ObjectiveTo investigate the mechanism of Yangxin Tongmai Formula （养心通脉方， YTF） in trea-ting coronary heart disease with blood stasis syndrome based on DNA methylation. MethodsSeventy-two SD rats were randomly divided into a control group （n=12） and a modeling group （n=60）. The modeling group was subjected to a high-fat diet， intragastric administration of vitamin D3， and subcutaneous injection of isoprenaline to establish the rat model of coronary heart disease with blood stasis syndrome. Forty-one successfully modeled rats were then randomly allocated into model group， YTF low-， medium-， and high-dose groups， and the atorvastatin calcium group， with 8 rats in each group and 1 rat reserved. The YTF low-， medium-， and high-dose groups received YTF at 6， 12， and 18 g/（kg·d） by gavage， respectively. The atorvastatin calcium group received atorvastatin calcium tablets at 1.8 mg/（kg·d） by gavage. The control group and the model group received 0.9% sodium chloride injection at 4 ml/（kg·d） by gavage. All administrations were performed once daily for 3 weeks. Twenty-four hours after the last administration， serum lipid levels including total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C）， myocardial enzymes including cardiac troponin T （cTnT）， creatine kinase MB （CK-MB）， and lactate dehydrogenase （LDH）， and inflammatory factors including interleukin-1β （IL-1β） and interleukin-10 （IL-10） were detected by ELISA. Pathological changes in myocardial tissue were observed via HE staining. Whole blood DNA methylation sequencing was used to analyze differential methylation gene expression among the control group， model group， and YTF high-dose group. Western Blotting was used to verify the protein levels of the key genes and downstream signaling pathways. ResultsCompared to the control group， the model group showed increased levels of TC， TG， LDL-C， cTnT， CK-MB， LDH， and IL-1β， along with decreased levels of HDL-C and IL-10 （P＜0.05 or P＜0.01）. Compared to the model group， all treatment groups exhibited decreased levels of TC， LDL-C， CK-MB， and LDH， along with increased IL-10 levels. Among these， the high-dose YTF group demonstrated superior efficacy in reducing cTnT levels compared to the other TCM groups （P＜0.05 or P＜0.01）. HE staining indicated that the YTF high-dose group ameliorated myocardial cell swelling， disordered arrangement， pyknosis， and disappearance of nuclei， thereby reducing myocardial cell damage. Whole blood DNA methylation sequencing identified 240 differentially methylated genes shared by the control group， model group， and YTF high-dose group， including 109 hypermethylated and 131 hypomethylated genes； eif2ak3 was identified as a key differentially methylated gene. Compared to the control group， the model group exhibited increased protein levels of eukaryotic translation initiation factor 2 alpha kinase 3 （eIf2ak3）， phosphorylated protein kinase RNA-like endoplasmic reticulum kinase （p-PERK）， activating transcription factor 4 （ATF4）， C/EBP homologous protein （CHOP）， and Bax， along with a decreased level of B-cell lymphoma-2 （Bcl-2） protein （P＜0.05 or P＜0.01）. Compared to the model group， the YTF high-dose group showed decreased protein levels of eIf2ak3， p-PERK， ATF4， CHOP， and Bax， and an increased level of Bcl-2 protein （P＜0.05 or P＜0.01）. ConclusionYTF may regulate key differentially methylated genes such as eIf2ak3 and the PERK/ATF4/CHOP signaling pathway， thereby inhibiting endoplasmic reticulum stress， reducing myocardial cell apoptosis， and exerting therapeutic effects in coronary heart disease blood stasis syndrome.

OBJECTIVE: To investigate the current status of clinical genetics specialization development and the diagnostic and therapeutic capabilities for hereditary diseases across medical institutions in Shanghai, and to assess the necessity and feasibility of establishing training bases for clinical genetics specialists. METHODS: By employing a cross-sectional survey design, the Clinical Genetics Committee of Shanghai Medical Association has conducted questionnaire surveys from March to April 2025 across 54 healthcare institutions in Shanghai (including 33 tertiary hospitals and 21 secondary hospitals). The survey involved administrative departments and medical personnel from 15 clinical specialties. The survey has covered current genetic disease diagnosis and treatment practices, relevant and specialised disease types, genetic department establishment, testing capabilities, personnel teams, and training requirements. RESULTS: The results revealed that 78.0% of clinical departments surveyed had treated patients with hereditary disorders. Shanghai possesses diagnostic and therapeutic expertise for over 95% of hereditary diseases listed in its rare disease catalogue, reflecting both the practical clinical demand for such conditions and the city's overall diagnostic and therapeutic strengths in this field. Nevertheless, significant disparities exist in the development of genetics departments across different tiers of healthcare institutions. Resources for genetic testing capabilities (including molecular, cellular, and biochemical testing) are also unevenly distributed across different tiers of hospitals. The survey further revealed that only 26.0% of departments believe that their current physician structure fully meets the diagnostic and treatment demands. Over 90% of departments consider standard training for clinical genetic specialists necessary, with 74.0% expressing willingness to participate in establishing training bases. Based on above findings and thorough deliberation, the Clinical Genetics Committee of the Shanghai Medical Association proposes advancing specialist training and discipline development through establishing a standard training system. The committee has drafted a three-year training protocol featuring a "joint training"-centered model, recommending a pilot-first, dynamically optimized strategy for steadily advancing training base development. CONCLUSION Shanghai faces substantial demand for genetic disease diagnosis and treatment, yet exhibits shortcomings in clinical genetics specialization development, resource allocation, and talent pipeline cultivation. To establish a standard training system holds significant practical importance and is underpinned by a broad demand.
Humans ; China ; Surveys and Questionnaires ; Genetic Diseases, Inborn/genetics* ; Cross-Sectional Studies ; Genetics, Medical/education* ; Genetic Testing

