Objective To investigate the therapeutic mechanism of Nuanxin Capsules(NXC)in ischemic heart failure(IHF)using network pharmacology and in vivo experimental validation.Methods Active components of NXC were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and SwissTargetPrediction database.Potential IHF-related targets were predicted via OMIM and GeneCards databases.Shared targets between NXC and IHF were identified to construct a"NXC-shared targets-IHF"network.Key bioactive components were screened,and protein-protein interaction(PPI)networks were built using STRING database.Core target modules were analyzed via CytoHubba plugin in Cytoscape 3.7.2.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were performed using Metascape.For in vivo validation,an IHF mouse model was established by permanent ligation of the left anterior descending coronary artery.After 4-week intervention,cardiac function/structure was assessed by echocardiography,histopathology by hematoxylin-eosin(HE)staining,lymphatic vessel density by immunofluorescence,and protein expression of vascular endothelial growth factor C(VEGFC)and vascular endothelial growth factor receptor 3(VEGFR3)by Western Blot.Results Network pharmacology identified 242 shared targets between NXC and IHF,with core components including apigenin,pongapin,naringenin,4',5,7,8-tetramethoxyflavone,and tangeretin.Four core molecular clusters were identified(e.g.,VEGFC,FLT4/VEGFR3).GO analysis revealed enrichment in cellular response to nitrogen compounds,positive regulation of cell migration/phosphorus metabolism,and inflammatory response modulation.KEGG pathways included cancer,lipid/atherosclerosis,and endocrine resistance pathways.In vivo experiments demonstrated that NXC significantly improved cardiac function,attenuated pathological changes and inflammatory infiltration,promoted lymphangiogenesis,and upregulated VEGFC/VEGFR3 protein expression in IHF mice.Conclusion NXC may ameliorate IHF by promoting cardiac lymphangiogenesis via VEGFC/VEGFR3 signaling.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Objective To investigate the expression levels and mutation status of phosphatidylinositol-4,5-bisphosphate3-kinase catalytic subunit alpha(PIK3CA)in endometrial cancer(EC)and evaluate its association with lymph node metastasis in EC.Methods We retrosepctively collected and analyzed EC genetic mutation testing data submitted to the Molecular Detection Center,The First Affiliated Hospital of Chongqing Medical University between July 2020 and June 2022.The mutation rate of PIK3CA gene was calculated based on the sequencing results of EC patients,and the correlation between PIK3CA mutations and clinical pathological parameters,as well as protein expression consistency,was analyzed accordingly.Results A total of 97 EC patients were enrolled in this study,and PIK3CA mutations were identified in approximately 48.5％(47 out of 97 cases).The rate of lymph node metastasis in patients with PIK3CA mutations was higher than that in patients with wild-type PIK3CA(21.3％vs.6.0％,P=0.027).Findings from univariate and multivariate logistic analyses indicated that histological subtype Ⅱ(odds ratio[OR]=5.51;95％CI,1.08-28.06;P=0.040),positive result for lymphovascular space invasion(LVSI)(OR=7.96;95％CI,1.37-46.44;P=0.021),and PIK3CA mutation(OR=8.58;95％CI,1.51-48.84;P=0.015)were independent risk factors for lymph node metastasis in EC.In addition,the receiver-operating characteristic(ROC)curves demonstrated that the combined use of clinicopathological parameters and PIK3CA mutations could more accurately predict lymph node metastasis in EC,with an area under the curve of 0.824(95％CI,0.678-0.970).It is noteworthy that there was a high consistency between PIK3CA mutations and its protein expression,and EC patients with positive expression of PIK3CA protein had a higher rate of lymph node metastasis(53.8％vs.9.1％,P=0.078).Conclusion PIK3CA somatic mutations are strongly correlated with lymph node metastasis in EC.

