BACKGROUND: Based on the China-VHD database, this study sought to develop and validate a Valvular Heart Disease- specific Age-adjusted Comorbidity Index (VHD-ACI) for predicting mortality risk in patients with VHD. METHODS & RESULTS: The China-VHD study was a nationwide, multi-centre multi-centre cohort study enrolling 13,917 patients with moderate or severe VHD across 46 medical centres in China between April-June 2018. After excluding cases with missing key variables, 11,459 patients were retained for final analysis. The primary endpoint was 2-year all-cause mortality, with 941 deaths (10.0%) observed during follow-up. The VHD-ACI was derived after identifying 13 independent mortality predictors: cardiomyopathy, myocardial infarction, chronic obstructive pulmonary disease, pulmonary artery hypertension, low body weight, anaemia, hypoalbuminaemia, renal insufficiency, moderate/severe hepatic dysfunction, heart failure, cancer, NYHA functional class and age. The index exhibited good discrimination (AUC, 0.79) and calibration (Brier score, 0.062) in the total cohort, outperforming both EuroSCORE II and ACCI (P < 0.001 for comparison). Internal validation through 100 bootstrap iterations yielded a C statistic of 0.694 (95% CI: 0.665-0.723) for 2-year mortality prediction. VHD-ACI scores, as a continuous variable (VHD-ACI score: adjusted HR (95% CI): 1.263 (1.245-1.282), P < 0.001) or categorized using thresholds determined by the Yoden index (VHD-ACI ≥ 9 vs. < 9, adjusted HR (95% CI): 6.216 (5.378-7.184), P < 0.001), were independently associated with mortality. The prognostic performance remained consistent across all VHD subtypes (aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, tricuspid valve disease, mixed aortic/mitral valve disease and multiple VHD), and clinical subgroups stratified by therapeutic strategy, LVEF status (preserved vs. reduced), disease severity and etiology. CONCLUSION The VHD-ACI is a simple 13-comorbidity algorithm for the prediction of mortality in VHD patients and providing a simple and rapid tool for risk stratification.

Recent studies have indicated that the expression of ubiquitin-specific protease 51 (USP51), a novel deubiquitinating enzyme (DUB) that mediates protein degradation as part of the ubiquitin‒proteasome system (UPS), is associated with tumor progression and therapeutic resistance in multiple malignancies. However, the underlying mechanisms and signaling networks involved in USP51-mediated regulation of malignant phenotypes remain largely unknown. The present study provides evidence of USP51's functions as the prominent DUB in chemoresistant triple-negative breast cancer (TNBC) cells. At the molecular level, ectopic expression of USP51 stabilized the 78 kDa Glucose-Regulated Protein (GRP78) protein through deubiquitination, thereby increasing its expression and localization on the cell surface. Furthermore, the upregulation of cell surface GRP78 increased the activity of ATP binding cassette subfamily B member 1 (ABCB1), the main efflux pump of doxorubicin (DOX), ultimately decreasing its accumulation in TNBC cells and promoting the development of drug resistance both in vitro and in vivo. Clinically, we found significant correlations among USP51, GRP78, and ABCB1 expression in TNBC patients with chemoresistance. Elevated USP51, GRP78, and ABCB1 levels were also strongly associated with a poor patient prognosis. Importantly, we revealed an alternative intervention for specific pharmacological targeting of USP51 for TNBC cell chemosensitization. In conclusion, these findings collectively indicate that the USP51/GRP78/ABCB1 network is a key contributor to the malignant progression and chemotherapeutic resistance of TNBC cells, underscoring the pivotal role of USP51 as a novel therapeutic target for cancer management.

