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 understand the antibody levels of diphtheria and tetanus among healthy population in Shanghai Pudong New Area, and to provide a scientific basis for improving the vaccine immunization strategy. Methods Random sampling was used to select healthy people of all ages in 16 communities in Shanghai Pudong New Area from 2018 to 2024, and serum samples were collected and tested for serum anti-diphtheria and tetanus toxin IgG antibodies by enzyme-linked immunosorbent assay (ELISA) method to analyze the antibody positivity rate (≥0.1 IU/ml) and the geometric mean concentration (GMC) of antibodies. Results A total of 3 312 serum samples were included, with a male-to-female ratio of 0.76:1, and 53.77% were local residents. The seropositivity rates and geometric mean concentrations (GMC) of both diphtheria and tetanus antibodies generally declined with increasing age, but exhibited a transient rebound in the 7y-. A total of 1 175 individuals (35.48%) were seropositive for diphtheria, with a GMC of 0.054 IU/mL. For tetanus, 988 individuals (29.83%) were seropositive, with a GMC of 0.033 IU/mL. Significant differences in seropositivity rates (χ²_diphtheria=950.005,χ²_tetanus=1 324.393) and GMC (H_diphtheria=1027.160,H_tetanus=1 142.007) were observed among different age groups (P<0.001). Significant differences in seropositivity rates (χ²_diphtheria=950.005,χ²_tetanus=1324.393) and GMC (H_diphtheria=1027.160,H_tetanus=1142.007) were also found across different years (P<0.001). Conclusion The prevalence of diphtheria and tetanus antibodies in the healthy population of Pudong New Area is relatively low, particularly among adults over 20 years of age with inadequate immunization. This underscores the need to reinforce the National Immunization Program (NIP) vaccine specifications for children under 6 years of age and implement an immunization strategy for adolescents or adults against diphtheria and tetanus.

Background/Aims: Chronic constipation is prevalent yet under-diagnosed across Asia, compromising quality of life and burdening healthcare systems. Cultural stigma, varied diets, and limited access to standardized diagnostic tools delay timely care. Methods: The Bali Chronic Constipation Roundtable in November 2024, brought together experts from 11 Asian countries. The group reviewed epidemiological data, analyzed multinational questionnaire on clinical practice pattern, and conducted structured discussions to identify key barriers and propose region-specific recommendations. Results: Chronic constipation prevalence varies across Asia, ranging from 1.8% in India to 16.6% in Japan, with women and the elderly disproportionately affected. Under-reporting persists owing to cultural taboos and widespread self treatment with laxatives and traditional medications. Although the Rome IV criteria remains the global standard, they may not fully reflect Asian symptom profiles, and diagnosis is limited by scarce motility laboratories. First line therapies such as dietary-fiber optimization and osmotic laxatives are widely available, but newer pharmacotherapies (prucalopride, linaclotide, lubiprostone, and elobixibat) remain costly and unevenly accessible. Biofeedback for dyssynergic defecation is underutilized due to limited availability. Experts recommend expanded regional research on to refine diagnostic criteria, coupled with enhanced physician education and public awareness. They advocate accessibility to second-line and novel therapies that incorporate culturally attuned regional guidelines, and improved access to gastrointestinal motility testing. Conclusions The Bali Chronic Constipation Roundtable highlighted Asia’s need for region specific diagnostics and management. Addressing diagnostic and treatment gaps will improve outcomes, while ongoing researcher clinician policy collaboration must standardize guidelines, advance research, and ensure equitable care across Asia.

Background: To investigate directional deviations between pilot holes and final pedicle screw trajectories in freehand placement and analyze risk factors for misplacement. While pedicle screws are widely used in thoracolumbosacral surgery, directional deviations between pilot holes and final screw trajectories remain understudied as potential risk factors for misplacement. Methods: Thirty-three patients undergoing posterior fixation were prospectively enrolled. Inertial measurement units (IMUs) tracked the spatial positions of pedicle finders and screwdrivers via custom software. Surgeons (n = 6) were stratified into senior, middle, and junior groups. Analyzed variables included the use of tapping, surgeon experience, spinal deformity status, screw tip morphology, and surgical parameters. Results: Among 198 implanted screws (6.00 ± 2.88/patient), all exhibited trajectory deviations (8.12° ± 3.47°). Tapping significantly reduced deviations (7.23° ± 3.23° vs. 8.87° ± 3.31°, p < 0.01). Senior surgeons achieved smaller deviations (7.34° ± 3.33°) than the middle group (8.60° ± 3.51°, p = 0.039) and junior group (8.68° ± 3.49°, p = 0.022). Multivariate analysis confirmed tapping (p = 0.001) and senior experience (p = 0.023) as protective factors. No significant associations emerged for spinal deformity (8.43° ± 3.73° vs. 7.97° ± 3.35°, p = 0.377), screw tip type (cylindrical, 8.43° ± 3.26° vs. tapered, 8.07 ± 3.51°; p = 0.637), obesity, or surgical position parameters. Conclusions Freehand pedicle screw placement consistently produces trajectory deviations from pilot holes, and surgeon experience and tapping are modifiable protective factors. The IMU-based tracking system enables quantitative surgical motion analysis, suggesting its utility for training optimization and technique standardization.

