ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

ObjectiveTo clarify whether METTL14 mediates the core role of acupuncture at Neiguan (PC6) in promoting myelination and improving behavior in young autistic rats through gene intervention technology. MethodsThe ASD model was established by intraperitoneal injection of valproic acid (VPA) in pregnant rats. Male offspring were intracerebroventricularly injected with adenovirus-packaged METTL14 shRNA (sh-METTL14) or its control (sh-NC) on postnatal day 1, with a model group set as well. Subsequently, the juvenile rats were divided into model group, acupuncture group, acupuncture+sh-NC group, and acupuncture+sh-METTL14 group. The acupuncture group received acupuncture at Neiguan (PC6) from postnatal day 7, once daily for 21 consecutive days. Neurobehavioral changes were evaluated by behavioral tests; METTL14 knockdown efficiency and the expression of METTL14, METTL3, and PTEN were detected by quantitative real-time PCR (qRT-PCR) and Western blot (WB); PTEN m⁶A levels were measured by RNA immunoprecipitation-qPCR (RIP-qPCR); myelin ultrastructure, expression of myelin basic protein (MBP) and neurofascin 155 (NF155), and dendritic spine density were observed using transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), immunofluorescence, qRT-PCR, and primary neuron culture. ResultsBehaviorally, knockdown of METTL14 significantly counteracted the beneficial effects of acupuncture in improving self-grooming, open field exploration, three-chamber social interaction, and Morris water maze learning and memory (P<0.05, P<0.01). Compared with the acupuncture+sh-NC group, the acupuncture+sh-METTL14 group showed significantly decreased mRNA and protein expression of hippocampal METTL14 (P<0.01), and the upregulating effects of acupuncture on METTL3 and PTEN expression were reversed (P<0.01). Meanwhile, knockdown of METTL14 significantly inhibited the acupuncture-induced increase in PTEN m⁶A levels (P<0.01). Morphologically, knockdown of METTL14 attenuated the improvement of myelin structure by acupuncture, reversed the downregulation of MBP and upregulation of NF155 induced by acupuncture, and blocked the increase in dendritic spine density (P<0.05, P<0.01). ConclusionMETTL14 is a key molecule mediating the therapeutic effect of acupuncture at Neiguan. Acupuncture at Neiguan upregulates METTL14, thereby enhancing m⁶A methylation modification of PTEN mRNA to stabilize its expression, ultimately promoting myelin development and improving behavioral symptoms in ASD juvenile rats. This preliminarily reveals the modern biological connotation of “opening Xuanfu and dredging myelin”.

Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

Objective:To develop rat models of oral mucosa ulcer using distinct experimental methodologies,fulfilling research requirements and adhering to the ethical standards for animal care.Methods:96 SD rats were randomly allocated into groups.The rats in control group(n=8)were regularly fed without other treatment.Those in chemical cauterization groups were treated by 20％,40％,60％of glacial acetic acid(GAA)on oral mucosa(n=8);in mechanical damage groups by 30 000 r/min high speed drill induced trauma of 10,20 and 30 mm2 respectively(n=8);in ionizing radiation groups were treated with 10,12,15,20 and 30 Gy on the mucosa respectively(n=8).After the ulcer was appeared,the morphology of the mucosa were observed,the mucosal tissue lesions were examined by HE,Masson and immunofluorescence staining,the expression of TNF-α and IL-1β were detected by qPCR and ELISA respectively,and the body conditions such as diet and body weight of the rats were observed,the pain,dis-tress and discomfor of the rats were evaluated by MORTON&Griffits Guidelines.Results:40％and 60％GAA,20 mm2 and 30 mm2 friction damage and ionizing radiation of 12 Gy or greater may induce oral mucosa ulcer with a diseas coruse of 6-7 d in SD rats.TNF-α and IL-1β mRNA expression in the damaged tissue,the related protein expression in blood serum of the rats were in-creased.MORTON&Griffits Guidelines analysis showed 40％GAA,20 mm2 friction damage and 12 Gy ionizing radiation induced the lowest scores of pain,distress and discomfort of the rats with compatible oral mocosa ulcere induced by the relevat treatment.Conclusion:40％GAA,20 mm2 of friction damage and 12 Gy of ionizing radiation can reliably establish oral mucosa ulcer models and minimize adverse effects on SD rats,and accord with ethical standards of 3R for laboratory animal.

