Autism spectrum disorder (ASD) is a neurodevelopmental condition with a steadily rising global prevalence, yet effective pharmacological interventions remain notably limited, highlighting an urgent need for safe, accessible, and mechanism-based therapeutic strategies. Physical exercise has emerged as a promising non-pharmacological intervention that ameliorates both core symptoms—social communication deficits and restricted repetitive behaviors—and associated features including cognitive dysfunction and motor impairments, in children and adolescents with ASD. However, the molecular mechanisms mediating these beneficial effects remain incompletely defined, impeding the development of evidence-based exercise prescriptions and biomarker-driven rehabilitation protocols. MicroRNAs (miRNAs) are evolutionarily conserved small non-coding RNAs that post-transcriptionally regulate approximately 60% of protein-coding genes. Within the central nervous system, miRNAs orchestrate diverse neurobiological processes including neural progenitor proliferation, neuronal differentiation, dendritic spine morphogenesis, synaptic plasticity, and neuroinflammatory homeostasis. Notably, miRNAs are remarkably stable in biological fluids and can be packaged into extracellular vesicles, rendering them attractive candidates as both mechanistic mediators and non-invasive peripheral biomarkers. Among the hundreds of miRNAs expressed in the brain, three—miR-132, miR-34a, and miR-146a—have emerged as particularly relevant to ASD pathophysiology. This review focuses on these three miRNAs for the following reasons: miR-132 is a master regulator of activity-dependent synaptic plasticity through its modulation of BDNF/MeCP2/PTEN signaling and has been consistently downregulated in ASD prefrontal cortex; miR-34a functions as a pro-apoptotic factor that suppresses Bcl-2-mediated neuronal survival pathways and is upregulated in ASD cerebellum; and miR-146a serves as a key brake on neuroinflammation via TLR7/IRAK1 signaling and shows region-specific dysregulation in ASD temporal lobe. We first summarize evidence from human post-mortem brain tissues and ASD animal models demonstrating the consistent dysregulation of these three miRNAs. Notably, the pathological consequences of these miRNA alterations—impaired synaptic plasticity, excessive neuronal apoptosis, and sustained neuroinflammation—are interconnected and collectively contribute to the heterogeneous symptomatology of ASD. We then present a synthesis of emerging evidence demonstrating that various exercise modalities, including swimming, treadmill running, and voluntary wheel running, can concurrently reverse these ASD-like behavioral phenotypes and normalize the expression of the three key miRNAs. These data provide the first direct experimental evidence linking exercise-induced miRNA modulation to ASD symptom improvement. On the basis of these findings, we propose an integrative “exercise-miRNA-ASD” framework wherein exercise functions as a multi-targeted modulator—simultaneously enhancing synaptic plasticity, promoting neuronal survival, and attenuating neuroinflammation—through coordinated regulation of the three miRNAs. Importantly, this framework is not merely descriptive but offers testable predictions: exercise-induced miRNA changes should be dose-dependent, show temporal correlation with behavioral improvements, and be blunted by miRNA-specific antagonists or CRISPR/Cas9-mediated knockout. Beyond its specific application to ASD, this framework has broader implications. The miR-132/BDNF, miR-34a/Bcl-2, and miR-146a/TLR7 pathways are not ASD-specific but represent fundamental neural stress and repair mechanisms that are dysregulated across Alzheimer’s disease (AD), traumatic brain injury, Parkinson’s disease (PD), and major depressive disorder. Exercise has been shown to modulate these same miRNAs in several of these conditions, suggesting that the “exercise-miRNA-neural function” axis may represent a conserved neuroprotective mechanism that transcends diagnostic boundaries. Thus, we propose that ASD serves as an ideal model disease for elucidating this universal mechanism, with findings potentially generalizable to other neurological disorders. We also critically evaluate current translational barriers: the near-absence of human clinical trials with serial miRNA profiling; the undefined dose-response relationships between exercise parameters and miRNA expression; the unresolved causality issue (current evidence demonstrates association, not causation); and the uncertain correlation between peripheral exosomal miRNA levels and brain miRNA dynamics. We argue that future research must prioritize CRISPR/Cas9-based miRNA manipulation in animal models combined with longitudinal exercise interventions to establish causality, and that cross-disease validation studies are essential to determine whether exercise-induced miRNA changes represent a shared neuroprotective signature or disease-specific responses. Ultimately, we envision a paradigm where a simple blood test measuring exosomal miR-132, miR-34a, and miR-146a levels could guide personalized exercise prescriptions, enabling precision rehabilitation for individuals with ASD and potentially other neurological conditions.

