ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan（RYZBW）in the treatment of initial and early knee osteoarthritis （KOA） through a prospective multicenter，randomized，double-blind，and placebo-parallel controlled trial. MethodFrom October 13^th， 2021 to December 25^th， 2021， 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital， Chinese Academy of Chinese Medical Sciences， and they were randomly divided into observation group and control group， with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education， and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks， and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score （WOMAC score）， and the secondary outcome measures were the response rate of visual scale （VAS） pain score， WOMAC sub item scores （joint pain， joint stiffness， and joint function）， quality of life （SF-12） score， and traditional Chinese medicine （TCM） syndrome score. Result（1） Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW， and the difference was statistically significant （P<0.05）. There was no significant difference between the two groups in improving VAS score response rate， WOMAC function score， WOMAC stiffness score， SF12-PCS （quality of life-physical health） score， SF12-MCS （quality of life-mental health） score， and TCM syndrome score. （2） Subgroup analysis. ① In terms of VAS score response rate， the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of （4， 5］， and the difference was statistically significant （P<0.05）. ② In terms of TCM syndrome score， for subjects aged ［56， 60］ and ［61， 65］， the decrease in total TCM syndrome score in the observation group was better than that in the control group， and the difference was statistically significant （P<0.05）. ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score， VAS score response rate， WOMAC pain score， WOMAC function score， and TCM syndrome score for patients with initial and early KOA， which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.

Objective To investigate the effect of linear echoendoscope guided precise endoscopic sphincterotomy(EST)on positive rates of bile amylase(BA)and bile bacteria as well as occult pancreaticobiliary reflux(OPBR)in patients with calculus of common bile duct after endoscopic retrograde cholangiopancreatography(ERCP).Methods The subjects of this study,146 patients with calculus of common bile duct who underwent EST for ERCP from June 2021 to February 2023,were divided into two groups based on EST type,each with 73 cases.Observation group was administrated with linear echoendoscope guided precise EST,control group was administrated traditional EST.The operation conditions of both groups were observed.Liver function indexes[total bilirubin(TBiL),conjugated bilirubin(CB)and alanine aminotransferase(ALT)],inflammatory and stress indicators[C-reactive protein(CRP),high mobility group box-1 protein(HMGB1),cortisol(Cor),norepinephrine(NE)],and the positive rates of BA and bile bacteria were compared between the two groups before operation and 1,3 days after operation.The postoperative complications and recurrence rate 12 months after operation were recorded.Results There was no significant difference in the success rate of lithotomy and operation time between the two groups(P>0.05).The intraoperative blood loss in the observation group was less than that in the control group,and the hospital stay was shorter than that in the control group,and the differences were statistically significant(P<0.05).1 and 3 days after surgery,TBiL,CB and ALT in two groups were lower than those before surgery,the differences were statistically significant(P<0.05),but there was no statistically significant difference between groups(P>0.05).1 and 3 days after surgery,serum CRP,HMGB1,Cor and NE levels and BA concentration in two groups were higher than those before surgery,and observation group was lower than control group,with statistical significance(P<0.05).The positive rate of biliary bacteria 1 and 3 days after surgery in the control group was higher than that before surgery,the difference was statistically significant(P<0.05);the positive rate of biliary bacteria in the observation group was not significantly different at different time points before and after surgery(P>0.05);the positive rate of biliary bacteria in the observation group was lower than that in the control group 1 and 3 days after surgery(P<0.05).The incidence of OPBR and postoperative recurrence rate at 12 months in the observation group(15.07%and 1.37%)were lower than those in the control group(57.53%and 10.96%),and the differences were statistically significant(P<0.05).Conclusion Linear echoendoscope guided precise EST is more effective in mitigating duodenal papillary sphincter injury,preventing duodenal-biliary reflux,inhibiting BA secretion and bacterial proliferation,and reducing the risk of OPBR than traditional EST.

