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08 October 2024, Volume 28 Issue 28 Previous Issue   

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Characterization of temporal and intensity parameters of early postural adjustment phase during gait initiation in stroke patients Zhao Zhuoyue, Liu Jiawen, Sun Changcheng, Zhang Gaoshuai, Zhang Ying, Xu Rui 2024, 28 (28):  4429-4435.  doi: 10.12307/2024.494 Abstract ( 199 )   PDF (1988KB) ( 115 )   Save BACKGROUND: Early postural adjustments serve as preparatory measures for forthcoming actions or potential disruptions in posture, thereby facilitating improved movement execution and mitigating destabilizing effects caused by posture interference. OBJECTIVE: To investigate the characteristics of temporal and intensity parameters of key lower limb muscles during early postural adjustment phase when stroke patients with varying levels of balance initiate walking at a self-selected comfortable pace.  METHODS: The characteristics of early postural adjustments in 16 stroke patients were observed. Sixteen patients were divided into a non-fall group (n=8) and a fall group (n=8) based on the history of falls and Berg Balance Scale scores. Noraxon inertial sensors and Noraxon Ultium EMG wireless surface electromyography were utilized to collect body kinematic data and surface electromyography data during gait initiation. Muscle activation time and activation sequence of six key muscles in the lower limbs (tibialis anterior, medial and lateral gastrocnemius, rectus femoris, lateral femoris and biceps femoris muscles) during the early postural adjustment phase, as well as normalized electromyography integral values for the four time windows (each 150 ms) before gait initiation, were analyzed. RESULTS AND CONCLUSION: Stroke patients with a history of falls exhibited earlier activation times for the six key muscles in the lower limbs during gait initiation compared with those in the non-fall group. The fall group demonstrated significantly earlier activation times for tibialis anterior, lateral head of gastrocnemius, and vastus lateralis (P < 0.01, P < 0.05). In contrast, the non-fall group displayed a consistent pattern of activating extensor muscles before flexor muscles, with thigh muscle activation preceding calf muscle activation. However, in the fall group, calf extensor muscle activation occurred prior to thigh extensor muscle activation, and the vastus lateralis was activated even earlier. The tibialis anterior was the last activated muscle in both groups. Specifically during T3 (> -300 to -150 ms), the tibialis anterior exhibited significantly higher activity in the fall group compared with the non-fall group (P < 0.05), while the lateral head of gastrocnemius demonstrated significant inhibition during T3 (P < 0.05) and the medial head of gastrocnemius showed significant inhibition during both T3 and T4 (> -150 to 0 ms) stages compared with the non-fall group (P < 0.01, P < 0.05). To conclude, stroke patients with varying balance abilities employ distinct early postural adjustment strategies prior to stepping, as evidenced by differences in muscle activation timing, recruitment order, and muscle activity amplitude. Patients at a high risk of falling exhibit prolonged duration of early postural adjustment and delayed initiation of gait, indicating earlier activation of the tibialis anterior muscle and inhibition of gastrocnemius muscle activity. These delays in gait initiation and variations in muscle recruitment strategies may contribute to unstable posture and an increased susceptibility to falls. Figures and Tables | References | Related Articles | Metrics

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Consistency between artificial intelligence and expert Greulich-Pyle atlas method for bone age assessment Li Lei, Pan Qile, Cai Guang, Li Zhipeng 2024, 28 (28):  4436-4440.  doi: 10.12307/2024.466 Abstract ( 154 )   PDF (1126KB) ( 22 )   Save BACKGROUND: Artificial intelligence-assisted bone age assessment has become a research hotspot. Domestic and foreign studies have shown that the rapid development of artificial intelligence technology in the field of medical imaging provides the possibility of more accurate and rapid assessment of bone age.  OBJECTIVE: To investigate the consistency between a domestically developed artificial intelligent Greulich-Pyle (GP) bone age assessment system and an expert manually assessed GP (expert GP), and to provide a basis for the feasibility of applying an artificial intelligent GP in clinical practice or in other fields.  METHODS: Wrist radiographs were sampled from children and adolescents aged 6-15 years, of whom 672 were male and 650 were female. Bone age assessment of the same wrist radiograph was performed using the artificial intelligent GP and the expert GP. The accuracy of the artificial intelligent GP reading results was assessed by the absolute value of the difference. The consistency of the bone age results was assessed by Pearson correlation and Bland-Altamn distribution; and the consistency of the assessment was checked by Kappa test.  RESULTS AND CONCLUSION: The absolute value of the difference (95% confidence interval) of the difference between artificial intelligent GP and expert GP for male and female was 0.39 years (0.37-0.41 years) and 0.32 years (0.29-0.34 years), respectively. The deviation of Bland-Altamn values for male and female was (-0.096±0.482) years and (0.014±0.415) years, respectively. The correlation results between artificial intelligent GP bone age and expert GP bone age for male and female were r=0.991 and r=0.992, respectively (P < 0.000 1). The median difference between all age groups for male and female was within 0.5 years. Kappa test values were greater than 0.4 for both sexes at all ages except for the 9-year age group for male. Overall Kappa values were 0.603 and 0.659 for male and female respectively. To conclude, there is a high degree of consistency between the artificial intelligence and expert evaluation results of GP bone age values in children and adolescents aged 6-15 years. Figures and Tables | References | Related Articles | Metrics

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In vivo distribution of Cornus cervi Colla and tracer kinetic analysis of its components that enter the blood and bone Hu Yanan, Du Haitao, Yu Yang, Dong Limin, Jing Tianyuan, Yin Wu, Wang Ping 2024, 28 (28):  4441-4446.  doi: 10.12307/2024.394 Abstract ( 134 )   PDF (2310KB) ( 67 )   Save BACKGROUND: Our previous studies found that the polypeptide of Cornus cervi Colla can promote bone growth, which has a good application prospect in the treatment of bone diseases. However, how Cornus cervi Colla works in the body and the principle are not clear. OBJECTIVE: To study the in vivo distribution and tracing of Cornus cervi Colla using fluorescence labeling and tracer technique. METHODS: Cornus cervi Colla was fluorescently labeled using fluorescein isothiocyanate, and the labeling results were detected by fluorescence imaging and UV spectral scanning. Successfully labeled Cornus cervi Colla was injected into mice by gavage, and the absorption of Cornus cervi Colla into blood was detected by laser confocal microscopy, and the distribution of Cornus cervi Colla in mice was detected by small animal in vivo imager. The distribution of Cornus cervi Colla in the mice was detected by laser confocal microscopy. Samples were taken from serum and bone at the time of the strongest fluorescence, and gel electrophoresis was carried out on serum and bone tissue protein solutions, and the components of Cornus cervi Colla absorbed into target organs were determined by secondary mass spectrometry. RESULTS AND CONCLUSION: The fluorescent markers were successfully separated by dextran gel chromatography, and the fluorescence imaging and ultraviolet spectrum scanning proved that the labeling was successful, and the fluorescence substitution degree of FITC-labeled Cornus cervi Colla was 0.953%. The fluorescence intensity of the components of Cornus cervi Colla in the blood showed that Cornus cervi Colla was most distributed in serum after oral administration for 2 hours. The fluorescence images of mice at different times were the same as those of bilateral femur and tibia, indicating that Cornus cervi Colla could play a role by entering the bone. Compared with UniProt database, secondary mass spectrometry showed that the peptide was a characteristic fragment of decorin. It is proved that decorin in Cornus cervi Colla can enter the bone to play a therapeutic role. Figures and Tables | References | Related Articles | Metrics