OBJECTIVES: To investigate the role of long noncoding RNA (lncRNA) HClnc1 in regulating proliferation, invasion, and migration of hepatocellular carcinoma (HCC) cells and the regulatory mechanism. METHODS: HClnc1 expression levels in liver cancer tissues were analyzed using data from the TCGA database. BrdU incorporation, plate cloning, and transwell assays were employed to examine the effects of HClnc1 silencing/overexpression and/or ODC1 silencing on proliferation, invasion, and migration of liver cancer cells. The effects of HClnc1 silencing on ODC1 protein and mRNA expression in the liver cancer cells were analyzed using qRT-PCR and Western blotting. The activity of ODC1 promoter was analyzed using a dual luciferase reporter gene assay. Pull-down experiment, mass spectrometry analysis, and chromatin immunoprecipitation (ChIP) assay were used for identification of HClnc1-binding proteins and their interactions. Protein interactions with the ODC1 promoter region and their binding efficiencies were investigated using RNA interference and ChIP analysis. RESULTS: HClnc1 was significantly overexpressed in HCC tissues. In liver cancer cells, HClnc1 silencing significantly inhibited cell proliferation, invasion, and migration, while HClnc1 overexpression promoted these behaviors. ODC1 silencing also suppressed malignant behaviors of liver cancer cells, and counteracted the effects of HClnc1 overexpression. Interference of HClnc1 obviously inhibited ODC1 promoter activity. RBBP5 and KAT2B proteins were identified to bind simultaneously with HClnc1. HClnc1 overexpression upregulated ODC1 protein expression, while interference of RBBP5 or KAT2B downregulated ODC1 protein expression and blocked HClnc1-induced upregulation of ODC1 protein. Both RBBP5 and KAT2B could directly bind to ODC1 promoter region; knocking out KAT2B or RBBP5 reduced the binding efficiency, while knocking out HClnc1 reduced the binding of both RBBP5 and KAT2B to ODC1 promoter region. CONCLUSIONS By targeting the RBBP5/KAT2B epigenetic modification complex, HClnc1 increases ODC1 promoter activity to enhance ODC1 transcription and promote the proliferation and migration of liver cancer cells.
Humans ; Cell Proliferation ; RNA, Long Noncoding/genetics* ; Cell Movement ; Liver Neoplasms/metabolism* ; Cell Line, Tumor ; Carcinoma, Hepatocellular/genetics* ; Promoter Regions, Genetic ; Gene Expression Regulation, Neoplastic

BackgroundAs a high prevalence disorder， schizophrenia has caused significant burden to family and society due to the impairment of occupational and social function. Currently， the dominant vocational training model in China follows a paternalistic， clinician-led decision-making approach. Although it improves patients' social function to some extent， it undermines their autonomy and treatment adherence. Therefore， it is urgently necessary to explore a new intervention method to enhance treatment compliance and social function in patients. ObjectiveTo explore the impact of shared decision-making oriented vocational training on social function in hospitalized schizophrenia patients， so as to provide references for rehabilitation interventions. MethodsA total of 68 patients diagnosed with schizophrenia according to the International Classification of Diseases， tenth edition （ICD-10） criteria were consecutively enrolled from January to June 2024 at The Third People's Hospital of Wenjiang Distric， Chengdu. Participants were randomly allocated into the research group （n=34） and the control group （n=34） using a random number table method. Both groups received routine rehabilitation training， while the research group received shared decision-making oriented vocational training for 12 weeks， 2 times a week for 2 hours each time. Before and at the 4^th and 12^th week of intervention， two groups were evaluated by General Self-Efficacy Scale （GSES）， Stigma Scale for Mental Illness （SSMI）， Scale of Social function of Psychosis Inpatients （SSFPI） and Inpatient Psychiatric Rehabilitation Outcome Scale （IPROS）. ResultsA total of 63 participants completed the study， with 30 cases in the research group and 33 cases in the control group. Repeated measures ANOVA revealed statistically significant time effects and interaction effects in both groups for GSES， SSMI， SSFPI and IPROS scores （F=20.451， 16.022； 26.193， 12.944； 23.957， 5.023； 11.776， 3.985， P<0.05 or 0.01）， while no significant group effects were observed （F=0.188， 0.742， 1.878， 0.474， P>0.05）. At the 12^th week of intervention， there were statistically significant differences in GSES， SSMI， SSFPI and IPROS scores between the two groups. ConclusionShared decision-making oriented vocational training may help to improve social function in patients with schizophrenia. ［Funded by 2023 Chengdu Medical Research Project （number， 2023468）］