OBJECTIVE To evaluate the characteristics of adverse drug event （ADE） associated with five therapeutic agents for Gaucher disease（imiglucerase， velaglucerase alfa， taliglucerase alfa， eliglustat，and miglustat）. METHODS ADE reports related to the above five drugs were retrieved from the FDA Adverse Event Reporting System （FAERS） database from January 2004 to September 2025. The reporting odds ratio （ROR） and proportional reporting ratio （PRR） methods were applied for data mining. system organ class （SOC） and preferred term （PT） from the Medical Dictionary for Regulatory Activities （MedDRA， version 26.0） drug ADE terminology were used for classification and statistical analysis of ADE. RESULTS A total of 4 329， 1 740， 500， 1 329 and 998 ADE reports were retrieved for the aforementioned five drugs， respectively， generating 4 612， 2 605， 776， 1 157 and 2 185 ADE signals. These signals involved 26 SOC， affecting 25， 26， 16， 19， and 19 SOC， respectively. The predominant SOCs were various injuries， poisoning and procedural complications， as well as infections and infestations. The top one PTs of each drug were as follows： bone infarction， zinc deficiency， failure to perform drug monitoring steps， ichthyosis， abnormal nerve conduction examination. New suspected PTs included weight gain and spontaneous abortion for imiglucerase and velaglucerase alfa， weight gain for taliglucerase alfa and eliglustat， and neuropsychiatric manifestations such as dementia and apathy for miglustat. In terms of severe ADEs， other serious medical events were predominant for imiglucerase and taliglucerase alfa； prolonged hospital stays were the main severe ADE for velaglucerase alfa and eliglustat； and death was the leading severe ADE for miglustat. CONCLUSIONS In clinical medication， apart from common ADE，for imiglucerase， clinicians should be alert to bone infarction， weight gain and spontaneous abortion， and strengthen monitoring related to bones， metabolism and pregnancy. For velaglucerase alfa， attention should be paid to zinc deficiency， bone infarction， weight gain and spontaneous abortion， with focused monitoring of nutritional status and pregnancy risks. For taliglucerase alfa， failure to perform drug monitoring steps and weight gain require vigilance， and medication procedures should be standardized along with regular weight monitoring. For eliglustat， clinicians need to watch out for ichthyosis and weight gain and pay close attention to skin conditions. For miglustat， bone infarction， abnormal nerve conduction examination and dementia should be closely monitored， with enhanced surveillance on nervous system function， infections and prognosis of critically ill patients，to ensure patient medication safety.

Objective To systematically explore the prescription source,prescription composition,drug origin and processing,functional indications and clinical application of the classic Tibetan medicine Sanwei Qiangwei Powder,so as to provide scientific basis for its in-depth development,rational utilization and follow-up research.Methods By using methods of literature review,the ancient and modern Tibetan medical classics and modern literature such as'Ocha Jinmai' sporadic secret collection 'Zhigong Yi Suan Ji' were retrieved,and the prescription origin,medicinal material origin,processing technology,prescription solution,usage and dosage were studied and analyzed.Results The Sanwei Qiangwei Powder originated from the 'Ocha Jinmai'(《()》)written by Qiangba Minimatongwatundan in the 15th century.The book was written much earlier than the literature included in the 'Catalogue of Ancient Classic Prescriptions(Second Batch)'-the 'Selection of Tibetan Medicine Prescriptions·Longevity Baoru' in the 19th century.The prescription consists of 15 copies of Rosa rugosa,7 copies of Herpetospermum caudigerum,and 3 copies of Terminalia chebula Retz.It plays a significant effect on hepatobiliary diseases such as biliary fever,liver fever,primary headache,and headache after drinking in clinical practice.It is the core prescription for the treatment of Chiba-type diseases and has high development value.There are differences in the use site,dosage ratio,usage and dosage of medicinal materials in different literatures,and the dosage has been clarified by textual research and expert consultation.Conclusion This study sorted out and clarified the key information of Sanwei Qiangwei Powder,which laid a theoretical foundation for the inheritance and development,innovative application and modernization research of the prescription.

