ObjectiveTo systematically characterize the in vitro chemical constituents of Entada phaseoloides and its absorbed prototype compounds and metabolites in a neuropathic pain （NP） model， thereby elucidating the potential pharmacological material basis underlying its analgesic activity. MethodsUltra-high-performance liquid chromatography coupled with quadrupole-Orbitrap high-resolution mass spectrometry （UHPLC-Q-Orbitrap HRMS） was used to analyze the constituents of the 80% methanol extract of E. phaseoloides. Thirty-six mice were divided into a blank group， low-， medium-， and high-dose E. phaseoloides extract groups （25， 50， and 100 mg·kg^-1， respectively）， an aspirin group （400 mg·kg^-1）， and a morphine group （10 mg·kg^-1）， with six mice in each group. The tail-flick threshold was measured. Twenty-four mice were randomly divided into a blank group and low-， medium-， and high-dose E. phaseoloides extract groups （25， 50， and 100 mg·kg^-1， respectively）， with six mice in each group， and motor coordination was evaluated. A spinal nerve ligation （SNL） model was established in mice. Twenty-four mice were randomly divided into a sham-operated （Sham） group， an SNL group， an SNL + E. phaseoloides extract group （750 mg·kg^-1）， and an SNL + pregabalin group （20 mg·kg^-1）， with 6 mice in each group. Mechanical allodynia and thermal hyperalgesia were evaluated. Behavioral assessments were combined to determine the optimal onset time of the analgesic effect， and plasma samples were collected at this time point. Absorbed components and metabolites were systematically identified based on accurate mass， MS/MS fragmentation patterns， retention time， and comparisons with literature data and reference standards. Meanwhile， network pharmacology， target similarity analysis， and molecular docking validation were integrated to evaluate the potential effects of absorbed components on disease intervention. ResultsCompared with the blank group， the high-dose E. phaseoloides extract group and morphine group showed significantly increased pain response thresholds （P<0.01）， without affecting motor coordination in normal mice. Compared with the Sham group， the SNL group exhibited significantly decreased thresholds for mechanical allodynia and thermal hyperalgesia （P<0.01）. Compared with the SNL group， the SNL + E. phaseoloides extract group and SNL + pregabalin group showed significantly increased thresholds for mechanical allodynia and thermal hyperalgesia （P<0.01）. The analgesic effect of E. phaseoloides was most significant at 2 h after administration. A total of 70 constituents were identified in vitro， and 22 prototype compounds and 29 metabolites were detected in plasma. The targets of the absorbed components were mainly enriched in biological processes associated with pain signal perception and transmission and showed a high degree of overlap with disease genes related to neuropathic pain. In addition， multiple components exhibited strong binding energies with core pain-related targets. Based on integrated analysis of in vitro content， plasma exposure levels， and target associations， ketanthamide A-β-D-pyranoside and ketengzide were identified as the most representative pharmacologically active substances responsible for the analgesic effect. ConclusionThis study systematically elucidates the material basis of E. phaseoloides intervention in neuropathic pain from three aspects， including chemical constituent characteristics， in vivo behavioral characteristics， and potential targets， providing important theoretical foundations and experimental support for further studies on its pharmacological mechanism and analgesic drug development.

In 2022， Hainan provincial government launched the project for the prevention and control of viral hepatitis with the goals of a hepatitis B screening rate of 90%， a diagnostic rate of 90%， and a treatment rate of 80% among people aged 18 years and above by the year 2025， and the main intervention measures include population-based prevention， case screening， antiviral therapy， and health management. As of December 31， 2024， a total of 6.875 million individuals in the general population had been screened for hepatitis B， with a screening rate of 95.6%. A total of 184 710 individuals with positive HBsAg were identified， among whom 156 772 were diagnosed through serological reexamination， resulting in a diagnostic rate of 84.9%. A total of 50 742 patients with chronic hepatitis B were identified， among whom 42 921 had hepatitis B-specific health records established for health management， with a file establishment rate of 84.6%. A total of 31 553 individuals received antiviral therapy， with a treatment rate of 62.2%. A total of 2.503 million individuals at a high risk of hepatitis C were screened， among whom 4 870 tested positive for HCV antibody and 3 858 underwent HCV RNA testing， resulting in a diagnostic rate of 79.2%， and 1 824 individuals with positive HCV RNA were identified， among whom 1 194 received antiviral therapy， with a treatment rate of 65.5%. In addition， 159 301 individuals with negative HBsAg and anti-HBs and an age of 20 — 40 years were inoculated with hepatitis B vaccine free of charge. Through the implementation of the project for the prevention and control of viral hepatitis， a large number of hepatitis patients have been identified， treated， and managed in the province within a short period of time， which significantly accelerates the efforts to eliminate the crisis of viral hepatitis.

Objective: To compare the biological characteristics of human induced pluripotent stem cell-derived platelet exosomes (hiPSC-Plt-Exos) with those of conventional apheresis platelet exosomes (Plt-Exos), specifically focusing on their differential abilities to enhance the proliferation and migration of human umbilical cord mesenchymal stem cells (hUC-MSCs). Methods: Exosomes were isolated from hiPSC-derived Plt and apheresis Plt concentrate using size exclusion chromatography. These exosomes were then characterized through nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), and Western blotting. Co-culture experiments into hUC-MSCs were conducted with hiPSC-Plt-Exos and apheresis Plt-Exos, respectively. Their effects on the proliferation and migration of hUC-MSCs were assessed via cell proliferation assays and scratch tests. Results: hiPSC-Plt-Exos and apheresis Plt-Exos exhibited comparable particle sizes, morphological features (such as the characteristic cup-shaped structure), and surface markers (including CD9 and HSP70). Notably, hiPSC-Plt-Exos demonstrated a significantly greater ability to enhance the proliferation and migration of hUC-MSCs compared to apheresis Plt-Exos (P<0.05). These differences provide critical comparative data for their application in various clinical contexts. Conclusion: This study establishes a theoretical foundation for developing precise therapeutic strategies based on hiPSC-Plt-Exos. Furthermore, it underscores the necessity of selecting the appropriate type of exosomes according to the specific disease microenvironment to achieve optimal therapeutic outcomes.

Objective: To analyze respiratory syncytial virus(RSV) outbreaks surveillance results and the epidemiological characteristics in kindergarten and school in Shenzhen during 2017-2023 , so as to provide a scientific reference for control and prevention of RSV. Methods: Epidemiological data and surveillance results of RSV outbreaks in kindergarten and school from 2017 to 2023 were collected for descriptive analyses. Results: A total of 31 RSV outbreaks were identified in kindergarten and school in 2017-2023 in Shenzhen, 346 cases were reported, the average incidence rate was 22.02%. The most annual RSV outbreaks were reported in 2020 with 14 outbreaks, followed by 8 outbreaks in 2023. A total of 64.52% of RSV outbreaks were identified in kindergarten with rest occurring in primary school or middle school. The greatest monthly count of outbreak was 18 (58.06%) in September, followed by 3 outbreaks (9.68%) in March and October. A total of 244 swab samples were collected, 169 samples were positive for respiratory viruses, the positive rate was 69.26%, 121 samples were positive for RSV,from 31 respiratory syncytical virus outbreaks 57 and samples were positive for other respiratory viruses(9 samples were positive for two respiratory viruses). A toral of 14(45.16%) outbreaks are caused by RSV alone, 17 outbreaks (54.84%) were caused by RSV and other respiratory viruses. Conclusions Most RSV outbreaks in kindergarten and school are reported after 2020 in Shenzhen, most RSV outbreaks occur in kindergarten, peak seasons of RSV outbreaks are autumn and spring.

Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

With the growing emphasis on maternal and child oral health, the significance of managing oral health across preconception, pregnancy, and infancy stages has become increasingly apparent. Oral health challenges extend beyond affecting maternal well-being, exerting profound influences on fetal and neonatal oral development as well as immune system maturation. This expert consensus paper, developed using a modified Delphi method, reviews current research and provides recommendations on maternal and child oral health management. It underscores the critical role of comprehensive oral assessments prior to conception, diligent oral health management throughout pregnancy, and meticulous oral hygiene practices during infancy. Effective strategies should be seamlessly integrated across the life course, encompassing preconception oral assessments, systematic dental care during pregnancy, and routine infant oral hygiene. Collaborative efforts among pediatric dentists, maternal and child health workers, and obstetricians are crucial to improving outcomes and fostering clinical research, contributing to evidence-based health management strategies.
Humans ; Pregnancy ; Female ; Infant ; Consensus ; Mouth Diseases/therapy* ; Pregnancy Complications/therapy* ; Oral Health ; Infant, Newborn ; Delphi Technique ; Oral Hygiene

Objective To meet the clinical need for dynamic monitoring on lactate metabolism in septic shock pa-tients,a time-series prediction model based on a long short-term memory(LSTM)network was developed to predict 24-hour lactate clearance rate at admission.Methods A multi-stage retrospective cohort design was adopted to en-roll septic shock patients admitted to the department of critical care medicine of a hospital from January 2018 to Sep-tember 2024.By conducting univariate analysis and LASSO combined feature screening,predictive factors were extracted from multidimensional clinical data.An end-to-end LSTM framework(two-layer 64/32 units,dropout rate=0.3)was constructed.A sliding window strategy(six-hour step size)was adopted for dynamic prediction and compared with traditional logistic model in terms of three dimensions:calibration(Brier score),discrimination(area under the curve[AUC]of time-dependent receiver operating characteristic[ROC]),and clinical practicality(deci-sion curve analysis).Consistency between model prediction result and actual lactate clearance rate was analyzed,and the accuracy of prediction was evaluated.Results A total of 112 septic shock patients were enrolled in the analysis,including 65 males and 47 females,with an average age of(67.35±7.28)years.65 patients were assigned in the lactate good clearance rate group(lactate good clearance rate≥10％)and 47 in the lactate poor clearance rate group(lactate good clearance rate＜10％);78 patients were in the training set and 34 in the validation set.Time-depen-dent AUC analysis revealed that the predictive performance of the LSTM model in the time windows of 6,12,and 24 hours were 0.89(0.85-0.93),0.91(0.88-0.95),and 0.92(0.89-0.96),respectively,superior to the logistic regression model(ΔAUC=0.085,P＜0.01).The core predictive factors included APACHE Ⅱ score(OR=1.38),lactate level at admission(OR=1.65),vasoactive drug dosage(OR=1.42),and 6-hour fluid resuscitation dosage(OR=1.35).The Pearson correlation coefficient between the predicted value of the model and the actual 24-hour lactate clearance rate was 0.83(P＜0.001),with an average absolute error of 8.2％.Decision curve analysis confirmed that when the threshold probability was 15％-60％,the LSTM model could increase clinical net benefits by 27.3％.The validation of each subgroup showed that the model maintained the optimal predictive performance(AUC=0.87)in the lung infection subgroup(n=16).Conclusion The LSTM-based dynamic prediction model for predicting 24-hour lactate clearance rate through integrating early admission indicators demonstrates excellent pre-dictive performance and clinical application value,which can provide important reference for individualized treatment decisions in septic shock patients.

