BACKGROUND:Various proteins,signaling pathways,and inflammatory mediators are involved in the pathophysiological process of osteoarthritis.The development of small molecule drugs targeting these proteins,signaling pathways,and inflammatory mediators can effectively delay the progression of osteoarthritis and ameliorate its clinical manifestations. OBJECTIVE:To review the research progress of small molecule drugs in the treatment of osteoarthritis based on the pathogenesis of osteoarthritis. METHODS:PubMed,CNKI,and WanFang databases were searched with English search terms"osteoarthritis,arthritis,osteoarthrosis,degenerative,arthritides,deformans,small molecule drugs,small molecule inhibitors,small molecule agents"and Chinese search terms"osteoarthritis,small molecule drugs,small molecule inhibitors."A total of 68 articles were included for review according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)Currently,studies concerning the pathogenesis of osteoarthritis remain unclear.The occurrence and development of osteoarthritis are strongly associated with proteins,cytokines,and signal transduction pathways,so its therapeutic mechanism is relatively complex.Currently,targeting proteins,cytokines,and signal transduction pathways related to osteoarthritis with small molecule drugs has become a major research focus.(2)Small molecule drugs frequently possess visible intracellular or extracellular targets and efficacy,containing enhancing cartilage repair,resisting joint degradation,attenuating inflammation,and relieving pain.Other anti-osteoarthritis small molecule drugs have shown promise in promoting stem cell chondrogenic differentiation and cartilage matrix reconstruction.(3)At present,small molecule drugs targeting the pathophysiological process of osteoarthritis to delay the progression of osteoarthritis are still in the experimental stage,but most of these small molecule drugs have shown the expected results in the experimental process,and there are no relevant studies to illustrate the efficacy of small molecule drugs in the treatment of osteoarthritis.(4)Small molecule drugs for the treatment of osteoarthritis have reached the expected experimental results in the basic experimental stage.Numerous studies have exhibited that small molecule drugs can target the suppression of specific proteins,cytokines,and signal transduction pathways that cause osteoarthritis,so as to treat osteoarthritis.Nevertheless,its safety and effectiveness still need to be identified by further basic and clinical studies.This process needs to be investigated and studied by more scholars.(5)At present,many scholars in and outside China have made contributions to the treatment of osteoarthritis.Compared with traditional treatment methods,small molecule drugs reveal better efficacy and safety in the basic experimental stage,and it is expected to become an emerging method for the treatment of osteoarthritis in the future to rid patients of pain.

Background/Aims: Liver transplantation is the most effective treatment for the sickest patients with acute-on-chronic liver failure (ACLF). However, the influence of donor age on liver transplantation, especially in ACLF patients, is still unclear. Methods: In this study, we used the data of the Scientific Registry of Transplant Recipients. We included patients with ACLF who received liver transplantation from January 1, 2007, to December 31, 2017, and the total number was 13,857. We allocated the ACLF recipients by age intogroup I (donor age ≤17 years, n=647); group II (donor age 18–59 years, n=11,423); and group III (donor age ≥60 years, n=1,787). Overall survival (OS), graft survival, and mortality were com-pared among the three age groups and the four ACLF grades. Cox regression was also analyzed. Results: The 1-, 3-, and 5-year OS rates were 89.6%, 85.5%, and 82.0% in group I; 89.4%, 83.4%, and 78.2% in group II; and 86.8%, 78.4%, and 71.4% in group III, respectively (p<0.001).When we analyzed the different effects of donor age on OS with different ACLF grades, in groupsII and III, we observed statistical differences. Finally, the cubic spline curve told us that the relative death rate changed linearly with increasing donor age. Conclusions Donor age is related to OS and graft survival of ACLF patients after transplanta-tion, and poorer results were associated with elderly donors. In addition, different donor ages have different effects on recipients with different ACLF grades.

