OBJECTIVE To conduct a reevaluation of the systematic review （SR）/meta-analysis on the use of Xianling gubao capsules （XLGBC） for knee osteoarthritis （KOA）， and provide evidence-based support for the clinical use of the drugs. METHODS Computerized searches including CNKI， Wanfang Data， VIP， China Biomedical Literature Database， the Cochrane Library， PubMed， Embase and Web of Science were conducted to collect systematic reviews （SR） or meta-analyses of XLGBC for the treatment of KOA from the inception to May 31st， 2024. The report quality， methodological quality， risk of bias and evidence quality were assessed using the PRISMA 2020 statement， AMSTAR 2 scale， ROBIS tool and GRADE tool， respectively. A comprehensive quality analysis of the quantitative results from the SR/meta-analysis was also performed. RESULTS A total of five SR/meta-analyses were included. The evaluation results based on the PRISMA 2020 statement showed that one study report was relatively complete （21 points）， while four studies had deficiencies （18-20 points）. The assessment using the AMSTAR 2 scale indicated that the methodological quality of all five studies was rated as very low. According to the ROBIS tool evaluation， the risk of comprehensive bias in all five studies was classified as high. GRADE tool evaluation revealed that among 49 outcome indicators， 5 （10.2%） were rated as moderate-quality evidence （10.2%）， 12 as low-quality evidence （24.5%）， and 32 as very low-quality evidence （65.3%）. The results of comprehensive quality analysis showed that the clinical efficacy， visual analogue scale score， pain relief time， comprehensive indexes of knee joint function， the levels of inflammatory factors and the incidence of adverse events in patients with XLGBC combined with conventional treatment were significantly better than conventional treatment alone （P＜0.05）. CONCLUSIONS Compared with conventional treatment， XLGBC in combination with conventional treatment for KOA may have some efficacy and safety advantages. However， due to the low quality of evidence for the outcome indicators included in the studies， the conclusions should be interpreted with caution.

OBJECTIVE To conduct a reevaluation of the systematic review （SR）/meta-analysis on the use of Xianling gubao capsules （XLGBC） for knee osteoarthritis （KOA）， and provide evidence-based support for the clinical use of the drugs. METHODS Computerized searches including CNKI， Wanfang Data， VIP， China Biomedical Literature Database， the Cochrane Library， PubMed， Embase and Web of Science were conducted to collect systematic reviews （SR） or meta-analyses of XLGBC for the treatment of KOA from the inception to May 31st， 2024. The report quality， methodological quality， risk of bias and evidence quality were assessed using the PRISMA 2020 statement， AMSTAR 2 scale， ROBIS tool and GRADE tool， respectively. A comprehensive quality analysis of the quantitative results from the SR/meta-analysis was also performed. RESULTS A total of five SR/meta-analyses were included. The evaluation results based on the PRISMA 2020 statement showed that one study report was relatively complete （21 points）， while four studies had deficiencies （18-20 points）. The assessment using the AMSTAR 2 scale indicated that the methodological quality of all five studies was rated as very low. According to the ROBIS tool evaluation， the risk of comprehensive bias in all five studies was classified as high. GRADE tool evaluation revealed that among 49 outcome indicators， 5 （10.2%） were rated as moderate-quality evidence （10.2%）， 12 as low-quality evidence （24.5%）， and 32 as very low-quality evidence （65.3%）. The results of comprehensive quality analysis showed that the clinical efficacy， visual analogue scale score， pain relief time， comprehensive indexes of knee joint function， the levels of inflammatory factors and the incidence of adverse events in patients with XLGBC combined with conventional treatment were significantly better than conventional treatment alone （P＜0.05）. CONCLUSIONS Compared with conventional treatment， XLGBC in combination with conventional treatment for KOA may have some efficacy and safety advantages. However， due to the low quality of evidence for the outcome indicators included in the studies， the conclusions should be interpreted with caution.

Objective To investigate whether there are sex differences in inflammatory bowel disease(IBD)among the offspring of mice with IBD.Methods BALB/c female mice were randomly divided into Na?ve and DSS groups.The mice in the Na?ve group drank autoclaved water freely,and the DSS group freely drank 2％dextran sodium sulfate(DSS)for 7 days before it was replaced with autoclaved water for 10 days.A total of 3～4 cycles were applied,and the IBD female mice were paired with healthy male mice in cages.When the pups were 8 weeks old,they were divided into the Con group and IBD group.The Con group drank autoclaved water freely for 7 days,and the IBD group drank 3％DSS for 7 days.During the modeling period,disease activity index was scored by monitoring body weight,fecal consistency,and the presence of blood in stool every day.Pathological sections were taken to observe changes in goblet cells and the mucus layer of colon tissues.The concentrations of interleukin(IL)-6,IL-1β,IL-33,and IL-10 in the colon were detected by enzyme-linked immunosorbent assay.Real-time quantitative PCR was used to determine the mRNA expression levels of tight-junction proteins and MUC-2 in the colon.Results Compared with female IBD mice,male IBD mice had higher DAI scores,significantly shorter colons,larger amounts of inflammatory infiltrate,more crypt abnormalities,and a higher absence of goblet cells in the colon;their relative mRNA expression of occludin mRNA was significantly reduced,levels of IL-6 and IL-33 were significantly increased,and level of IL-10 was significantly decreased.Conclusions The symptoms of colitis in the offspring of IBD mice were more severe in male than in female mice,a result that was mainly attributed to the more severely impaired intestinal epithelial barrier function in males.