AIM:To investigate the antitumor activity and targets of baicalein(Bai)in pancreatic cancer using network pharmacology combined with in vitro and in vivo experiments.METHODS:The targets of Bai and pancreatic can-cer were analyzed via multi-data screening.A protein-protein interaction network was constructed using STRING,and core targets were identified via Cytoscape.Functional enrichment was analyzed by Gene Ontology(GO)and Kyoto Ency-clopedia of Genes and Genomes(KEGG).Antitumor effects of Bai were assessed in pancreatic cancer cells Aspc-1 and Bxpc-3 using MTT and colony formation assays for proliferation,flow cytometry for apoptosis and cell cycle analysis,and Transwell assays for migration and invasion.A xenograft tumor model was established to evaluate tumor proliferation,im-munohistochemistry was performed to detect the protein expression of AKT in tumor tissues,and Western blot was used to analyze the expression levels of AKT,β-catenin,N-cadherin and Slug.RESULTS:A total of 108 overlapping targets were identified between Bai and pancreatic cancer.Among these,7 core targets were recognized,including proto-onco-gene tyrosine-protein kinase Src,heat shock protein 90 alpha family class A member 1(HSP90AA1),estrogen receptor 1(ESR1),tumor protein p53(TP53),epidermal growth factor receptor(EGFR),AKT1,and mitogen-activated protein ki-nase 3(MAPK3).The GO analysis revealed significant enrichment in oxidative stress response,protein phosphorylation,and serine/threonine kinase activity.The KEGG analysis primarily enriched the PI3K/AKT,MAPK and Ras signaling pathways.The MTT and colony formation assays showed that Bai inhibited the viability of Aspc-1 and Bxpc-3 cells in a dose-dependent manner(72 h IC50 values were 73.6 μmol/L and 83.4 μmol/L,respectively)and reduced cell colony for-mation(P<0.05 or P<0.01).Flow cytometry confirmed that Bai induced apoptosis of Aspc-1 and Bxpc-3 cells(P<0.01)and blocked the cell cycle at the G0/G1 phase(P<0.05 or P<0.01).Transwell experiments indicated that Bai inhibited the migration and invasion of Aspc-1 and Bxpc-3 cells(P<0.05 or P<0.01).In vivo,Bai significantly inhibited the growth of Aspc-1 cell xenograft tumors(P<0.01).Immunohistochemistry revealed a significant reduction in AKT expression in tu-mor tissues(P<0.01),and Western blot showed decreased expression of AKT,β-catenin,N-cadherin and Slug in both Aspc-1 and Bxpc-3 cells(P<0.01).CONCLUSION:Baicalein inhibits pancreatic cancer cell proliferation,migration,and invasion,potentially through down-regulation of AKT,β-catenin,N-cadherin,and Slug expression.

