ObjectiveTo investigate the pathogenic spectrum and epidemiological characteristics of diarrheal disease in Fengxian District of Shanghai, and to provide scientific basis for the prevention and control of diarrheal diseases. MethodsBasic information of the initial adult cases visited diarrheal disease surveillance sentinel hospital in Fengxian District, Shanghai, was collected from August 2013 to 2023, and fecal samples were collected at 1∶5 sampling intervals to isolate and identify 5 kinds of diarrheagenic Escherichia coli (DEC), Salmonella (SAL), Vibrio parahaemolyticus, Campylobacter, Vibrio cholerae, Shigella and Yersinia enterocolitica (YE). Simultaneously, nucleic acid detection was performed for 3 kinds of rotavirus, 2 kinds of norovirus, intestinal adenovirus, astrovirus and sapovirus. ResultsA total of 1 861 cases of newly diagnosed diarrheal disease were reported, with the peak in July to August. Additionally, 704 surveillance samples were detected, with a total positive detection rate of 50.57%. The detection rates of bacterial, viral and mixed infection were 25.14%, 21.02% and 4.40%, respectively. Among the pathogens detected, DEC accounted for the highest (17.61%, 124/704), followed by norovirus (16.48%, 116/704), rotavirus (6.39%, 45/704), SAL (5.97%, 42/704) and Campylobacter (3.84%, 27/704). DEC detected were mainly enteroaggregative Escherichia coli and enterotoxigenic Escherichia coli, with no detection of Vibrio cholerae, Shigella and YE. The highest total pathogen detection rate was observed from June to September, and the detection peaks of norovirus were from March to June and from October to December, whereas that of DEC was from June to October. The detection rate of rotavirus peaked from January to February, but which was not detected between 2020‒2023. The SAL positive rate peak was in September, whereas that of Campylobacter was from July to September. ConclusionThe main pathogens detected in Fengxian District from 2013‒2019 are DEC, norovirus, rotavirus, SAL and Campylobacter. Different pathogens have different detection peaks, with bacteria predominating in summer and viruses in winter and spring. Prevention and control measures should be carried out according to the epidemiological characteristics of different seasons.

OBJECTIVE To compare the efficacy and safety of different daily doses of aspirin in the prevention of preeclampsia （PE）. METHODS The case-control studies and prospective randomized controlled trials on aspirin with daily dose ≥ 100 mg （trial group） vs. ＜100 mg （control group） in the prevention of PE were retrieved from PubMed， Medline， Embase， the Cochrane Library， CNKI， China Biomedical Literatue Database and Wanfang Data from base-building to January 2025. After literature screening， data extraction and quality evaluation， meta-analysis was performed by using RevMan 5.3 software. RESULTS A total of 11 literatures were included， involving 3 052 pregnant women. Meta-analysis showed the incidence of PE [RR＝0.63， 95%CI （0.53，0.76）， P＜0.000 01]， gestational hypertension [RR＝0.69， 95%CI （0.50，0.94），P＝0.02]， preterm birth [RR＝0.56， 95%CI （0.47，0.66）， P＜0.000 01]， and intrauterine growth retardation [RR＝0.73，95%CI （0.61，0.87），P＝0.000 5] in trial groups were significantly lower than control group. The incidence of postpartum hemorrhage between the two groups had no statistically significant difference [RR＝1.17， 95%CI （0.90，1.53），P＝0.25]. Subgroup analysis showed that the incidence of PE in Chinese pregnant women taking 150 mg of aspirin was significantly higher than taking 100 mg of aspirin [RR＝3.40， 95%CI （1.29， 8.93）， P＝0.01]； but there was no significant difference between the two groups in the incidences of postpartum hemorrhage， preterm birth （P＞0.05）. CONCLUSIONS Aspirin with daily dose ≥100 mg is more effective in preventing PE than daily dose ＜100 mg， with lower rates of gestational hypertension， preterm birth， and intrauterine growth retardation. It does not increase the risk of postpartum hemorrhage. For pregnant women in China， daily dose 100 mg of aspirin may be more effective in preventing PE than 150 mg.