In the context of global warming, protecting outdoor workers from occupational heat exposure has become an important public health concern. This review summarized the principle, applicability, and limitation of three categories of wet bulb globe temperature (WBGT) prediction models: empirical regression models, heat-balance models, and machine-learning models. Drawing on international experience from the United States, Europe, and Japan, this review further examined the technical challenges of applying WBGT-based prediction models to large-scale occupational heat stress early warning systems. In response to gaps in occupational heat stress management in China, WBGT should be considered a core assessment indicator to support a transition from passive response to proactive intervention. A localized implementation pathway is proposed, incorporating mechanism-based model calibration, regional parameter adaptation, and multi-source data fusion. Strengthening collaboration between public health and meteorological departments and developing platform-based flexible intervention strategies for workers in new forms of employment may improve the targeting of occupational heat stress early warning and health protection. Future research should focus on physics-constrained machine learning, refined microenvironmental prediction, and individualized risk assessment to support the development of a digitally enabled occupational heat-health protection framework.

OBJECTIVE To provide evidence for further improving the rules governing the renewal round of national centralized drug procurement with volume-based purchasing （VBP） program for insulin.METHODS Based on publicly available policy documents， selection outcomes， and interview data， policy text analysis， descriptive statistical analysis， the Wilcoxon signed-rank test， and thematic analysis were used to compare the procurement rules and selection outcomes between the initial and renewal rounds of the national VBP programs for insulin， and to examine the mechanisms linking rule adjustments to changes in selection outcomes.RESULTS Compared with the initial round， the renewal round retained the six procurement groups and 11 bidding units， reduced the maximum valid bid price by 40%， and introduced competitive bidding selection， revival selection， and a price line for Category A products. A total of 42 products were selected in the initial round and 49 in the renewal round， including 37 that remained selected， 5 that exited， and 12 that were newly selected in the renewal round. Within the same procurement groups， the price range decreased significantly in the renewal round compared with the initial round （ P ＝0.031）， whereas the difference in average price between the two was not statistically significant （ P ＝0.063）. Domestic manufacturers were more likely to enter the A1 category， whereas multinational manufacturers were more likely to remain in categories B/C. Mechanism analysis suggested that the price line shaped the boundary of selected prices， while the classification and volume-allocation rules linked manufacturers’ bidding decisions to expected procurement volumes， potentially altering bidding incentives and corresponding to changes in the distribution of selection outcomes.CONCLUSIONS The renewal round of the insulin VBP program established an interrelated mechanism involving price boundaries， volume-based incentives， and supply constraints through the use of price lines， product classification， and contracted volume allocation. These rule adjustments corresponded to changes in the structure of selected products， price distributions， and manufacturer classifications. Future policy refinement should strengthen the coordination among reasonable price ranges， volume-based incentives， and supply performance.

Objective:To explore the efficacy and safety of olverembatinib in treatment of chronic myeloid leukemia (CML) progressed to acute lymphoblastic leukemia with D241E mutation.Methods:The diagnosis and treatment of a patient with D241E mutant CML progressed to acute lymphoblastic leukemia admitted to the Fourth People's Hospital of Jinan in December 2018 were retrospectively analyzed, and relevant literature was reviewed.Results:The patient was a 47-year-old female, and her blood test result was abnormal during physical examination. She was diagnosed as CML and received treatment with imatinib and dasatinib for 2 years. The disease progressed to philadelphia chromosome (Ph)-positive acute B-lymphoblastic leukemia with BCR-ABL mutation (a D241E mutation). After 3 courses of chemotherapy combined with a targeted drug (ponatinib), the patient achieved complete remission, while the minimal residual disease continued to be positive. The patient received 1 course of chemotherapy combined with olverembatinib from the 4th course of treatment. After olverembatinib monotherapy maintenance therapy for 36 months, the patient achieved molecular complete remission with minimal residual disease. The patient developed complications such as skin pigmentation and elevated lipid levels, but all complications were tolerable.Conclusions:The application of olverembatinib in D241E mutant CML progressed to acute lymphoblastic leukemia can help patients obtain sustained molecular biological remission and good safety.

