ObjectiveTo investigate the recurrence of ischemic stroke (IS) and to analyze the association between four indices of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) and the risk of IS recurrence by analyzing the follow-up data related to IS in the community-based natural population of Songjiang District, Shanghai, so as to provide a scientific basis for improving the prognosis of stroke patients in the community and controlling IS recurrence. MethodsA prospective follow-up study was conducted among the IS patients in the community-based cohort population, collecting data about patient’s age, gender, disease history, biochemical indicators, and etc. Cox regression model and restricted cubic spline model were used to analyze the relationship between different levels of plasma lipids and the recurrence of IS in these patients. ResultsA total of 1 368 patients with IS were included. The total follow-up duration was 7 171.46 person-years, with a median follow-up time of 6.24 years. There were 420 cases of IS recurrence, resulting in a cumulative recurrence rate of 30.70%. The results of multivariate Cox regression analysis showed that the recurrence risk of IS was reduced when the baseline TC and LDL-C levels of IS patients were in the ranges of 4.65‒5.67 mmol·L^-1 and 2.52‒3.46 mmol·L^-1, respectively. The results of restricted cubic spline analysis showed a U-shaped relationship between baseline TC and LDL-C levels and the recurrence risk in IS patients. ConclusionThe cumulative recurrence rate of patients with IS in the community of Songjiang District in Shanghai is high, and the levels of TC and LDL-C at baseline survey are correlated with the recurrence of IS in these patients. It is suggested to pay more attention to the levels of LDL-C and TC in patients with IS, so as to improve the prognosis.

Objective To establish a high-performance liquid chromatography method to detect empagliflozin and related substances in empagliflozin bulk drug and tablets,and to provide technical support for quality control and unified monitoring of empagliflozin bulk drug and its tablets.Methods A liquid chromatography development system with the full factorial design of experiments and the Box-Behnken model was used to screen and optimize the chromatographic parameters.Related substances were detected in empagliflozin API and empagliflozin tablets from different companies with the optimized chromatographic parameters.Results The optimized chromatographic parameters were obtained:Shim-pack GIST C18-AQ column(250 mm×4.6 mm,5 μm)was used,column temperature was 15 ℃,gradient elution with water-acetonitrile as mobile phase was as below,flow rate was 1.2 mL·min-1,detection wavelength was set at 224 nm.The specificity of the method is good,with recoveries ranging from 94.8％to 101.7％,and RSD ranging from 0.5％to 3.1％.The known single impurity in APIs and tablets is less than 0.05％,any other unknown single impurity is less than 0.06％,and the total amount of impurities are less than 0.3％.The related substances of supervised sampling are under good control.Conclusion The method is reliable and robust for determining related substances of empagliflozin and its tablets.

Objective:To report the nationwide surveillance results of pathogenic profiles and antimicrobial resistance patterns of Gram-positive bloodstream infections in China in 2023.Methods:The clinical isolates of Gram-posttive bacteria from blood cultures were collected in member hospitals of National Bloodstream Infection Bacterial Resistant Investigation Collaborative System（BRICS）during January to December 2023. Antimicrobial susceptibility testing was performed using the dilution method recommended by the Clinical and Laboratory Standards Institute（CLSI）. Statistical analyses were conducted using WHONET 5.6 and SPSS 25.0 software.Results:A total of 4 385 Gram-positive bacterial isolates were obtained from 60 participating center. The top five pathogens were Staphylococcus aureus（ n=1 544，35.2%），coagulase-negative Staphylococci（ n=1 441，32.9%）， Enterococcus faecium（ n=574，13.1%）， Enterococcus faecalis（ n=385，8.8%），and α-hemolytic Streptococci（ n=187，4.3%）. The prevalence of methicillin-resistant Staphylococcus aureus（MRSA）and methicillin-resistant coagulase-negative Staphylococci（MRCNS）was 26.2%（405/1 544）and 69.8%（1 006/1 441），respectively. Notably，all Staphylococci remained susceptible to glycopeptide or daptomycin. Staphylococcus aureus demonstrated excellent susceptibility（>97.0%）to cephalobiol，rifampicin，trimethoprim-sulfamethoxazole，linezolid，minocycline，tigecycline，and eravacycline. No Enterococcus exhibiting resistance to linezolid were detected. Glycopeptide resistance was uncommon but more frequent in Enterococcus faecium（resistance to vancomycin and teicoplanin：both 1.7%）compared to Enterococcus faecalis（both 0.3%）. The detection rates of MRSA and MRCNS exhibited significant regional variations across the country（ χ2=17.674 and 148.650，respectively，both P<0.001）. No vancomycin-resistant Enterococci were detected in central China. Institutional comparison demonstrated higher prevalence of MRSA（ χ2=14.111， P<0.001）and MRCNS（ χ2=4.828， P=0.028）in provincial hospitals than that in municipal hospitals. Socioeconomic analysis identified elevated detection rates of both MRSA（ χ2=18.986， P<0.001）and MRCNS（ χ2=4.477， P=0.034）in less developed regions（per capita GDP