Acute liver injury (ALI) serves as a critical precursor and major etiological factor in the progression and ultimate manifestation of various hepatic disorders. The prevention and treatment of ALI is still a serious global challenge. Given the limited therapeutic options for ALI, exploring novel targeted therapeutic agents becomes imperative. The potential therapeutic efficacy of inhibiting RIPK2 is highlighted, as it may provide significant benefits by attenuating the MAPK pathway and NF-κB signaling. Herein, we propose a CMD-OPT model, a two-stage molecular optimization tool for the rapid discovery of RIPK2 inhibitors with optimal properties. Compound RP20, which targets the ATP binding site, demonstrated excellent kinase specificity, ideal oral pharmacokinetics, and superior therapeutic effects in a model of APAP-induced ALI, positioning RP20 as a promising preclinical candidate. This marks the first application of RIPK2 inhibitors in ALI treatment, opening a novel therapeutic pathway for clinical applications. These results highlight the efficacy of the CMD-OPT model in producing lead compounds from known active molecules, showcasing its significant potential in drug discovery.

Andrographolide sulfonate (AS) is a sulfonated derivative of andrographolide extracted from Andrographis paniculata (Burm.f.) Nees, and has been approved for several decades in China. The present study aimed to investigate the novel therapeutic application and possible mechanisms of AS in the treatment of rheumatoid arthritis. Results indicated that administration of AS by injection or gavage significantly reduced the paw swelling, improved body weights, and attenuated pathological changes in joints of rats with adjuvant-induced arthritis. Additionally, the levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-1β in the serum and ankle joints were reduced. Bioinformatics analysis, along with the spleen index and measurements of IL-17 and IL-10 levels, suggested a potential relationship between AS and Th17 cells under arthritic conditions. In vitro, AS was shown to block Th17 cell differentiation, as evidenced by the reduced percentages of CD4⁺ IL-17A⁺ T cells and decreased expression levels of RORγt, IL-17A, IL-17F, IL-21, and IL-22, without affecting the cell viability and apoptosis. This effect was attributed to the limited glycolysis, as indicated by metabolomics analysis, reduced glucose uptake, and pH measurements. Further investigation revealed that AS might bind to hexokinase2 (HK2) to down-regulate the protein levels of HK2 but not glyceraldehyde-3-phosphate dehydrogenase (GAPDH) or pyruvate kinase M2 (PKM2), and overexpression of HK2 reversed the inhibition of AS on Th17 cell differentiation. Furthermore, AS impaired the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signals in vivo and in vitro, which was abolished by the addition of lactate. In conclusion, AS significantly improved adjuvant-induced arthritis (AIA) in rats by inhibiting glycolysis-mediated activation of PI3K/AKT to restrain Th17 cell differentiation.
Animals ; Th17 Cells/immunology* ; Diterpenes/pharmacology* ; Arthritis, Rheumatoid/metabolism* ; Proto-Oncogene Proteins c-akt/immunology* ; Glycolysis/drug effects* ; Cell Differentiation/drug effects* ; Phosphatidylinositol 3-Kinases/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Humans ; Andrographis paniculata/chemistry* ; Arthritis, Experimental/drug therapy* ; Interleukin-17/immunology* ; Signal Transduction/drug effects*

Penicillin G acylases (PGAs) are industrially important enzymes primarily used for the synthesis of first- and second-generation cephalosporins or penicillins. This study aims to establish a high-efficiency biosynthetic system for cefradine on the purpose of significantly enhancing its catalytic efficiency in cefradine synthesis and developing its potentials for industrial application. In this study, we identified and engineered penicillin G acylase and obtained a highly active mutant KsPGA M7(M168F/F313G) for the synthesis of cefradine. The mutant achieved a conversion rate over 95% in the scaled-up reaction. To validate its industrial applicability, we immobilized both the wild-type and mutant enzymes and applied them in continuous flow reactions, which achieved a space-time yield of 2 800 g/(L·d). This study lays a foundation for the future applications of penicillin G acylases in the industrial synthesis of cefradine.
Penicillin Amidase/biosynthesis* ; Protein Engineering/methods* ; Cephradine/metabolism* ; Escherichia coli/metabolism* ; Enzymes, Immobilized/metabolism* ; Recombinant Proteins/biosynthesis*

