Genetically modified pigs for welfare assurance is crucial for conducting xenotransplantation. However, traditional experimental animal ethics principles cannot address the social benefits issues brought about by xenotransplantation, and there is a lack of ethical justification for the assurance of experimental animal welfare. Degrazia and Bechtel proposed six principles for the welfare of experimental animals: the principle of no alternative methods, the principle of expected net benefits, the principle of adequate defense of harm, the principle of no harm without necessity, the principle of basic needs and the principle of harm limit. This paper conducts an ethical-level argumentation on the six principles for the welfare of genetically modified pigs in xenotransplantation, and points out that these six principles are of great significance in closely integrating the social benefits of xenotransplantation with the welfare of genetically modified pigs, emphasizing the moral status of genetically modified pigs, and providing standards for the ethical review of the welfare of genetically modified pigs.

This paper summarizes Professor ZHAO Jiping's acupuncture diagnostic and therapeutic approach for tic disorders (TD). Focusing on the pathological characteristics of tic disorder (TD), this study analyzes TD's multilayered disease localization. Based on disease-based differentiation, it is proposed that the fundamental pathological location lie in the liver and brain, while the manifestation is in the sinew meridians. The core pathogenesis is characterized as "internal stirring of wind due to liver hyperactivity, upward disturbance of the mind in the brain, and external disharmony of the sinews", based on which the fundamental therapeutic principles are established as calming the liver and extinguishing wind, tranquilizing the mind and awakening the brain, and dredging and regulating the sinews. In clinical practice, attention is paid to meridian and acupoint examination, integrating the four diagnostic methods to assess the deficiency or excess of the liver, the state of the mind, and the condition of the sinews. Acupoint selection emphasizes three regulatory strategies: (1) liver regulation: Taichong (LR3), Hegu (LI4) are selected to soothe the liver and regulate qi; (2) brain regulation: Baihui (GV20), Shenting (GV24), Yintang (GV24⁺), Fengchi (GB20) are selected to calm the mind and stabilize the spirit; (3) sinew regulation: Yanglingquan (GB34), Zusanli (ST36), Quchi (LI11) are selected to regulate qi and blood and relax the sinews. Manipulation techniques, as well as various acupuncture and moxibustion methods, are also emphasized. A differential treatment framework of "layered disease localization-corresponding pathogenesis-precise acupoint selection and technique" has been established to provide a clinical guide for the diagnosis and treatment of TD.
Humans ; Acupuncture Therapy/history* ; Tic Disorders/diagnosis* ; Acupuncture Points ; Meridians ; Diagnosis, Differential ; China