Objective:To report the results of bacterial resistant investigation collaborative system（BRICS）on the distribution and antimicrobial resistance profile of clinical Gram-negative bacteria isolates from bloodstream infections in China in 2023，and provide reference for clinical tretment of bloodstream infections and prevention and control of bacterial resistance.Methods:The clinical isolates of Gram-negative bacteria from blood cultures in member hospitals of BRICS were collected during January 2023 to December 2023. Antibiotic susceptibility tests were conducted by agar dilution or broth dilution methods recommended by Clinical and Laboratory Standards Institute（CLSI）. WHONET 5.6 and SPSS 25.0 were used to analyze the data.Results:During the study period，11 492 strains of Gram-negative bacteria were collected from 60 hospitals，of which 10 098（87.9%）were Enterobacterales and 1 394（12.1%）were non-fermentative bacteria. The top 5 bacterial species were Escherichia coli（50.0%）， Klebsiella pneumoniae（26.1%）， Pseudomonas aeruginosa（5.1%）， Acinetobacter baumannii complex（5.0%）and Enterobacter cloacae complex（4.1%）. The ESBL-producing rates in Escherichia coli， Klebsiella pneumoniae and Proteus mirablilis were 46.8%（2 685/5 741），18.3%（549/2 999）and 44.0%（77/175），respectively. The prevalence of carbapenem-resistant Escherichia coli（CREC）and carbapenem-resistant Klebsiella pneumoniae（CRKP）were 1.3%（76/5 741）and 15.0%（450/2 999）；32.9%（25/76）and 78.0%（351/450）of CREC and CRKP were sensitive to ceftazidime/avibactam combination，respectively. 94.7%（72/76）and 90.2%（406/450）of CREC and CRKP were sensitive to aztreonam/avibactam combination. Furthermore，57.9%（44/76）and 79.1%（356/450）were sensitive to imipenem/relebactam combination. The prevalence of carbapenem-resistant Acinetobacter baumannii（CRAB）complex was 64.6%（370/573），while more than 80.0% of CRAB complex was sensitive to tigecycline，eravacycline and polymyxin B. The prevalence of carbapenem-resistant Pseudomonas aeruginosa（CRPA）was 17.0%（99/581）. There were differences in the composition ratio of Gram-negative bacteria in bloodstream infections and the prevalence of important Gram-negative bacteria resistance among different regions in China，with statistically significant differences in the prevalence of CREC，CRKP，CRPA and CRAB complex（ χ2=10.6，28.6，10.8 and 19.3， P<0.05）. The prevalence of ESBL-producing Escherichia coli， CREC，CRAB complex and CRKP were higher in provincial hospitals than those in municipal hospitals（ χ2=12.5，9.8，12.7 and 57.8，all P<0.01）. Conclusions:Gram-negative bacteria are the main pathogens causing bloodstream infections in China，and Escherichia coli is ranked in the top，while the trend of Klebsiella pneumoniae increases continuously with time. CRKP infection shows a slow upward trend，CREC infecton maintains a low prevalence level，and CRAB complex infection continues to exhibit a high prevalence rate. The composition and resistance patterns of pathogens causing bloodstream infections vary to some extent across different regions and levels of hospitals in China.

Objective To explore the relationship between NANOS3 and P-bodies in oocytes and the mechanism of their interaction during early oogenesis.Methods The co-localization of NANOS3 and dead box helicase 6(DDX6)in day post postnatal 1(1dpp)mouse oocytes was observed by immunofluorescence,and the interaction between NANOS3 and DDX6 was detected by immunoprecipitation.NANOS3 and DDX6 full-length plasmids were constructed to transfect HEK293T cells,and the mechanism of their interaction was investigated by immunofluorescence and immunoprecipitation.NANOS3 transfected HeLa cells to investigate whether NANOS3 had the ability of liquid-liquid phase separation(LLPS)by live-cell imaging.The proteins recruited by P-bodies in early oogenesis were identified by DDX6-immunoprecipitation-mass spectrometry(DDX6-IP-MS).Results NANOS3 and DDX6 colocalized and interacted with each other in 1dpp mouse oocytes.However,the co-localization of NANOS3 and DDX6 was not observed in HEK293T cells that had been transfected,but co-immunoprecipitation still demonstrated an interaction between these two proteins.Besides,live-cell imaging revealed that NANOS3 exhibited dynamic fluid-like properties within cells,which may promote the formation of P-bodies through LLPS.Finally,DDX6-IP-MS revealed that DDX6 might recruit NANOS3 into P-bodies by binding to the NANOS3 interacting protein Pumilio.Conclusion NANOS3 serves as a specific component of P-bodies in neonatal oocytes and may be involved in the regulation of early oogenesis.

The immune system is the cornerstone of the human body to resist danger and maintain homeostasis.The dysfunc-tion of the immune system leads to autoimmune diseases,tumors and other immune-related diseases.The mechanisms of the activation and regulation of the immune system is the frontier research field of life science and medicine.Circadian rhythms control individual ac-tivities and behaviors at various levels such as cells,tissues,organs,and play a key regulatory role in the immune system.Innate im-munity and adaptive immunity are strictly regulated by the biological clock,and the clock control genes in immune cells have diversi-fied effects on cell migration,development,functional differentiation and activation.This article summarizes the circadian regulation of innate and adaptive immunity,and discusses the association and potential intervention value of the biological clock with immune-re-lated diseases as a representative of autoimmune diseases.

