ObjectiveA middle cerebral artery occlusion (MCAO) mouse model is established by electrocoagulation of the middle cerebral artery. The study examines the mechanism by which exosomes (EXO) derived from human amniotic mesenchymal stem cells (hAMSCs) improve ischemic stroke and regulate neural ferroptosis-related injury. MethodsThirty-two SPF-grade male C57BL/6J mice aged 6 - 8 weeks were randomly divided into four groups (n=8 per group): sham group (Sham), model group (MCAO), MCAO plus normal saline group (MCAO+NaCl), and MCAO plus exosome group (MCAO+EXO). The mouse MCAO model was established by electrocoagulation of the middle cerebral artery. Mice in the Sham group underwent exposure of the middle cerebral artery without electrocoagulation. Twenty-four hours before MCAO induction, mice in the MCAO+EXO group received a tail vein injection of 100 μL of exosomes derived from the culture supernatant of hAMSCs at a concentration of 9.5×10¹¹ particles/mL. Mice in the MCAO+NaCl group were injected with an equal volume of normal saline via the tail vein. Twenty-four hours after model establishment, neurological deficits were evaluated using the Longa neurological deficit scoring system. Cerebral infarct volume was assessed by 2,3,5-triphenyltetrazolium chloride (TTC) staining. Hematoxylin and eosin (HE) staining was performed to evaluate morphological changes of neurons in the ischemic brain regions. The contents of ferrous iron (Fe²⁺), malondialdehyde (MDA), total glutathione (total GSH), oxidized glutathione (GSSG), and reduced glutathione (GSH) in the infarct core and peri-infarct regions were determined using microcolorimetric assays to evaluate differences among groups. The mRNA expression levels of ferroptosis-related factors, including nuclear factor erythroid 2-related factor 2 (NRF2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) in the infarct core and peri-infarct regions were measured by real-time quantitative PCR. Protein expression levels of NRF2, SLC7A11, and GPX4 in the infarct and peri-infarct regions of each group were analyzed by Western blotting. ResultsCompared with the MCAO group, the Longa neurological deficit score was significantly reduced in the MCAO+EXO group (P<0.01). Prominent cerebral infarction was observed in the MCAO group, whereas the infarct volume ratio was markedly decreased in the MCAO+EXO group compared with the MCAO group (P<0.001). Histopathological analysis revealed that mice in the MCAO group exhibited obvious neuronal damage, including cytoplasmic vacuolar degeneration, nuclear pyknosis and fragmentation, unclear nuclear structure, and disorganized neuronal arrangement, compared with the Sham group. In contrast, neurons in the MCAO+EXO group showed relatively preserved morphology, with intact cellular structures and large, regular nuclei located centrally within the cells. Biochemical analysis demonstrated that Fe²⁺ and MDA levels in the infarct core and peri-infarct regions were significantly increased in the MCAO group compared with the Sham group (P<0.001). These levels were significantly reduced in the MCAO+EXO group compared with the MCAO group (P<0.01). In addition, total glutathione (total GSH), oxidized glutathione (GSSG), and reduced glutathione (GSH) levels were markedly decreased in the MCAO group relative to the Sham group (P<0.01). Compared with the MCAO group, the MCAO+EXO group exhibited significantly increased levels of total GSH and GSH (P<0.001), while no significant change was observed in GSSG levels (P>0.05). Furthermore, both mRNA and protein expression levels of nuclear factor erythroid 2-related factor 2 (NRF2), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) were significantly downregulated in the MCAO group compared with the Sham group (P<0.01, P<0.001). In contrast, both mRNA and protein expression levels of NRF2, SLC7A11, and GPX4 were significantly upregulated in the MCAO+EXO group compared with the MCAO group (P<0.05). ConclusionIn the mouse MCAO model, tail vein injection of exosomes derived from hAMSCs can improve motor function, reduce infarct area, protect neuronal cell morphology, and reduce the degree of nerve injury. Exosomes may exert a protective effect by activating the NRF2/SLC7A11/GPX4 pathway and reducing ferroptosis in neuronal cells of MCAO model mice.