Objective To conduct a comprehensive review of the risk factors for post-transplant pulmonary infection in kidney transplant recipients. Methods Following the methodology guidelines for systematic reviews, the research question was clearly defined. Systematic searches were conducted in both Chinese and English literature databases, with the search period ranging from the establishment of the database to May 1, 2025. Two researchers independently screened and extracted the risk factors related to post-transplant pulmonary infection in kidney transplant recipients, and the research results were qualitatively described. Results A total of 45 articles were finally included, involving 30 risk factors for post-transplant pulmonary infection in kidney transplant recipients, including five aspects as donor factors, recipient factors, disease factors, treatment factors and laboratory test result factors. Conclusions The occurrence of post-transplant pulmonary infection in kidney transplant recipients is related to donor factors, recipient factors, disease factors, treatment factors and laboratory test result factors, providing a reference for clinical prevention, screening, and intervention.

ObjectiveTo investigate the role of interleukin （IL）-17A in acute inhalational pneumonia induced by the highly drug-resistant and hypervirulent Staphylococcus aureus strain USA300-R in mice. MethodsAn acute inhalational pneumonia model was established in mice using an aerosolized pulmonary delivery technique. RNA sequencing （RNA-seq） and enzyme-linked immunosorbent assay （ELISA） were employed to examine the expression dynamics of Il17a mRNA and IL-17A protein， respectively， in the lungs of infected mice. Il17a knockout （Il17a^-/-） mice were generated using CRISPR/Cas9 gene editing technology. The survival rate， body weight， bacterial load in lung tissue， and histopathological changes were compared between Il17a^-/- and wild-type （WT） mice following inhalational infection with USA300-R. Results12 hours after USA300-R infection， compared to pre-infection， the expression level of Il17a mRNA in lung tissue and the level of IL-17A protein in bronchoalveolar lavage fluid （BALF） increased by approximately 50-fold （P<0.01） and 6-fold （P<0.001）， respectively. Compared to WT mice， Il17a^-/- mice exhibited approximately 10-fold higher bacterial loads in lung tissue at both 12 and 24 hours post-infection （P<0.001， P<0.05）. However， they showed significantly attenuated lung histopathological injury， reduced alveolar wall thickening， markedly decreased neutrophil infiltration， and an approximately 50% improvement in survival rate （P<0.05）. ConclusionIn acute Staphylococcus aureus USA300-R inhalational pneumonia， IL-17A contributes to bacterial clearance by recruiting neutrophils； however， excessive neutrophil infiltration exacerbates pulmonary inflammation and injury， reduces survival rates， and represents a potential therapeutic target.