Objective To explore the mediating role of mobile phone dependency and self-rated health in the relationship between adverse childhood experiences(ACEs)and mental health among young adults.Methods A cross-sectional study was conducted using cluster random sampling among 1 611 young adults(mean age 26.30 years)from a region in Hainan Province.Participants completed the childhood trauma questionnaire(short form),the mobile phone addiction index,the depression-anxiety-stress scale(simplified Chinese version),and a self-rated health questionnaire.Pearson correlation analysis and mediation effect analysis were employed to examine the relationships among ACEs,mobile phone dependency,self-rated health,and mental health.Results ACEs,mobile phone dependency,and self-rated health were all significantly correlated with mental health(all P＜0.01).ACEs had a direct negative effect on mental health(direct effect=0.221,95%confidence interval[CI]0.150-0.293).Furthermore,ACEs exerted indirect effects on mental health through 3 pathways:the independent mediation of mobile phone dependency(indirect effect=0.081,95%CI 0.035-0.130),the independent mediation of self-rated health(indirect effect=0.034,95%CI 0.011-0.062),and the chain mediation of mobile phone dependency and self-rated health(indirect effect=0.009,95%CI 0.004-0.015).Conclusion ACEs have a significant impact on the mental health of young adults,with mobile phone dependency and self-rated health serving as key mediators.Interventions aimed at reducing mobile phone dependency and improving health status may help mitigate the negative impact of childhood trauma on mental health,thereby promoting psychological well-being in this population.

Myeloid cell leukemia-1 (MCL-1) is an anti-apoptotic protein that plays a key role in promoting cell survival in multiple myeloma, acute myeloid leukemia and non-Hodgkin lymphoma. MCL-1 is highly expressed in a variety of hematological malignancies, which is one of the important factors leading to poor prognosis and chemoresistance in patients with hematological malignancies. Therefore, MCL-1 is an important therapeutic target for hematological malignancies. Several MCL-1 inhibitors have entered clinical trials, including S63845, AZD5991, S64315, AMG-176, and AMG-397. The treatment plans used for hematological malignancies include monotherapy with MCL-1 inhibitors, as well as combination therapy with B cell lymphoma 2 inhibitors or immunomodulatory drugs, all indicating that MCL-1 inhibitors may be a breakthrough point for targeted treatment of hematological malignancies.

Objective:To explore the value of ultrasonic velocity vector imaging(VVI)in assessing motion abnormality of myocardial segment of hyperthyroid heart disease.Methods:A total of 76 patients with hyperthyroid heart disease who admitted to hospital from August 2019 to August 2021 were selected.According to the damage degree of ascending aorta of patients,30 patients whose inner diameter of ascending aorta was greater than 30 mm were included in the"inner diameter>30mm"group,and 46 patients whose inner diameter of ascending aorta was less than 30 mm were included in the"inner diameter<30mm"group.Additionally,40 healthy individuals who underwent physical examinations during the same period were selected as the healthy control group.All subjects underwent routine echocardiography examination,and the images were imported into the velocity vector imaging(VVI)workstation.And then,the clear and standard two-dimensional grayscale dynamic images were selected to conduct analysis.The left ventricle was tracked and analyzed,and the left ventricular long axis,the apical four chamber,and the velocity of reaching peak value,the time of 50%velocity and the time of 75%velocity of longitudinal myocardial movement of 18 segments of two chambers,as well as the mitral valve level of short axis,the velocity of reaching peak value of reaching peak value,the time of 50%velocity and the time of 75%velocity of radial myocardial movement of 12 segments of horizontal section of papillary muscle,of three cardiac cycles were stored and recorded.Results:There were significant differences in the time to peak of longitudinal contraction at the basal segment and middle segment of left ventricular lateral wall,and the basal segment of front wall,the basal segment,middle segment and apical segment of inferior wall,as well as the basal segment,middle segment and apical segment of posterior wall among three groups(F=45.02,23.19,8.70,19.82,16.17,18.07,36.85,48.65,36.64,P<0.05),respectively.There were significant differences in the velocity and time of reaching peak value of the radial contraction of the levels of papillary muscle and mitral valve of short axis of left ventricular inferior wall among the three groups(F=15.44,40.35,P<0.001),respectively.Conclusion:VVI technique can accurately detect the subtle changes of the synchronization of myocardial systolic motion of left ventricular short axis and long axis of patients with hyperthyroid heart disease,which has higher application value in assessing the abnormalities of myocardial segmental motion of patients with hyperthyroid heart disease.