Objective To systematic evaluate the impact of applying the clinical nursing pathway(CNP)on epidural anesthetic analgesia natural delivery.Methods The randomized controlled trial(RCT)and quasi-experimental researches on the application of CNP in epidural anesthetic analgesia natural delivery were retrieved from PubMed,Cochrane Library,Embase,Web of Science,China Knowledge Network database,Wanfang database,VIP and the Chinese Biomedical Literature Database.The retrieval time limit was from January 1,2014,to July 31,2024 with no language limitation.The meta analysis on the included studies was performed by applying RevMan5.4.1.Results A total of 5 RCTs and 2 quasi-experimental studies were in-cluded,involving 979 parturients with deliveries.The meta analysis showed that compared with the conven-tional nursing,CNP could shorten the duration of the first stage of labor(MD=—1.06,95％CI:—1.95——0.17,P=0.02)and the duration of the second stage of labor(MD=—0.12,95％CI:—0.21——0.03,P=0.006);decreased the rate of perineal lateral incision(RR=0.73,95％CI:0.65-0.83,P＜0.001)and inci-dence rate of postpartum urinary retention(RR=0.35,95％CI:0.20-0.63,P＜0.001);and shortened the time to lactation initiation(SMD=—1.52,95％CI:—2.38——0.66,P＜0.001).There was no influence on reducing postpartum 24 h hemorrhage amount(SMD=—0.51,95％CI:—1.23-0.21,P=0.16).The study subjects were divided into the primipara women subgroup and unclassified parturients subgroup.Compared with the conventional nursing group,compared with the conventional nursing,CNP had no impact on the dura-tion of the first stage of labor(MD=—0.32,95％CI:—0.61-0.98,P=0.63)and the duration of the second stage of labor(MD=—0.11,95％CI:—0.25-0.04,P=0.15)in the primipara women subgroup.CNP could reduce the postpartum 24 h hemorrhage volume in the unclassified parturients subgroup(SMD=—1.47,95％CI:—1.72——1.21,P＜0.001).Conclusion Application of CNP in parturients labor analgesia could reduce the perineal lateral incision rate and incidence rate of postpartum urinary retention and shorten the time to lac-tation initiation.Due to the heterogeneity among studies,the impact of CNP on the labor duration and the bleeding amount within postpartum 24 h still requires more high-quality studies to be conducted in the future for verification.

Objective:To investigate the differences in clinical outcomes of septic children with varying serum zinc levels,and to analyze the relationship between reduced serum zinc levels and organ dysfunction as well as 28-day mortality in septic children.Methods:This study conducted a retrospective analysis of clinical data from pediatric patients diagnosed with sepsis or septic shock in the Department of critical care medicine of the children's Hospital of Soochow University between January 2017 and December 2022.Clinical characteristics,organ dysfunction,and prognosis were compared between two groups:children with low serum zinc levels and those with normal zinc levels.Results:The serum zinc level of septic children within 24 hours of admission was 9.60(5.52,13.80)μmol/L,with 50.54%(94/186)of the children exhibiting low serum zinc levels(<10.07 μmol/L).Compared to the normal serum zinc group,the low serum zinc group had a significantly lower Pediatric Critical Illness Score(PCIS)[(78.71±9.35)vs.(85.12±8.51),P=0.005]and higher 28-day mortality(46.80%vs.14.13%,P<0.001).The low serum zinc group also had a higher proportion of invasive mechanical ventilation(64.89%vs.47.82%,P=0.019),renal replacement therapy(15.59%vs.3.26%,P=0.003),and use of vasoactive drugs(56.38%vs.30.43%,P<0.001).The rate of underlying conditions in the low serum zinc group was significantly higher than that in the normal serum zinc group(57.44%vs.36.95%,P=0.005).Additionally,the low serum zinc group had a higher incidence of disseminated intravascular coagulation(DIC),respiratory failure,acute kidney injury,shock,and multiple organ dysfunction syndrome(MODS)compared to the normal serum zinc group(P<0.05).Serum zinc levels had predictive value for 28-day mortality in septic children(AUC=0.813;95%CI:0.725～0.902;P<0.001).A serum zinc level of less than 6.950 μmol/L predicted the death of septic children with a sensitivity of 0.618 and a specificity of 0.902.Conclusion:Sepsis in children is commonly associated with low serum zinc levels,especially in those with underlying conditions such as hematologic and oncologic disorders.Sepsis patients hypozincemia with a higher incidence of DIC,respiratory failure,acute kidney injury,shock,and MODS.A serum zinc level below 6.95 μmol/L serves as a significant predictor of 28-day mortality in children with severe sepsis.