Objective: To characterize longitudinal trajectories of testicular development in boys and breast development in girls, so as to provide reference data for understanding patterns of pubertal sexual maturation. Methods: Based on the Shanghai Pudong New Area Cohort Study on Growth, Development and Health in Children and Adolescents, a baseline survey was conducted in 2020 using a mult stage cluster random sampling method. A total of 2 184 children who completed all follow ups during the primary school period from 13 elementary schools in Pudong New Area,Shanghai,with annual follow ups during 2021-2025. Testicular volume and Tanner stage of breast development were assessed by professional physicians using standardized visual inspection and palpation. The age distribution of testicular volume and breast development was fitted by using cumulative link mixed models and Turnbull s nonparametric maximum likelihood estimation method. Results: Median ages for testicular volumes of 2, 3, 4 and 5 mL in boys were 7.07, 9.24, 10.29, and 11.57 years old, respectively. Median ages for Tanner breast stages Ⅱ, Ⅲ, Ⅳ, and Ⅴ in girls were 8.55 , 10.17, 11.18, and 13.78 years old, respectively. Based on overweight and obesity, stratified analysis showed that earlier pubertal onset among overweight/obesity children, and the key milestones for pubertal initiation were testicular volume reaching 4 mL in boys and breast Tanner II in girls for 10.29, 10.83; 8.18, 9.00 years. Conclusion Overweight and obesity are associated with earlier pubertal initiation,but there are certain gender and developmental stage specific patterns.

ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

The digitization of traditional Chinese medicine (TCM) has generated vast amounts of data. However, these data are characterized by significant heterogeneity and complex semantic structures, posing substantial challenges for systematic integration and intelligent analysis, and limiting its potential for modern clinical and computational research. To address the challenges posed by the high heterogeneity and complex structure in TCM data, we designed and developed the TCM Data Hub platform, which is powered by the YiYuan large language models (LLMs). This platform aims to enhance intelligent data processing capabilities and unlock the potential for clinical application of TCM data through systematic integration and efficient utilization, thereby bridging the gap between traditional knowledge and modern computational research. This study first analyzed the heterogeneity and complexity of TCM information with respect to data types, structures, and semantics. A standardized data framework was constructed to enhance data integration and interoperability. Based on the TCM Intelligent Computing Platform of the China Academy of Chinese Medical Sciences, we trained the YiYuan LLMs to acquire domain-specific semantic understanding of TCM, thereby improving the platform’s comprehension of specialized terminology and knowledge systems. Leveraging the natural language processing capabilities of the LLMs, we developed a human-in-the-loop data processing system to enable efficient extraction, cleansing, and structured organization of TCM data. In addition, utilizing Vue and Java technologies, we developed multiple LLM-powered intelligent agents and systems, including a human-in-the-loop data processing system, as well as automated prescription mining and network pharmacology analysis agents. Task-specific agents tailored to TCM data processing were developed to enhance the model’s effectiveness in clinical knowledge discovery. System functionality and platform infrastructure were implemented using Java and Vue technologies.The TCM Data Hub platform has completed system construction and core functionality implementation. It supported integrated management and efficient access to 8 key types of TCM data: prescriptions, materia medica, ingredients, targets, diseases (Western medicine), diseases (TCM), syndromes, and therapeutic methods. The human-in-the-loop data processing system achieved an accuracy of 95.34% in structuring TCM data and supported annotation for data requiring manual labeling. The intelligent agent-driven big-data analytics module enabled 1-click, end-to-end workflows for TCM prescription mining, herb-syndrome association analysis, network pharmacology, and molecular biology research, completing a full data mining task in approximately 30 minutes. Users can interact with and manipulate data through a visual front-end interface. The system demonstrated stable performance, strong scalability, and a user-friendly experience. Empowered by the YiYuan LLMs, the TCM Data Hub platform significantly improves the accessibility, usability, and intelligence of TCM data. It effectively bridges traditional TCM knowledge with modern intelligent technologies, providing robust data support and intelligent tools for TCM research and clinical applications.