Background/Aims: Liver transplantation is the most effective treatment for the sickest patients with acute-on-chronic liver failure (ACLF). However, the influence of donor age on liver transplantation, especially in ACLF patients, is still unclear. Methods: In this study, we used the data of the Scientific Registry of Transplant Recipients. We included patients with ACLF who received liver transplantation from January 1, 2007, to December 31, 2017, and the total number was 13,857. We allocated the ACLF recipients by age intogroup I (donor age ≤17 years, n=647); group II (donor age 18–59 years, n=11,423); and group III (donor age ≥60 years, n=1,787). Overall survival (OS), graft survival, and mortality were com-pared among the three age groups and the four ACLF grades. Cox regression was also analyzed. Results: The 1-, 3-, and 5-year OS rates were 89.6%, 85.5%, and 82.0% in group I; 89.4%, 83.4%, and 78.2% in group II; and 86.8%, 78.4%, and 71.4% in group III, respectively (p<0.001).When we analyzed the different effects of donor age on OS with different ACLF grades, in groupsII and III, we observed statistical differences. Finally, the cubic spline curve told us that the relative death rate changed linearly with increasing donor age. Conclusions Donor age is related to OS and graft survival of ACLF patients after transplanta-tion, and poorer results were associated with elderly donors. In addition, different donor ages have different effects on recipients with different ACLF grades.

Background/Aims: Liver transplantation is the most effective treatment for the sickest patients with acute-on-chronic liver failure (ACLF). However, the influence of donor age on liver transplantation, especially in ACLF patients, is still unclear. Methods: In this study, we used the data of the Scientific Registry of Transplant Recipients. We included patients with ACLF who received liver transplantation from January 1, 2007, to December 31, 2017, and the total number was 13,857. We allocated the ACLF recipients by age intogroup I (donor age ≤17 years, n=647); group II (donor age 18–59 years, n=11,423); and group III (donor age ≥60 years, n=1,787). Overall survival (OS), graft survival, and mortality were com-pared among the three age groups and the four ACLF grades. Cox regression was also analyzed. Results: The 1-, 3-, and 5-year OS rates were 89.6%, 85.5%, and 82.0% in group I; 89.4%, 83.4%, and 78.2% in group II; and 86.8%, 78.4%, and 71.4% in group III, respectively (p<0.001).When we analyzed the different effects of donor age on OS with different ACLF grades, in groupsII and III, we observed statistical differences. Finally, the cubic spline curve told us that the relative death rate changed linearly with increasing donor age. Conclusions Donor age is related to OS and graft survival of ACLF patients after transplanta-tion, and poorer results were associated with elderly donors. In addition, different donor ages have different effects on recipients with different ACLF grades.

ObjectiveTo explore the mechanism by which Buyang Huanwutang regulates the glutathione peroxidase 4 （GPX4）-acyl-CoA synthetase long-chain family member 4 （ACSL4） axis to inhibit ferroptosis and promote neurological functional recovery after spinal cord injury （SCI）. MethodsNinety rats were randomly divided into five groups： sham operation group， model group， low-dose Buyang Huanwutang group （12.5 g·kg^-1）， high-dose Buyang Huanwutang group （25 g·kg^-1）， and Buyang Huanwutang + inhibitor group （25 g·kg^-1 + 5 g·kg^-1 RSL3）. The SCI model was established by using the allen method. Tissue was collected on the 7th and 28th days after operation. Motor function was assessed by using the Basso-Beattie-Bresnahan （BBB） scale. Hematoxylin-eosin （HE）， Nissl， and Luxol fast blue （LFB） staining were performed to observe spinal cord histopathology. Transmission electron microscopy was used to examine mitochondrial ultrastructure. Immunofluorescence staining was used to detect the number of NeuN-positive cells and the fluorescence intensity of myelin basic protein （MBP）， GPX4， and ACSL4. Real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） was used to analyze the mRNA expression of GPX4 and ACSL4. Enzyme linked immunosorbent assay （ELISA） was performed to measure the levels of reactive oxygen species （ROS）， malondialdehyde （MDA）， glutathione （GSH）， and superoxide dismutase （SOD）. Colorimetric assays were used to determine the iron content in spinal cord tissue. ResultsCompared to the sham operation group， the model group exhibited significantly reduced BBB scores （P<0.01）， severe pathological damage in spinal cord tissue， and marked mitochondrial ultrastructural disruption. In addition， the model group showed a decrease in the number of NeuN-positive cells （P<0.01）， reduced fluorescence intensity of MBP and GPX4 （P<0.01）， lower levels of GSH and SOD （P<0.01）， and downregulated mRNA expression of GPX4 （P<0.01）. Moreover， compared to the sham operation group， the model group had elevated levels of ROS， MDA， and tissue iron content （P<0.01）， along with increased fluorescence intensity and mRNA expression of ACSL4 （P<0.01）. Compared with the model group and Buyang Huanwutang + inhibitor group， the Buyang Huanwutang group showed significantly improved BBB scores （P<0.05， P<0.01） and exhibited less severe spinal cord tissue damage， reduced edema and inflammatory cell infiltration， increased neuronal survival， and more intact myelin structures. Additionally， mitochondrial ultrastructure was significantly improved in the Buyang Huanwutang group. Compared to the model group and Buyang Huanwutang + inhibitor group， the Buyang Huanwutang group significantly increased the number of NeuN-positive cells and the fluorescence intensity of MBP （P<0.05， P<0.01）. Furthermore， Buyang Huanwutang significantly increased the fluorescence intensity and mRNA expression of GPX4 （P<0.01） and decreased the fluorescence intensity and mRNA expression of ACSL4 （P<0.01） compared to the model group and Buyang Huanwutang + inhibitor group. Finally， the Buyang Huanwutang group significantly decreased ROS， MDA， and tissue iron content （P<0.01） and significantly increased GSH and SOD levels （P<0.01） compared to the model group and Buyang Huanwutang + inhibitor group. ConclusionBuyang Huanwutang inhibits ferroptosis through the GPX4/ACSL4 axis， reduces secondary neuronal and myelin injury and oxidative stress， and ultimately promotes the recovery of neurological function.