Objective　To explore the application of time series models based on meteorological factors in the population density of Aedes albopictus in Hainan Province, and to provide a scientific basis for the prevention and control of dengue fever in Hainan Province. Methods　The density of Aedes albopictus in different habitats in 18 cities and counties of Hainan Province from 2017 to 2022 was monitored monthly using the double-mosquito net trapping index and the Breteau index. Mann-Kendall trend test was used to analyze the temporal trends of the two density indices; Spearman's correlation analysis was employed to assess the correlation strength between each meteorological factor and the two indexes, eliminating unrelated variables, and further selecting the final variables through the full-subset regression method. Three time-series models were constructed for the two density indices, with root mean square error (RMSE), mean absolute error (MAE), and other accuracy metrics used to determine the optimal model; predictions for the density indices for 2023-2024 were made. All statistical analyses were performed in R (4.3.1). Results　The net trapping and Breteau indices showed an overall decrease over the years (Z-values of Mann-Kendall trend test were -6.15 and -4.03, respectively, and P<0.05). The meteorological factor most strongly associated with the trap index was the monthly average minimum temperature; monthly mean minimum temperature and monthly mean relative humidity were strongly correlated with the Breteau index. Based on various evaluation indicators, the multivariate time series model demonstrated the highest accuracy. The study predicts one to two peaks in both the trap index and Breteau Index for the years 2023 and 2024, with peak periods occurring between June to September and May to September, respectively. The predicted value for 2023 aligns with the measured value, demonstrating outstanding predictive accuracy. Conclusions　This study has introduced meteorological factors into the seasonal time series model, allowing for more accurate predictions of the density of Aedes albopictus in Hainan Province from 2023 to 2024, providing a model framework for the prevention and control of dengue fever in Hainan Province.

Parkinson′s disease (PD) is a debilitating neurodegenerative disorder that exhibits an escalating prevalence with advancing age. The management of PD adheres to a comprehensive therapeutic approach integrating pharmacological interventions, surgical procedures, rehabilitative exercises, and supportive care measures. In recent years, with the deepened understanding of the pathogenesis underlying PD, non-invasive neuromodulation therapy is heralding a new frontier in the clinical diagnosis and management of PD.

Abstract: Objective　To explore the tolerance of Aedes albopictus to typical insecticides and mutations in its knockdown resistance (kdr) and acetylcholinesterase number one (ace-1) genes in Hainan Province. Methods　Ae. albopictus larvae were collected from Danzhou, Sanya, Qiongzhong, Qionghai, Changjiang, and Wanning in Hainan Province in 2020 and 2021 to assess their resistance to 10 insecticides. Surviving samples from the resistance tests were examined for mutations in genes encoding acetylcholinesterase (AChE) and voltage-gated sodium channel (VGSC) using DNA Sanger sequencing. Results　The 24-hour corrected mortality rates of adult Ae. albopictus in different areas of Hainan to deltamethrin (0.03%), permethrin (0.40%), Beta-cypermethrin (0.40%), Beta-cypermethrin (0.08%), and lambda-cyhalothrin (0.07%) ranged from 5.56% to 83.33%, 29.89% to 92.22%, 26.67% to 97.78%, 11.11% to 88.89%, and 40.00% to 83.33%, respectively. The mortality rates after 24-hour exposure to propoxur (0.05%), bendiocarb (0.20%), malathion (0.50%), fenitrothion (0.20%), and chlorpyrifos (2.00%) ranged from 94.89% to 100.00%, among which the Ae.albopictus population from Changjiang showed a mortality rate of 97.78% to propoxur, and populations from Sanya, Wanning, and Qionghai showed mortality rates of 94.89%, 96.67%, and 96.67% to malathion respectively. The mortality rate of Ae.albopictus populations in Sanya and Qionghai to fenitrothion was 97.78%, while in other populations, it was 100.00%. Sequencing results showed that the kdr gene exhibited a mutation solely at locus 1534, featuring four alleles: wild-type TTC/F and the mutant types TGT(TGC)/C, TCC/S, and TTG/L with the mutation frequencies of 40.47%, 22.25%, 36.44%, and 0.85%, respectively. There are seven types of these mutations: wild-type homozygotes F/F, wild-type/mutant heterozygotes F/C, F/S, and F/L, mutant heterozygotes S/C, and wild-type homozygotes C/C and S/S, with mutation frequencies of 19.92%, 6.78%, 32.63%, 1.69%, 11.44%, 13.14%, and 14.41%, respectively. Notably, No related amino acid mutations were detected at position 119 of the ace-1 gene. Conclusions　The Ae.albopictus populations in various areas of Hainan Province have developed a high resistance to pyrethroid insecticides such as deltamethrin, permethrin, beta-cypermethrin, and beta-cyfluthrin, but are sensitive or possibly resistant to carbamates and organophosphates insecticides. The resistance gene mutations mainly occur at position 1 534 of the kdr gene, suggesting that its mutation frequency could be a significant factor contributing to resistance in Ae. albopictus in Hainan.