Objective:To evaluate the cumulative live birth rate (CLBR) and cost-effectiveness of fixed versus adjusted follicle-stimulation hormone (FSH) dosages in infertile women with different ovarian responses during their first assisted reproductive technology (ART) cycle.Methods:A retrospective real-world cohort study was conducted on 5 419 infertile women who underwent their first ART treatment at the Department of Reproductive Medicine of the First Affiliated Hospital of Nanjing Medical University between January 2013 and December 2017. All patients received an individualized starting dosage of gonadotropin. Based on whether FSH dosages were adjusted during controlled ovarian stimulation (COS), patients were divided into fixed-dosage group ( n=2 061) and adjusted-dosage group ( n=3 358). Clinical outcomes and FSH cost-effectiveness were compared between the two groups across different ovarian response groups, with CLBR as the primary outcome. Propensity score matching (PSM) and multivariable logistic regression were used to adjust for potential confounders. Results:FSH dosage adjustments were found in 62.0% (3 358/5 419) of cycles during COS. After PSM, baseline characteristics were comparable between the two groups (all P>0.05). After adjusting for confounders using multivariable logistic regression, FSH dosage adjustment was not significantly associated with CLBR ( OR=1.06, 95% CI: 0.94-1.20, P=0.332). Compared with the adjusted-dosage group, the fixed-dosage group showed no significant differences in CLBR in poor-, normal-, and high-responder groups (all P>0.05). The incidence of ovarian hyperstimulation syndrome (OHSS) did not differ significantly between the two groups ( P>0.05). In poor-, normal-, and high-responder groups, the total FSH dosages in the fixed-dose group [1 350 (375, 1 825) U, 1 200 (375, 1 500) U and 525 (375, 1 128) U, respectively] were significantly lower than those in the adjusted-dose group [1 875 (1 425, 2 294) U, P=0.001; 1 425 (450, 1 875) U, P<0.001; 600 (375, 1 425) U, P=0.020]. Similarly, average FSH costs in different ovarian response groups in the fixed-dosage group [4 725.0 (1 312.5, 6 387.5) yuan, 4 200.0 (1 312.5, 5 250.0) yuan and 1 837.5 (1 312.5, 3 947.3) yuan, respectively] were significantly lower than those in the adjusted-dosage group [6 562.5 (4 987.5, 8 028.1) yuan, P=0.001; 4 987.5 (1 575.0, 6 562.5) yuan, P<0.001; 2 100.0 (1 312.5, 4 987.5) yuan, P=0.020]. For normal-responders, the FSH cost per high-quality embryo in the fixed-dosage group [1 365.0 (875.0, 2 537.5) yuan] was significantly lower than that in the adjusted-dosage group [2 056.3 (1 268.8, 3 412.5) yuan, P<0.001]. Conclusion:FSH dosage adjustment during COS is not associated with CLBR or the incidence of OHSS. However, the fixed-dose group exhibited lower total FSH dosages and costs across different ovarian response populations. In the context of ART being covered by medical insurance, fixed FSH dosage may represent a more cost-effective ovarian stimulation protocol.

In recent years,natural antimicrobial biomaterials have received widespread attention due to their rich sources,broad anti-microbial spectrum,high antimicrobial activity,good biocompatibility,etc.They play an important role in caries prevention and treat-ment by inhibiting the formation of biofilm and removing the formed biofilm.In this paper,we summarize the inhibitory effects of differ-ent natural antimicrobial biomaterials on Streptococcus mutans,the main caries-causing organism,and its biofilm,with a view to provi-ding theoretical references for caries prevention and treatment.

Objective This study aimed to investigate the antimicrobial resistance profiles of bacterial strains isolated from pediatric intensive care units(PICU)in China for better antimicrobial therapy.Methods Clinical isolates were collected from 17 institutions,including tertiary care children's hospitals and pediatric department of tertiary general hospitals in China from January 1,2020 to December 31,2022.Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems.Results were interpreted according to the breakpoints released by the Clinical and Laboratory Standards Institute(CLSI)in 2020.Results A total of 10 688 isolates were collected,including gram-positive organisms(39.2％)and gram-negative organisms(60.8％).The top three organisms were S.aureus(13.6％,1 453/10 688),A.baumannii(10.0％,1 067/10 688),and coagulase-negative Staphylococcus(9.9％,1 058/10 688).Multi-drug resistant organisms(MDROs)were very common in children.The prevalence of methicillin-resistant Staphylococcus aureus(MRSA),carbapenem-resistant Enterobacterales(CRE),carbapenem-resistant E.coli,carbapenem-resistant K.pneumoniae(CRKP),carbapenem-resistant A.baumannii(CRAB),and carbapenem-resistant P.aeruginosa(CRPA)was 41.1％,19.4％,8.8％,30.9％,67.4％,and 28.8％,respectively.Overall,more than 50％of Enterobacteriales isolates were resistant to cephalosporins,while nearly 25％of Enterobacteriales isolates were resistant to carbapenems.MDROs were highly resistant to commonly used antibiotics.More than 80％of CRE and CRAB strains were resistant to all beta-lactam antibiotics.CRE and CRAB showed low resistance rates to tigecycline and polymyxin.CRPA showed lower resistance rates to piperacillin,beta-lactamase inhibitor combinations than the resistance rates to third and fourth generation cephalosporins.All of the Staphylococcus and Enterococcus isolates were susceptible to vancomycin and tigecycline.None of PRSP strains isolated from meningitis and nonmeningitis samples were resistant to rifampicin,vancomycin,or linezolid.The prevalence of β-lactamase-negative ampicillin-resistant(BLNAR)strains was 43.3％in Haemophilus influenzae.Conclusions MDROs were prevalent in PICU.It is necessary to establish an effective multidisciplinary team(MDT)to control the antimicrobial resistance.