OBJECTIVES: Esophageal squamous cell carcinoma (ESCC) is characterized by complex pathogenesis and poor prognosis. In recent years, epithelial-mesenchymal transition (EMT) in tumor initiation and progression has attracted increasing attention. Enhancer of zeste homolog 2 (EZH2), which is aberrantly expressed in various tumors, may be closely related to the EMT process. This study aims to examine the expression and correlation of EZH2 and EMT markers in ESCC cells and tissues, evaluate the effects of EZH2 knockdown on ESCC cell proliferation, invasion, and migration, and explore how EZH2 contributes to the malignant biological behavior of ESCC. METHODS: Bioinformatics analyses were used to assess EZH2 expression levels in ESCC. Small interfering RNA was used to knock down EZH2 in ESCC cell lines EC109 and EC9706. Cell proliferation, invasion, and migration were evaluated using cell counting kit-8 (CCK-8), wound healing, and Transwell assays. Protein and mRNA expression levels of EZH2, E-cadherin (E-cad), and vimentin (Vim) were detected by Western blotting and real time fluorogenic quantitative PCR (RT-qPCR), respectively. Immunohistochemical (IHC) staining was performed on 70 ESCC tissue samples and 40 paired adjacent normal tissues collected from the First Affiliated Hospital of Shihezi University between 2010 and 2016 to assess the expression of EZH2, E-cad, and Vim, and to analyze their associations with clinicopathological feature and patient prognosis. RESULTS: Bioinformatics analysis showed that EZH2 was highly expressed in ESCC (P<0.001), and high EZH2 expression was associated with worse prognosis (P<0.001). CCK-8, wound healing, and Transwell assays demonstrated that EZH2 knockdown significantly suppressed the proliferation, invasion, and migration of ESCC cells (P<0.001). In addition, Vim expression was significantly reduced, while E-cad expression was significantly increased at both protein and mRNA levels in EZH2-silenced cells (all P<0.05). IHC staining analysis revealed higher expression of EZH2 and Vim and lower expression of E-cad in ESCC tissues compared to adjacent normal tissues. Kaplan-Meier survival analysis showed that low expression of EZH2 and Vim and high expression of E-cad were associated with longer survival (all P<0.05). CONCLUSIONS EZH2 promotes malignant biological behavior in ESCC by mediating EMT. Elevated EZH2 expression is associated with poor prognosis in ESCC patients.
Humans ; Enhancer of Zeste Homolog 2 Protein/physiology* ; Esophageal Squamous Cell Carcinoma/pathology* ; Epithelial-Mesenchymal Transition/genetics* ; Esophageal Neoplasms/metabolism* ; Cell Proliferation ; Cell Line, Tumor ; Cell Movement ; Cadherins/genetics* ; Vimentin/genetics* ; Male ; Female ; Middle Aged ; Neoplasm Invasiveness ; Prognosis ; RNA, Small Interfering/genetics* ; Gene Expression Regulation, Neoplastic

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*

Objective:To analyze the epidemiological and clinical features of infectious diseases of the central nervous system (CNS).Methods:A cross-sectional study and analysis were conducted to summarize the epidemiological and clinical characteristics of 9 918 patients with CNS infectious diseases, who were diagnosed and treated at 29 hospitals across China from January 1, 2001 to December 31, 2020. Data collected included demographic data, clinical manifestations, health economic indicators, and prognostic outcomes.Results:Among the 9 918 collected cases of CNS infectious diseases, 5 559 were male (56.0%) and 4 359 were female (44.0%), with an onset age of 38 (25, 53) years. Education level: slightly more junior high school education (2 651 cases, 26.7%), and less elementary school education and below (2 181 cases, 22.0%) were found. Occupational distribution: farmers were found predominant (3 215 cases, 32.4%), followed by workers (1 826 cases, 18.4%) and students (1 633 cases, 16.5%). Clinical manifestations: headache (6 074 cases, 61.2%), fever (5 869 cases, 59.2%) and positive meningeal irritation signs (2 273 cases, 22.9%) were the 3 most common clinical manifestations, followed by nausea and (or) vomiting (2 095 cases, 21.1%), impaired consciousness (2 077 cases, 20.9%), psychiatric symptom (1 866 cases, 18.8%) and epilepsy (1 627 cases, 16.4%), etc., and cranial nerve involvement was found in 669 cases (6.7%). Major pathogens included viruses in 6 814 cases (68.7%), Mycobacterium tuberculosis in 1 677 cases (16.9%), common bacteria in 864 cases (8.7%), fungi in 254 cases (2.6%), spirochetes of syphilis in 183 cases (1.8%), parasites in 121 cases (1.2%), and rickettsiae in 5 cases (0.1%). Urban-rural distribution: slightly more cases were found in the countryside (5 418 cases, 54.6%) than in the towns (4 500 cases, 45.4%). Distribution of onset by season: 2 412 cases (24.3%) fell ill in spring, 2 835 cases (28.6%) in summer, 2 187 cases (22.1%) in fall, and 2 484 cases (25.0%) in winter. Health economics: the duration of hospitalization was 15 (8, 27) days, and the cost of hospitalization was 1.53 (0.91, 3.02)×10 000 yuan. Prognosis: 9 531 cases (96.1%) were cured or improved, and 92 cases (0.9%) died. Conclusions:The pathogens responsible for CNS infectious diseases are predominantly viruses. Although the incidence is slightly higher during the summer months, the overall seasonal pattern is not particularly pronounced. These infections are more commonly observed in young and middle-aged males and present with a diverse range of clinical manifestations, contributing to a significant disease burden.

