Objective: To investigate the differences in enolase and laminin levels in vaginal epithelial tissues between mice successfully infected withGardnerellaand mice not infected with Gardnerella, providing information for further exploration of the correlation between enolase and laminin levels and the incidence of bacterial vaginosis. Methods: Gardnerella strains isolated, purified, and identified from vaginal secretions of patients with bacterial vaginosis were used to infect the vagina of mice and establish a mouse model of bacterial vaginosis. Successful and failed mice was defined as successful and failed groups, respectively. Differential expression of enolase and laminin in the vaginal epithelial tissue of two groups of mice was detected by Western blot. Modeling success rate was statistically analyzed, and the expression differences of enolase and laminin was compared between two groups. Results: One strain of Gardnerella vaginalis infected 10 SPF grade KM mice, 7 mice met the diagnostic criteria for bacterial vaginosis, and 3 mice failed to model, with a success rate of 70%. Western blot was used to detect protein expression levels, and the levels of laminin and enolase in the successfully modeled mouse vaginal epithelial tissue were significantly higher than those in the failed modeling group, with statistical differences between the two groups(P<0.05). Conclusion Enolase and laminin may be involved in the occurrence of bacterial vaginosis, however, further research is needed to determine the mechanisms through which they trigger the occurrence and development of the disease.

Objective To identify the biomarkers for early rheumatoid arthritis(RA)diagnosis and explore the possible immune regulatory mechanisms.Methods The differentially expressed genesin RA were screened and functionally annotated using the limma,RRA,batch correction,and clusterProfiler.The protein-protein interaction network was retrieved from the STRING database,and Cytoscape 3.8.0 and GeneMANIA were used to select the key genes and predicting their interaction mechanisms.ROC curves was used to validate the accuracy of diagnostic models based on the key genes.The disease-specific immune cells were selected via machine learning,and their correlation with the key genes were analyzed using Corrplot package.Biological functions of the key genes were explored using GSEA method.The expression of STAT1 was investigated in the synovial tissue of rats with collagen-induced arthritis(CIA).Results We identified 9 core key genes in RA(CD3G,CD8A,SYK,LCK,IL2RG,STAT1,CCR5,ITGB2,and ITGAL),which regulate synovial inflammation primarily through cytokines-related pathways.ROC curve analysis showed a high predictive accuracy of the 9 core genes,among which STAT1 had the highest AUC(0.909).Correlation analysis revealed strong correlations of CD3G,ITGAL,LCK,CD8A,and STAT1 with disease-specific immune cells,and STAT1 showed the strongest correlation with M1-type macrophages(R=0.68,P=2.9e-08).The synovial tissues of the ankle joints of CIA rats showed high expressions of STAT1 and p-STAT1 with significant differential expression of STAT1 between the nucleus and the cytoplasm of the synovial fibroblasts.The protein expressions of p-STAT1 and STAT1 in the cell nuclei were significantly reduced after treatment.Conclusion CD3G,CD8A,SYK,LCK,IL2RG,STAT1,CCR5,ITGB2,and ITGAL may serve as biomarkers for early diagnosis of RA.Gene-immune cell pathways such as CD3G/CD8A/LCK-γδ T cells,ITGAL-Tfh cells,and STAT1-M1-type macrophages may be closely related with the development of RA.