Abstract: Objective　To understand the level of Aedes aegypti resistance in Hainan and to provide a reference for developing local preventive and control measures against the dengue vector Ae. aegypti. Methods In 2020, Aedes aegypti larvae and pupae were collected from Danzhou and Changjiang in Hainan Province and reared to the first filial generation (F1). The adult mosquito contact tube method was used to determine the resistance of Aedes aegypti to commonly used insecticides. The allele-specific PCR (AS-PCR) was used to detect the mutations in V1016G and F1534C knockdown resistance (kdr) gene in Aedes aegypti. Results There was no significant difference in the knockdown rate of Ae. aegypti from Changjiang and Danzhou after 1 hour of exposure to four pyrethroids insecticides, namely deltamethrin (0.03%), permethrin (0.40%), beta-cypermethrin (0.04%) and lambda-cyhalothrin (0.02%). However, the 24-hour mortality rates of Ae. aegypti from Changjiang and Danzhou city were 95.56%, 85.56%, 81.11%, 48.89% and 94.44%, 68.60%, 61.11%, 30.00%, respectively. Except for deltamethrin (0.03%), the other differences were statistically significant. Aedes aegypti in Changjiang showed 100.00% mortality to propoxur (0.03%) and bendiocarb (0.20%), while in Danzhou, these rates were 100.00% and 98.89%, respectively. Ae. aegypti both from Changjiang and Danzhou showed 100.00% mortality to malathion (1.50%) and chlorpyrifos (0.80%), and mortality rates to 0.25% fenthion were 100.00% and 98.89%, respectively. V1016G and F1534C mutations were found in Ae. aegypti from Danzhou and Changjiang with mutation frequencies of 12.50% (20/160) and 97.50% (156/160), showing significant differences (χ2=233.54, P<0.001). In Changjiang, Aedes aegypti exhibited both V1016G and F1534C mutations with frequencies of 20.00% and 100.00%, respectively, whereas in Danzhou, only F1534C mutations occurred with a frequency of 98.75%. Conclusions Ae. aegypti in Hainan Province exhibited varying levels of resistance to four insecticides: deltamethrin, permethrin, beta-cypermethrin, and lambda-cyhalothrin, but showed sensitivity to propoxur, bendiocarb, malathion, and chlorpyrifos. The primary knockdown resistance gene mutation was F1534C.

Knee osteoarthritis （KOA） is a common degenerative joint disease characterized primarily by the degeneration and damage of knee joint cartilage， accompanied by osteophyte formation and inflammation. In recent years， the prevalence of KOA has been increasing globally， significantly impacting the quality of life patients. However， the pathogenesis of KOA remains not fully understood， and current treatment methods are limited. Therefore， finding new therapeutic strategies is a research hotspot. Previous studies have found that the onset of KOA is related to abnormal mitochondrial regulation. Mitochondria， functioning as secondary messengers， play crucial roles in cellular respiration， reactive oxygen species （ROS） generation， and adenosine triphosphate （ATP） production through oxidative phosphorylation. Mitochondrial quality control is a pivotal mechanism for maintaining the morphology， quantity， and quality of mitochondria. The connection between mitochondrial quality control and the pathogenesis of KOA involves several factors， such as mitochondrial oxidative stress， mitophagy， imbalances in mitochondrial biogenesis， abnormal mitochondrial dynamics （fission and fusion）， and dysregulation of calcium ions. Metabolic abnormalities in the body lead to mitochondrial structural damage， which in turn contributes to the onset and progression of KOA. Traditional Chinese medicine （TCM） has made some progress in intervening in mitochondrial quality control， employing multi-faceted， multi-pathway， and multi-target strategies to treat KOA. Several studies have shown that mitochondrial quality control may be one of the therapeutic targets of TCM in treating KOA. However， there is currently a lack of comprehensive reviews summarizing the TCM interventions in mitochondrial quality control for treating KOA. This paper systematically reviewed the research progress in TCM treatment of KOA based on five aspects of mitochondrial quality control， aiming to provide a theoretical basis for the clinical prevention and treatment of KOA.