Objective To investigate whether carotid artery stenting （CAS） is a protective factor against the progression of white matter hyperintensity （WMH） volume in patients with carotid artery stenosis. Methods A prospective study was conducted for the clinical， imaging， and follow-up data of patients with carotid artery stenosis who were treated in Zhejiang Provincial People's Hospital from January 2021 to June 2023. A total of 99 participants were included in this study， among whom 48 received CAS treatment （CAS group） and 51 did not receive CAS treatment （non-CAS group）. The two groups were analyzed in terms of baseline data and WMH volume during the 1-year follow-up. Results There were no significant differences in baseline data between the two groups （P>0.05）. There was no significant difference in overall WMH volume after follow-up between the two groups （P>0.05）， but compared with the non-CAS group， the CAS group showed a significantly lower degree of the progression of WMH volume within one year （-0.27 ml vs 2.82 ml， P<0.001）. There was a significant difference in the proportion of patients with new-onset stroke within one year between the CAS group and the non-CAS group （18.75% vs 37.25%， P=0.041）. The binary logistic regression analysis showed that CAS was an independent protective factor against the progression of WMH volume（OR=-0.37， 95%CI -0.78 to -0.03，P=0.046） and new-onset stroke within one year （OR=0.28， 95% CI 0.09 to 0.83， P=0.022）. Conclusion CAS is a protective factor against the progression of WMH volume and can effectively reduce the risk of stroke recurrence in patients with carotid artery stenosis.

Background/Aims: Liver transplantation is the most effective treatment for the sickest patients with acute-on-chronic liver failure (ACLF). However, the influence of donor age on liver transplantation, especially in ACLF patients, is still unclear. Methods: In this study, we used the data of the Scientific Registry of Transplant Recipients. We included patients with ACLF who received liver transplantation from January 1, 2007, to December 31, 2017, and the total number was 13,857. We allocated the ACLF recipients by age intogroup I (donor age ≤17 years, n=647); group II (donor age 18–59 years, n=11,423); and group III (donor age ≥60 years, n=1,787). Overall survival (OS), graft survival, and mortality were com-pared among the three age groups and the four ACLF grades. Cox regression was also analyzed. Results: The 1-, 3-, and 5-year OS rates were 89.6%, 85.5%, and 82.0% in group I; 89.4%, 83.4%, and 78.2% in group II; and 86.8%, 78.4%, and 71.4% in group III, respectively (p<0.001).When we analyzed the different effects of donor age on OS with different ACLF grades, in groupsII and III, we observed statistical differences. Finally, the cubic spline curve told us that the relative death rate changed linearly with increasing donor age. Conclusions Donor age is related to OS and graft survival of ACLF patients after transplanta-tion, and poorer results were associated with elderly donors. In addition, different donor ages have different effects on recipients with different ACLF grades.