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SRT1720, an activator of silent information regulator 1, alleviates acute traumatic brain injury in a rat model Qian Longjie, Su Wenli, Zhu Wenxian, Wang Yixin 2024, 28 (28):  4447-4454.  doi: 10.12307/2024.348 Abstract ( 142 )   PDF (2570KB) ( 74 )   Save BACKGROUND: It has been shown that in a mouse model of acute traumatic brain injury, the transcriptional and translational levels of silent information regulator 1 (SIRT1) activated by drugs significantly elevates the expression of SIRT1 in brain tissue, reduces inflammatory and oxidative stress in brain tissue, and improves neurological function. OBJECTIVE: To investigate the mechanism of intraperitoneal injection of SRT1720, an activator of SIRT1, to alleviate acute traumatic brain injury in rats.  METHODS: Ninety Sprague-Dawley rats were randomized into three groups (n=30 per group): a sham group (without modeling), a model group and an activator group. Animal models of acute traumatic brain injury were established in the latter two groups. At 6 hours after modeling, the sham, model and activator groups were injected intraperitoneally with dimethyl sulfoxide solution, methylsulfoxide solution and SRT1720 once a day for 28 days, respectively. The time points for sampling were set, and rats’ neurological function, brain tissue water content, brain tissue oxidative stress and inflammatory response, brain tissue morphology, apoptosis and angiogenesis, and the protein expression of SIRT1 in brain tissue were detected and measured.   RESULTS AND CONCLUSION: Compared with the sham group, the modified neurological deficit score, brain tissue water content and apoptosis rate of rats were increased in the model group at 7, 14 and 28 days of injection (P < 0.05); compared with the model group, the modified neurological deficit score, brain tissue water content and apoptosis rate of rats were decreased in the activator group (P < 0.05). Compared with the sham group, the levels of reactive oxygen radicals and myeloperoxidase in the brain tissue were increased (P < 0.05), the levels of malondialdehyde, tumor necrosis factor α and interleukin 6 in the serum were increased (P < 0.05), and the levels of superoxide dismutase in the serum were decreased in the model group at 7, 14 and 28 days of injection (P < 0.05). Compared with the model group, the levels of reactive oxygen radicals and myeloperoxidase in the brain tissue were decreased (P < 0.05), the levels of malondialdehyde, tumor necrosis factor α and interleukin 6 in the serum were decreased (P < 0.05), and the levels of superoxide dismutase in the serum were increased in the activator group at 7, 14 and 28 days of injection (P < 0.05). Immunohistochemical staining at 7, 14 and 28 days of injection showed that the number of new vessels in the brain tissue was higher in the model group than the sham group (P < 0.05) as well as higher in the activator group than the model group (P < 0.05). Western blot assay indicated that at 7, 14 and 28 days of injection, the expression of SIRT1 protein in the brain tissue was lower in the model group than the sham group (P < 0.05) and higher in the activator group than the model group (P < 0.05). Hematoxylin-eosin staining showed that at 7, 14 and 28 days of injection, the degree of brain injury in the activator group was less than that in the model group. To conclude, intraperitoneal injection of the SIRT1 signal activator SRT1720 can significantly reduce oxidative and inflammatory stress in the brain tissue, inhibit neuronal apoptosis, promote angiogenesis, and alleviate brain injury in rats with acute traumatic brain injury. Figures and Tables | References | Related Articles | Metrics

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CircCDR1as/miR-7-5p/RAF1 axis promotes autophagy levels in steroid-induced necrosis of the femoral head Zhai Sheng, Aikeremujiang • Aerken, Zhang Zheng, Rixiati • Paerhati, Hao Feihu 2024, 28 (28):  4455-4460.  doi: 10.12307/2024.453 Abstract ( 151 )   PDF (2328KB) ( 45 )   Save BACKGROUND: Autophagy may be involved in the pathological process of steroid-induced necrosis of the femoral head (SINFH). Some studies have confirmed that circular RNAs (circRNAs) have a regulatory mechanism in SINFH; however, whether circCDR1as affects autophagy in SINFH has not been investigated. OBJECTIVE: To explore the level of autophagy and the regulatory mechanism of circCDR1as in SINFH.  METHODS: Gene expression profiles of SINFH and control rats were extracted from the GSE26316 dataset and differential expression analysis was performed. Subsequently, the biological functions of differentially expressed genes were analyzed. Then, the target miRNAs of circCDR1as and the target genes of target miRNAs were predicted. Further, the target genes were compared with the differentially expressed genes to construct the regulatory network of circCDR1as. In addition, femoral head samples from patients with SINFH and healthy control individuals were collected. Bone marrow mesenchymal stem cells were also applied for cellular experiments and randomly divided into bone marrow mesenchymal stem cell group, model group (methylprednisolone-treated), model+si-NC group, and model+si-CDR1as group. RT-qPCR was used to detect the expression of circCDR1as and target genes in cells and tissue samples. Western blot was used to examine the expression of autophagy proteins. The luciferase reporter gene vectors, pmirGLO-CDR1as (WT), pmirGLO-RAF1 (WT), pmirGLO-CDR1as (MUT), and pmirGLO-RAF1 (MUT), were constructed and transfected into the cells. miR-7-5p mimic and mimic NC groups were established. The target-regulatory relationship of the circCDR1as network was detected. RESULTS AND CONCLUSION: A total of 1 283 differentially expressed genes were identified between the SINFH and control groups, which were mainly involved in apoptotic and autophagic signaling pathways. Prediction analysis revealed that circCDR1as targeted 6 miRNAs, which in turn regulated 305 target genes. Among these target genes, 31 showed differential expression in SINFH. Among the differentially expressed target genes, RAF1, involved in autophagy, was selected as a key gene, leading to the construction of the circCDR1as/miR-7-5p/RAF1 regulatory network. Compared with the control group, circCDR1as, RAF1, and autophagy levels were upregulated in patients with SINFH and in hormone-induced bone marrow mesenchymal stem cells (P < 0.05), while miR-7-5p expression was downregulated (P < 0.05). Knockdown of circCDR1as significantly decreased cellular autophagy levels (P < 0.05). Dual-luciferase reporter assays confirmed the targeting relationships between circCDR1as and miR-7-5p, as well as between miR-7-5p and RAF1. To conclude, the CircCDR1as/miR-7-5p/RAF1 may potentially promote SINFH through autophagy. Targeting circCDR1as is a potential strategy for partial autophagic repair in the treatment of SINFH. Figures and Tables | References | Related Articles | Metrics

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Icariin regulates acidic microenvironment to alleviate pain caused by postmenopausal osteoporosis in the elderly Xue Chunyang, Wang Xiuhui 2024, 28 (28):  4461-4468.  doi: 10.12307/2024.491 Abstract ( 171 )   PDF (2261KB) ( 45 )   Save BACKGROUND: Previous studies have demonstrated that icariin has important roles in promoting bone formation and inhibiting bone resorption, but its effects on osteoporosis-mediated bone pain have not been reported. OBJECTIVE: To investigate the possible mechanism of icariin alleviating bone pain in postmenopausal senile osteoporosis. METHODS: (1) Animal experiment: 200 C57BL/6 mice were randomly divided into 4 groups: sham group (n=50), model group (n=50), icariin treatment group (n=50), and carbonic anhydrase II inhibitor (Brinzolamide) treatment group (n=50). Ovariectomy was performed on C57BL/6 mice to establish a postmenopausal osteoporosis model in all groups except the sham group. The icariin group was given icariin on the second day after modeling, and pain behavior tests (Von Frey, Hot Plate, and Tail Flick tests) were performed every 2 weeks for 20 weeks. After sampling, bone mass was detected by microCT, osteoclast activity was detected by hematoxylin-eosin and tartrate-resistant acid phosphatase staining, and neuronal morphology and related ion channel expression were detected by tissue immunofluorescence staining. (2) Cell experiment: Osteoclast precursor cells derived from mouse bone marrow were extracted and induced to differentiate into osteoclasts using the RANKL/M-CSF system in vitro and supplemented with icariin of different concentrations (1 and 10 μmol/L). Tartrate-resistant acid phosphatase staining was used to detect osteoclast differentiation, ghost pen cyclic peptide staining was used to detect osteoclast actin ring, bone plate absorption assay was used to detect osteoclast osteophagy function, pH value of the system was detected by pH meter, and expression of osteoclast differentiation-related proteins was detected by western blot. In addition, mouse dorsal root ganglion-derived nerve cells were extracted and treated with icariin. Cell counting kit-8 was used to detect neuronal activity and CGRP staining was used to detect neuronal morphology. RESULTS AND CONCLUSION: Compared with the model group, the icariin treatment group had higher bone mineral density, fewer tartrate-resistant acid phosphatase-positive osteoclasts in bone tissue, decreased neuronal activity, and decreased neuronal transient receptor potential vanilloid subtype 1 channel and carbonic anhydrase II expression. Behavioral results showed that the icariin treatment group was less sensitive to pain than the model group. Icariin inhibited osteoclast differentiation and bone phagocytosis in vitro. Icariin enhanced the activity of dorsal root ganglion neurons and inhibited the expression of calcitonin gene-related peptide and transient receptor potential vanilloid subtype 1 channels in dorsal root ganglia in a relatively non-toxic pH range. To conclude, icariin alleviates bone pain caused by postmenopausal osteoporosis by regulating the acidic microenvironment through its effect on osteoclasts. Figures and Tables | References | Related Articles | Metrics

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Metformin pretreatment induces cardiac autophagy to reduce myocardial injury in septic mice Tian Yong, Zhou Ying, Gu Yongxiang, Yang Guohui 2024, 28 (28):  4469-4476.  doi: 10.12307/2024.340 Abstract ( 155 )   PDF (1349KB) ( 76 )   Save BACKGROUND: Sepsis complicated by myocardial injury is characterized by a high mortality. Metformin can prevent sepsis-induced myocardial dysfunction by exerting anti-inflammatory effects, improving oxidative stress, and reducing apoptosis. However, it is unclear whether metformin-induced autophagy plays an important role in the protective effect against sepsis-induced myocardial injury. OBJECTIVE: To explore the effect of metformin pretreatment on myocardial injury in septic mice. METHODS: A total of 40 male Kunming mice were randomly divided into sham operation group, model group, metformin group, and metformin+3-methyladenine group, with 10 mice in each group. The latter two groups were intraperitoneally injected with metformin for 14 days at a fixed time every day, and the metformin+3-methyladenine group was intraperitoneally injected with 3-methyladenine 1 hour before modeling. Twenty-four hours after the last injection of metformin, cecal ligation and perforation were used to construct a model of myocardial injury in septic mice. The sham operation group was not ligated and perforated. All mice were sacrificed 24 hours after surgery, and blood and myocardial specimens were collected. The levels of inflammatory factors and myocardial injury markers in serum were detected by ELISA. The mRNA expression of autophagy markers LC3B and p62 in myocardial tissue was detected by RT-qPCR. The protein expression of LC3B, Beclin-1, p62, p-AMPK, and AMPK in myocardial tissue was detected by western blot. The pathological changes in myocardial tissue were detected by hematoxylin-eosin staining. RESULTS AND CONCLUSION: Autophagy was inhibited in septic mice with myocardial injury. Compared with the sham operation group, the levels of serum tumor necrosis factor-α, interleukin-1β, interleukin-6, creatine kinase isoenzyme, and troponin T were increased in the model group (P < 0.05), but there was no significant difference in p62, LC3II/LC3I, and p-AMPK/AMPK between the two groups (P > 0.05). Compared with the model group, the levels of tumor necrosis factor-α, interleukin-6, creatine kinase isoenzyme, troponin T, and p62 were decreased in the metformin group (P < 0.05), while LC3II/LC3I, p-AMPK/AMPK and Beclin-1 level were increased (P < 0.05). Compared with the metformin group, the levels of tumor necrosis factor-α, interleukin-6, creatine kinase isoenzyme, troponin T, and p62 were increased in the metformin+3-methyladenine group (P < 0.05), while LC3II/LC3I and Beclin-1 level were decreased (P < 0.05). Myocardial hematoxylin-eosin staining indicated that myocardial fibers arranged normally in the sham operation group, but disorderedly in the model group, with interstitial edema and a large number of infiltrated inflammatory cells. A small amount of vacuolar changes were observed in the metformin group. The arrangement of myocardial fibers in the metformin+3-methyladenine group was slightly disordered, with more vacuolar changes. To conclude, metformin pretreatment may reduce myocardial injury in septic mice by activating the AMPK signaling pathway and inducing autophagy. Figures and Tables | References | Related Articles | Metrics

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Effects of Shujin Jiannao Prescription on cell apoptosis in rats with hypoxic-ischemic brain injury Jiang Yu, Xu Lin, Zhao Yalin, Liu Gang, Zhang Yaqi, Bai Huizhong, Ren Jingpei, Zeng Jie, Mu Xiaohong 2024, 28 (28):  4477-4483.  doi: 10.12307/2024.395 Abstract ( 125 )   PDF (1447KB) ( 120 )   Save BACKGROUND: Perinatal hypoxic-ischemic brain injury is one of the most common causes of cerebral palsy. Shujin Jiannao Prescription is an experienced formula for treating cerebral palsy and improving blood supply to the brain developed by the Dongzhimen Hospital, Beijing University of Chinese Medicine. OBJECTIVE: To explore the possible mechanism of Shujin Jiannao Prescription in treating hypoxic-ischemic cerebral palsy.  METHODS: Sixty-four 7-day-old Sprague-Dawley rats were randomly divided into six groups. There were 12 rats in each of the control and model groups as well as 10 animals in each of the minocycline group, and the low-, medium-, and high-dose groups of Shujin Jiannao Prescription. The neonatal rat ischemic-hypoxic cerebral palsy model was established in all groups except for the control group. After successful modeling, rats in each drug group were respectively gavaged with minocycline and Shujin Jiannao Prescription at a dose of 4, 8, and 16 g/kg per day for 1 week. Body mass of rats was measured and behavioral changes were detected before and after drug administration. Hematoxylin-eosin staining was used to observe the histomorphology of hippocampal CA1 region of rat brain tissue, and immunohistochemistry and western blot were used to detect the expression levels of Bcl-2, Bax, and Caspase-3 in the brain tissue of rats. RESULTS AND CONCLUSION: Compared with the model group, medium- and high-dose Shujin Jiannao Prescription significantly increased the body mass of rats (P < 0.05). Compared with the model group, minocycline effectively prolonged the suspension time of ischemic-hypoxic cerebral palsy rats (P < 0.05), while medium- and high-dose Shujin Jiannao Prescription significantly prolonged the suspension time, shortened the inclined plane test time, and increased the Longa score of rats (P < 0.05). The pathological results showed that after drug intervention, only a small number of neuronal cells in the brain tissue of rats were necrotic, the cells were more neatly arranged, the cell structure was more complete, and only part of the cell nuclei became smaller. Compared with the model group, minocycline and medium- and high-dose Shujin Jiannao Prescription reduced the expression of Bax Caspase-3 (P < 0.05), medium- and high-dose Shujin Jiannao Prescription increased the expression of Bcl-2 (P < 0.05), and Bcl-2/Bax protein expression was increased in minocycline and three Shujin Jiannao Prescription groups (P < 0.05). In addition, the protein expression was increased in a dose-dependent manner after intervention with Shujin Jiannao Prescription, and there was no significant difference between the minocycline and three Shujin Jiannao Prescription groups (P > 0.05). To conclude, the mechanism by which Shujin Jiannao Prescription treats ischemic-hypoxic cerebral palsy in rats may be to enhance the expression of anti-apoptotic protein Bcl-2, inhibit the expression of pro-apoptotic protein Bax, and reduce the expression of Caspase-3, ultimately inhibiting the apoptosis of hippocampal neuronal cells in rats with cerebral palsy. Within a certain range, the higher dose of Shujin Jiannao Prescription indicates the better therapeutic effect, and the high-dose Shujin Jiannao Prescription is as effective as minocycline. Figures and Tables | References | Related Articles | Metrics

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Electroacupuncture improves morphological structure of the detrusor muscle and bladder function in rats with spinal cord injury Jiao Ziyuan, Zhuo Yue, Liang Roujun, Ding Qiangsheng, Zeng Xuejiu, Xu Ming, Zhang Hong 2024, 28 (28):  4484-4490.  doi: 10.12307/2024.461 Abstract ( 137 )   PDF (1597KB) ( 77 )   Save BACKGROUND: Numerous clinical and basic studies have shown that electroacupuncture can improve the function of neurogenic bladder after suprasacral spinal cord injury. OBJECTIVE: To observe the effects of electroacupuncture on bladder function and connective tissue growth factor expression in rats with suprasacral spinal cord injury. METHODS: Forty-eight female Sprague-Dawley rats were randomly divided into four groups (n=12 per group): the blank group did not receive any treatment; the sham-operated group only exposed the T8 subvertebral spinal cord; in the model group established, a T8 subvertebral spinal cord transection injury model was established; in the electroacupuncture group, the T8 subvertebral spinal cord transection injury model was established, and electroacupuncture intervention at Ciliao (BL32), Zhongji (RN03) and Sanyinjiao (SP06) was given at 19 days after modeling, 20 minutes once a day, for 10 continuous days. After the intervention, the relevant indicators were detected. RESULTS AND CONCLUSION: Urodynamics: Compared with the blank group, the leakage point pressure, maximum bladder capacity and maximum bladder pressure of rats in the model group increased (P < 0.05). Compared with the model group, the leakage point pressure, maximum bladder capacity and maximum bladder pressure of rats in the electroacupuncture group decreased (P < 0.05). Hematoxylin-eosin staining: Compared with the blank group, the bladder epithelial cells in the model group were arranged in a disordered manner, the lamina propria was destroyed, the detrusor muscle bundles were hypertrophied, the muscle fibers were arranged in a disordered manner, and the tissue edema was obvious. Compared with the model group, the bladder epithelial cells in the electroacupuncture group were arranged in a regular and orderly manner, and the degree of bladder fibrosis and tissue edema was relatively reduced. Masson staining: The degree of bladder detrusor muscle fibrosis was severe in the model group and it was lighter in the electroacupuncture group than in the model group. Transmission electron microscopy: Mitochondria in the bladder tissue in the model group were swollen and vacuolated, the morphology of the detrusor muscle was twisted and distorted, and the muscle gap was widened. Compared with the model group, mitochondria in the electroacupuncture group had a slightly clearer contour and were less vacuolated, and the muscle gap was narrowed. Western blot detection: The protein expression of connective tissue growth factor in the detrusor muscle of the bladder was elevated in the model group compared with the blank group (P < 0.05). Compared with the model group, the protein expression of connective tissue growth factor in the bladder detrusor muscle was decreased in the electroacupuncture group (P < 0.05). To conclude, electroacupuncture at Ciliao (BL32), Zhongji (RN03) and Sanyinjiao (SP06) acupoints can improve the morphology, structure and function of the bladder in rats with suprasacral spinal cord injury, and the mechanism of action may be related to the down-regulation of connective tissue growth factor protein expression in the detrusor muscle. Figures and Tables | References | Related Articles | Metrics