Objective:To investigate the efficacy of radiotherapy in patients with advanced esophageal cancer receiving first-line chemoimmunotherapy.Methods:A retrospective analysis was conducted on the data of 137 patients with Stage Ⅳ esophageal squamous cell carcinoma (ESCC) treated at our hospital from January 2018 to May 2023. These patients were divided into two groups: a group treated with first-line chemoimmunotherapy combined with radiotherapy (chemoimmunotherapy + radiotherapy group, n = 43) and a group treated with only chemoimmunotherapy ( n = 94). Inverse probability of treatment weighting (IPTW) was applied to balance baseline characteristics between the groups. With overall survival (OS) and progression-free survival (PFS) as study endpoints, the survival data were analyzed using the Kaplan-Meier method, the log-rank test, and the Cox regression method. Results:Before calibration, the chemoimmunotherapy + radiotherapy group significantly outperformed the sole chemoimmunotherapy group in median PFS (13.6 months vs. 7.0 months; HR: 0.501, 95% CI: 0.309-0.811, P = 0.005). After calibration using the COX proportional-hazards model for age, gender, Eastern Cooperative Oncology Group (ECOG) performance status, smoking history, T/N/M stage, and tumor location, the chemoimmunotherapy + radiotherapy group still had significant advantages in PFS (14.7 months vs. 7.0 months; HR: 0.441, 95% CI: 0.261-0.745, P = 0.002). IPTW analysis further confirmed this trend (13.9 months vs. 7.0 months; HR: 0.492, 95% CI: 0.304-0.795, P < 0.001). Specifically, the median OS of the chemoimmunotherapy + radiotherapy group demonstrated significant improvement in all analyses: pre-calibration (29.5 months vs. 18.0 months; HR: 0.507, 95% CI: 0.297-0.867, P = 0.013), after calibration using the Cox model (27.5 months vs. 16.7 months; HR: 0.470, 95% CI: 0.266-0.830, P = 0.009), and after calibration using IPTW (29.5 months vs. 16.9 months; HR: 0.448, 95% CI: 0.262-0.764, P < 0.001). Conclusions:The combination of radiotherapy and first-line chemoimmunotherapy can significantly improve survival outcomes of patients with advanced ESCC, suggesting its potential as a standard treatment strategy.

Background and Aims:Laparoscopic pancreaticoduodenectomy(LPD)has become a preferred approach for periampullary tumors,yet delayed gastric emptying(DGE)remains a frequent complication that hampers postoperative recovery.The nasojejunal feeding tube(NJT)is commonly used for early enteral nutrition,but its impact on DGE is controversial.This study aimed to evaluate whether intraoperative NJT placement increases the risk of DGE after LPD and to assess its influence on postoperative recovery outcomes.Methods:A retrospective cohort of 319 patients who underwent LPD at Provincial Hospital Affiliated to Shandong First Medical University from April 2017 to November 2023 was analyzed.Patients were divided into two groups based on intraoperative NJT placement(NJT group,n=200;non-NJT group,n=119).The incidence of DGE and postoperative outcomes were compared.Multivariate logistic regression and propensity score matching(PSM)were performed to identify independent risk factors for DGE.Results:The incidence of grade B/C DGE was significantly higher in the NJT group than in the non-NJT group(36.5%vs.21.8%,P=0.006).NJT placement was associated with longer postoperative hospital stay and higher hospitalization costs(both P<0.05).Multivariate analysis revealed intraoperative NJT placement(OR=1.960,95%CI=1.142-3.363,P=0.015)and intraoperative blood loss>400 mL(OR=1.921,95%CI=1.155-3.194,P=0.012)as independent risk factors for DGE.These findings were consistent after PSM.Conclusions:Prophylactic intraoperative NJT placement confers no additional benefit for postoperative recovery after LPD and is associated with a higher risk of DGE,prolonged hospitalization,and increased medical costs.Routine NJT placement should therefore be avoided,and individualized strategies should be adopted to minimize postoperative complications and enhance recovery.