Objective To elucidate the mechanisms of trauma-induced coagulopathy(TIC),clarify the specific pathogenic factors and pathophysiological processes,and discover the effective diagnostic indicators and therapeutic targets.Methods Transcriptomic data of traumatic hemorrhagic shock patients were obtained from the Gene Expression Omnibus(GEO)to identify differentially expressed genes(DEGs).Coagulation-related genes(CRGs)from the Kyoto Encyclopedia of Genes and Genomes(KEGG)were intersected with DEGs.Machine learning algorithms,including least absolute shrinkage and selection operator(LASSO)and random forest(RF),were applied to identify key genes.The CIBERSORT algorithm was used to analyze the correlation between key genes and immune cell infiltration.Through consensus clustering,subtype analysis was conducted on trauma patients to compare the infiltration of immune cells.A rat model of traumatic hemorrhagic shock was established to validate coagulation function and the expression of key genes.Results The dataset included samples from 17 healthy controls and 478 patients with traumatic hemorrhagic shock.A total of 6 315 DEGs were identified under the screening criterion of corrected P<0.05.Gene set enrichment analysis(GSEA)showed that the up-regulated DEGs were significantly enriched in the glucose metabolism pathway,while the down-regulated DEGs were enriched in the immune reaction-related pathways.Through cross-analysis of DEGs and CRGs,a total of 65 differentially expressed coagulation-related genes(DE-CRGs)were screened out.GO functional enrichment showed that these genes were mainly located in secreting granular membranes and platelet α-granules,and were involved in physiological processes such as blood coagulation,regulation of body fluid levels,and wound healing.KEGG pathway analysis revealed that these genes were significantly enriched in pathways such as platelet activation,complement and coagulation cascade reactions,Rap1 signaling pathway,and human cytomegalovirus infection.Six key DE-CRGs were identified through machine learning.Receiver operating characteristic(ROC)curve analysis indicated that these genes had good diagnostic efficacy.CIBERSORT analysis revealed a significant correlation between key genes and immune cell infiltration.Patients were classified into two subtypes based on the six key genes:subtype A was rich in CD8+T cells and activated NK cells,presented an immune-active state;subtype B was mainly composed of monocytes and resting NK cells,with insufficient activation of immune pathways.Animal experiments on rats showed that hemorrhagic shock can lead to coagulation dysfunction.The results of qRT-PCR further confirmed that the expression trend of key genes was consistent with the results of bioinformatics analysis.Conclusion In this study,through transcriptomics and machine learning methods,six key genes closely related to TIC were systematically screened out,namely GNA13,PIK3R3,ITGAM,MAPK14,PPP1CC and LYN,and their close connections with coagulation function and immune infiltration were revealed.Animal experiments have further verified the value of these genes as potential diagnostic and therapeutic targets.