Osteoporosis （OP） is a systemic metabolic disease with a strong correlation with age. The prevalence of osteoporosis is rising annually as a consequence of the growing issue of population ageing. The current treatments for OP have numerous shortcomings. In contrast， traditional Chinese medicine has a long history and a rich species diversity. Furthermore， recent years have seen an increase in the number of studies examining the anti-OP properties of traditional Chinese medicine. This may provide a safe and effective alternative strategy for the treatment of OP. The zebrafish， due to its favourable optical transparency and high homology with human genes， has been extensively employed as an animal research model in the investigation of human skeletal-related disease mechanisms and drug screening. This paper presents a review of anti-osteoporosis studies of traditional Chinese medicine using zebrafish as a model for osteoporosis. It also provides a summary of the experimental evaluation methods involved in such studies， an analysis of the current status of traditional Chinese medicine in the treatment of osteoporosis using zebrafish as a model， and a summary of the mechanism of action and the signalling pathways involved in traditional Chinese medicine in the anti-osteoporosis treatment of zebrafish. The current research status of Chinese medicine in the treatment of OP was analysed， as well as the mechanism of action of Chinese medicine against OP and the signalling pathways involved. Furthermore， the advantages and disadvantages of various zebrafish modelling methods of OP were compared with those of traditional animal models. The objective of this study is to provide a reference for the evaluation method of the zebrafish model in the study of bone-related diseases， as well as for the study of the mechanism of action of traditional Chinese medicine against OP and for the reference of the research and development of new drugs.

The study was conducted among 120 general practitioners (GPs) in Shanghai Fengxian District from August 2022 to March 2024, the participants were randomly divided into two age-matched groups with 60 GPs in each group. The intervention group completed a 3-month SPOC (Small Private Online Course)program, including two weeks of narrative medicine theory (concepts, questioning skills, parallel medical record writing, and professionalism) followed by monthly writing practices (three parallel records per month) and group discussions. Both groups performed routine clinical tasks, while the control group received no narrative medicine training. Baseline data were collected, Jefferson Empathy Scale scores, and Doctor-Patient Communication Skills Evaluation Scale scores were evaluated pre- and post-intervention. There were no significant differences in empathy ( P>0.05) or communication skills ( P>0.05) between two groups before the intervention. Post-intervention, both groups showed improved empathy (both P<0.05) and communication skills (both P<0.05) after intervention, while the intervention group were outperforming the control group in both measures ( P<0.05). These findings suggest that SPOC-based narrative competence training effectively enhances the empathy and doctor-patient communication abilities of general practitioners.

Objective To obtain the data of radiological diagnosis and treatment resource distribution at medical institutions of different levels and in various cities, understand the status of resource allocation, provide policy-making basis and suggestions for optimizing the allocation of radiological diagnosis and treatment resources within the province, and offer data and references for related research. Methods A basic situation questionnaire survey was conducted on radiological diagnosis and treatment institutions in Hunan Province. Data were reviewed, analyzed, and statistically processed using Excel software to understand the allocation situation of radiological diagnosis and treatment resources in Hunan Province. Results As of 2022, there were 3031 radiological diagnosis and treatment institutions, 19770 radiation workers, and 6617 pieces of radiological diagnostic and treatment equipment. There were 80 radiation treatment institutions, 49 nuclear medicine institutions, 178 interventional radiology institutions, and 3028 X-ray imaging diagnosis institutions. There were 1077 radiation workers in radiation treatment, 461 radiation workers in nuclear medicine, 3369 radiation workers in interventional radiology, and 14,863 radiation workers in X-ray imaging diagnosis. There were 135 pieces of radiation treatment equipment, 56 pieces of nuclear medicine equipment, 262 pieces of interventional radiology equipment, and 6164 pieces of X-ray imaging diagnosis equipment. Conclusion Primary and lower grade medical institutions in Hunan Province account for a relatively high proportion of the total number of medical institutions, whereas radiological diagnostic and treatment resources are predominantly concentrated in tertiary medical institutions, demonstrating a unbalanced allocation of radiological diagnosis and treatment resources in various cities. In terms of the overall allocation of radiological diagnosis and treatment resources, interventional radiology is superior to the national average, nuclear medicine and X-ray imaging diagnosis are comparable to the national averages, and radiation treatment is lower than the national average. The total GDP is not the decisive factor in determining the development of local medical levels. It is suggested that relevant authorities should improve the rationality of the planning for the allocation of radiological diagnosis and treatment resources, promote the allocation of radiological diagnosis and treatment resources to the grassroots and underdeveloped areas through various measures, and thus achieve the goal of balanced resource allocation.