Myasthenia gravis(MG)is an autoimmune disease characterized primarily by skeletal muscle weakness and,in severe cases,respiratory involvement.Western medical treatment predominantly relies on immunosuppressants,but long-term administration often leads to notable side effects.In contrast,traditional Chinese medicine(TCM)offers the advantage of multi-target interventions.However,the pathogenesis of MG has not been fully elucidated,and the establishment of animal models that accurately reflect the clinical characteristics of both Chinese and Western medicine is essential for mechanism research and new drug development.This paper systematically reviews the etiology and pathogenesis,diagnostic criteria,and progress of animal model research for MG from both Chinese and Western medicine perspectives.In Western medicine,the pathogenesis of MG is closely related to genetic susceptibility,environmental factors,and autoantibody-mediated postsynaptic membrane damage.In TCM,MG is classified under the category of"flaccidity syndrome",attributed to congenital deficiencies and acquired malnourishment.Western diagnostic criteria involve a combination of clinical symptoms,fatigue testing,serum antibody assays,and electrophysiological evaluation.In contrast,TCM diagnosis emphasizes the integration of primary and secondary symptoms with tongue and pulse pattern differentiation.Currently available animal models mainly include experimental autoimmune myasthenia gravis(EAMG)and passive transfer myasthenia gravis(PTMG).The Toredo acetylcholine receptor(AChR)induced EAMG model aligns well with Western diagnostic criteria,but poorly matches secondary symptoms in TCM.The synthetic AChR peptide model is widely used,but shows low conformity with TCM syndromes.Models induced by muscle-specific tyrosine kinase(MuSK),low-density lipoprotein receptor-related protein 4(LRP4),and transgenic models demonstrate high innovation but exhibit low clinical conformity.Evaluation of these models requires integration of behavioral,electrophysiological,and immunological indicators.However,a systematic framework for modelling TCM syndromes is still lacking.Future research should integrate TCM-based etiological modelling methods with the Western pathological mechanisms to construct disease-syndrome combination models.Additionally,it is crucial to establish a TCM syndrome evaluation system based on"validation by prescription",as well as to improve the scientific rigor and practicality of animal models by the incorporation of emerging technologies.This review provides a theoretical foundation for optimizing MG animal model design,advancing the research on the combination of Chinese and Western medicine,and supporting efficacy assessment and mechanism exploration of Chinese herbal prescriptions.

Background and Aims:Postoperative pancreatic fistula(POPF)is one of the most severe and common complications following pancreaticoduodenectomy(PD)and is a major cause of mortality after PD.Given the multiple risk factors associated with PD-POPF,developing an effective predictive model is of significant clinical importance.This study was conducted to explore the predictive performance of the triglyceride-glucose(TyG)index combined with serological indicators for POPF following PD.Methods:The preoperative general data,laboratory indicators within one week before surgery,and postoperative complication data of 291 patients who underwent PD at the Department of General Surgery,Second Hospital of Lanzhou University,from January 2019 to June 2024,were retrospectively collected.Patients were randomly divided into a modeling group(203 cases)and a validation group(88 cases)using a computer-generated random number method at a 7∶3 ratio.Univariate Logistic regression and multivariate binary Logistic regression(Back-Wald method)were performed on the modeling group data.Based on regression analysis results,a predictive model was constructed and visualized using a nomogram.The discriminative ability of the nomogram model was evaluated by the area under the receiver operating characteristic(ROC)curve(AUC).A calibration curve was used to assess the agreement between predicted and actual probabilities,and a decision curve analysis was conducted to evaluate the clinical application value of the model.Subgroup analysis was performed on potential factors influencing the outcome variables.Results:Among the 291 patients,70 developed POPF,with 49 cases in the modeling group and 21 in the validation group.There was no statistically significant difference between the two groups(all P>0.05).Univariate analysis in the modeling group identified body mass index(BMI),triglycerides,TyG index,albumin(ALB),platelet count(PLT),absolute lymphocyte count(LYM),and absolute neutrophil count(NEUT)as significant factors associated with POPF(all P<0.05).Multivariate analysis revealed that BMI,TyG index,ALB,PLT,LYM,and NEUT were independent influencing factors for POPF(all P<0.05).A PD-POPF risk prediction model and nomogram were constructed based on these results.The model achieved an AUC of 0.80(0.73-0.86),and when applied to the validation group,the ROC analysis yielded an AUC of 0.80(0.70-0.90).The calibration curves of both the modeling and validation groups closely aligned with the standard curve.Subgroup analysis indicated that tumor nature and tumor stage had minimal impact on PD-POPF risk factors,demonstrating good model stability.Conclusion:The TyG index,along with BMI,PLT,NEUT,ALB,and LYM,is closely associated with PD-POPF occurrence.The risk prediction model based on the TyG index and these influencing factors exhibits good predictive performance and holds significant clinical value for guiding early intervention.