Objective To explore the predictive value of dose surface histogram(DSH)in image guided radiotherapy(IGRT)for radiotherapy-induced acute radiation proctitis(ARP)in cervical cancer(CCA).Methods Totally 380 patients with CCA IGRT admitted to some hospital from May 2019 to May 2023 were selected prospectively and randomly divided into a control group(n=1 80)and an experimental group(n=200).The patients in the 2 groups were followed up and the incidence rates of ARP were counted,and rectal dose distribution was evaluated using dose volume histogram(DVH)in the control group and DSH in the experimental group.The predictive values of DVH and DSH for ARP were evaluated and compared using ROC curves.Statistical analysis was performed using SPSS 21.0 software.Results The two groups did not have statistically significant difference in the incidence rate of ARP(P＞0.05),while there were significant differences in the evaluation indicators of the rectal dose distribution(P＜0.05).V40,V50,S40 and S50 proved to have low predictive values for grade Ⅰ-Ⅳ ARP with AUC 0.700(P＜0.05);V60 and S60 had moderate predictive values for grade Ⅰ-Ⅳ ARP with AUC greater than 0.700 and less than or equal to 0.900(P＜0.05);V70,V78,S70 and S7s showed high predictive values for grade Ⅰ-Ⅳ ARP with AUC higher than 0.900(P＜0.05).Delong's test results indicated that DVH and DSH had no significant differences in AUC when used to predict gradeⅠ-Ⅳ ARP(allP＞0.05).Conclusion DSH is essentially the same as DVH when used for the prediction of grade Ⅰ-Ⅳ ARP due to CCA IGRT,and thus can be used for the supplementation and optimization of radiotherapy planning systems.[Chinese Medical Equipment Journal,2025,46(3):48-53]

Objective To elucidate the mechanisms of trauma-induced coagulopathy(TIC),clarify the specific pathogenic factors and pathophysiological processes,and discover the effective diagnostic indicators and therapeutic targets.Methods Transcriptomic data of traumatic hemorrhagic shock patients were obtained from the Gene Expression Omnibus(GEO)to identify differentially expressed genes(DEGs).Coagulation-related genes(CRGs)from the Kyoto Encyclopedia of Genes and Genomes(KEGG)were intersected with DEGs.Machine learning algorithms,including least absolute shrinkage and selection operator(LASSO)and random forest(RF),were applied to identify key genes.The CIBERSORT algorithm was used to analyze the correlation between key genes and immune cell infiltration.Through consensus clustering,subtype analysis was conducted on trauma patients to compare the infiltration of immune cells.A rat model of traumatic hemorrhagic shock was established to validate coagulation function and the expression of key genes.Results The dataset included samples from 17 healthy controls and 478 patients with traumatic hemorrhagic shock.A total of 6 315 DEGs were identified under the screening criterion of corrected P<0.05.Gene set enrichment analysis(GSEA)showed that the up-regulated DEGs were significantly enriched in the glucose metabolism pathway,while the down-regulated DEGs were enriched in the immune reaction-related pathways.Through cross-analysis of DEGs and CRGs,a total of 65 differentially expressed coagulation-related genes(DE-CRGs)were screened out.GO functional enrichment showed that these genes were mainly located in secreting granular membranes and platelet α-granules,and were involved in physiological processes such as blood coagulation,regulation of body fluid levels,and wound healing.KEGG pathway analysis revealed that these genes were significantly enriched in pathways such as platelet activation,complement and coagulation cascade reactions,Rap1 signaling pathway,and human cytomegalovirus infection.Six key DE-CRGs were identified through machine learning.Receiver operating characteristic(ROC)curve analysis indicated that these genes had good diagnostic efficacy.CIBERSORT analysis revealed a significant correlation between key genes and immune cell infiltration.Patients were classified into two subtypes based on the six key genes:subtype A was rich in CD8+T cells and activated NK cells,presented an immune-active state;subtype B was mainly composed of monocytes and resting NK cells,with insufficient activation of immune pathways.Animal experiments on rats showed that hemorrhagic shock can lead to coagulation dysfunction.The results of qRT-PCR further confirmed that the expression trend of key genes was consistent with the results of bioinformatics analysis.Conclusion In this study,through transcriptomics and machine learning methods,six key genes closely related to TIC were systematically screened out,namely GNA13,PIK3R3,ITGAM,MAPK14,PPP1CC and LYN,and their close connections with coagulation function and immune infiltration were revealed.Animal experiments have further verified the value of these genes as potential diagnostic and therapeutic targets.

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome