At present， the systematic excavation of the clinical experience and academic thought of the Sichuan school of Chinese medicine vis-à-vis its dominant disease entities remains fragmentary， and replicable paradigms are scarce. Confronted with empirical fragmentation， data heterogeneity and decision-making subjectivity， the standardised distillation， inheritance and clinical translation of these distinctive experiences has become a critical bottleneck constraining the development of the Sichuan school. The integration of artificial-intelligence technologies in data processing， pattern recognition and intelligent decision-making has rendered deep mining of traditional Chinese medicine（TCM） clinical knowledge and patterns imperative. Constructing an intelligent modern TCM diagnostic-therapeutic-evaluative system is now the obligatory route for inheritance and innovation in Chinese medicine， and simultaneously provides a technological breakthrough for intelligent decision paradigms in the dominant diseases of the Sichuan school. Accordingly， this study adopts the regional academic school as its point of entry， focuses on the dominant diseases of the Sichuan school， and proposes an innovative pathway of "four-dimensional data-multi-modal fusion-multi-agent decision-making". Specifically， four data dimensions are defined and instantiated： （Ⅰ） knowledge from classical medical literature and historical case records. （Ⅱ） objective four-diagnosis phenotypic data. （Ⅲ） master physicians' prescribing regularities. （Ⅳ） characteristic mechanisms of renowned formulae. Leveraging multi-modal data fusion and generative artificial intelligence， the entire causal chain of Famous Physicians and Renowned Formulas is explicated to reconstruct the diagnostic-therapeutic cognitive logic of the regional school. Finally， a multi-agent collective-decision model is established and refined for the dominant diseases of the Sichuan school， capable of generating precise， individualised treatment regimens and thereby advancing an intelligent diagnostic-therapeutic paradigm that delivers more efficient and accurate clinical decision support.

Tailored lipid nanoparticles (LNPs)-mediated small interfering RNA (siRNA) nanomedicines show promise in treating liver disease, such as acute liver injury (ALI) and non-alcoholic steatohepatitis (NASH). However, constructing LNPs that address biosafety concerns, ensure efficient delivery, and target specific hepatic subcellular fractions has been challenging. To evade above obstacles, we develop three novel self-degradable "gemini-like" ionizable lipids (SS-MA, SS-DC, SS-MH) by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head. Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release, improving both biosafety and siRNA delivery efficiency. Furthermore, the distance of ester bond and tertiary amino head significantly influences the LNPs' pK _a, thereby affecting endosomal escape, hemolytic efficiency, absorption capacity of ApoE, uptake efficiency of hepatocytes and liver accumulation. We also develop the modified-mannose LNPs (M-LNP) to target liver macrophages specifically. The optimized M-MH_LNP@TNFα exhibits potential in preventing ALI by decreasing tumor necrosis factor α (TNFα) levels in the macrophages, while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol O-acyltransferase 2 (DGAT2) in the hepatocytes. Our findings provide new insights into developing novel highly effective and low-toxic "gemini-like" ionizable lipids for constructing LNPs, potentially achieving more effective treatment for hepatic diseases.

Perimenopause raises the risk and incidence of depression, whereas the underlying molecular mechanism remains unclear. Disturbed glucose regulation has been widely documented in depressive disorders, which renders the brain susceptible to various stresses such as estrogen depletion. However, whether and how glucose dysfunction regulates depression-like behaviors and neuronal damage in perimenopausal transition remains unexplored. Here, a prominent depressive phenotype was found in perimenopausal mice induced by the ovarian toxin 4-vinylcyclohexene diepoxide (VCD). The VCD depression susceptible group (VCD^SS) and the VCD depression resilient group (VCD^RES) were determined using a ROC-based behavioral screening approach. We found that the hippocampus, a crucial region linked to depression, had hyperglycemia and mitochondrial abnormalities. Interestingly, oral administration of the SGLT2 inhibitor empagliflozin (EMPA) and intrahippocampal glucose infusion suggest a close relationship between hyperglycemia in the hippocampus and the susceptibility to depression. We verified that cytochrome c oxidase 7c (COX7C) downregulation is a potential cause of the high glucose-induced neuronal injury using proteomic screening and biochemical validations. High glucose causes COX7C to be ubiquitinated in a S-phase kinase associated protein 1 (SKP1)-dependent manner. According to these results, SKP1/COX7C represents a unique therapeutic target and a novel molecular route for treating perimenopausal depression.

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OBJECTIVE: The objective of our study was to evaluate the vaccine effectiveness (VE) of the pentavalent rotavirus vaccine (RV5) among < 5-year-old children in three provinces of China during 2020-2024 via a propensity score-matched test-negative case-control study. METHODS: Electronic health records and immunization information systems were used to obtain data on acute gastroenteritis (AGE) cases tested for rotavirus (RV) infection. RV-positive cases were propensity score matched with RV-negative controls for age, visit month, and province. RESULTS: The study included 27,472 children with AGE aged 8 weeks to 4 years at the time of AGE diagnosis; 7.98% (2,192) were RV-positive. The VE (95% confidence interval, CI) of 1-2 and 3 doses of RV5 against any medically attended RV infection (inpatient or outpatient) was 57.6% (39.8%, 70.2%) and 67.2% (60.3%, 72.9%), respectively. Among children who received the 3rd dose before turning 5 months of age, 3-dose VE decreased from 70.4% (53.9%, 81.1%) (< 5 months since the 3rd dose) to 63.0% (49.1%, 73.0%) (≥ 1 year since the 3rd dose). The three-dose VE rate was 69.4% (41.3%, 84.0%) for RVGE hospitalization and 57.5% (38.9%, 70.5%) for outpatient-only medically attended RVGE. CONCLUSION Three-dose RV5 VE against rotavirus gastroenteritis (RVGE) in children aged < 5 years was higher than 1-2-dose VE. Three-dose VE decreased with time since the 3rd dose in children who received the 3rd dose before turning five months of age, but remained above 60% for at least one year. VE was higher for RVGE hospitalizations than for medically attended outpatient visits.
Humans ; Rotavirus Vaccines/immunology* ; China/epidemiology* ; Case-Control Studies ; Child, Preschool ; Infant ; Rotavirus Infections/epidemiology* ; Male ; Propensity Score ; Female ; Vaccine Efficacy ; Gastroenteritis/virology* ; Vaccines, Attenuated ; Rotavirus

ObjectiveTo obtain the epidemiological characteristics of re-positive cases infected with SARS-CoV-2 in Pudong New Area from March to July 2022, including clinical manifestations, duration of a negative nucleic acid conversion after tested for re-positive, and length of time from the discharge of the initial infection to the most recent re-positivity, so as to provide a scientific basis for the prevention and control of COVID-19. MethodsA questionnaire survey was conducted among the re-positive cases infected with SARS-CoV-2 after discharged from hospital/quarantine facility in Pudong New Area, and descriptive epidemiological methods were used for characteristics analysis. ResultsA total of 2 422 re-positive cases met the inclusive and exclusive criteria, with males accounting for 61.02%. The age distribution mainly fell between 18 and <60 years old, accounting for 62.39%. Clinical manifestations were predominantly asymptomatic (72.15%), followed by cough (12.03%) and sore throat (6.58%). Among the stratified randomized sample of 416 individuals, there were statistically significant differences in symptoms (χ²=262.667, P<0.001), clinical typing (χ²=12.996, P=0.001), and duration of a negative nucleic acid conversion (χ²=142.578, P<0.001) between the initial positive and re-positive instances. Besides, statistically significant differences in symptoms (χ²=13.696, P=0.016) and self-perception of the severity of re-infection (χ²=7.923, P=0.048) between the initial and re-positive cases were observed by different genders. ConclusionAmong re-positive cases, males experienced milder symptoms compared to females, and the self-perception of symptoms during re-positivity is milder than that in the initial positive infection. The length of time for negative nucleic acid conversion during the initial positive period is shorter than that during the re-positive period.

Compounds isolated from Epimedium include the total flavonoids of Epimedium , icariin, and its metabolites (icaritin, icariside I, and icariside II), which have similar molecular structures. Modern pharmacological research and clinical practice have proved that Epimedium and its active components have a wide range of pharmacological effects, especially in improving sexual function, hormone regulation, anti-osteoporosis, immune function regulation, anti-oxidation, and anti-tumor activity. To date, we still need a comprehensive source of knowledge about the pharmacological effects of Epimedium and its bioactive compounds on the male reproductive system. However, their actions in other tissues have been reviewed in recent years. This review critically focuses on the Epimedium , its bioactive compounds, and the biochemical and molecular mechanisms that modulate vital pathways associated with the male reproductive system. Such intrinsic knowledge will significantly further studies on the Epimedium and its bioactive compounds that protect the male reproductive system and provide some guidances for clinical treatment of related male reproductive disorders.
Male ; Epimedium/chemistry* ; Humans ; Genitalia, Male/drug effects* ; Flavonoids/therapeutic use* ; Animals