Objective·To study the alterations in vestibular hair cell morphology and function of ATPase plasma membrane Ca2+transporting 2 oblivion(Atp2b2 Oblivion)heterozygous mice at different ages.Methods·Atp2b2 Oblivion heterozygous male mice aged 2 months and 8 months were selected with ten in each kind and C57BL/6J wild-type mice with the same gender,age and number were selected as the control group.Expression patterns of ATP2B2 in vestibular hair cells and numbers of hair cells in the striola zone and the extra striola zone in the two groups of mice at different ages were observed and calculated respectively through immunofluorescence assay.Hair bundle structures were detected by scanning electron microscopy(SEM),and mitochondria and ribbon synapse structures were observed by transmission electron microscopy(TEM).Vestibular evoked potential(VsEP),vestibular evoked myogenic potential(VEMP),rotarod rod test,and balance beam test were adopted for the evaluation of vestibular functions.Results·ATP2B2 was mainly expressed in the hair bundle of vestibular hair cells in the two groups of mice.Hair cell numbers in the striola zone and the extra-striola zone did not exhibit any differences between Atp2b2 Oblivion heterozygous mutant mice and wild-type mice of 2-month-old and 8-month-old.No visible structural abnormality in the hair bundle could be seen through SEM.TEM results implied no morphological abnormality in mitochondria or ribbon synapses in the 2-month-old heterozygous mutant mice,while vacuolar degeneration was discovered in the mitochondria under the cuticular plate in the 8-month-old heterozygous mutant mice with the normal ribbon synapses and the normal mitochondria near the innervation site.VsEP and VEMP thresholds of 2-month-old and 8-month-old Atp2b2 Oblivion heterozygous mutant mice were significantly elevated compared with the wild-type mice.Analysis of VsEP waveform manifested prolonged P1 latency and declined P1N1 amplitude in heterozygous mutant mice(P＜0.05).Results of rotarod rod test and balance beam test acquired from 2-month-old Atp2b2 Oblivion heterozygous mutant mice were not significantly different from the wild-type mice,while the ability of the mutant mice to accomplish the tests descended significantly at 8 months of age compared with the wild-type mice(P＜0.05).Conclusion·Atp2b2 Oblivion heterozygous mutant mice showed defective vestibular electrophysiological function at 2 months old,and abnormalities in vestibule-related behaviors can be detected at 8 months old.The vestibular function ofAtp2b2 Oblivion heterozygous mutant mice deteriorate progressively.

Objective To identify the biomarkers for early rheumatoid arthritis(RA)diagnosis and explore the possible immune regulatory mechanisms.Methods The differentially expressed genesin RA were screened and functionally annotated using the limma,RRA,batch correction,and clusterProfiler.The protein-protein interaction network was retrieved from the STRING database,and Cytoscape 3.8.0 and GeneMANIA were used to select the key genes and predicting their interaction mechanisms.ROC curves was used to validate the accuracy of diagnostic models based on the key genes.The disease-specific immune cells were selected via machine learning,and their correlation with the key genes were analyzed using Corrplot package.Biological functions of the key genes were explored using GSEA method.The expression of STAT1 was investigated in the synovial tissue of rats with collagen-induced arthritis(CIA).Results We identified 9 core key genes in RA(CD3G,CD8A,SYK,LCK,IL2RG,STAT1,CCR5,ITGB2,and ITGAL),which regulate synovial inflammation primarily through cytokines-related pathways.ROC curve analysis showed a high predictive accuracy of the 9 core genes,among which STAT1 had the highest AUC(0.909).Correlation analysis revealed strong correlations of CD3G,ITGAL,LCK,CD8A,and STAT1 with disease-specific immune cells,and STAT1 showed the strongest correlation with M1-type macrophages(R=0.68,P=2.9e-08).The synovial tissues of the ankle joints of CIA rats showed high expressions of STAT1 and p-STAT1 with significant differential expression of STAT1 between the nucleus and the cytoplasm of the synovial fibroblasts.The protein expressions of p-STAT1 and STAT1 in the cell nuclei were significantly reduced after treatment.Conclusion CD3G,CD8A,SYK,LCK,IL2RG,STAT1,CCR5,ITGB2,and ITGAL may serve as biomarkers for early diagnosis of RA.Gene-immune cell pathways such as CD3G/CD8A/LCK-γδ T cells,ITGAL-Tfh cells,and STAT1-M1-type macrophages may be closely related with the development of RA.