Objective:To investigate the differences in clinical and imaging characteristics of patients with recent small subcortical infarct (RSSI) stratified by different etiological subtypes.Methods:A retrospective, consecutive analysis was conducted on 696 RSSI patients admitted to the West China Hospital, Sichuan University, from January 2019 to May 2024. Based on clinical and imaging data, patients were stratified into 3 etiological subgroups: presumed cerebral small vessel disease (CSVD)-related RSSI, coexisting carrier large artery stenosis, and coexisting proximal extracranial/intracranial large artery stenosis. The clinical characteristics, vascular risk factors, infarct imaging features, and CSVD markers were compared across the 3 groups. Additionally, the differences in clinical and imaging features based on the location of infarcts (anterior vs posterior circulation) and infarct size (<15 mm vs ≥15 mm) were examined. Results:Among the 696 patients, 557 (80.0%) had presumed CSVD-related RSSI, 68 (9.8%) had coexisting carrier large artery stenosis, and 71 (10.2%) had coexisting proximal extracranial/intracranial large artery stenosis. The patients with presumed CSVD-related RSSI were the youngest [60 (53, 69) years], followed by those with coexisting carrier large artery stenosis [64 (55, 69) years] and those with coexisting proximal extracranial/intracranial large artery stenosis [69 (55, 75) years; H=9.523, P=0.013]. Among RSSI patients with coexisting proximal extracranial/intracranial large artery stenosis, the proportion of those with diabetes (38/71, 53.5%) was the highest, whereas the proportion was 210/557 (37.7%) in the presumed CSVD-related group and 31/68 (45.6%) in the group with coexisting carrier large artery stenosis (χ 2=8.027, P=0.023). Patients with RSSI combined with proximal extracranial/intracranial large artery stenosis had more infarction sites in the pons and a higher proportion of proximal infarction. However, there were no significant differences among the 3 groups in terms of infarct size, or CSVD imaging markers. In the anterior versus posterior circulation comparison, patients with posterior circulation RSSI ( n=360) had a significantly higher age of onset [63(55, 72) years vs 60(52, 59) years, U=51 335.500, P<0.001], had higher prevalence of hypertension and diabetes, and showed higher NIHSS scores [3(2, 6) vs 3(1, 5), U=57 840.500, P=0.028]. The anterior circulation group ( n=366) showed a higher proportion of lacunas [152/336 (45.2%) vs 118/360 (32.8%), χ2=11.364, P<0.001], while the posterior circulation group had a greater prevalence of severe perivascular spaces in the basal ganglia [254/360 (70.6%) vs 203/336 (60.4%), χ2=7.879, P=0.005] and deep white matter hyperintensities grading≥2 [124/360 (34.4%) vs 90/336 (26.8%), χ2=4.787, P=0.029]. There were no statistically significant differences in the distribution of infarcts between anterior and posterior circulations or in CSVD imaging markers between RSSI patients with infarction lesions ≥15 mm ( n=290) and <15 mm ( n=406). Conclusions:Approximately 20% of RSSI cases are related to large artery stenosis. These patients tend to be older at onset and have a higher prevalence of diabetes. Compared to presumed CSVD-related RSSI cases, RSSI cases related to large artery stenosis show no significant differences in infarct imaging features and CSVD imaging markers, suggesting that large artery stenosis in RSSI may be an epiphenomenon rather than a direct causative factor.

Objective To explore the distribution of common TCM syndromes and symptoms of insomnia;To prepare for the construction of the theoretical framework and item pool of syndrome diagnosis and efficacy evaluation scale.Methods TCM guideline standards of insomnia,textbooks and journals over the years were retrieved,the information of TCM syndromes,syndrome elements and symptoms was extracted,the guideline textbook and journal database were established,and descriptive statistics,association rules,systematic clustering,factor analysis,potential categories and implicit structure analysis were carried out.Results Totally 116 guide standards and textbooks over the years were included,and 454 articles of journals were included.The high-frequency symptoms accounted for≥3%of the guide textbooks and journal databases were 87 and 79 categories,respectively,and the cumulative proportion was 87.48%and 87.75%,respectively.According to the analysis results,five common TCM syndromes and their characteristic symptom classification of insomnia were finally deduced.According to the frequency/person time distribution,they were heart and spleen deficiency syndrome,yin deficiency and fire hyperactivity syndrome,liver fire disturbing heart syndrome,phlegm heat disturbing heart syndrome,heart and gallbladder qi deficiency syndrome.Conclusion There are five common TCM syndromes of insomnia,and the characteristic symptoms of each TCM syndrome provide a reference source for the theoretical framework of syndrome diagnosis and efficacy evaluation scale and the establishment of item pool.

Objective To explore the effect of microRNA-381-3p(miR-381-3p)/MuRF1 axis on cardiopulmonary injury in hypoxia-induced pulmonary hypertension(HPH)mice and its potential mechanisms.Methods Sixty mice were randomly assigned to four groups:the normal control group(NC),the hypobaric hypoxia-induced pulmonary hypertension(HPH)group,the HPH+agomir control group and the HPH+miR-381-3p agomir analog group(HPH+miR-381-3p agomir),with 15 mice in each group.The HPH mouse model was established using a low-pressure and hypoxic artificial chamber.Three weeks prior to the establishment of the HPH model,miR-381-3p agomir and its corresponding control agomir were prepared by dissolving them in RNA-free phosphate-buffered saline(PBS)according to the experimental requirements.These solutions were administered via tail vein injection at a dose of 10 mg/kg,twice weekly for three consecutive weeks.Right heart function was assessed using echocardiography.Right ventricular systolic pressure(RVSP)was measured via cardiac catheterization.Pulmonary vascular remodeling was evaluated through hematoxylin and eosin(HE)staining.Levels of inflammatory cytokines in bronchoalveolar lavage fluid were quantified using enzyme-linked immunosorbent assay(ELISA).Real-time quantitative fluorescent PCR(RT-qPCR)was employed to analyze the mRNA expression levels of miR-381-3p and MuRF1.Potential targets of miR-381-3p were predicted,and pathway enrichment analysis was conducted.A dual-luciferase reporter gene assay was performed to confirm the direct regulatory effect of miR-381-3p on MuRF1.Results Compared with the NC group,the mRNA expression of miR-381-3p was significantly decreased in both the HPH group and the HPH+agomir control group,whereas the mRNA expression of MuRF1 was significantly increased(P＜0.05).In contrast,compared with the HPH group and the HPH+agomir control group,the mRNA expression of miR-381-3p was significantly increased in the HPH+miR-381-3p agomir group,while the mRNA expression of MuRF1 was significantly decreased(P＜0.05).Additionally,compared with the NC group,RVSP,right ventricular anterior wall thickness(RVAW),right ventricular hypertrophy index(RVHI),right ventricular collagen volume fraction(CVF),distal pulmonary artery wall thickness ratio(WT),pulmonary artery wall area ratio(WA),as well as IL-1β,IL-6 and TNF-α levels in alveolar lavage fluid were significantly increased in the HPH group and the HPH+agomir control group,whereas the right ventricular diameter(RVID)was significantly decreased(P＜0.05).Conversely,compared with the HPH group and the HPH+agomir control group,RVSP,RVAW,RVHI,right ventricular CVF,WT,Wa and RVID were decreased in the HPH+miR-381-3p agomir group,and IL-1β,IL-6,and TNF-α levels of alveolar lavage fluid were significantly decreased(P＜0.05).Furthermore,the downstream target genes of miR-381-3p were predicted in the database,and MuRF1 was a potential target,and the Cytoskeleton in muscle cells ranked first in the significant enrichment of target genes.Compared with WT-MuRF1+mimic control group,the luciferase activity was decreased in the WT-MuRF1+miR-381-3p mimic group(P＜0.05).There was no significant difference in the luciferase activity between the Mut-MuRF1+mimic control group and the Mut-MuRF1+miR-381-3p mimic group.Conclusion Overexpression of miR-381-3p can improve cardiopulmonary injury in HPH mice,and the mechanism may be related to the targeted inhibition of MuRF1 by miR-381-3p.

