1.A Mechanistic Framework of Exercise-induced Amelioration of Autism Spectrum Disorder via miR-132, miR-34a, and miR-146a
Xiao YANG ; Ya-Qi XUE ; Xin-Jian SHU ; Yan-Yan WANG ; Niu LIU
Progress in Biochemistry and Biophysics 2026;53(8):2210-2219
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.
2.Research progress on outdoor wet bulb globe temperature prediction models and their application to early warning for occupational heat stress
Xiaojun ZHANG ; Luyang WANG ; Xin SUI ; Xiaoshun WANG ; Tian LAN ; Yun ZHENG ; Dongsheng NIU ; Xiaowen DING
Journal of Environmental and Occupational Medicine 2026;43(8):1032-1038
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.
3.Low-level laser therapy for the treatment of male infertility and erectile dysfunction
Yuanjie NIU ; Zhongcheng XIN ; Guiting LIN ; Pan DING ; Jiancheng PAN ; Yuhong FENG ; Yinglu GUO
Journal of Peking University(Health Sciences) 2025;57(4):627-632
Low-level laser therapy(LLLT),a noninvasive photobiomodulation technique,employs red or near-infrared(NIR)light(600-1 000 nm)with power outputs ranging from 5 to 500 mW.It exerts therapeutic effects through molecular mechanisms,specifically the activation of cytochrome C oxidase(CCO)and the modulation of intracellular signaling pathways.By enhancing mitochondrial adenosine triphosphate(ATP)synthesis,LLLT mitigates oxidative stress,regulates the reactive oxygen species(ROS)/glutathione peroxidase(GSH-Px)/superoxide dismutase(SOD)axis,and activates key path-ways,including phosphatidylinositol 3-kinase/protein kinase B(PI3K/Akt)and mitogen-activated pro-tein kinase/extracellular signal-regulated kinase(MAPK/ERK).These mechanisms confer antioxidant,anti-inflammatory,and pro-regenerative properties to LLLT,making it a viable intervention for dermato-logical conditions,oncological therapies,and musculoskeletal disorders.Recent preclinical studies un-derscore LLLT's potential in male reproductive health.Specifically,it ameliorates cavernosal fibrosis and endothelial dysfunction in erectile dysfunction(ED)models by upregulating the PI3K/Akt and MAPK/ERK pathways.In the context of sperm biology,LLLT enhances motility and acrosomal integrity in both fresh and cryopreserved spermatozoa.This is achieved through mitochondrial metabolic reprogramming,such as CCO-mediated electron transport chain activation,redox homeostasis restoration,and epigenetic modulation involving DNA methylation and histone acetylation.Additionally,LLLT alleviates scrotal heat-induced oligospermia by promoting seminiferous epithelial differentiation,elevating serum testoster-one levels,and suppressing lipid peroxidation.These findings highlight the translational potential of LLLT in regenerative medicine,particularly for male sexual and reproductive disorders.Future research efforts should focus on interdisciplinary collaborations spanning life sciences,engineering,and physics.The goal is to optimize laser parameters,including wavelength,irradiance,and treatment duration,and establish standardized protocols.Rigorous preclinical and clinical investigations are paramount to validate the safety,efficacy,and long-term outcomes of LLLT,ultimately paving the way for its integration into precision medicine frameworks for urological and reproductive therapies.
4.Application of phased target teaching combined with case teaching method in neurosurgery intern nurses
Feng SUN ; Xin ZHANG ; Aihua NIU ; Dongmei LI ; Chao WANG ; Lijun LIANG
Chinese Journal of Modern Nursing 2025;31(9):1211-1215
Objective:To explore the application effect of phased target teaching combined with case teaching method in neurosurgery intern nurses.Methods:A convenient sampling method was used to select 96 intern nurses in the neurosurgery department of Shandong Provincial Hospital Affiliated to Shandong First Medical University from January 2022 to December 2023. The participants were divided into a control group and an observation group. The control group received conventional teaching, while the observation group was given phased target teaching combined with case teaching method based on the control group's curriculum. The clinical work ability, critical thinking ability, teaching performance, teaching satisfaction and cooperation of the intern nurses in both groups were compared.Results:After the intervention, the observation group scored higher in clinical work ability, critical thinking ability, teaching satisfaction and cooperation, teaching performance compared to the control group ( P<0.05) . Conclusions:The application of phased target teaching combined with case teaching method for neurosurgery intern nurses can improve their clinical work ability, critical thinking ability, academic performance, teaching satisfaction and cooperation. This method is worth recommending.