BACKGROUND:In recent years,epidemiological studies have shown that sleep patterns are risk factors for osteoarthritis,but the causal relationship between sleep characteristics and osteoarthritis remains unknown. OBJECTIVE:To investigate the causal relationship between seven sleep phenotypes and osteoarthritis,thereby providing a theoretical foundation for clinical prevention and intervention of osteoarthritis. METHODS:Seven sleep-related features,namely sleep duration,wake-up time,daytime napping,morning/evening preference,snoring,insomnia,and hypersomnia,were selected from published genome-wide association studies.Instrumental variables for these sleep-related features were extracted.Instrumental variables for knee osteoarthritis and hip osteoarthritis were obtained from publicly available genome-wide association studies.Causal relationships between sleep characteristics and outcome risks were evaluated using two-sample and multivariable Mendelian randomization analyses.The inverse variance weighted method was employed as the primary Mendelian randomization approach.Various methods,including weighted median,weighted mode,Mendelian randomization-Egger regression,Mendelian randomization pleiotropy-residual sum and outlier,were utilized to detect and correct for the presence of pleiotropy. RESULTS AND CONCLUSION:The results of the inverse variance-weighted method in the two-sample Mendelian randomization study revealed a detrimental causal association between the duration of sleep and the incidence risk of knee osteoarthritis[odds ratio(OR)=0.621,95%confidence interval(CI):0.470-0.822,P=0.001].Concurrently,insomnia displayed a positive causal connection with hip osteoarthritis risk(OR=2.016,95%CI:1.249-3.254,P=0.005).Sensitivity analysis affirmed the robustness of these causal relationships,and Mendelian randomization-Egger intercept analysis found no evidence of potential horizontal pleiotropy(knee osteoarthritis:P=0.468,hip osteoarthritis:P=0.551).Moreover,the results from the multivariable Mendelian randomization analysis showed that the causal association between insomnia and hip osteoarthritis lacked statistical significance(P=0.715).In contrast,sleep duration exhibited a direct negative causal relationship with the incidence risk of knee osteoarthritis(OR=0.526,95%CI:0.336-0.824,P=0.005).Reverse Mendelian randomization analysis indicated that knee osteoarthritis did not influence sleep duration(P=0.757).These findings indicate a negative correlation between sleep duration and incidence risk of knee osteoarthritis,suggesting that correcting insufficient sleep might mitigate the incidence risk of knee osteoarthritis.

Abstract： Objective　To analyze the epidemiological characteristics of scrub typhus in Hainan Province from 2008 to 2023, forecast the epidemic trend in 2024, and provide a scientific basis for the prevention and control measures of scrub typhus in Hainan Province. Methods　The data of scrub typhus cases reported in Hainan Province from 2008 to 2023 were collected. Descriptive epidemiological methods were employed to analyze the temporal, spatial, and population distribution characteristics of scrub typhus. The simple moving average, seasonal decomposition, and seasonal autoregressive moving average (SARIMA) models were used to progressively deconstruct and analyze the epidemic patterns of scrub typhus in Hainan Province from 2008 to 2023 and predict its incidence trend in 2024. Results　A total of 4 300 scrub typhus cases were reported in Hainan Province from 2008 to 2023, with an average annual reported incidence of 2.75/100 000, and the annual reported incidence showed an increasing trend (Z=0.517, P=0.006). The population distribution characteristics were mainly among individuals aged 50-<70 years and those engaged in agriculture, forestry, fishery, and animal husbandry, with statistically significant differences (all P<0.001). There was an obvious seasonality in the temporal distribution, with cases primarily occurring from April to November, and peaking in October. In terms of regional distribution, the top four cities and counties with the highest cumulative reported cases were Qionghai City (826 cases), Wenchang City (558 cases), Chengmai County (486 cases), and Haikou City (452 cases), accounting for 54.00% of the total number of cases, and there were statistically significant differences in the number of reported cases among different cities (χ2=7 755.55, P<0.001). The SARIMA (1,0,2)(0,1,1)12 model fitted the incidence of scrub typhus in Hainan Province from 2008 to 2023 and predicted 364 cases in 2024, roughly equivalent to the number of cases in 2023. Conclusions　The incidence of scrub typhus in Hainan Province shows an overall increasing trend. Individuals aged 50-<70 years and those engaged in agriculture, forestry, fishery, and animal husbandry are the high-risk populations, with a prolonged peak incidence period. The number of predicted cases for 2024 is expected to remain consistent with 2023. Therefore, scientific interventions targeting high-risk populations before the peak incidence may improve the effectiveness of scrub typhus prevention and control.