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.

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.

Objective To analyze trend changes of disease burden of hypertensive nephropathy (HTN) between 2012 and 2023 in Chongqing, and to provide the suggestion for HTN prevention and treatment. Methods Death cases of HTN from Chongqing death registration data between 2012 and 2023 were analyzed to calculate indicators such as mortality, age standardization mortality rate (ASMR), rate of years of life lost (YLL) and Average years of life lost. The mortality of HTN between male and female, urban and rural were compared by Chi-square test. The trend change was explained by average annual percent of change (AAPC). Results The mortality and standardized mortality of HTN in Chongqing decreased from 5.44/100 000 and 3.13/100 000 in 2012 to 2.76/100 000 and 1.07/100,000 in 2023 respectively. The average annual percent change (AAPC) was -5.41% and -8.35% respectively, and the differences in the change trends were statistically significant (P<0.01). The mortality and standardized mortality of HTN in males and females decreased with AAPC of 5.50%, 8.07%, 5.27% and 8.69% respectively, and the differences in the change trends were all statistically significant (all P< 0.05). From 2012 to 2014, 2019 and 2021, the mortality rate of HTN in rural areas was higher than that in urban areas (all P < 0.05). The mortality and standardized mortality of HTN in rural areas decreased with AAPC of 6.58% and 9.46% respectively, and the differences in the change trends were all statistically significant (all P<0.05). The rate of YLL and standardized YLL of HTN in Chongqing decreased from 96.02/100 000 and 60.42/100 000 in 2012 to 44.98/100 000 and 21.49/100 000 in 2023 respectively. The AAPC was -5.83% and -7.80% respectively, and the differences in the change trends were statistically significant (both P < 0.05). AYLL of HTN were 17.88 years in 2012, and it was 17.08 years in 2023. There were no statistically significant differences in the changes (both P > 0.05). The standardized AYLL of HTN in rural areas increased at an average annual rate of 1.14%, and the difference was statistically significant (P < 0.05). Conclusion The mortality and YLL rate of HNT in Chongqing was lower than it in China. Moreover, its trend was decreased. It should be strengthened early screening and healthy management of HNT.

BACKGROUND:Human placental mesenchymal stem cells have been shown to be effective in inhibiting the development of pulmonary fibrosis,but the underlying mechanisms remain unclear. OBJECTIVE:To investigate the therapeutic effect and related mechanism of human placental mesenchymal stem cells on silica-induced pulmonary fibrosis in human embryonic lung fibroblasts(MRC-5). METHODS:CCK-8 assay was used to detect the effects of different mass concentrations of silica on the proliferation of MRC-5 at different time points.Immunofluorescence staining was used to screen out the best stimulating mass concentration and time of silica for subsequent experiments.MRC-5 cells were divided into blank group,silica group,and silica + human placental mesenchymal stem cell group.In the blank group,cells were not treated.In the silica group,MRC-5 cells were stimulated with 100 μg/mL silica for 48 hours.In the silica + human placental mesenchymal stem cell group,MRC-5 cells were stimulated with 100 μg/mL silica for 48 hours and then co-cultured with human placental mesenchymal stem cells for 24 hours.Immunofluorescence staining was used to detect the expression of α-smooth muscle actin and collagen type I in cells of each group.Western blot assay was used to detect the expressions of pulmonary fibrosis-related proteins and TGF-β1/Smad 3 signaling pathway-related proteins in cells of each group. RESULTS AND CONCLUSION:(1)CCK-8 assay results suggested that 100 μg/mL silica was the best mass concentration and time to stimulate MRC-5 cells for 48 hours.(2)Immunofluorescence staining results showed that the expression of α-smooth muscle actin and collagen type I in the silica + human placental mesenchymal stem cell group was significantly lower than that in the silica group.(3)Western blot assay results showed that compared with the silica group,the protein expression levels of α-smooth muscle actin,collagen type I,N-cadherin,fibronectin,transforming growth factor-β1,p-Smad3,and Smad3 in the silica + human placental mesenchymal stem cell group were decreased,and the expression of E-cadherin was increased.The difference was statistically significant(P<0.05).(4)The results showed that human placental mesenchymal stem cells had a significant therapeutic effect on silica-induced pulmonary fibrosis.Human placental mesenchymal stem cells can inhibit the development of pulmonary fibrosis by regulating transforming growth factor-β1/Smad3 signaling pathway.

Objective To analyze the factors affecting the risk of hepatocellular carcinoma(HCC)in patients with chronic hepatitis B-associated cirrhosis(CHB-Cir)complicated by essential hypertension(EH)and explore the impact of EH on HCC risk in patients with CHB-Cir.Methods This study was conducted among the patients with CHB-Cir with or without EH received antiviral therapy in the Infectious Disease Department,Third Affiliated Hospital of Xinxiang Medical University from January,2017 to January,2024.The cases with insufficient follow-up time or missing data were excluded.The patients were subjected to propensity score matching in a 1:1 ratio to form an EH group and a non-EH group.The Kaplan-Meier method was used to compare the cumulative incidence of HCC between the two groups,and the Cox proportional hazards regression model was used to analyze the risk of HCC and the factors affecting HCC risk.Results A total of 390 CHB-Cir patients(274 male and 116 female patients)were enrolled in this study,including 195 with EH and 195 without EH.In these patients,EH was significantly correlated with the occurrence of HCC(HR=1.69,P=0.002).Multivariate analysis suggested that the male gender(HR=1.73,P=0.005),a family history of liver cancer(HR=2.23,P<0.001),elevated alpha-fetoprotein(HR=2.83,P=0.001),elevated glutathione reductase(HR=1.53,P=0.046),reduced high-density lipoprotein(HR=1.46,P=0.027),and elevated low-density lipoprotein(HR=2.29,P=0.003)were all significantly correlated with HCC occurrence,while elevated triglycerides(HR=0.37,P<0.001)was a protective factor against HCC.In the EH group,treatment with non-RASIs drugs(HR=2.77,P=0.021)and no treatment/diuretic treatment(HR=7.18,P<0.001)were significantly correlated with HCC occurrence.Conclusion Hypertension increases the risk of HCC in patients with CHB-Cir,suggesting the importance of controlling hypertension in these patients.

Objective To analyze the factors affecting the risk of hepatocellular carcinoma(HCC)in patients with chronic hepatitis B-associated cirrhosis(CHB-Cir)complicated by essential hypertension(EH)and explore the impact of EH on HCC risk in patients with CHB-Cir.Methods This study was conducted among the patients with CHB-Cir with or without EH received antiviral therapy in the Infectious Disease Department,Third Affiliated Hospital of Xinxiang Medical University from January,2017 to January,2024.The cases with insufficient follow-up time or missing data were excluded.The patients were subjected to propensity score matching in a 1:1 ratio to form an EH group and a non-EH group.The Kaplan-Meier method was used to compare the cumulative incidence of HCC between the two groups,and the Cox proportional hazards regression model was used to analyze the risk of HCC and the factors affecting HCC risk.Results A total of 390 CHB-Cir patients(274 male and 116 female patients)were enrolled in this study,including 195 with EH and 195 without EH.In these patients,EH was significantly correlated with the occurrence of HCC(HR=1.69,P=0.002).Multivariate analysis suggested that the male gender(HR=1.73,P=0.005),a family history of liver cancer(HR=2.23,P<0.001),elevated alpha-fetoprotein(HR=2.83,P=0.001),elevated glutathione reductase(HR=1.53,P=0.046),reduced high-density lipoprotein(HR=1.46,P=0.027),and elevated low-density lipoprotein(HR=2.29,P=0.003)were all significantly correlated with HCC occurrence,while elevated triglycerides(HR=0.37,P<0.001)was a protective factor against HCC.In the EH group,treatment with non-RASIs drugs(HR=2.77,P=0.021)and no treatment/diuretic treatment(HR=7.18,P<0.001)were significantly correlated with HCC occurrence.Conclusion Hypertension increases the risk of HCC in patients with CHB-Cir,suggesting the importance of controlling hypertension in these patients.

Objective To investigate the correlation between biofilm gene,efflux pump gene,biofilm forming ability and drug resistance of Acinetobacter baumarmii(AB)isolated from the patients of clinical infectious diseases.Methods A total of 119 non-repeating Acinetobacter baumannii isolates(74 MDR-AB strains and 45 non-multi-drug resistant strains)were collected.The effector pump genes(adeB,adeJ,adeG,adeS and adeR)and biofilm-related genes(bap,ompA,csuA,csuB,csuC,csuD,csuE,abaI,bfmR,bfmS)were detected by PCR.Bacterial biofilm was constructed in vitro with 24-well cell culture plates,and the formation of biofilm was qualitatively observed by crystal violet staining.Results Acinetobacter baumannii was resistant to most of the commonly used antibiotics and sensitive to tigacycline,polymyxin B and minocycline.The overall detection rate of biofilm-related genes was about 80％,and the detection rates of bap,csuB,csuC and csuD genes in multi-drug resistant bacteria were significantly higher than those in non-multi-drug resistant bacteria(P＜0.05).The detection rate of active effector pump genes was less than 70％,and the detection rate of adeB,adeJ,adeS and adeR genes in multidrug-resistant bacteria was significantly higher than that in non-multidrug-resistant bacteria(P＜0.05).The adeG carrying rate was opposite.Three multidrug-resistant strains and five non-multidrug-resistant strains did not carry the above efflux pump related genes,and no abeM gene was detected in all strains.The formation of biofilm was observed in 95.80％of strains.Conclusion Acinetobacter baumannii in hospital is mostly multidrug-resistant strains,most of which have strong biofilm forming ability.Multidrug-resistant bacteria have higher biofilm gene and effluent-pump gene carrying rate,which may be involved in the regulation and formation of multidrug resistance.