Objective To understand the epidemiological characteristics and trends of postoperative pneumonia(POP)in tertiary general hospitals in Jiangsu Province,and provide theoretical basis for carrying out targeted pre-vention and control measures.Methods Surgery patients from 22 tertiary general hospitals in 12 cities in north,central,and south of Jiangsu Province from January 1,2022 to December 31,2023 were chosen as studied subjects,occurrence of POP was analyzed and compared.Results A total of 848 274 surgical procedures were performed in 22 hospitals,and 3 606 cases of POP occurred,with an incidence of 0.43％.The incidence in 2023 was 0.37％,which was lower than that in 2022(0.49％),with statistically significant difference(P＜0.001).The top three de-partments with high incidence of POP were neurosurgery(6.71％),cardiothoracic surgery(2.91％),and general surgery(0.77％).Among hospitals of different grades,the incidence of POP in tertiary first-class hospitals was 0.44％,which was higher than that in other tertiary hospitals(0.37％).There was no statistically significant difference in the incidence of POP between municipal and district/county hospitals(P＞0.05).The incidence of POP in hospitals with a bed:infection control full-time staff ratio＜200∶1 was lower than that in hospitals with the ratio ≥200∶1(0.39％vs 0.47％,P＜0.001),while the incidence of POP in hospitals with a proportion ≥30％of full-time staff being doctors was higher than that in hospitals with a proportion＜30％(0.45％vs 0.36％,P＜0.001).The incidence of POP in male patients was higher than that in female patients(0.62％vs 0.26％,P＜0.001).The incidence of POP in elderly patients aged≥65 was higher than that in patients aged＜65(0.73％vs 0.26％,P＜0.001).A total of 2 667 strains of infectious pathogens were detected,with the top three being Acine-tobacter baumannii,Klebsiella pneumoniae,and Pseudomonas aeruginosa,accounting for 28.95％,22.72％,and 15.45％,respectively.The detection rates of carbapenem-resistant Acinetobacter baumannii(CRAB),carba-penem-resistant Klebsiella pneumoniae(CRKP),and carbapenem-resistant Pseudomonas aeruginosa(CRPA)were 60.75％,21.45％,and 32.28％,respectively.The detection rate of CRKP decreased in 2023 compared with 2022,with statistically significant difference(P＜0.05).Conclusion The overall incidence of POP in tertiary general hos-pitals in Jiangsu Province is relatively low,but there are significant differences among different hospitals.There-fore,perioperative prevention and control measures should be carried out based on the epidemiological characteristics of patients.

Objective:To construct a multimodal induction educational system suitable for standardized pediatric residency training bases, and to evaluate its effectiveness, thereby obtaining suggestions for further improvement.Methods:Twelve residents newly enrolled in the 2023 standardized residency training program who commenced their first-year training were included as study subjects. The induction educational system comprised multiple modules: department introduction, training plan and assessment requirements, departmental workflow, routine diagnosis and treatment of major diseases, specialized skills/procedures, and lifestyle guidance. Training materials and methods were tailored to the characteristics of each training module. Checklists were used for supervision and review, and a competency checklist was designed to evaluate residents' mastery of the training at two weeks of induction, which would guarantee the effectiveness of the training. A questionnaire survey, powered by wjx.cn, was used to obtain the experience and suggestions from the residents and ward instructors on induction education, and content ranking analysis was performed on the survey results.Results:The survey revealed that, before starting a new rotation, residents' top three educational needs were departmental workflow, routine diagnosis and treatment of common diseases, and specialized skills/procedures. Residents preferred face-to-face lectures and demonstrations by attending physicians or senior residents; instructors suggested improving relevant materials (such as resident physician manuals and video materials) and face-to-face lectures. The residents considered the current induction educational system to be greatly beneficial in basic theories, treatment principles, basic skills, and auxiliary examination processes.Conclusions:Through the above research, a multimodal induction educational system suitable for the standardized pediatric residency training base in the Peking University First Hospital has been preliminarily established, and suggestions for further improvement have been obtained, which is conducive to further improving the system and residents' post competency.