ObjectiveTo determine whether Jinshui Huanxian component formula Ⅱ （ECC-JHF Ⅱ） and matrix hardness interfere with the process of epithelial-mesenchymal transition （EMT） during pulmonary fibrosis by regulating integrin β₁ （ITG β₁）， and to elucidate the underlying mechanism. MethodsA pulmonary fibrosis mouse model was established by a single intratracheal instillation of bleomycin （BLM）. To observe the disease progression at various time points， the mice were sacrificed before modeling and on days 7， 14， 21， 28 and 42 after modeling for assessment of relevant indicators. To evaluate the therapeutic effect of drug intervention， the mice were given ECC-JHF Ⅱ and pirfenidone （PFD） by gavage starting on day 29 after modeling for 14 days of treatment， after which the mice were sacrificed. Pulmonary function， pathological changes， collagen deposition， lung tissue hardness and EMT markers were detected. Polyethylene glycol （PEG） composite hydrogels with different hardness were prepared in vitro using biomaterials such as eight-arm polyethylene glycol thiol （PEG-SH） and eight-arm polyethylene glycol maleimide （PEG-MAL）. Human type Ⅱ alveolar epithelial cells cultured in hard matrix culture dishes were treated with low， medium， and high doses of ECC-JHF Ⅱ （15.31， 30.63， 61.25 mg·L^-1） to observe the intervention effect of ECC-JHF Ⅱ on EMT induced by transforming growth factor beta 1 （TGF-β₁）. Human type Ⅱ alveolar epithelial cells cultured on soft （3.8 kPa） and hard （culture dishes， ~ GPa） matrices were treated with ECC-JHF Ⅱ， respectively. The mRNA and fluorescence expression levels of the epithelial marker E-cadherin （CDH1）， the mesenchymal marker N-cadherin （CDH2） and vimentin （VIM）， as well as ITG β₁， were detected by real-time quantitative polymerase chain reaction （Real-time PCR） and immunofluorescence. Western blot was used to detect the protein expression of CDH1， CDH2 and ITG β₁， and the biomechanical mechanism of ECC-JHF Ⅱ on EMT and pulmonary fibrosis was further verified by knocking down and specific activation of ITG β₁. ResultsECC-JHF Ⅱ treatment improved BLM-induced pulmonary fibrosis in mice， as evidenced by significantly increased minute ventilation （MV） and 50% expiratory flow at tidal volume （EF₅₀） （P<0.05）， and significantly increased tidal volume （TV） after treatment （P<0.01） compared with the model group. Immunohistopathological analysis revealed attenuated inflammation and alveolar injury， reduced deposition of type Ⅰ collagen （Col-Ⅰ）， and significantly decreased lung tissue stiffness （P<0.01）， thereby alleviating disease progression. The real-time PCR results showed that， compared with the model group， the ECC-JHF Ⅱ group showed increased CDH1 expression and decreased CDH2 and VIM expression in mouse lung tissues （P<0.05， P<0.01）， indicating that ECC-JHF Ⅱ inhibited the EMT process to ameliorate pulmonary fibrosis. In vitro experimental results showed that both ECC-JHF Ⅱ and matrix softening reversed the EMT phenotype switch. Specifically， compared with the hard matrix group， the cells cultured on the soft matrix exhibited significantly upregulated expression of the epithelial marker CDH1 （P<0.01） and significantly downregulated expression of the mesenchymal markers CDH2 and VIM （P<0.05）. Furthermore， ECC-JHF Ⅱ inhibited the expression of ITG β₁ both in vitro and in vivo. Knockdown and specific activation of ITG β₁ further confirmed that ITG β₁ is involved in the regulatory process by which ECC-JHF Ⅱ inhibits EMT and ameliorates pulmonary fibrosis. ConclusionECC-JHF Ⅱ and matrix softening can block the EMT process and ameliorate pulmonary fibrosis， and the underlying mechanism may be associated with the inhibition of ITG β₁-mediated mechanotransduction. This study reveals a novel mechanism of ECC-JHF Ⅱ intervention in pulmonary fibrosis from a biomechanical perspective.

Endometriosis is a common estrogen-dependent disease in women of childbearing age,often leading to chronic pelvic pain,infertility,ovarian cancer,and other serious complications,and jeopardizing the health of women.The pathogenesis of endometriosis is complex and involves the alteration of multiple signaling pathways mediated by hormones,immunity,genetics,and the environment,and their interactions.Wnt/β-catenin signaling is involved in the regulation of embryonic development and tissue homeostasis,and it has recently been implicated in the pathogenesis of endometriosis via multiple pathways.This review considers the biological characteristics of the Wnt/β-catenin signaling pathway and summarizes the main mechanisms and signaling pathways involved in the pathogenesis of endometriosis,as well as the curr-ent research status of the regulation of this signaling pathway by traditional Chinese medicine for the treatment of endometriosis.We aim to clarify how the Wnt/β-catenin signaling pathway affects the development of endometriosis,and suggest that future studies should focus on exploring its potential role as an indicator for the clinical prediction and early diagnosis of endometriosis,thus providing theoretical support for the early diagnosis of this condition and the development of targeted drugs.