The MGF300-4L protein of African swine fever virus(ASFV),a virulence-associated fac-tor,degrades IKKβ through the chaperone-mediated autophagy and enhances the stability of IKBαto suppress the generation of IL-1β and TNF-α regulated by the NF-κB signaling pathway.To iden-tify the host proteins interacting with MGF300-4L,PK-15 cells were transfected with the eukary-otic plasmid expressing MGF300-4L and analyzed using immunoprecipitation-mass spectrometry(IP-MS)to identify the host proteins that interact with MGF300-4L.Additionally,gene ontology(GO)and KEGG pathway enrichment analyses were conducted.Furthermore,molecular docking a-nalysis,co-immunoprecipitation,and laser confocal microscopy assays were performed to validate the host proteins interacting with MGF300-4L.The IP-MS analysis identified 145 host proteins that potentially interact with MGF300-4L.Subsequent GO and KEGG pathway enrichment analy-ses revealed that these proteins are predominantly involved in metabolic,cellular,and innate immune responses.Through molecular docking prediction,co-immunoprecipitation assay,and laser confocal microscopy,we identified the interaction between MGF300-4L and STAT1.This study provides critical insights into the mechanisms underlying the interactions between MGF300-4L and the host proteins.

AIM:To investigate the immunosuppressive effects of M2-like tumor-associated macrophages(M2-TAMs)on CD8+T cells within the tumor microenvironment of esophageal cancer.METHODS:Multiplex fluores-cence immunohistochemistry was used to analyze the distribution of immune cells in esophageal cancer tissues.An in vitro co-culture system was established,and flow cytometry along with Calcein-AM/PI staining was employed to assess the im-pact of M2-TAMs on CD8+T cell function.The GEPIA database was utilized to evaluate the prognostic significance of PDCD1 expression in esophageal cancer patients and to analyze the correlations between gene expressions.Immunohisto-chemistry(IHC)was performed to detect the expression of TGF-β1 in esophageal cancer tissues.Flow cytometry and en-zyme-linked immunosorbent assay(ELISA)were used to measure PD-1,IFN-γ and TNF-α expression in CD8+T cells fol-lowing treatment with a TGF-β1 inhibitor.RESULTS:Compared with early-stage(stage I)esophageal cancer patients,the patients with advanced disease(stages Ⅱ to Ⅳ)exhibited dynamic changes in the infiltration of CD4+T cells,CD8+T cells,Tregs,and M2-TAMs within tumor tissues,with significant correlations observed among these cell populations(P<0.05).The distribution of M2-TAMs and Tregs was positively correlated with poor prognosis(P<0.05),while that of CD8+T cells was negatively correlated(P<0.05).In contrast,CD4+T cell infiltration showed no significant association with clinical outcomes(P>0.05).Co-culture of CD8+T cells with M2-TAMs resulted in significant downregulation of CD107a,granzyme B,IFN-γ and TNF-α expression(P<0.01).Additionally,M2-TAM-treated CD8+T cells co-cultured with esophageal cancer cells led to reduced apoptosis of cancer cells.High expression of PDCD1 was significantly associated with poor prognosis(P<0.05),and significant correlations were observed between CD8A and PDCD1 expression,as well as between TGF-β1 and CD274 gene expression(P<0.01).TGF-β1 was also significantly associated with CD163+macro-phage infiltration and the progression of esophageal cancer(P<0.05).Treatment with a TGF-β1 inhibitor in the M2-TAM and CD8+T cell co-culture system significantly down-regulated PD-1 expression and increased the secretion of IFN-γ and TNF-α(P<0.01).CONCLUSION:The TGF-β1 derived from M2-TAMs inhibits the antitumor activity of CD8+T cells in the esophageal cancer microenvironment,suggesting potential therapeutic targets for overcoming immunosuppression in esophageal cancer.