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: Cassiae Semen (CS, Juemingzi in Chinese) has been used for thousands of years in ancient Chinese history for relieving constipation, improving liver function as well as preventing myopia. Here we aimed to elucidate the anti-steatosis effect and underlying mechanism of CS against non-alcoholic fatty liver disease (NAFLD). METHODS: High-performance liquid chromatography (HPLC) was used to identify the major components of CS water extract. Mice were fed with a high-fat and sugar-water (HFSW) diet to induce hepatic steatosis and then treated with CS. The anti-NAFLD effect was determined by measuring serum biomarkers and histopathology staining. Additionally, the effects of CS on cell viability and lipid metabolism in oleic acid and palmitic acid (OAPA)-treated HepG2 cells were measured. The expression of essential genes and proteins involved in lipid metabolism and autophagy signalings were measured to uncover the underlying mechanism. RESULTS: Five compounds, including aurantio-obtusin, rubrofusarin gentiobioside, cassiaside C, emodin and rhein were simultaneously identified in CS extract. CS not only improved the diet-induced hepatic steatosis in vivo, as indicated by decreased number and size of lipid droplets, hepatic and serum triglycerides (TG) levels, but also markedly attenuated the OAPA-induced lipid accumulation in hepatocytes. These lipid-lowering effects induced by CS were largely dependent on the inhibition of fatty acid synthase (FASN) and the activation of autophagy-related signaling, including AMP-activated protein kinase (AMPK), light chain 3-II (LC3-II)/ LC3-1 and autophagy-related gene5 (ATG5). CONCLUSION Our study suggested that CS effectively protected liver steatosis via decreasing FASN-related fatty acid synthesis and activating AMPK-mediated autophagy, which might become a promising therapeutic strategy for relieving NAFLD.

Objective:To explore the effects and dose-response relationship of Tai Chi for type 2 diabetes mellitus(T2DM)and to evaluate the methodological quality of the included trials and evidence quality of the outcomes.Methods:Nine major English and Chinese databases were searched for randomized controlled trials of Tai Chi for T2DM from inception to December 2021.The effects and dose-response relationships were assessed with a meta-analysis and meta-regression using Stata.16.The methodological quality of the included studies was assessed using the risk of bias tool.The evidence quality of the outcomes was assessed using the GRADE tool.Results:A total of 24 studies with 1314 patients were included.Compared with the usual care,Tai Chi improved HbA1c(MD=-0.80％,95％Cl[-1.05,-0.54],P＜.001,I2=18.29％,very low-quality evidence),FBG(SMD=-0.58,95％Cl[-0.86,-0.31],P＜.001,I2=53.2％,low-quality evidence),fasting insulin(FIN),diastolic blood pressure,BMI,and the outcomes of quality of life(QoL)in patients with T2DM.However,when Tai Chi was compared with other exercise,there was no between-group difference in the HbA1c,FBG,TC,TG,HDL,LDL,BMI,and waist circumference(WC).Furthermore,the findings showed that an increase at every 18 weeks in length or an 823-h increase in the total time of Tai Chi intervention resulted in approximately a one unit reduction in the SMD of FBG.Conclusion:Compared with usual care,Tai Chi may improve HbA1c(with clinical significance),FBG,FIN,BMI,diastolic blood pressure,and outcomes of QoL in T2DM patients.The effects of Tai Chi were similar to those of other exercises on the HbA1c,FBG,TC,TG,HDL,LDL,BMI,and WC.Given the overall poor methodological quality and evidence quality,these findings should be treated cautiously.

Malaria still threatens global health seriously today. While the current discoveries of antimalarials are almost totally focused on single mode-of-action inhibitors, multi-targeting inhibitors are highly desired to overcome the increasingly serious drug resistance. Here, we performed a structure-based drug design on mitochondrial respiratory chain of