Objective To explore the changes in neural activity in patients with type 2 diabetes mellitus(T2DM)and their corre-lation with executive function,and to analyze the neural mechanisms underlying the decline in executive function in T2DM patients.Methods Thirty-one T2DM patients(T2DM group)and thirty-two healthy controls(HC)(HC group)matched for body mass index(BMI)underwent resting-state functional magnetic resonance imaging(rs-fMRI)scans and N-back task tests were included.Differ-ences in the amplitude of low-frequency fluctuation(ALFF),regional homogeneity(ReHo),and seed-based functional connectivity(FC)between the two groups were compared,and partial correlation analyses were performed between the difference results and N-back task performance.Results The T2DM group showed prolonged reaction time(RT)in the 1-back and 2-back tasks.T2DM patients exhibited increased ALFF in the bilateral caudate nucleus,left medial superior frontal gyrus,and right postcentral gyrus,as well as elevated ReHo in the right putamen.FC analysis revealed significant alterations in FC between the caudate nucleus,putamen,and multiple brain regions in T2DM patients,with some of these FC changes significantly correlated with RT and accuracy(ACC)in the N-back task.Conclusion The decline in executive function in T2DM patients may be associated with abnormal neural activity in brain regions such as the striatum,salience network,and frontoparietal control network.FC further decreases under increased cognitive load.These findings provide evidence for the study of the neural mechanisms of executive function impairment in T2DM patients.

Objective To establish a stable liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for detecting gamma-aminobutyric acid(GABA)in plasma,and to evaluate the value of GABA detection in the diagnosis of sleep disorders.Methods GABA was detected using a UPLC Xevo TQs system.The method was pre-validated and its performance was verified to establish a reference range for healthy individuals.The difference in plasma GABA levels between apparently healthy individuals and patients with sleep disorders was compared.Results We employed deuterated compounds as isotopic internal standards and utilized an Amide chromatographic column for separation.The mobile phase was 0.050%formic acid in water and 90%acetonitrile in water containing 0.175%formic acid and 5 mmol/L ammonium acetate with gradient elution in the column temperature of 35℃.The linear range for the detection of GABA by LC-MS/MS was 0.05-10.00 μmol/L,with a lower limit of quantification of 0.02 μmol/L,the inter-day CV<3.00%and intra assay CV<4.00%,respectively,and the recovery rate was 101.06%-109.02%.The reference ranges for plasma GABA were established by analyzing 300 healthy controls stratified by age:18-34 years(0.08-0.15 μmol/L),35-49 years(0.10-0.20 μmol/L),and≥50 years(0.12-0.23 μmol/L).Then plasma GABA was used as a biomarker for auxiliary diagnosis of sleep disorders in analyzing 221 patients and 300 healthy controls,which revealed that AUC values were 0.510(P=0.850),0.686(P=0.002),and 0.890(P<0.001)in the groups of 18-34 years,35-49 years,and≥50 years,respectively,with optimal cut-off values of 0.09,0.10 and 0.11 μmol/L.Conclusion A reliable LC-MS/MS method for detecting GABA has been established,which can detect plasma GABA levels sensitively and accurately and can be used in assisting the clinical diagnosis of sleep disorders.