Background Air pollution is a major public health concern. Air Quality Health Index (AQHI) is a very important air quality risk communication tool. However, AQHI is usually constructed by single-pollutant model, which has obvious disadvantages. Objective To construct an AQHI based on the joint effects of multiple air pollutants (J-AQHI), and to provide a scientific tool for health risk warning and risk communication of air pollution. Methods Data on non-accidental deaths in Yunnan, Guangdong, Hunan, Zhejiang, and Jilin provinces from January 1, 2013 to December 31, 2018 were obtained from the corresponding provincial disease surveillance points systems (DSPS), including date of death, age, gender, and cause of death. Daily meteorological (temperature and relative humidity) and air pollution data (SO₂, NO₂, CO, PM_2.5, PM₁₀, and maximum 8 h O₃ concentrations) at the same period were respectively derived from China Meteorological Data Sharing Service System and National Urban Air Quality Real-time Publishing Platform. Lasso regression was first applied to select air pollutants, then a time-stratified case-crossover design was applied. Each case was matched to 3 or 4 control days which were selected on the same days of the week in the same calendar month. Then a distributed lag nonlinear model (DLNM) was used to estimate the exposure-response relationship between selected air pollutants and mortality, which was used to construct the AQHI. Finally, AQHI was classified into four levels according to the air pollutant guidance limit values from World Health Organization Global Air Quality Guidelines (AQG 2021), and the excess risks (ERs) were calculated to compare the AQHI based on single-pollutant model and the J-AQHI based on multi-pollutant model. Results PM_2.5, NO₂, SO₂, and O₃ were selected by Lasso regression to establish DLNM model. The ERs for an interquartile range (IQR) increase and 95% confidence intervals (CI) for PM_2.5, NO₂, SO₂ and O₃ were 0.71% (0.34%–1.09%), 2.46% (1.78%–3.15%), 1.25% (0.9%–1.6%), and 0.27% (−0.11%–0.65%) respectively. The distribution of J-AQHI was right-skewed, and it was divided into four levels, with ranges of 0-1 for low risk, 2-3 for moderate risk, 4-5 for high health risk, and ≥6 for severe risk, and the corresponding proportions were 11.25%, 64.61%, 19.33%, and 4.81%, respectively. The ER (95%CI) of mortality risk increased by 3.61% (2.93–4.29) for each IQR increase of the multi-pollutant based J-AQHI , while it was 3.39% (2.68–4.11) for the single-pollutant based AQHI . Conclusion The J-AQHI generated by multi-pollutant model demonstrates the actual exposure health risk of air pollution in the population and provides new ideas for further improvement of AQHI calculation methods.

OBJECTIVE To study the repair effect and mechanism of Zhixu burn ointment on deep second-degree burned model rats. METHODS The deep second-degree burned model was established with a temperature-controlled apparatus. The model rats were randomly divided into model group， Jingwanhong ointment group and Zhixu burn ointment high-dose， medium-dose and low-dose groups （specifications were 20 g core+20 mL wetting agent， 10 g core+20 mL wetting agent， 5 g core+20 mL wetting agent， respectively）. Another blank control group （only dehairing treatment， no modeling） was set up， with 10 rats in each group. The rats in each administration group were given corresponding drugs， the rats in the blank control group were not treated， and the rats in the model group were given normal saline once a day for 21 d. The healing of burn wounds and histomorphological changes of burned skin in each group of rats were observed， and the healing rate of wounds was calculated； the levels of vascular endothelial growth factor （VEGF）， interleukin-1β （IL-1β）， IL-6 and tumor necrosis factor-α（TNF-α） in the wound skin tissue of rats were detected by enzyme-linked immunosorbent assay； immunohistochemical method was used to detect the expression levels of VEGF and platelet endothelial cell adhesion molecule-1 （CD31） protein in burned skin tissue. RESULTS Compared with model group， the wound area of the rats in the Jingwanhong ointment and Zhixu burn ointment groups gradually decreased and healed significantly by day 21， and the wound healing rate was significantly higher （P＜0.05 or P＜0.01）； thicker new epidermal layer was seen in the skin tissue， and connective tissue and new blood vessels were significantly increased in the dermis； the expression levels of IL-1β， IL-6 and TNF-α were significantly decreased （P＜0.05 or P＜0.01）， and the expression levels of VEGF and CD31 protein were significantly increased （P＜0.05 or P＜0.01） in the burned skin tissue. CONCLUSIONS Zhixu burn ointment can repair the skin of deep second-degree burned model rats， and the mechanism may be related to reducing the inflammatory response of burn wound and promoting the angiogenesis.