Objective:To estimate and analyze the occurrence of post-thyroidectomy syndrome (PTS) following endoscopic thyroidectomy via areola approach (ETAA) vs open thyroidectomy (OT) .Methods:Data of 903 consecutive cases, aged from 20 to 66 with 231 males and 672 females, in Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, from Jan. 2016 to Dec. 2017 were analyzed retrospectively. They were enrolled according to the same criteria. Based on different procedures, the cases were divided into ETAA group (n=162) and OT group (n=741) . Intraoperative procedure was according to unified principle. Drainage tube was removed if 24-hour drainage volume was less than 20 ml. Following-up was implemented by telephone or outpatient clinic. Data of 2 groups of 5 PTS items during 1 m, 3 m, 6 m and 1 y postoperatively and the scores of the medical outcomes study short form 36-item health survey (SF-36) V2 were analyzed by independent sample t test and repeated measures analysis of variance. Results:The patients of 2 groups were all followed up for more than 1 y with 43 cases censored (4.8%) . Demographic data of the rest of 2 groups were not different statistically ( P>0.05) . Median of every phase scores of the 5 items of PTS were 0 to 1. Scores of the 5 items were decreased gradually in accordance with time factor ( P=0.000) . The scores of peculiar feeling at the surgical site and discomfort in neck were different statistically during 1 m and 3 m postoperatively ( P=0.000) . Incidence of peculiar feeling at the surgical site in 1 m and 3 m postoperatively in ETAA group (54, 38.8% and 8, 5.8%) was higher than that in OT group (153, 21.2% and 20, 2.8%) . However, incidence of discomfort in neck in ETAA group (14, 10.1% and 0) was lower than in OT group (194, 26.9% and 53, 7.4%) . The other 3 items at all phases were not different statistically ( P>0.05) . The SF-36 V2 scores at 1 y postoperatively of 2 groups were not different statistically ( P=0.458) . Conclusions:PTS is a common symptom after OT or ETAA. It is frequent within early phase after thyroidectomy and is decreased significantly within 6 m. Peculiar feeling at the surgical site occurs less in OT than in ETAA in early postoperative phase and discomfort in neck occurs more, conversely.

Objective:To investigate the prevalence, risk factors and outcomes of diastasis recti abdominis (DRA) in multiparas after the second delivery.Methods:From June 2017 to September 2019, 300 multiparas with an average age of (31.7±4.0) years (26 to 43 years) after the second delivery were recruited at 6 weeks postpartum from two hospitals in Wenzhou. There were 171 multiparas with two natural births,36 multiparas with one natural birth and one caesarean delivery, and 93 multiparas with two caesarean deliveries. The interrectus distance (IRD) was measured with palpation at 6 weeks, 6 months and 12 months after delivery. Data on age, height, weight before pregnancy and delivery, baby′s birth weight, abdominal circumference before pregnancy and delivery, fetus number, delivery mode and occupation type were collected. Strength and endurance of abdominal muscle was assessed using manual muscle testing and curl-ups, low back pain was assessed using Oswestry disability index(ODI), urinary incontinence was assessed with International Consultation on Incontinence guestionnaire-incontinentia urinae (ICIQ-UI) short form (ICIQ-SF), and quality of life was assessed using 36-item short form health survey (SF-36).Results:Prevalence of DRA was 51.7%(155/300), 39.3%(116/295) and 27.7%(80/289) 6 weeks, 6 months and 12 months after delivery, respectively. Logistic regression analysis indicated that age ( OR=1.39, 95 %CI:1.02-1.91, P=0.38), abdominal circumference ratio ( OR=2.31, 95 %CI:1.23-4.33, P=0.01), twins ( OR=11.41, 95 %CI:2.15-60.76, P<0.01), and cesarean section ( OR=1.44, 95 %CI:1.06-1.95, P=0.02) were the risk factors of DRA at 12 months after delivery. At 12 months after delivery, the multiparas with DRA had weaker strength and endurance of abdominal muscle ( Z=-3.62, P<0.01; Z=-8.91, P<0.01), more serious low back pain ( Z=-2.10, P=0.04), and lower quality of life on physical health ( t=-3.34, P<0.01) than the multiparas without DRA. No difference in prevalence and severity of urinary incontinence and quality of life on psychological health was found when comparing multiparas with and without DRA (χ 2=0.66, P=0.42; Z=-1.18, P=0.24; t=0.91, P=0.36). Conclusion:Multipara after the second delivery has great likelihood for DRA.Age, abdominal circumference ratio, twins, and cesarean section are the risk factors of DRA. DRA is related to abdominal muscle dysfunction, low back pain, and quality of life.