5.Survival advantage of first-line chemoimmunotherapy combined with radiotherapy for advanced esophageal squamous cell carcinoma: A propensity score matching analysis
Peixin FENG ; Qing HOU ; Ningning YAO ; Wenjuan ZHANG ; Bochen SUN ; Wenxia NIU ; Anqi ZHAO ; Wenlu CHEN ; Baixue WU ; Yuying ZHOU ; Yiwen ZHANG ; Yu LIANG ; Xin CAO ; Wei BAI ; Jianting LIU ; Shuangping ZHANG ; Jianzhong CAO
Chinese Journal of Radiological Medicine and Protection 2025;45(8):766-773
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.
6.Association between intraoperative nasojejunal tube placement and delayed gastric emptying after laparoscopic pancreaticoduodenectomy
Meng LIU ; Heng WANG ; Xiaohan KONG ; Faji YANG ; Zheyu NIU ; Yijie HAO ; Xin WANG ; Huaqiang ZHU ; Hengjun GAO ; Jun LU ; Xu ZHOU
Chinese Journal of General Surgery 2025;34(9):1934-1945
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.
7.Analysis of Animal Models of Myasthenia Gravis Based on Its Clinical Characteristics in Chinese and Western Medicine
Yuhan CHEN ; Jinling CHEN ; Xin LI ; Yanhua OU ; Si WANG ; Jingyi CHEN ; Xingyi WANG ; Jiali YUAN ; Yuanyuan DUAN ; Zhongshan YANG ; Haitao NIU
Laboratory Animal and Comparative Medicine 2025;45(2):176-186
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.
8.Predictive value of the triglyceride-glucose index combined with serological indicators for pancreatic fistula after pancreaticoduodenectomy
Jubao NIU ; Wenkai JIANG ; Cunbin LI ; Xin LI ; Hui ZHANG
Chinese Journal of General Surgery 2025;34(3):445-454
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.
9.Progress in the Study of the Chemical Composition and Biological Activity of Hypericum Attenuatum Choisy
Xiling FAN ; Wenjun LIU ; Xueni NIU ; Liang CAO ; Jinzhou TIAN ; Xin WANG ; Zhenzhong WANG ; Wei XIAO
World Science and Technology-Modernization of Traditional Chinese Medicine 2025;27(6):1578-1591
Hypericum attenuatum Choisy.is dry whole grass of the genus Hypericum L.,is a kind of commonly used folk medicinal herbs more than 2400 years.And it is often used to treat heart disease,hemostasis,scald.Based on a review of domestic and international literature,the main chemical components of Hypericum attenuatum Choisy.include PPAPs,flavonoids,and volatile oil,of which PPAPs and xanthone have received the attention of a large number of scholars because of their complex and novel structures and unique pharmacological effects.Modern pharmacological studies have shown that Hypericum attenuatum Choisy.exerts various pharmacological activities,including anti-arrhythmia,reducing blood sugar,anti-tumor,anti-virus,anti-inflammation,as well as the treatment of depression.As a valuable folk medicine,there is relatively little related traditional Chinese medicine products,this review focus on its phytochemistry,and pharmacology,providing a comprehensive perspective and novel ideas for exploring its current and potential applications.
10.Construction of A Mouse Model of Liver Cancer Resistant to PD-1 Monoclonal Antibody and Analysis of Its Metabolic Changes
Xin-ru NIU ; Xia WANG ; Zhi-ting SHU ; Zi-lan XU ; Xiao-li QIU ; Wei DAI ; Liang-qian ZHANG ; Xiang-liang DENG
Progress in Modern Biomedicine 2025;25(12):1931-1941,1954
Objective:To establish a mouse model of liver cancer resistant to PD-1 monoclonal antibody and analyze the changes in its metabolomics to explore the potential mechanism of drug resistance.Methods:BALB/c mice were randomly divided into control and treatment groups after being loaded with tumor,and a normal group was additionally set up.The normal and control groups were injected with saline,and the treatment group was injected with PD-1 monoclonal antibody,after which the mice in the treatment group were screened for drug resistant and response groups.Observed the drug-resistant situation,body mass,tumor growth and survival rate of mice in each group,calculate the spleen index.The pathological features of tumor tissues were observed by HE staining method.Serum metabolites were detected by non-targeted metabolomics.Finally,a bivariate Pearson correlation analysis was conducted between the differential serum metabolites and tumor size.Results:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established,and the drug resistance rate of the mice was 50%.Compared with the normal and response groups,mice in the resistant group showed an increase in body weight,a significant increase in tumor volume,a decrease in survival rate,and a significant increase in splenic index.There was less lymphocyte infiltration in the tumor tissue.Metabolomics analysis showed that the serum levels of glutamic acid and aspartic acid increased and malic acid decreased in the resistant mice compared with the response group,and these changes were closely related to the arginine biosynthesis pathway.Conclusions:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established.The changes in its peripheral serum metabolomics mainly involve arginine metabolism and the related changes of aspartate,malate and glutamate.

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