ObjectiveTo analyze stroke mortality data from Yuyao, Zhejiang Province, from 2015 to 2022, and to provide references for the development of effective stroke prevention and control strategies in Yuyao and similar county-level cities or districts. MethodsData on all stroke-related deaths in Yuyao from 2015 to 2022 were collected. Metrics including crude mortality rate (CMR), Chinese-standardized mortality rate, world-standardized mortality rate, truncated mortality rate (35‒64 years), cumulative mortality rate (0‒74 years), premature mortality rate, potential years of life lost (PYLL), average years of life lost (AYLL), PYLL rate (PYLLR), and average annual percentage change (AAPC) were calculated. Differences between groups were compared using the Chi-square test. Linear regression was utilized to calculate AAPC and analyze mortality trends. ResultsFrom 2015 to 2022, a total of 6 533 stroke deaths were recorded among residents in Yuyao, with ischemic stroke accounting for 70.60% and hemorrhagic stroke accounting for 29.40%. The average CMR was 97.67/100 000, China-standardized mortality rate was 45.82/100 000, and world-standardized mortality rate was 32.10/100 000. No statistically significant differences were observed in CMR, China-standardized morality rate, or world-standardized mortality rate over the 8 years (all P>0.05). Stroke deaths primarily occurred in winter (from December to February of next year), accounting for 31.21% of the cases. Male stroke mortality rate (108.15/100 000) was significantly higher than female mortality rate (87.49/100 000, χ²=73.195, P<0.001). Stroke mortality rate increased significantly with age (χ²_trend=17 839.150, P<0.001), peaking at 1 867.82/100 000 in the ≥85-year-old age group. Hemorrhagic stroke mortality rate was higher than ischemic stroke mortality rate in the 10‒64-year-old age group, whereas ischemic stroke mortality rate exceeded hemorrhagic stroke mortality rate in those aged 65 years and above. The PYLL caused by stroke mortality was 11 014.00 person-years, with an AYLL of 10.98 years, and a PYLLR of 1.87‰. ConclusionStroke mortality in Yuyao has remained relatively stable. A community-based comprehensive chronic disease intervention mechanism should be established, with a focus on males and the elderly. This mechanism should integrate community health education, stroke risk assessment, screening and intervention, two-way patient referral systems, and tiered rehabilitation services to reduce mortality rate and mitigate life expectancy loss.

Blood brain barrier (BBB) injury is the main pathological manifestation of many neurological diseases. Glycocalyx is the gel layer covering the lumen side of vascular endothelial cells, which plays an important role in regulating BBB function. However, glycocalyx is very fragile and easily damaged in various neurological diseases, leading to BBB destruction. This article focuses on the potential role of glycocalyx in cerebrovascular disease, the possible mechanisms related to glycocalyx and BBB injury, and explores the potential therapeutic strategies for protecting and restoring endothelial glycocalyx.

Objective:To synthesize the real experiences of medical staff's organizational silence behavior.Methods:A systematic search was conducted in databases including PubMed, Web of Science, Embase, Cochrane Library, CINAHL, EBSCO, ProQuest, China National Knowledge Infrastructure, Wanfang Data, VIP, and China Biology Medicine disc, collecting qualitative studies on medical staff's experiences related to organizational silence behavior. The search period covered the establishment of the databases until June 2024. The quality of the included studies was assessed using the Joanna Briggs Institute's qualitative research quality evaluation standards, and results were integrated using an aggregative synthesis approach.Results:A total of 10 studies were included, with 65 findings summarized into 11 new categories, which were further synthesized into four overarching conclusions: organizational silence is complex, with respect and concern coexisting, many factors contribute to organizational silence, medical staff experience negative emotions as a result of organizational silence, there is a desire for recognition and support.Conclusions:The experience of organizational silence behavior among medical staff is complex. Managers should focus on this issue, encourage individuals to voice their concerns, provide diverse support mechanisms, and enhance positive experiences to reduce the prevalence of organizational silence.