Transcription factor EB(TFEB),which belongs to the microphthalmia/transcription factor E(MiTF/TFE)family,is mainly functioned as regulator involved in regulating lysosomal function and autophagy.It plays an im-portant role in lipid metabolism via modulating lysosomal lipid degradation,mitochondrial β-oxidation of fatty acid,and in-tracellular cholesterol efflux.TFEB inhibits the development of metabolic associated fatty liver disease(MAFLD)and o-besity by regulating the autophagy and the expression of lipid metabolism-related genes.Additionally,it prevents the for-mation of foam cell from macrophages and vascular smooth muscle cells by restraining lipid accumulation,thereby attenua-ting the progression of atherosclerosis.TFEB promotes lipophagy to relieve lipid accumulation and lipid accumulation-in-duced insulin resistance,and β-cell failure,deferring diabetes-related lipid metabolic disorders.In summary,TFEB plays a key role in lipid metabolism and associated lipid disorder diseases,and serves as a potential clinical target to correct lipid dysmetabolism in vivo.

Objective:To investigate the effect of graded rehabilitation intervention on cardiac function,self-man-agement ability,exercise tolerance,sleep quality and quality of life in patients with chronic heart failure(CHF).Methods:This randomized controlled study enrolled 125 patients with CHF admitted to Lu'an People's Hospital be-tween April 2020 and October 2023.Patients were divided into control group(n=62)and intervention group(n=63).Participants in the control group received routine rehabilitation intervention,while those in the intervention group received additional graded rehabilitation intervention.Both groups were intervened for 3 months.Cardiac function indexes,6min walking distance(6MWD),metabolic equivalent(METs),scores of exercise of self-care a-gency(ESCA),Pittsburgh sleep quality index(PSQI)and the MOS item short from health survey(SF-36),and in-cidence of adverse events during the intervention were compared between the two groups.Results:Compared to pa-tients in the control group,those in intervention group had significant lower left ventricular end-diastolic volume(LVEDV)[(108.19±2.96)ml vs.(129.51±3.34)ml],left ventricular end-systolic volume(LVESV)[(50.68±2.28)ml vs.(67.38±2.68)ml],score of Pittsburgh sleep quality index(PSQI)[(8.30±1.87)points vs.(13.99±2.06)points](P＜0.001 all),and significant higher left ventricular ejection fraction(LVEF)[(58.17±2.08)％vs.(50.70±1.63)％],ESCA score[(148.29±19.48)points vs.(124.68±15.93)points],6MWD[(413.58±15.11)m vs.(372.22±14.62)m],METs[(6.88±0.64)kcal·kg-1·h-1 vs.(6.13±0.62)kcal·kg-1·h-1],total SF-36 score[(128.97±6.62)points vs.(104.35±5.46)points](P＜0.001 all).The inci-dence of adverse events in the intervention group was significantly lower than that in the control group(5.00％vs.18.33％,P=0.023).Conclusion:The graded rehabilitation intervention may improve the heart function,self-management ability,exercise tolerance,sleep quality and quality of life in CHF patients,and has high safety.

In order to determine the causative agents responsible for the lethality of tumor disease in breeders,liver,spleen and other tissues of dead chickens were collected,and pathogen detection,se-quencing and genetic evolution analysis were carried out by PCR.The results showed that all three samples were negative for reticuloendotheliosis virus(REV),samples 1 and 2 wereavian leukosis virus subgroup J(ALV-J)positive,and sample 3 was positive for ALV-J and Marek's disease virus(MDV),which preliminarily determined that the breeder died of ALV-J infection or ALV-J and MDV mixed infection.Among them,the ALV-J gp85 gene had the highest nucleotide homology with the reference strain of ALV-J,ranging from 87.70％to 99.30％,and was in the same branch with the reference strain of subgroup J.Amino acid homology ranged from 78.00％to 96.20％,with some mutations.The nucleotide homology between the MDV meq gene and the vv+strain was the highest,which was 98.00％-99.00％,and they were in the same branch.The homology of amino acids was 95.90％-98.20％,and there were multiple mutation sites,among which the 176th amino acid destroyed the original Pro repeat of the virus MDV meq due to the mutation of Pro to Arg or Ala,which may lead to the enhancement of its virulence.This study will provide a reference for the prevention and control of neoplastic diseases in breeders in this region.

Deutetrabenazine(DTBZ)is a selective oral small molecule inhibitor of vesicular monoamine transporter 2(VMAT2).Its pharmacological action works by inhibiting VMAT2,thereby reducing the release of presynaptic dopamine and alleviating tardive dyskinesia symptoms caused by long-term use of dopamine receptor antagonists.Compared with tetrabenazine,DTBZ has longer half-life,lower peak plasma concentration,and smaller plasma concentration fluctuations.Clinical studies demonstrate that DTBZ significantly improves abnormal involuntary movement in patients with tardive dyskinesia and has a favourable safety profile.Based on available clinical evidence and practical experience,this paper discuss the common questions about DTBZ including the suitable population,dose,duration of treatment,combination administration with antipsychotics,efficacy assessment and application in special populations.This article aimed to provide guidance and recommendations on clinical application of DTBZ for clinicians.