Objective:To investigate the impact of evaluating the alcohol intake on all-cause mortality in patients with metabolic-associated fatty liver disease（MAFLD）and metabolic dysfunction and alcohol-related liver disease（MetALD）.Method:The retrospective study included patients aged 20 to 74 years with hepatic steatosis diagnosed by ultrasound，with data from the Third National Health and Nutrition Examination Survey（NHANES III）between 1988 and 1994. Participants were categorized into light，moderate，and heavy drinking groups according to daily alcohol intake. Multivariable-adjusted hazard ratios（aHR）and their 95% confidence intervals（ CI）were calculated by Cox proportional risk regression modeling to assess the effect of alcohol intake on all-cause mortality. Results:A total of 2 322 patients were included in the study. Males accounted for 50.2%（1 166/2 322），with a age of 42.0（31.3，57.0）years，a median follow-up of 316.0（270.0，337.0）months，and an all-cause mortality rate of 1.48% per person-year. There were 1，763 cases in the light drinking group，333 in the moderate drinking group，and 226 in the heavy drinking group.The all-cause mortality rates for patients in the three drinking groups were 1.38%，1.67%，and 2.10% per person-year，respectively. The moderate（a HR=1.37，95% CI：1.12 to 1.67， P=0.002）and heavy（a HR=1.45，95% CI：1.17 to 1.80， P=0.001）drinking groups were independently associated with increased all-cause mortality following covariate adjustment. There was a difference in all-cause mortality for alcohol intake in non-type 2 diabetes mellitus（T2DM）patients under 60 years of age（ P<0.05），but the difference was not statistically significant between non-T2DM patients over 60 years of age and T2DM patients of all ages（ P>0.05）according to the analysis of diabetes status and age subgroups. Conclusion:Alcohol intake has a dose-dependent negative effect on patients with MAFLD and MetALD. The risk of all-cause mortality increased significantly with increasing alcohol intake.

Objective:To explore the effectiveness of the"full-chain"integrated medical and elderly care service model in addressing key issues in medical-nursing services such as weak medical support capacity and insufficient provision of community-and home-based medical-nursing services.Methods:The development pathway for the"full-chain"integrated medical-elderly care service standardization system,encompassing core components such as operational mechanisms,smart platforms,policy documents,and quality control systems was systematically outlined.Effectiveness based on dimensions including service coverage,quality improvement,talent development,and social benefits was evaluated.With standardization as the core driver,the'1234567'management model was innovatively implemented.Results:The model leveraged the downward allocation of high-quality resources from tertiary general hospitals to strengthen subdistrict community health service centers.By collaborating with subdistrict elderly-care service centers,it established"subdistrict medical-elderly care and wellness service centers".These centers enhanced the capabilities of"community-embedded elderly-care complexes",including community daytime care centers,established two-way referral channels between medical and elderly care services,aligned with healthcare demands to provide elderly individuals with reliable medical support.It reduced the burden on families and society,stimulated market vitality,boosted domestic demand,promoted the development of integrated medical-elderly care and wellness initiatives,thereby advancing the silver economy.With provincial government endorsement,the model had been applied to 203 communities across 37 counties by the end of 2024.Conclusion:The established"full-chain"integrated medical-elderly care service model facilitates regional high-quality development in integrated care by consolidating healthcare group resources and seamlessly connecting the service chain across hospitals,nursing homes,community institutions,and home-based settings,thereby creating a practical paradigm for comprehensive elderly care service delivery.

Cancer stands as a significant global public health challenge, and cancer screening serves as a pivotal strategy for reducing its mortality. Presently, only a limited number of cancer types have appropriate screening methods available. Traditional single-cancer screening approaches are fraught with limitations, including invasiveness, low accuracy, and poor patient compliance. Multi-cancer early detection (MCED) leveraging liquid biopsy technology enables non-invasive and efficient early detection of multiple cancers by analyzing biomarkers such as cell-free DNA, cell-free RNA, proteins, and metabolites in blood and other bodily fluids. This innovative approach substantially broadens the spectrum of detectable cancers and enhances population coverage, showcasing immense potential for improving existing cancer screening strategies. This expert consensus comprehensively reviews the progress of liquid biopsy-based MCED, biomarker selection and detection technologies, the criteria for cancer type selection, research design and clinical utility evaluation, as well as implementation pathways. The overarching goal of this consensus is to offer scientific guidance for further research and the widespread adoption of MCED, thereby facilitating the continuous optimization of cancer screening strategies.