Objective:To understand the characteristics of sexualized drug use (SDU) among men who have sex with men (MSM) in Chengdu and classify their behavioral patterns by applying the two-step cluster (TSC) algorithm and by exploring the association between SDU patterns and high risk sexual behaviors, in order to provide a reference basis for the development of HIV prevention interventions.Methods:Supported by an MSM-friendly organization in Chengdu from December 2021 to February 2022, MSM were recruited by on-site survey and peer referral to collect information on sociodemographics, SDU characteristics, sexual behaviors, STD diagnosis, and HIV status. TSC was performed to classify the characteristics of SDU, and the differences between groups were compared. Chi-square test and multiple binary logistic regressions were used to identify the relationship between SDU clusters and HIV-related risk sexual behaviors.Results:A total of 727 MSM were surveyed, and 39.8% (289/727) of the respondents reported SDU experience with a same-sex partner in the last six months. TSC clustered SDU-MSM into three behavioral pattern groups. There were significant differences in monthly income, types of drugs used for SDU, mode, frequency, polydrug use, multiple sexual partners, non-adherence to condom use, and group sex among the three groups of SDU-MSM ( P<0.05). Multivariate binary logistic regression analysis showed that the third category of SDU-MSM was 2.22 (95% CI: 1.06-4.66) times more likely than the first category not to use condoms consistently; the third and second categories were 2.82 (95% CI: 1.18-6.77) times and 8.78 (95% CI: 3.42-22.42) times. Conclusions:The prevalence of SDU among MSM in Chengdu was more than 1/3, and different SDU clustering pattern was associated with high-risk sexual behaviors. MSM with higher SDU frequency, drug use, and polydrug abuse are more difficult to adhere to condom use and more likely to have group sex and high risk sexual behaviors, increasing the risk of STD and HIV infection, and need to strengthen SDU surveillance and intervention.

Glycolytic metabolism enzymes have been implicated in the immunometabolism field through changes in metabolic status. PGK1 is a catalytic enzyme in the glycolytic pathway. Here, we set up a high-throughput screen platform to identify PGK1 inhibitors. DC-PGKI is an ATP-competitive inhibitor of PGK1 with an affinity of K _d = 99.08 nmol/L. DC-PGKI stabilizes PGK1 in vitro and in vivo, and suppresses both glycolytic activity and the kinase function of PGK1. In addition, DC-PGKI unveils that PGK1 regulates production of IL-1β and IL-6 in LPS-stimulated macrophages. Mechanistically, inhibition of PGK1 with DC-PGKI results in NRF2 (nuclear factor-erythroid factor 2-related factor 2, NFE2L2) accumulation, then NRF2 translocates to the nucleus and binds to the proximity region of Il-1β and Il-6 genes, and inhibits LPS-induced expression of these genes. DC-PGKI ameliorates colitis in the dextran sulfate sodium (DSS)-induced colitis mouse model. These data support PGK1 as a regulator of macrophages and suggest potential utility of PGK1 inhibitors in the treatment of inflammatory bowel disease.

Objective: To investigate the willingness to use three types of pre-exposure prophylaxis (PrEP) and its associated factors among MSM in Chengdu. Methods: A total of 793 MSM were recruited through Chengdu Tongle Health Consultation Service Centre between November 2021 to January 2022. Data were collected, including demographic characteristics, sexual behaviors in the last six months, PrEP-related stigma, HIV anticipated stigma, MSM internalized stigma, and willingness to use three types of PrEP. Univariate and multivariate logistic regression models were conducted to investigate the associated factors of willingness in using the three types of PrEP. Results: Among 793 participants, willingness to take on-demand PrEP was higher (68.3%). Higher education and multiple sexual partners increased the willingness to use oral PrEP, higher education [compared with junior high school or below, high school or technical secondary school (aOR=2.43, 95%CI: 1.13-5.21), junior college (aOR=2.67, 95%CI: 1.27-5.61), bachelor degree (aOR=3.21, 95%CI: 1.52-6.74), master degree or above (aOR=3.77, 95%CI: 1.54-9.26)], multiple sexual partners (aOR=1.54, 95%CI: 1.12-2.11) were positively associated with daily oral PrEP. HIV anticipated stigma was positively associated with the willingness in using all three types of PrEP: daily oral PrEP (aOR=1.07, 95%CI: 1.02-1.12), on-demand PrEP (aOR=1.09, 95%CI: 1.03-1.15), and injectable PrEP every 8 week (aOR=1.06, 95%CI: 1.01-1.11). Conclusions: The overall willingness in using PrEP in MSM in Chengdu is relatively high, and the promotion of PrEP is highly feasible. In the future, we should continue to promote publicity and education on HIV and PrEP-related knowledge in this population, improve the cognitive level, and guide MSM to establish the correct motivation for PrEP use.
Male ; Humans ; Pre-Exposure Prophylaxis ; Homosexuality, Male ; Sexual and Gender Minorities ; Sexual Behavior ; HIV Infections/prevention & control*