Objective·To explore the potential role of SUMO-specific protease 1(SENP1)in ferroptosis.Methods·The Cancer Genome Atlas(TCGA)database was used to analyze the correlation between the expression levels of SENP1 and the ferroptosis-related genes,acyl-CoA synthetase long chain family member 4(ACSL4)and glutathione peroxidase 4(GPX4).Ferroptosis in human fibrosarcoma HT1080 cells,murine fibrosarcoma MCA-205 cells,and human embryonic kidney 293T cells was induced by RAS-selective lethal 3(RSL3).Quantitative real-time PCR(RT-qPCR)and Western blotting were used to detect the expression of SENP1.In 293T cells,immunoprecipitation-mass spectrometry was used to investigate the interacting proteins of SENP1 in the process of ferroptosis.The Flag-SENP1 plasmid was transiently transfected into 293T cells,and the overexpression efficiency of SENP1,along with the expression levels of ferroptosis-related genes ACSL4 and GPX4,was assessed by RT-qPCR and Western blotting.Results·TCGA database analysis showed that the expression of SENP1 was positively correlated with ACSL4 and negatively correlated with GPX4 in most tumor tissues.RT-qPCR and Western blotting showed that the expression level of SENP1 was significantly down-regulated in RSL3-treated HT1080,MCA-205,and 293T cells.Immunoprecipitation-mass spectrometry showed that SENP1 enriched SUMO molecules in the process of ferroptosis.Western blotting showed that the level of ACSL4 protein increased after SENP1 overexpression,and there was no significant change in the level of GPX4 protein.RT-qPCR showed that after SENP1 overexpression,there was no significant change in the mRNA levels of ACSL4 and GPX4.Conclusion·SENP1 gene expression is downregulated during ferroptosis,and may regulate the stability of ferroptosis-related protein ACSL4.

Objective:To explore the clinical features of death in children with acute encephalopathy associated with influenza and corona virus disease 2019（COVID-19）and to enhance pediatrician's understanding of this disease.Methods:Clinical data of children with influenza and COVID-19-related acute encephalopathy hospitalized in Pediatric Intensive Care Unit of Children's Hospital Affiliated to Soochow University from September 2021 to July 2023 were retrospectively analyzed.The cases were divided into survival group and death group according to outcome.The general condition，clinical manifestations，auxiliary examination and treatment between the two groups were compared and analyzed.Results:A total of 41 pediatric patients were enrolled.In the death group,there were 17 cases,including 15 cases of acute necrotizing encephalopathy (ANE); among them,there were 7 male patients and 10 female patients,with a median age of 3.50 years.Eight patients were infected with influenza A virus,3 with influenza B virus,and 6 with SARS-CoV-2.The survival group comprised 24 cases,including 10 cases of ANE; among them,there were 16 male patients and 8 female patients,with a median age of 4.33 years.Fourteen patients were infected with influenza A virus,4 with influenza B virus,and 6 with SARS-CoV-2.None of the patients in the death group has received influenza and COVID-19 vaccines within 1 year before infection.Common symptoms were fever and disturbance of consciousness in the death group，eight cases had mild cough，seven cases had convulsions ≥three times，one case had two convulsions，nine cases had only one seizure，of which five cases were epileptic status.One case had delirium before convulsions.Seventeen cases began to fall into a coma (6.50±1.50) hours after their first onset of convulsion.Two patients had secondary pulmonary infection.Nine cases showed significantly elevated interleukin-6,while 17 cases had normal cerebrospinal fluid cell counts and 14 cases had elevated protein levels.All 17 cases underwent cranial CT scans,among which 13 showed symmetric necrosis of the bilateral thalami.All patients in the death group underwent glucocorticoid and intravenous immunoglobulin pulse therapy.Eleven patients received continuous renal replacement therapy,ten patients received intrathecal dexamethasone injection,and two patients were treated with tocilizumab.One patient underwent extracorporeal membrane oxygenation.Among the eight influenza patients,neuraminidase inhibitors were first administered 48 hours after the onset of fever.None of the six patients infected with SARS-CoV-2 received nirmatrelvir/ritonavir antiviral treatment.The causes of death in 17 patients included ANE(15 cases) and secondary infections(2 cases).Compared with the survival group,the incidence of brainstem involvement,shock,and low Glasgow coma scores (GCS ≤ 4) were significantly higher in the death group(15/17 vs.2/24， χ 2=26.18， P<0.001；16/17 vs.5/24， χ 2=21.39， P<0.001；14/17 vs.5/24， χ 2=15.15， P<0.001). Conclusion:Acute encephalopathy is primarily characterized by recurrent convulsions and disturbances of consciousness.Influenza and COVID-19 are the main causes.Cranial imaging is helpful for clinical diagnosis.Involvement of the brainstem,occurrence of shock,and GCS≤4 are associated with a higher fatality rate of ANE.