs of blood flow restriction training that improve cognitive function, in order to provide theoretical support and practical guidance for the safe and effective application of this technology. METHODS: PubMed, Web of Science, and CNKI databases were retrieved using “blood flow restriction training, pressure training, blood flow restriction therapy, blood flow restriction, pressure blood block training, blood block, cognitive function, cognitive ability” as Chinese keywords and “blood flow restriction therapy, KAATSU training, KAATSU volume, resistance training, BFR therapy, BFRT, blood flow restriction exercise, cognition, cognitive function” as English keywords. The search deadline was October 2022. Relevant inclusion criteria were established according to the research needs and finally 84 articles were included for further review. RESULTS AND CONCLUSION: The experimental studies regarding the influence of blood flow restriction training on cognitive ability mainly select healthy people as subjects in an attempt to explore its application value in healthy elderly populations. However, in general, there are few studies on elderly people and patients with cognitive dysfunction. Blood flow restriction training can be used as a key factor to trigger positive neural adaptation to a certain extent by applying hypoxic stimulation to the extremity to induce transient brain oxygen deficiency. Blood flow restriction training can significantly improve the levels of bioactive molecules related to the improvement of cognitive function, mainly including insulin-like growth factor 1, growth hormone, vascular endothelial growth factor, brain-derived neurotrophic factor, lactic acid, hypoxia-inducible factor 1α, peroxisome proliferator-activated receptor-γ coactivation factor 1α and norepinephrine. The formulation of blood flow restriction training application programs involves the selection of training participants, the determination of exercise factors and the setting of cuff pressure and its width. Future studies should pay attention to the comparison of the application effects of different blood flow restriction training methods in different populations, so as to make the clinical application of blood flow restriction training more perfect and reasonable, providing more theoretical basis for blood flow restriction training to improve cognitive function in patients with cognitive dysfunction. Figures and Tables | References | Related Articles | Metrics

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Effects of different resistance training programs on bone mineral density in postmenopausal women: a network Meta-analysis Wang Zhenyu, Xia Yuan, Lu Yue, Pan Xinyong, Li Yongjie 2023, 27 (28):  4586-4592.  doi: 10.12307/2023.571 Abstract ( 270 )   PDF (1956KB) ( 70 )   Save OBJECTIVE: Resistive exercises can effectively increase bone mineral density in postmenopausal women, but there is no consensus on the choice of exercise intensity and exercise frequency. This paper evaluates the effect of different resistance training programs on bone mineral density in postmenopausal women based on a network Meta-analysis.  METHODS: We systematically searched CNKI, WanFang, China Biomedical Database (CBM), ProQuest, PubMed, Cochrane Library, Embase, and Web of Science for literature regarding the use of resistance training programs to improve the bone mineral density of postmenopausal women. The search time was from database inception to May 2022. The two reviewers dependently screened the included literature, extracted relevant data, evaluated the risk quality of the literature using the Cochrane manual and the PEDro scale, and conducted a Meta-analysis using Stata 16.0.  RESULTS: A total of 20 studies including 1 087 subjects were included. Results from the network Meta-analysis showed that (1) compared with the control group, the medium-intensity resistance training was significantly better in improving lumbar and femoral neck bone mineral density (P < 0.05). In terms of improving the bone mineral density of the total hip and femoral greater trochanter, the moderate-intensity resistance training was better, but there was no significant difference among the groups (P > 0.05). (2) In terms of exercise frequency, the 3 days/week moderate-intensity resistance exercise was better than 2 days/week moderate-intensity resistance exercise to improve the bone mineral density of the lumbar vertebra. Moreover, at the exercise frequency of 3 days/week, moderate-intensity exercise was significantly better than low- and high-intensity exercises (P < 0.05). (3) The cumulative probability ranking results showed that the moderate-intensity resistance training of 3 days/week was the best in improving the bone mineral density of the lumbar vertebra, femoral neck, total hip, and greater trochanter.  CONCLUSION: Based on the current evidence, moderate-intensity resistance exercise with a frequency of 3 days per week can be selected to improve the reduced bone mineral density in postmenopausal women. The above conclusions need to be verified by more high-quality research. Figures and Tables | References | Related Articles | Metrics