The vagina contains at least a billion microbial cells,dominated by lactobacilli.Here we perform metagenomic shotgun sequencing on cervical and fecal samples from a cohort of 516 Chinese women of reproductive age,as well as cervical,fecal,and salivary samples from a second cohort of 632 women.Factors such as pregnancy history,delivery history,cesarean section,and breastfeeding were all more important than menstrual cycle in shaping the microbiome,and such information would be necessary before trying to interpret differences between vagino-cervical micro-biome data.Greater proportion of Bifidobacterium breve was seen with older age at sexual debut.The relative abundance of lactobacilli especially Lactobacillus crispatus was negatively associated with pregnancy history.Potential markers for lack of menstrual regularity,heavy flow,dysmenor-rhea,and contraceptives were also identified.Lactobacilli were rare during breastfeeding or post-menopause.Other features such as mood fluctuations and facial speckles could potentially be predicted from the vagino-cervical microbiome.Gut and salivary microbiomes,plasma vitamins,metals,amino acids,and hormones showed associations with the vagino-cervical microbiome.Our results offer an unprecedented glimpse into the microbiota of the female reproductive tract and call for international collaborations to better understand its long-term health impact other than in the settings of infection or pre-term birth.

Objectives:The COVID-19 has been the public health issues of global concern, but the incubation period was still under discussion. This study aimed to estimate the incubation period distribution of COVID-19.Methods:The exposure and onset information of COVID-19 cases were collected from the official information platform of provincial or municipal health commissions. The distribution of COVID-19 incubation period was estimated based on the Log- normal, Gamma and Weibull distribution by interval-censored data estimation method.Results:A total of 109 confirmed cases were collected, with an average age of 39.825 years. The median COVID-19 incubation period based on Log-normal, Gamma, and Weibull distribution were 4.958 ( P25- P75: 3.472-7.318) days, 5.083 ( P25- P75: 3.511-7.314) days, and 5.695 ( P25- P75: 3.675-7.674) days, respectively. Gamma distribution had the largest log-likelihood result. Conclusions:The distribution of COVID-19 incubation period followed the Gamma distribution, and the interval-censored data estimation method can be used to estimate the incubation period distribution.

Objective: To investigate the antimicrobial resistance and molecular epidemiology of foodborne Yersinia (Y.) enterocolitica in Pudong New District of Shanghai. Methods: Four kinds of raw food samples were collected in retail circulation sites in Pudong from 2012 to 2016. Cold enrichment method was used to isolate Y. enterocolitica and further detection of biotype, serotype, virulent genes, antimicrobial susceptibility of the isolates and pulsed field gel electrophoresis (PFGE) were conducted. Results: A total of 3 900 raw food samples were collected during this period, including poultry product (n=590), livestock product (n=1 074), aquatic product (n=1 488), vegetable (n=748), in which 111 (2.8%) were contaminated by Y. enterocolitica. The detection rates of Y. enterocolitica in poultry product samples (5.3%, 31/590) and livestock product samples (4.5%, 48/1 074) were higher than those in aquatic product samples (1.6%, 24/1 488) and vegetable samples (1.1%, 8/748). The predominant biotype was 1A (95.5%) and predominant serotype was O∶8 (42.3%). All the strains lacked ail, ystA, yadA and virF genes, which encoded pathogenic Y. enterocolitica. Seventy six (68.5%) strains harbored ystB gene, in which 35 (31.5%) belonged to 1A/O∶8/ystB pattern. Most strains were resistant to ampicillin (74.8%) and amoxicillin/clavulanic acid (70.3%), and non-sensitive rate to Cefoxitin was over 50.0%. No third generation cephalosporin or fluoroquinolone resistant strains were detected, but 38.7% (43/111) strains were multidrug resistant (MDR). Serotype O∶8 and O∶5 strains had 44 and 18 PFGE patterns, respectively. Conclusions The main foodborne exposure sources of Y. enterocolitica in raw food were poultry and livestock products in Pudong New District. 1A/O∶8/ystB was the predominant pattern with potential pathogenicity despite lacks of typical pathogenic virulent genes. The antimicrobial resistant rates of Y. enterocolitica were at a low level, but MDR strains still existed. Molecular types of the isolates showed highly genetic diversity.