The immune system is the cornerstone of the human body to resist danger and maintain homeostasis.The dysfunc-tion of the immune system leads to autoimmune diseases,tumors and other immune-related diseases.The mechanisms of the activation and regulation of the immune system is the frontier research field of life science and medicine.Circadian rhythms control individual ac-tivities and behaviors at various levels such as cells,tissues,organs,and play a key regulatory role in the immune system.Innate im-munity and adaptive immunity are strictly regulated by the biological clock,and the clock control genes in immune cells have diversi-fied effects on cell migration,development,functional differentiation and activation.This article summarizes the circadian regulation of innate and adaptive immunity,and discusses the association and potential intervention value of the biological clock with immune-re-lated diseases as a representative of autoimmune diseases.

Objective To observe the correlations of artificial intelligence(AI)measured parameters on anteroposterior and lateral spinal X-ray films with the severity of adolescent idiopathic scoliosis(AIS).Methods Totally 1 786 AIS patients were retrospectively enrolled.Parameters including Cobb angle(CA),coronal balance distance(CBD),T1 slope(T1S),pelvic tilt(PT),sacral slope(SS),apical vertebral translation(AVT),thoracic trunk shift(TTS),thoracic kyphosis(TK)and sagittal vertical axis(SVA)on anteroposterior and lateral spinal X-ray films were measured using uAI DR scoliosis analysis system.The severity of AIS was evaluated according to CA,and the correlations between other parameters and the severity of AIS were explored.The above parameters were compared under different severity levels and coronal/sagittal equilibrium states.Multivariate logistic regression analysis was performed to screen the independent impact factors on the severity of AIS.Results Significant differences of the above parameters were found among different severity levels except for SVA(all P＜0.001).With the aggravation of AIS,CA,CBD,AVT and TTS increased successively(all P＜0.001).T1S of severe AIS was higher than that of mild and moderate AIS(both P＜0.001),PT and SS of moderate and severe AIS were all bigger,while their TK were smaller than those of mild AIS(all P＜0.001).Significant differences of CA,T1S,PT,SS,AVT,TTS and TK were found between coronal balanced and imbalanced AIS(all P＜0.05),while of TK were found between sagittal balanced and unbalanced AIS(P=0.026).CBD,T1S,PT,SS,AVT and TTS were all positively correlated(r,=0.136-0.606,all P＜0.001),while TK was negatively correlated(r,=—0.404,P＜0.001)with the severity of AIS.T1S,AVT and TTS were all independent impact factors of the severity of AIS(all P＜0.001).Conclusion Among AI measured parameters on anteroposterior and lateral spinal X-ray films,CBD,T1S,PT,SS,AVT and TTS were positively correlated,while TK was negatively correlated with the severity of AIS.

Objective To observe the correlations of artificial intelligence(AI)measured parameters on anteroposterior and lateral spinal X-ray films with the severity of adolescent idiopathic scoliosis(AIS).Methods Totally 1 786 AIS patients were retrospectively enrolled.Parameters including Cobb angle(CA),coronal balance distance(CBD),T1 slope(T1S),pelvic tilt(PT),sacral slope(SS),apical vertebral translation(AVT),thoracic trunk shift(TTS),thoracic kyphosis(TK)and sagittal vertical axis(SVA)on anteroposterior and lateral spinal X-ray films were measured using uAI DR scoliosis analysis system.The severity of AIS was evaluated according to CA,and the correlations between other parameters and the severity of AIS were explored.The above parameters were compared under different severity levels and coronal/sagittal equilibrium states.Multivariate logistic regression analysis was performed to screen the independent impact factors on the severity of AIS.Results Significant differences of the above parameters were found among different severity levels except for SVA(all P＜0.001).With the aggravation of AIS,CA,CBD,AVT and TTS increased successively(all P＜0.001).T1S of severe AIS was higher than that of mild and moderate AIS(both P＜0.001),PT and SS of moderate and severe AIS were all bigger,while their TK were smaller than those of mild AIS(all P＜0.001).Significant differences of CA,T1S,PT,SS,AVT,TTS and TK were found between coronal balanced and imbalanced AIS(all P＜0.05),while of TK were found between sagittal balanced and unbalanced AIS(P=0.026).CBD,T1S,PT,SS,AVT and TTS were all positively correlated(r,=0.136-0.606,all P＜0.001),while TK was negatively correlated(r,=—0.404,P＜0.001)with the severity of AIS.T1S,AVT and TTS were all independent impact factors of the severity of AIS(all P＜0.001).Conclusion Among AI measured parameters on anteroposterior and lateral spinal X-ray films,CBD,T1S,PT,SS,AVT and TTS were positively correlated,while TK was negatively correlated with the severity of AIS.