ObjectiveUltra-performance liquid chromatography-quadrupole/electrostatic field orbitrap high resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS/MS） was used to investigate the metabolism and distribution of nardosinone in rats， then metabolic pathways were speculated. MethodRats were administered with 30 mg·kg^-1 of nardosinone suspension by gavage for 3 consecutive days， and plasma， urine， feces， and tissues of heart， liver， spleen， lung， kidney， brain， stomach， and intestine were collected at predetermined time points. After treatment， the samples were processed for UPLC-Q-Exactive Orbitrap MS/MS， and the MS data were analyzed using Xcalibur 2.2 software. The metabolites were searched by comparing the base peak chromatogram and extracted ion chromatogram between the treated group and blank group， and based on the relative retention time（t_R）， quasi-molecular ion peak， precise molecular mass， and fragment ions of MS/MS， the elemental composition were searched using databases such as SciFinder and PubChem， as well as referring to relevant literature， the possible metabolites were identified and the metabolic pathways were inferred. ResultA total of 30 metabolites of nardosinone were identified， including 15， 19， 12， 7， 4， 11， 8， 13， 13， 8 and 12 metabolites in urine， feces， plasma， brain， heart， liver， spleen， lung， kidney， stomach and intestine， respectively. The main metabolic pathways of nardosinone in rats were hydroxylation， dehydroxylation， reduction， dehydrogenation， hydration， dehydration， carboxylation， glucuronidation， and dehydroxy-isopropyl. ConclusionNardosinone can be metabolized by phase Ⅰ and phase Ⅱ metabolism in rats， and the metabolites are widely distributed in the major organs. The results of this study can provide a basis for further research on the pharmacodynamic material basis， pharmacological mechanism and clinical application of nardosinone.

ObjectiveTo understand the incidence and death of female breast cancer patients and the premature death caused by breast cancer in Putuo District of Shanghai， and to reduce the incidence of breast cancer， mortality and the probability of early death， and to provide reference for realizing the control target of the probability of early death of major chronic diseases. MethodsThe incidence and death data of the registered female residents with breast cancer in Putuo District of Shanghai from 2004 to 2019 were collected using Shanghai Population-based tumor registration management system. The crude incidence rate， standardized incidence rate， crude mortality rate， standardized mortality rate， age-specific incidence rate， age-specific mortality rate and other indicators were calculated. The Joinpoint regression model was used to calculate the annual percentage change （APC） and average annual percentage change （AAPC） of breast cancer incidence， mortality and premature death probability， and to analyze the changing trend. ResultsFrom 2004 to 2019， the crude incidence of breast cancer in Putuo District of Shanghai increased from 75.76/10⁵ to 95.77/10⁵ （APC=2.26%， t=6.05， P<0.01）， while the standardized incidence did not decrease significantly during 2004‒2008 （APC=-4.83%， t=-1.81， P=0.10） and showed an upward trend after 2008 （APC=1.67%， t=2.84， P=0.02）. The crude mortality rate changed from 18.52 per 10⁵ to 21.63 per 10⁵ （APC= 1.51%， t=1.52， P=0.15）， and the standardized mortality rate decreased from 9.91/10⁵ to 7.44/10⁵ （APC=-1.46%， t=-2.43， P=0.03）. The incidence rate in the group of 30‒69 years increased from 98.39/10⁵ to 111.75/10⁵ （APC=1.14%， t=3.05， P=0.01）， and the mortality rate increased from 16.13/10⁵ to 19.30/10⁵ （APC=0.48%， t=0.84， P=0.41）. The incidence rate of patients aged ≥70 years varied from 165.68/10⁵ to 139.53/10⁵ （APC=1.54%， t=1.25， P=0.23）， and the mortality rate changed from 85.08/10⁵ to 56.64/10⁵ （APC=-0.18%， t=-0.08， P=0.94）. The probability of premature death from breast cancer decreased from 7.73‰ to 6.61‰ （APC=-1.56%， t=-2.30， P=0.04）. ConclusionThe risk of female breast cancer morbidity and death can not be ignored， and the control pressure of premature death probability is still large. Attention should be paid to the age group of 30‒69 years old， and further measures should be taken to control the increase of incidence and to reduce mortality， so as to reduce the probability of premature death of female breast cancer， and promote the realization of the overall control goal of premature death probability.