In recent years,the prevalence of porcine infectious pleuropneumonia caused by Actinoba-cillus pleuropneumoniae(APP)has significantly increased in large-scale pig farms in China.The i-solation,identification,and biological characteristic testing of newly prevalent strains have impor-tant clinical significance.This study isolated four suspected APP strains(named XB2T-56,JMTLP-443,YD-THB-755,SYZJ-291)from lung samples of pig farms suspected of outbreaks of porcine infectious pleuropneumonia in Hubei Province.They were identified by PCR amplification,and multiplex PCR serological typing,the biological properties were tested by detecting the growth a-bility,hemolytic activity and biofilm forming ability.The drug resistance of the strains was ana-lyzed by drug sensitivity testing,and the virulence of one strain(XB2T-56)in mice and piglets was evaluated.The PCR identification result showed that all four clinical isolates were APP serotype 15 strains.These four strains grew slower than serotype 1 standard strains,had weaker hemolytic activity,but could form stronger biofilms.These strains are all less sensitive to cephalosporin,tylo-sin,sulfamethoxazole,and doxycycline,but sensitive to cefotaxime and enrofloxacin.The mice and piglet infection experiments showed that the isolated strain XB2T-56 has strong virulence.Artifi-cial intranasal infection causes acute death in piglets,with typical symptoms of pleuropneumonia in the lungs,and serotype 15 strains can be isolated from the lesion site.This study indicates that the APP serotype 15 strain has strong virulence,providing new date for the clinical epidemiological characteristics of APP.

In recent years,the prevalence of porcine infectious pleuropneumonia caused by Actinoba-cillus pleuropneumoniae(APP)has significantly increased in large-scale pig farms in China.The i-solation,identification,and biological characteristic testing of newly prevalent strains have impor-tant clinical significance.This study isolated four suspected APP strains(named XB2T-56,JMTLP-443,YD-THB-755,SYZJ-291)from lung samples of pig farms suspected of outbreaks of porcine infectious pleuropneumonia in Hubei Province.They were identified by PCR amplification,and multiplex PCR serological typing,the biological properties were tested by detecting the growth a-bility,hemolytic activity and biofilm forming ability.The drug resistance of the strains was ana-lyzed by drug sensitivity testing,and the virulence of one strain(XB2T-56)in mice and piglets was evaluated.The PCR identification result showed that all four clinical isolates were APP serotype 15 strains.These four strains grew slower than serotype 1 standard strains,had weaker hemolytic activity,but could form stronger biofilms.These strains are all less sensitive to cephalosporin,tylo-sin,sulfamethoxazole,and doxycycline,but sensitive to cefotaxime and enrofloxacin.The mice and piglet infection experiments showed that the isolated strain XB2T-56 has strong virulence.Artifi-cial intranasal infection causes acute death in piglets,with typical symptoms of pleuropneumonia in the lungs,and serotype 15 strains can be isolated from the lesion site.This study indicates that the APP serotype 15 strain has strong virulence,providing new date for the clinical epidemiological characteristics of APP.

The study was conducted among 120 general practitioners (GPs) in Shanghai Fengxian District from August 2022 to March 2024, the participants were randomly divided into two age-matched groups with 60 GPs in each group. The intervention group completed a 3-month SPOC (Small Private Online Course)program, including two weeks of narrative medicine theory (concepts, questioning skills, parallel medical record writing, and professionalism) followed by monthly writing practices (three parallel records per month) and group discussions. Both groups performed routine clinical tasks, while the control group received no narrative medicine training. Baseline data were collected, Jefferson Empathy Scale scores, and Doctor-Patient Communication Skills Evaluation Scale scores were evaluated pre- and post-intervention. There were no significant differences in empathy ( P>0.05) or communication skills ( P>0.05) between two groups before the intervention. Post-intervention, both groups showed improved empathy (both P<0.05) and communication skills (both P<0.05) after intervention, while the intervention group were outperforming the control group in both measures ( P<0.05). These findings suggest that SPOC-based narrative competence training effectively enhances the empathy and doctor-patient communication abilities of general practitioners.