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Significance of PI3K/Akt/HIF-1α signaling pathway expression in nucleus pulposus cells at different oxygen concentrations in delaying intervertebral disc degeneration Zhou Minghan, Zhang Hui, Zheng Xianbo, Xu Wuji 2024, 28 (28):  4491-4497.  doi: 10.12307/2024.469 Abstract ( 113 )   PDF (1502KB) ( 12 )   Save BACKGROUND: Intervertebral disc degeneration is a condition caused by the combined effects of various factors, such as cellular apoptosis, oxidative stress, and inflammatory responses. Currently, it is believed that the core of this condition lies in the degeneration and apoptosis of nucleus pulposus cells (NPCs). However, the specific pathological mechanisms remain unclear. OBJECTIVE: By investigating the expression of the phosphatidylinositol-3 kinase (PI3K)/protein kinase B (Akt)/hypoxia-inducible factor 1-alpha (HIF-1α) signaling pathway and the apoptosis of NPCs under different oxygen concentrations, to clarify the biological characteristics of NPCs under varying oxygen levels, and to explore the mechanisms of intervertebral disc degeneration. METHODS: Normal and degenerated NPCs were collected. The second-generation cells were used for imaging identification. The third-generation cells were cultured in the following conditions: 37°C, air, 100% humidity. Leibovitz’s medium containing 100 μmol/L CoCl2 and 10% fetal bovine serum medium containing 100 μmol/L H2O2 were used to create distinct oxygen concentration environments for the third-generation cells, allowing for the investigation of cellular responses and behaviors under normal, low oxygen, and oxidative stress conditions. The third-generation cells were divided into six groups: normal NPCs+hypoxia, normal NPCs+normoxia, normal NPCs+oxidative stress, degenerated NPCs+hypoxia, degenerated NPCs+normoxia, and degenerated NPCs+oxidative stress groups. Cell viability and proliferation were assessed using the cell counting kit-8 method. Cell apoptosis was detected using flow cytometry. RT-PCR and western blot assay were utilized to examine the protein and mRNA expression levels of PI3K, AKT, and HIF-1α. RESULTS AND CONCLUSION: At different oxygen concentrations, the cell proliferation rate of both normal and degenerated NPCs decreased as the oxygen concentration increased. Conversely, the apoptosis rate increased as the oxygen concentration rose (P < 0.05). With the normal NPCs+hypoxia group as the control group, the effect of degenerated NPCs on the apoptosis rate was highly significant (P < 0.001). Oxygen concentration had a highly significant impact on both NPC proliferation rate and apoptosis rate (P < 0.001). The interaction between cell degeneration and oxygen concentration significantly affected both NPC proliferation and apoptosis rates (P < 0.05). At different oxygen concentrations, the protein and mRNA expression levels of PI3K, AKT, and HIF-1α in normal NPCs were highest under low oxygen concentration, followed by oxidative stress environment, and lowest under normoxia. In degenerated NPCs, the protein and mRNA expression levels of PI3K, AKT, and HIF-1α decreasd as the oxygen concentration increased. The protein and mRNA expression levels of PI3K and Akt in normal NPCs were significantly higher than those in degenerated NPCs (P < 0.05). With the normal NPCs+hypoxia group as the control group, the effects of normal or degenerated NPCs, as well as oxygen concentration, on the protein and mRNA expression of PI3K, AKT, and HIF-1α were highly significant. The interaction between cell degeneration and oxygen concentration also had an extremely significant effect on the protein and mRNA expression of PI3K, AKT, and HIF-1α (P < 0.001). To conclude, there is a close correlation between the proliferation and apoptosis of NPCs and both oxygen concentration and the cellular functional state. The PI3K/Akt/HIF-1α signaling pathway exhibits antagonistic regulatory effects under various cellular functional states and different oxygen concentration environments. The mechanism may be associated with the activation of the PI3K/Akt signaling pathway, which consequently transcribes HIF-1α, thus maintaining the balance of reactive oxygen species metabolism. This pathway plays a significant role in inhibiting oxidative stress, antagonizing NPCs apoptosis, and consequently delaying intervertebral disc degeneration. Figures and Tables | References | Related Articles | Metrics

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Eriodictyol accelerates glucocorticoid-induced apoptosis by promoting osteoblast autophagy Ma Yunfeng, Han Xiaofei 2024, 28 (28):  4498-4504.  doi: 10.12307/2024.459 Abstract ( 136 )   PDF (1500KB) ( 45 )   Save BACKGROUND: Glucocorticoid-induced osteoporosis is a common complication of systemic glucocorticoid therapy, which is mainly characterized by its inhibitory effect on osteoblasts. Eriodictyol inhibits osteoclast differentiation and osteoporosis-induced by ovariectomy. However, it is unclear whether eriodictyol regulates glucocorticoid-induced osteoblasts.  OBJECTIVE: To explore whether eriodictyol plays a role in glucocorticoid-induced osteoblast apoptosis and its potential regulatory mechanisms.  METHODS: Dexamethasone-pretreated osteoblasts MC3T3‐E1 were treated with the different concentrations (0, 0.5, 1, 2.5, 5, 10 μmol/L) of eriodictyol or 5 μmol/L 3-methyladenine, an autophagy inhibitor, and then transfected with heme oxygenase 1 overexpression vector (pcDNA-HMOX1) and empty vector (pcDNA vector). Cell proliferation and apoptosis were assessed by using cell counting kit-8 assay and flow cytometry, respectively. The activity of caspase-3 was detected with ELISA. Western blot assay was used to detect the protein expression of autophagy-related proteins LC3-II/LC3-I, p62, Atg5 and Atg12, the expression of apoptotic related proteins Bax and Bcl-2, as well as the protein expression of AMPK and p-AMPK.  RESULTS AND CONCLUSION: Low concentrations of eriodictyol were non-toxic to MC3T3-E1 cells and promoted cell proliferation, as well as increased the expression of autophagy related proteins LC3-II/LC3-I, p62, Atg5 and Atg12, decreased caspase-3 enzyme activity, inhibited Bax protein expression, promoted Bcl-2 protein expression and reduced dexamethasone-induced apoptosis in MC3T3-E1 cells in a dose-dependent manner. Moreover, eriodictyol significantly promoted heme oxygenase 1 expression in osteoblasts, whereas overexpression of heme oxygenase 1 promoted AMPK phosphorylation, activated autophagy, and inhibited dexamethasone-induced osteoblast apoptosis. While 3-methyladenine treatment counteracted the effects of heme oxygenase 1 overexpression on MC3T3-E1 cells. To conclude, low concentration of Eriodictyol is non-toxic to osteoblasts and activates AMPK signaling pathway by upregulating the expression of heme oxygenase 1, thereby promoting autophagy and inhibiting dexamethasone-induced osteoblast apoptosis. Eriodictyol has great potential for the treatment of glucocorticoid-induced osteoporosis.  Figures and Tables | References | Related Articles | Metrics

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Molecular mechanism of PANoptosis in diagnostic markers and subtyping of osteoporosis Ding Qiang, Xiong Bo, Liu Jinfu, Tian Zhao, Rong Xiangbin, Chen Limin, Tao Hongcheng, Li Hao, Zeng Ping 2024, 28 (28):  4505-4510.  doi: 10.12307/2024.431 Abstract ( 146 )   PDF (2994KB) ( 170 )   Save BACKGROUND: It has been hypothesized that PANoptosis may be involved in the pathologic process of osteoporosis, but there have been no studies addressing the mechanisms of PANoptosis genes in osteoporosis. OBJECTIVE: To analyze the biological mechanism of PANoptosis regulators in the occurrence and development of osteoporosis.  METHODS: The GSE56815 dataset was obtained from the Gene Expression Omnibus database and PANoptosis genes were extracted for differential analysis. The key genes of PANoptosis were screened by random forest tree model to construct a disease risk prediction model. Consensus clustering algorithm, single sample genome enrichment analysis and immune infiltration analysis were used to explore the differences between different PANoptosis molecular subtypes. Herbal drugs that regulate the key genes of PANoptosis were predicted through Coremine medical database, a medical ontology information retrieval platform.  RESULTS AND CONCLUSION: Based on the four PANoptosis key genes (CASP1, CASP10, MEFV, and TNF), the diagnostic markers of osteoporosis were determined, and the risk prediction model was constructed and verified. Osteoporosis was divided into two different PANoptosis subtypes (clusters A, B and gene clusters A, B), and the PANoptosis scores of cluster B and gene cluster B were higher than those of cluster A and gene cluster A, respectively. Traditional Chinese drugs such as ginseng which can regulate the key genes of PANoptosis were predicted by the Coremine medical database. Figures and Tables | References | Related Articles | Metrics

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Identification of biomarkers associated with ferroptosis and pyroptosis for the potential diagnosis of postmenopausal osteoporosis Li Shudong, Liang Xuezhen, Luo Di, Li Jiacheng, Yan Bozhao, Li Gang 2024, 28 (28):  4511-4515.  doi: 10.12307/2024.493 Abstract ( 139 )   PDF (2632KB) ( 48 )   Save BACKGROUND: Ferroptosis and pyroptosis may play a role in the development of postmenopausal osteoporosis. There may be relevant biomarkers for the diagnosis of postmenopausal osteoporosis. OBJECTIVE: To search for the key genes related to ferroptosis and pyroptosis in postmenopausal osteoporosis using bioinformatics so as to further elucidate their biological mechanisms. METHODS: The data sets GSE56815 and GSE7429 of postmenopausal osteoporosis were downloaded from the GEO database, the national comprehensive gene expression database of the United States, and the two data sets were preprocessed. The differential expression analysis of the data was carried out by the limma package of R software, and the enrichment analysis was performed by DIVID and KOBAS. The protein-protein interaction network was mapped by STRING and Cytoscape, the Hub gene was selected by CytoHubba, and the key genes were screened by the ferroptosis database and pyroptosis database. The CIBERSORT package was used to determine the immune infiltration of postmenopausal osteoporosis samples and to analyze the correlation between key genes and immune cells RESULTS AND CONCLUSION: A total of 30 differential genes of postmenopausal osteoporosis were screened in the experimental samples, of which 9 genes were up-regulated and 21 genes were down-regulated. The enrichment of GO and KEGG pathways showed that the differences were mainly in “serine-type endopeptidase activity,” “innate immune response,” “special particle lumen,” and “renin secretion.” The protein-protein interaction network showed the correlation of differential genes and the top 10 Hub genes with “Degree” value were selected using CytoHubba. Hub gene was intersected with the FerrDb database and cell pyroptosis dataset to obtain key genes ELANE and LCN2. Receiver operating characteristic curve and box diagram showed that the expression of ELANE and LCN2 in serum samples of postmenopausal osteoporosis was significantly lower than that in normal samples, indicating a good diagnostic value. Immune infiltration analysis showed that ELANE may be related to memory resting CD4+ T cells, M0 and M2 macrophages. LCN2 may be related to M0 macrophages. Figures and Tables | References | Related Articles | Metrics

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Semen cuscutae in the treatment of osteoarthritis: network pharmacology analysis and experimental validation Zhang Tiandong, Peng Qingping, Liu Huan, Feng Jianguo, Yi Qian, Huang Wenhua 2024, 28 (28):  4516-4521.  doi: 10.12307/2024.456 Abstract ( 168 )   PDF (3387KB) ( 94 )   Save BACKGROUND: Semen cuscutae has the effect of tonifying the liver and kidney system and benefiting the essence. The main pathogenesis of osteoarthritis is deficiency of the liver and kidneys. Therefore, it is hypothesized that there is a link between semen cuscutae and osteoarthritis. OBJECTIVE: To explore the potential relationship between osteoarthritis and semen cuscutae and validate the mechanism of semen cuscutae based on the network pharmacology and molecular docking analysis. METHODS: First, the active ingredients and targets of semen cuscutae were screened in TCMSP, and the genes related to osteoarthritis were collected in the disease databases GeneCard’s, OMIM and TTD. The intersected genes were taken and then subjected to a series of analyses and screened for hub genes. Through the enrichment analysis of hub genes, the pathway of semen cuscutae acting on osteoarthritis was selected. The role of hub genes was verified by molecular docking. Therefore, the appropriate active ingredients of semen cuscutae were selected for experimental verification. RESULTS AND CONCLUSION: There were 11 active ingredients of semen cuscutae, 66 intersection target genes of semen cuscutae and osteoarthritis, and 12 hub genes, including tumor necrosis factor, interleukin 1B, TP53, RAC-alpha serine/threonine protein kinase (AKT1), vascular endothelial growth factor A, matrix metalloproteinase 9, prostaglandin peroxidase 2, cystatinase 3, epidermal growth factor, peroxisome proliferator-activated receptor gamma, interleukin 10, vascular cell adhesion factor 1. After the enrichment analysis of the hub genes, the classical inflammatory pathway, nuclear factor-κB signaling pathway, was selected for subsequent validation of semen cuscutae to alleviate osteoarthritic inflammation. Through the results obtained after molecular docking of each active ingredient and the hub gene of the pathway prostaglandin peroxidase 2, sesamin with the highest affinity was selected for subsequent cell experiments, and the experimental results confirmed that sesamin, the active ingredient of semen cuscutae, could reduce the expression of cyclooxygenase 2 by inhibiting the nuclear factor-κB signaling pathway induced by interleukin-1β. To conclude, sesamin, the active ingredient of semen cuscutae, reduces the expression of cyclooxygenase 2 by inhibiting the nuclear factor-κB signaling pathway induced by interleukin-1β, thereby improving inflammation in osteoarthritis and expanding the therapeutic effect of semen cuscutae in osteoarthritis. Figures and Tables | References | Related Articles | Metrics

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Pulsed electromagnetic fields inhibit knee cartilage degeneration in aged rats Yin Linwei, Huang Xiarong, Sun Guanghua, Liu Jing, Zhong Peirui, Wang Jinling, Chen Jiaqian, Wen Xing, Gan Shaoting, Hu Wentao, Li Mengmeng, Zhou Jun 2024, 28 (28):  4522-4527.  doi: 10.12307/2024.464 Abstract ( 94 )   PDF (1151KB) ( 57 )   Save BACKGROUND: Pulsed electromagnetic fields, as an important physical therapy, are exactly effective in the treatment of osteoarthritis, but the mechanism has not been fully clarified. OBJECTIVE: To observe the effect of pulsed electromagnetic field on the degeneration of knee joint cartilage in aged rats. METHODS: Eight 6-month-old Sprague-Dawley rats were selected as the young group and were subjected to normal diet with no treatment. Sixteen 22-month-old Sprague-Dawley rats were randomly divided into old group (n=8) and pulsed electromagnetic field group (n=8). The rats in the pulsed electromagnetic field group were subjected to a pulsed electromagnetic field intervention, once a day, 5 days per week for continuous 8 weeks. The rats in the old group were given no treatment. All rats were anesthetized and executed after 8 weeks for the detection of relevant indexes. RESULTS AND CONCLUSION: Compared with the young group, serum type II collagen C-terminal peptide level was increased in the old group (P < 0.05); compared with the old group, serum type II collagen C-terminal peptide level was decreased in the pulsed electromagnetic field group (P < 0.05). Micro-CT showed that the bone volume fraction, bone mineral density, and number of bone trabeculae decreased (P < 0.05) and the trabecular separation increased  (P < 0.05) in the tibia of rats in the aged group compared with the young group; and the bone volume fraction, bone density, and number of trabeculae increased (P < 0.05) and the trabecular separation decreased (P < 0.05) in the tibia of rats in the pulsed electromagnetic field group compared with the aged group. The tibial plateau Safranin O-fast green staining showed that the articular cartilage structure of rats in the aged group was disorganized, and the number of chondrocytes was obviously reduced, and the tidal line could not be distinguished. The above results were improved in the pulsed electromagnetic field group. RT-qPCR and western blot assay showed that the mRNA and protein expression levels of matrix metalloproteinase 1, matrix metalloproteinase 13, P53 and P21 in the articular cartilage and subchondral bone of rats were elevated in the aged group compared with the young group (P < 0.05) and decreased in the pulsed electromagnetic field group compared with the old group (P < 0.05). To conclude, pulsed electromagnetic fields may improve osteoarthritis in aged rats by inhibiting chondrocyte senescence, alleviating articular cartilage degradation and inhibiting subchondral bone osteoporosis through suppressing the expression of P53/P21.  Figures and Tables | References | Related Articles | Metrics

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Effects of emodin on the proliferation, apoptosis and oxidative stress of chondrocytes in osteoarthritis Chen Chen, Zheng Runquan, Zhang Guichun 2024, 28 (28):  4528-4534.  doi: 10.12307/2024.470 Abstract ( 122 )   PDF (1530KB) ( 98 )   Save BACKGROUND: Previous studies have shown that silent mating-type information regulator 2 homolog 1 (SIRT1)-mechanistic target of rapamycin (mTOR) signaling plays an important role in the progression of osteoarthritis. Emodin has a protective effect on osteoarthritic chondrocytes. OBJECTIVE: To investigate the effects of emodin on the proliferation, apoptosis and oxidative stress of osteoarthritic chondrocytes based on the SIRT1-mTOR signaling.  METHODS: Rat chondrocytes were isolated and cultured in vitro. Osteoarthritic chondrocyte model in vitro was induced by 10 ng/mL interleukin-1β. Cell counting kit-8 method was used to determine the viability of rat chondrocytes treated with 0, 20, 40, 80, 120, 160 µmol/L emodin, and the appropriate concentration of emodin was selected. Rat chondrocytes isolated and cultured in vitro were randomly divided into control group, model group, low-dose emodin group, high-dose emodin group, EX527 group, and high-dose emodin+EX527 group. In vitro osteoarthritis model was constructed by induction of 10 ng/mL interleukin 1β in all groups except the control group. The cells in the latter four groups were correspondingly treated with emodin or/and EX527. The proliferation and apoptosis of chondrocytes in each group were detected by cell counting kit-8, Edu staining and flow cytometry respectively. The relative content of reactive oxygen species and the levels of malondialdehyde, superoxide dismutase, catalase, and glutathione peroxidase in chondrocytes of rats in each group were measured with the kit. The expression of proteins related to cell matrix degradation, apoptosis and the SIRT1-mTOR pathway-related proteins in each group were detected by western blot.  RESULTS AND CONCLUSION: Compared with the control group, the survival rate of chondrocytes, the positive rate of Edu, the levels of superoxide dismutase, catalase, and glutathione peroxidase, and the expression of Bcl-2 and SIRT1 proteins in the model group were decreased, while the apoptosis rate, the relative content of reactive oxygen species, the level of malondialdehyde, the expression of Bax, matrix metalloproteinase 3, matrix metalloproteinase 9 proteins, and p-mTOR/mTOR were increased (P < 0.05). Compared with the model group, the survival rate of chondrocytes, the positive rate of Edu, the levels of superoxide dismutase, catalase, and glutathione peroxidase, and the expression of Bcl-2 and SIRT1 proteins in the low- and high-dose emodin groups were increased, while the apoptosis rate, the relative content of reactive oxygen species, the level of malondialdehyde, the expression of Bax, matrix metalloproteinase 3, matrix metalloproteinase 9 proteins, and p-mTOR/mTOR were decreased (P < 0.05). Compared with the low- and high-dose emodin groups, the indexes of EX527 group showed the opposite trend (P < 0.05). Compared with the high-dose emodin group, the survival rate of chondrocytes, the positive rate of Edu, the levels of superoxide dismutase, catalase, and glutathione peroxidase, and the expression of Bcl-2 and SIRT1 proteins in the high-dose emodin+EX527 group were decreased, while the apoptosis rate, the relative content of reactive oxygen species, the level of malondialdehyde, the expression of Bax, matrix metalloproteinase 3, matrix metalloproteinase 9 proteins, and p-mTOR/mTOR were increased (P < 0.05). To conclude, emodin can inhibit oxidative stress of osteoarthritic chondrocytes by activating the SIRT1-mTOR signaling, thereby promoting chondrocyte proliferation and reducing apoptosis. Figures and Tables | References | Related Articles | Metrics

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Gastrodin intervention attenuates inflammatory injury in ischemic stroke rats Guan Jinqi, Sun Pingping, Bian Jing, Yan Xue, Zhang Weimin 2024, 28 (28):  4535-4540.  doi: 10.12307/2024.467 Abstract ( 120 )   PDF (1483KB) ( 21 )   Save BACKGROUND: Gastrodin has anti-inflammatory effects and is mainly used in clinical practice for the treatment of ischemic stroke, and its mechanism of action is still unclear. OBJECTIVE: To explore the mechanism of gastrodin intervention on inflammatory injury in ischemic stroke rats. METHODS: Fifty Sprague-Dawley rats were divided into sham-operated group, model group, positive control group, high-dose gastrodin group and low-dose gastrodin group by the randomized numerical method, with 10 rats in each group. Ischemic stroke models were established by the middle cerebral artery occlusion method in all groups of rats except for the sham operation group. Administration in each group started on the 3rd day after surgery, and the rats in the positive control group were intraperitoneally injected with edaravone injection (6 mg/kg), the rats in the high- and low-dose gastrodin groups were intraperitoneally injected with 50 and 10 mg/kg gastrodin injection respectively, and the rats in the sham-operated and model groups were intraperitoneally injected with the equal volume of physiological saline. After 14 days of continuous treatment in each group, the pathological changes in rat brain tissue were observed, and the positive expression of NLRP3 inflammasome and the expression of inflammatory response-related proteins and their mRNAs were detected. RESULTS AND CONCLUSION: Compared with the sham-operated group, the volume of cerebral infarction became larger in the model group; the structure of brain tissue was loose, irregular cavities could be observed, and the number of neurons was reduced and irregularly arranged; the positive expression of NLRP3 inflammasome increased (P < 0.01); and the protein and mRNA expression levels of Toll-like receptor 4, myeloid differentiation factor 88, apoptosis-associated speck-like protein containing a caspase-recruitment domain, Caspase-1, and interleukin-1β increased (P < 0.01). Compared with the model group, the volume of cerebral infarction became smaller in the high- and low-dose gastrodin groups; the neurons were regularly arranged, increased in number, and uniformly distributed; the positive expression of NLRP3 inflammasome was decreased (P < 0.05); the protein and mRNA expression levels of Toll-like receptor 4, myeloid differentiation factor 88, apoptosis-associated speck-like protein containing a caspase-recruitment domain, Caspase-1, and interleukin-1β were decreased in the high-dose gastrodin group (P < 0.01); Toll-like receptor 4 protein expression showed no significant changes in the low-dose gastrodin group, and the protein and mRNA expression of the other inflammatory response-associated factors decreased (P < 0.05, P < 0.01). To conclude, gastrodin attenuates inflammatory injury in ischemic stroke rats, and its mechanism of action may be related to the inhibition of inflammatory response-associate factor expression. Figures and Tables | References | Related Articles | Metrics

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Effect of arch shapes and missing second premolars on anchorage during maxillary molar distalization with clear aligners Wang Shiyu, Huang Yangyang, Liu Hao, Yang Li, Fan Dian, Yuan Changyong, Wang Penglai 2024, 28 (28):  4541-4546.  doi: 10.12307/2024.462 Abstract ( 123 )   PDF (1398KB) ( 42 )   Save BACKGROUND: The reciprocal force generated by the molar distalization with clear aligners can lead to anchorage loss. The effect of arch shapes and missing second premolars on anchorage has not been reported. OBJECTIVE: To analyze the effect of arch shapes and missing second premolars on anchorage during molar distalization with clear aligners using the finite element method.  METHODS: Cone-beam CT data from an adult male were acquired from the database to establish the maxilla-upper dentition-periodontium-rectangular attachment-clear aligner model. The distal movement amount designed on the bilateral second molars was set to 0.25 mm. First, there were two groups in the study: second premolar bilateral presence and absence groups. Then, four subgroups in each group were created: tapered arch, ovoid arch, square Class II Division 1 arch, and Class II Division 2 arch groups. The Ansys software was used to calculate the displacement of the anchorage tooth and the stress of the periodontal ligament. RESULTS AND CONCLUSION: Mesial tipping and extrusion of first molars and premolars, labial inclination and intrusion of anterior teeth occurred during the upper second molar distalization with clear aligners. When the bilateral second premolars were missing, the mesial displacement of first molars increased significantly while that of first premolars and anterior teeth decreased in all groups. The square Class II Division 1 arch group showed the least anterior labial inclination, while the tapered arch group showed the most. There was no significant difference between the ovoid arch group and the tapered arch group. Moreover, the magnitude of tipping in the square Class II Division 2 arch group was slightly higher than that in the Class II Division 1 arch group. The stress of the periodontal ligament of the anchorage teeth was concentrated on the cervical and apical regions of the teeth. And the lowest stress level was detected in the square arch group. Compared with the other groups, the stress on the labial cervical area of the periodontal ligaments was also significantly relieved in the square arch group. To conclude, the square arch is more favorable in terms of anterior anchorage control and periodontal ligament stress distribution. Anterior labial inclination efficiency can be increased in cases of Class II Division 2 by designing the anterior labial inclination in conjunction with molar distalization. If the second premolar is missing during molar distalization, it is not conducive to opening up the space in the area of the missing tooth. Figures and Tables | References | Related Articles | Metrics

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Neuroprotective mechanism by which fenofibrate regulates superoxide dismutase 2 expression in transgenic C57BL/6J mice Ma Jianglei, Zhang Huijie, Zhang Chenfang, Yang Xitong, Cheng Jianjie, Wang Guangming 2024, 28 (28):  4547-4552.  doi: 10.12307/2024.454 Abstract ( 102 )   PDF (1166KB) ( 69 )   Save BACKGROUND: Oxidative injury is considered to be one of the important factors of cerebral ischemia-reperfusion injury. Superoxide dismutase 2 (SOD2) is a key mitochondrial antioxidant molecule, and fenofibrate can regulate the expression of SOD2 by activating peroxisome proliferator-activated receptor α. OBJECTIVE: To explore whether the mechanism of fenofibrate in the treatment of cerebral ischemia-reperfusion injury depends on the expression of SOD2.  METHODS: The TALENs system was used to construct SOD2 transgenic mice. The transgenic mice were genotyped by PCR and DNA sequencing techniques. The expression of SOD2 protein in transgenic mice was detected by western blot assay. Wild-type and SOD2 transgenic mice were randomly divided into four groups: wild-type control group (n=6), wild-type fenofibrate group (n=6), SOD2 transgenic control group (n=5) and SOD2 transgenic fenofibrate group (n=5). A mouse model of middle cerebral artery occlusion was prepared using the suture-occlusion method. After 90 minutes of ischemia, the thread was removed to reperfuse cerebral blood flow for 30 minutes. A cerebral blood flow monitor was used to monitor local cerebral blood flow. Brain tissue slices were taken for 2,3,5-triphenyltetrazolium chloride staining to analyze the situation of cerebral infarction in each group.  RESULTS AND CONCLUSION: After PCR and DNA sequencing analysis, nine SOD2+/+ transgenic mice were successfully constructed. After cerebral ischemia-reperfusion, the wild-type fenofibrate group showed partial recovery of cerebral blood flow and significantly reduced cerebral infarction volume compared with the wild-type control group (P < 0.001). There was no significant difference in cerebral blood flow and cerebral infarction volume between the SOD2 transgenic fenofibrate group and the SOD2 transgenic control group. The SOD2 transgenic control was superior to the wild-type control group in terms of improving cerebral blood flow and cerebral infarction (P < 0.001). There were also no significant differences in cerebral blood flow and cerebral infarction volume between the wild-type fenofibrate group and the SOD2 transgenic control group and between the wild-type fenofibrate group and the SOD2 transgenic fenofibrate group. To conclude, the expression of SOD2 is one of the mechanisms of fenofibrate in the treatment of cerebral ischemia-reperfusion injury. Figures and Tables | References | Related Articles | Metrics

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Changes and biological significance of ferroptosis in a mouse model of bloodstream infection induced by different bacteria Zhang Zhibin, Wang Chu, Han Ying, Wang Jia, Lyu Junqing, Lin Xuerong, Yuan Meng, Han Shuchi 2024, 28 (28):  4553-4558.  doi: 10.12307/2024.465 Abstract ( 125 )   PDF (964KB) ( 73 )   Save BACKGROUND: It is of great significance to find new diagnostic markers of the disease and molecular targets for the treatment of the disease and the alleviation of organ injury. Ferroptosis is a newly discovered form of cell death. Overactivation of ferroptosis in animal models of sepsis is associated with the activation of inflammatory response and the injury of the liver, heart, kidney and other important organs, but the relationship between ferroptosis and bloodstream infection is not very clear. OBJECTIVE: To study the changes and biological significance of ferroptosis in a mouse model of blood stream infection induced by different bacteria.  METHODS: Blood stream infection models induced by gram negative bacteria Escherichia coli, Klebsiella pneumoniae and gram positive bacteria Staphylococcus aureus and Enterococcus faecalis were established in SPF-grade ICR male mice, with 42 mice in each group. The mRNA expression levels of ferroptosis marker genes transferrin receptor 1 and glutathione peroxidase 4 in the liver, myocardium and kidney were detected at 0.5, 1, 3, 6, 12, 24 and 48 hours after modeling. Another 18 SPF-grade ICR male mice were selected and randomly divided into dimethyl sulfoxide (DMSO) control group, DMSO+Klebsiella pneumoniae group, and Ferrostatin-1+Klebsiella pneumoniae group, with 6 mice in each group. In the latter two groups, animal models of Klebsiella pneumoniae bloodstream infection were established by tail vein injection of Klebsiella pneumoniae suspension, and 5 mg/kg Ferrostatin-1 and an equal dose of DMSO were given intraperitoneally 1 hour prior to the modeling of bloodstream infection, respectively. Serum levels of alanine aminotransferase, aspartate aminotransferase, blood creatinine, blood urea nitrogen, phosphocreatine kinase isoenzyme, lactate dehydrogenase, and mRNA expression levels of ferroptosis marker genes in various tissues were assayed at 6 hours after modeling. RESULTS AND CONCLUSION: After bloodstream infection modeling, the mRNA expression levels of transferrin receptor 1 in the liver, myocardium and kidney of bloodstream infection mice with different bacteria increased first and then decreased; and the mRNA expression level of glutathione peroxidase 4 decreased first, then increased, and reached the peak at 6 hours after modeling. The changes in transferrin receptor 1 and glutathione peroxidase 4 mRNA levels in bloodstream infection mice induced by gram-negative bacteria were more significant than those in blood stream infection mice induced by gram-positive bacteria, especially in bloodstream infection mice induced by Klebsiella pneumoniae. At 6 hours after bloodstream infection induced by Klebsiella pneumoniae, the levels of alanine aminotransferase, aspartate aminotransferase, serum creatinine, blood urea nitrogen, creatine phosphate kinase isoenzyme, lactate dehydrogenase in mice were significantly increased. Before modeling, Ferrostatin-1 intervention significantly reduced the levels of alanine aminotransferase, aspartate aminotransferase, serum creatinine, blood urea nitrogen, creatine phosphate kinase isoenzyme, and lactate dehydrogenase. All these findings indicate that the activation of ferroptosis in bloodstream infection mice induced by different bacteria is obvious, and the activation of ferroptosis in bloodstream infection mice induced by gram-negative bacteria is more obvious. Inhibition of iron death significantly attenuates liver, myocardial, and kidney injury in the mouse model of bloodstream infection induced by Klebsiella pneumoniae. Figures and Tables | References | Related Articles | Metrics

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Effect of molar distalization with clear aligners on occlusal vertical dimension in different vertical craniofacial patterns Peng Yi, Li Xiaolong 2024, 28 (28):  4559-4564.  doi: 10.12307/2024.458 Abstract ( 159 )   PDF (1652KB) ( 62 )   Save BACKGROUND: Previous studies have shown that clear aligners can achieve molar distalization effectively, but it is not yet clear how the vertical dimensions change in patients with different vertical craniofacial patterns after molar distalization . OBJECTIVE: To evaluate the effect of molar distalization with clear aligners on occlusal vertical dimension in different vertical craniofacial patterns.  METHODS: Forty patients (13 cases of Class I malocclusion, 20 cases of Class II malocclusion, and 7 cases of Class III malocclusion) were selected, including 13 cases in the high angle group, 17 cases in the average angle group, and 10 cases in the low angle group. Among them, the age ranged from 10 to 53 years, with an average of 28.5 years. All patients were subjected to clear aligners for molar distalization. Lateral cephalometric films were taken before and after treatment. Cephalometric measurements, including the sagittal and vertical indicators of teeth and jaws, were measured by the same orthodontist, and each indicator was measured 3 times and averaged. RESULTS AND CONCLUSION: After orthodontic treatment, the crowded dentition was corrected, the overbite and overjet were back to normal and the lateral profile was improved significantly in all 40 patients. The GoGn-SN in the high angle group decreased by 0.4°, while the GoGn-SN in the average and low angle groups increased by less than 1°, the ANS-Me in the three groups increased by less than 1 mm. There was no statistically significant difference before and after treatment. There was a statistically significant decrease in the U6-PP in the low angle group by 0.47 mm (P < 0.01). The L1-MP and the U1-SN in the average angle group significantly decreased by 0.83 mm (P < 0.05) and by 6.46° (P < 0.001), respectively. In conclusion, molar distalization with clear aligner treatment can control the vertical dimension effectively, prevent clockwise mandibular rotation, and maintain the lower face height. Patients with high angle can also undergo invisible orthodontics to distal molars. The realization rate of the anterior tooth intrusion movement by using clear aligners is insufficient, and the intrusion design should be increased to prevent the elongation phenomenon in anterior teeth. Figures and Tables | References | Related Articles | Metrics

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Effects of long intergenic non-protein coding RNA 00707 on chondrocyte injury and inflammatory factor secretion in osteoarthritis Chu Kai, Sun Jianhua 2024, 28 (28):  4565-4571.  doi: 10.12307/2024.463 Abstract ( 104 )   PDF (1349KB) ( 57 )   Save BACKGROUND: Long intergenic non-protein coding RNA 00707 (LINC00707) and microRNA-423-5p (miR-423-5p) are both involved in the occurrence and development of osteoarthritis. Starbase predicts that LINC00707 and miR-423-5p have complementary sequences, but whether LINC00707 and miR-423-5p interact to regulate the progress of osteoarthritis still needs further research. OBJECTIVE: To investigate whether LINC00707 targets miR-423-5p to affect chondrocyte injury and inflammatory factor secretion in osteoarthritis.  METHODS: Articular chondrocytes were divided into eight groups: (1) blank control group was given no treatment; (2) interleukin (IL)-1β group was cultured with 10 ng/mL IL-1β for 48 hours; (3) IL-1β+si-NC group was transfected with si-NC and then treated with 10 ng/mL IL-1β for 48 hours; (4) IL-1β+si-LINC00707 group was transfected with si-LINC00707 and then treated with 10 ng/mL IL-1β for 48 hours; (5) IL-1β+miR-NC group was transfected with miR-NC and then treated with 10 ng/mL IL-1β for 48 hours; (6) IL-1β+miR-423-5p group was transfected with miR-423-5p mimic and then treated with 10 ng/mL IL-1β for 48 hours; (7) IL-1β+si-LINC00707+anti-miR-NC group was co-transfected with si-LINC00707 and anti-miR-NC and then treated with 10 ng/mL IL-1β for 48 hours; (8) IL-1β+si-LINC00707+anti-miR-423-5p group was co-transfected with si-LINC00707 and anti-miR-423-5p and then treated with 10 ng/mL IL-1β for 48 hours. Relevant tests were performed at the end of the intervention. RESULTS AND CONCLUSION: Compared with the blank control group, the mRNA expression of LINC00707, apoptosis rate, protein expression of C-caspase3 and C-caspase9, and levels of tumor necrosis factor-α and IL-6 in articular chondrocytes were increased in the IL-1β group, while there was a decrease in miR-423-5p expression and IL-10 level (P < 0.05). Compared with the IL-1β group, the mRNA expression of LINC00707, apoptosis rate, protein expression of C-caspase3 and C-caspase9, and levels of tumor necrosis factor-α and IL-6 in articular chondrocytes were decreased in the IL-1β+si-LINC00707 group, while miR-423-5p expression and IL-10 level increased (P < 0.05). Compared with the IL-1β+miR-NC group, the protein expression of C-caspase3 and C-caspase9 and levels of tumor necrosis factor-α and IL-6 in articular chondrocytes were decreased in the IL-1β+miR-423-5p group, while miR-423-5p expression and IL-10 level increased (P < 0.05). Compared with the IL-1β+si-LINC00707+anti-miR-NC group, apoptosis rate, protein expression of C-caspase3 and C-caspase9, and levels of tumor necrosis factor-α and IL-6 in articular chondrocytes were increased in the IL-1β+si-LINC00707+anti-miR-423-5p group, while miR-423-5p expression and IL-10 level decreased (P < 0.05). To conclude, inhibiting LINC00707 by targeting miR-423-5p can reduce IL-1β-induced apoptosis and inflammation in articular chondrocytes. Figures and Tables | References | Related Articles | Metrics

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Mechanism of m6A methylation regulating bone metabolism for prevention and treatment of osteoporosis Chen Xiangshan, Liu Hua, Sun Weikang, Li Huanan 2024, 28 (28):  4572-4577.  doi: 10.12307/2024.457 Abstract ( 137 )   PDF (1059KB) ( 70 )   Save BACKGROUND: The pathogenesis of osteoporosis is complex, and its essence is the weakening of bone formation and the enhancement of bone absorption caused by various reasons, resulting in the imbalance of bone metabolism. In recent years, N6-methyladenosine has been found(N6-methyladenosine, m6A) methylation can prevent and treat osteoporosis by regulating bone metabolism. OBJECTIVE: Taking the regulation of bone metabolism by m6A methylation as an entry point, to systematically sort out and summarize the research progress of m6A methylation in osteoporosis, so as to provide certain theoretical reference bases for the search of new therapeutic targets for osteoporosis.  METHODS: CNKI, WanFang, VIP, PubMed, MEDLINE, Nature, and Cochrane databases were retrieved for relevant literature published from database inception to 2023. The keywords were “osteoporosis, m6A methylation, bone metabolism, bone marrow mesenchymal stem cells, osteoblasts, osteoclasts” in Chinese and English. Duplicates and obsolete non-referenced documents were excluded, and a total of 73 standard papers were included for further review. RESULTS AND CONCLUSION: m6A methylation can affect the activity and differentiation of bone marrow mesenchymal stem cells, osteoblasts, and osteoclasts through various pathways to regulate bone metabolism and prevent osteoporosis. The regulatory process of m6A methylation is extremely complex, and its related proteins play different roles in different cells. Even in the same kind of cells, the same type of proteins may have radically different roles, regulating different physiological and pathological processes. Figures and Tables | References | Related Articles | Metrics

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The role and mechanism of TLRs/MyD88/NF-κB signaling pathway in multiple sclerosis Chen Ying, Xia Tianqin, Hua Jianlin, Yin Jinzhu, Song Lijuan, Wang Qing, Yu Jiezhong, Huang Jianjun, Ma Cungen 2024, 28 (28):  4578-4585.  doi: 10.12307/2024.424 Abstract ( 134 )   PDF (1197KB) ( 92 )   Save BACKGROUND: Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system mediated by T cells. The Toll-like receptors (TLRs)/myeloid differentiation factor 88 (MyD88)/nuclear factor kappa-B (NF-κB) signaling pathway plays an important role in the development of the disease. Exploring the specific mechanism of the signaling pathway is essential for further treatment of the disease and improving the prognosis of patients. OBJECTIVE: To review the TLRs/MyD88/NF-κB signaling pathway and its role in multiple sclerosis/experimental autoimmune encephalomyelitis models, which provides new ideas and strategies for the treatment of multiple sclerosis by inhibiting the TLRs/MyD88/NF-κB signaling pathway.  METHODS: The literature related to the topic from January 2002 to December 2022 was searched in CNKI, WanFang and PubMed databases. A total of 61 articles were finally included for analysis. RESULTS AND CONCLUSION: The TLRs/MyD88/NF-κB signaling pathway is an important pathway that triggers a pro-inflammatory immune response. The TLRs/MyD88/NF-κB signaling pathway plays an important role in the development of multiple sclerosis by regulating the antigen presentation of dendritic cells, destroying the integrity of the blood-brain barrier, and promoting the activation of T cells, B cells and microglia. By targeting TLRs, MyD88 and NF-κB molecules, inhibiting the activation or signal transduction of TLRs, MyD88 and NF-κB, and reducing the secretion of pro-inflammatory factors, multiple sclerosis can be treated. Animal studies have shown that active ingredients of traditional Chinese medicines, such as flavonoids and glycosides, and traditional Chinese medicine compound formulas, such as Buyang Huanwu Tang, can also treat experimental autoimmune encephalomyelitis by regulating the TLRs/MyD88/NF-κB signaling pathway, which points to the direction of searching for medicines targeting the TLRs/MyD88/NF-κB signaling pathway for the treatment of multiple sclerosis. Figures and Tables | References | Related Articles | Metrics

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A meta-analysis of the effect of post-activation potentiation on athletic performance after activation of lower-extremity relative strength levels Zhang Junjie, Zhou Wei, Liu Haiyuan, Guo Chenggen 2024, 28 (28):  4586-4592.  doi: 10.12307/2024.468 Abstract ( 164 )   PDF (1834KB) ( 159 )   Save OBJECTIVE: The effect of post-activation potentiation on sports performance is characterized by increased muscle mobility and increased rate of muscle force generation. In this paper, Meta-analysis is used to quantitatively evaluate the effects of post-activation potentiation on sprint speed, jumping performance, and kinetic parameters (peak impulse, peak power, maximum ground reaction force, rate of force generation, etc.) after activation of relative strength levels in the lower limbs. METHODS: Electronic databases such as CNKI, WanFang, Web of Science, PubMed, and Medline were retrieved for randomized control, random crossover, or clear grouping according to the relative strength levels of the lower limbs (non-randomized controls) on the post-activation potentiation effect after activation induced by the relative strength level of the lower limbs. Free weight equipment and rapid telescopic compound exercises were used as main intervention methods in each group. The publication time of the literature was from the inception of each database until August 5, 2023. Endnote software was used to manage the literature. Literature quality assessment was conducted using the PEDro scale for randomized controlled trials and ROBINS-I 2.0 standards for non-randomized controlled trials. Revman5.4 and Stata15.0 software were used to conduct publication bias evaluation, subgroup analysis and sensitivity analysis of the extracted data, and forest plots were produced for Meta-analysis. RESULTS: Eleven documents (seven randomized controlled trials and four non-randomized controlled trials) were finally included, including 216 subjects. Overall, the methodological quality of the literature was high. According to the grouping standard of 1-repetition maximum/body mass > 2 for the strong group and 1-repetition maximum/body mass ≤ 2 for the normal group, there were 99 subjects in the strong group and 117 subjects in the normal group, all of whom were male. The positive effect of post-activation potentiation on sprint performance in the strong group was significantly higher than that in the normal group [standardized mean difference (SMD)=-1.34, 95% confidence interval (CI): -1.74 to -0.93, P < 0.000 01]; the positive effect of post-activation potentiation on vertical jump height showed no significant difference between the strong and normal group (SMD=0.30, 95% CI: -0.07 to 0.66, P=0.11); the positive effect of post-activation potentiation showed no significant difference between the strong and normal groups in terms of peak impulse (SMD=-0.07, 95% CI:-0.62 to 0.47, P=0.61], peak power (SMD=0.21, 95% CI:-0.29 to 0.72, P=0.12), maximum ground reaction force (SMD=0.31, 95% CI: -0.20 to 0.81, P=0.16) and force generation rate (SMD=0.36, 95% CI: -0.11 to 0.82, P=0.39). CONCLUSION: The post-activation potentiation effect in the strong group can significantly increase the short-distance sprint speed. The potentiation effect after activation of the relative strength level of the lower limbs has similar effects on the kinematic and kinetic parameters, including explosive vertical jump height, peak impulse, peak power, maximum ground reaction force and force generation rate. Figures and Tables | References | Related Articles | Metrics