Objective:To evaluate the short-term efficacy and safety of a preoperative combination of programmed cell death protein-1 (PD-1) inhibitor with either oxaliplatin + capecitabine (CapeOx) or oxaliplatin + tegafur gimeracil oteracil potassium (SOX) in the treatment of locally advanced immunotherapy-sensitive gastric cancer (LAGC) or adenocarcinoma of the esophagogastric junction (AEG).Methods:The cohort of this retrospective descriptive case series comprised patients with LAGC or AEG whose cancers had been determined to be immunotherapy- sensitive by endoscopic biopsy before treatment in the Gastrointestinal Cancer Center, Unit III, Peking University Cancer Hospital and Institute from 1 August 1 2021 to 31 January 2024. Patients with any one of the following three characteristics were immunotherapy-sensitive: (i) PD-L1 combined positive score (CPS) ≥5; (ii) microsatellite instability-high (MSI-H) / mismatch repair deficiency (dMMR); or (iii) Epstein-Barr virus-encoded RNA (EBER) positivity. All study patients received PD-1 inhibitors combined with CapeOx or SOX as a neoadjuvant or conversion treatment strategy before surgery. Patients with immune system diseases, distant metastases, or human epidermal growth factor receptor 2 positivity were excluded. Factors analyzed included pathological complete response, clinical complete response, major pathological response, R0 resection rate, surgical conversion rate, and safety of the treatment, including immune-related adverse events (irAEs) and surgical complications.Results:The study cohort comprised 39 patients (28 men and 11 women) of median age 62 (range 44–79) years. After the above-described preoperative treatment, radical resection of the 14 tumors that were initially considered unresectable was achieved (surgical conversion rate: 14/14). Twenty-three of the remaining 25 patients underwent radical resection. The last two patients achieved clinical complete responses and opted for a "non-surgical strategy" (watch and wait). Overall, 37 patients (94.9%) underwent radical resection, with an R0 resection rate of 100% (37/37), pathological complete response rate of 48.6% (18/37), and major pathological response rate of 62.2% (23/37). Of the 24 patients with CPS ≥ 5 (non-MSI-H/dMMR and non-EBER positive), 11 achieved pathological complete responses and one with CPS=95 achieved a clinical complete response. Of the eight patients with MSI-H/dMMR, six achieved pathological complete responses and one a clinical complete response. Of the seven patients with EBER positivity, one achieved a pathological complete response. After excluding patients with major pathological complete responses, there was a statistically significant difference in CPS scores between preoperative biopsy specimens and postoperative surgical specimens in 13 patients (7.769±5.570 vs. 15.538±16.870, t=2.287, P=0.041). All patients tolerated preoperative immunotherapy well; nine patients (9/39, 23.1%) had Grade I–II irAEs. There were no Grade III–IV irAEs. The five patients with pyloric obstruction before treatment tolerated normal diets after treatment. The incidence of postoperative complications among all patients who underwent surgery was 18.9% (7/37), including one case of Grade IIIA anastomotic leakage, one of Grade IIIA intestinal obstruction, one of Grade II abdominal hemorrhage, two of Grade II abdominal infection, one of Grade I intestinal obstruction. Additionally, one patient developed COVID-19 postoperatively. All patients recovered with symptomatic treatment. Conclusion:We found that preoperative treatment of patients with LAGC or AEG of one of three types (CPS≥5, dMMR+MSI-H, and EBER positivity) with a PD-1 inhibitor combined with CapeOx or SOX chemotherapy achieved promising effectiveness and safety, with high surgical conversion, R0 resection, and complete response rates.