Objective To analyze the medication rules of Chinese herbal concentrated-granule for the treatment of hypertension nationwide using data mining and knowledge graph methods,thus to provide evidence for expanding its application in treating hypertension.Methods From January 2022 to March 2023,Chinese herbal concentrated-granule prescriptions for hypertension prescribed by traditional Chinese medicine experts nationwide were collected.Microsoft Excel was used to analyze the frequency,properties and flavors,meridian tropism,and efficacy categories of the medicinals.Hierarchical clustering was applied for cluster analysis,and the Neo4j graph database was utilized to construct an information knowledge graph illustrating the relationships between regions and medicinals.Results A total of 2 600 Chinese herbal concentrated-granule prescriptions were included,involving 370 medicinals.The top six frequently-used medicinals were Poria(Fuling),Glycyrrhizae Radix et Rhizoma(Gancao),Atractylodis Macrocephalae Rhizoma(Baizhu),Citri Reticulatae Pericarpium(Chenpi),Paeoniae Radix Alba(Baishao),and Angelicae Sinensis Radix(Danggui).The properties of the medicinals were mainly warm and mild,and their flavors were usually sweet,pungent,and bitter.The medicinals frequently have the meridian tropism of the spleen,lung,and liver meridians.Hierarchical clustering yielded seven clusters.The information knowledge graph of region-medicinals relationships revealed that medicinals used in five or more regions were Baishao,Baizhu,Chenpi,Pinelliae Rhizoma(Banxia),Fuling,Gastrodiae Rhizoma(Tianma),Bupleuri Radix(Chaihu),Chuanxiong Rhizoma(Chuanxiong),Salviae Miltiorrhizae Radix et Rhizoma(Danshen),Danggui,Gancao,and Astragali Radix(Huangqi).Conclusion Chinese herbal concentrated-granule for hypertension usually consist of tonifying medicinals,with sweet and warm properties,and having the meridian tropism of the spleen meridian.And the medicinals composed of the prescriptions often have the actions of calming the liver and suppressing yang,strengthening the spleen and removing dampness,and nourishing the liver and kidney.

In the context of medical insurance payment reform,the sample hospital has implemented performance management optimization to effectively address the challenges posed by diagnosis-intervention packet(DIP)payment.Reform measures focused on disease quality,rational diagnosis and treatment,operational management,medical technological value,and policy orientation,and they have significantly optimized service ability and performance evaluation indexes of the hospital.Main achievements included a reduction in the cost consumption index and an increase in the clinical performance index,with the overall DIP payment rate increasing from 88.86%to 103.23%and a marked improvement in operational management.The quality control and operational efficiency of the hospital have been effectively enhanced by choosing proper DIP payment evaluation indexes and improving performance management,and provided strong support for the high-quality development of the hospital.

Objective To assess the incidence of contrast-induced nephropathy(CIN)in patients with chronic thromboembolic pulmonary hypertension(CTEPH)after receiving balloon pulmonary angioplasty(BPA),and to evaluate the effect of the contrast agents on renal function.Methods A total of 143 CTEPH patients,who received BPA at the China-Japan Friendship Hospital of China from December 2018 to May 2022,were enrolled in this study.The clinical data,hemodynamic indicators,and serum creatinine(SC)concentrations within one week before and 48-72 h after BPA were collected.The estimated glomerular filtration rate(eGFR)was calculated according to the Modification of Diet in Renal Disease(MDRD)formula.The SC concentration and eGFR changes before and after each BPA procedure were compared.The incidence of CIN and its risk factors were evaluated,and the changes in hemodynamics,SC and eGFR after the initial and last time of BPA treatment were analyzed.Results A total of 192 BPA procedures were performed in 115 CTEPH patients,including 88 BPA procedures in males and 103 BPA procedures in females.The mean amount of contrast agent used for each BPA was(145.58±47.26)mL.After BPA,12 patients developed 13 times of CIN,with an incidence of 6.8％.There was no significant differences(P＞0.05)in the baseline characteristics and SC concentration before BPA between CIN patients and non-CIN patients.In terms of the hemodynamic indexes,the mixed venous oxygen saturation(SvO2)in CIN patients was significantly lower than that in non-CIN patients(58.58％±10.38％vs.66.15％±8.02％,P=0.002),and no statistically significant differences(P＞0.05)in the other hemodynamic indexes existed between CIN group and non-CIN group.No statistically significant differences in SC concentration and eGFR existed before and after each BPA procedure.In patients who had received several BPA procedures,significant improvements in the SC[(78.09±18.760)μmol/L vs.(82.26±21.37)μmol/L,P＜0.001]and eGFR[(86.08±21.22)mL/(min·1.73 m2)vs.(82.07±22.05)mL/(min·1.73 m2),P=0.007]was achieved when compared with their baseline values.Conclusion CTEPH patients may develop CIN after receiving BPA treatment.After receiving several BPA treatments the patient's clinical symptoms and hemodynamics can be improved,and the patient's renal function is also significantly improved.

This study investigates the mechanism by which Xintong Granules improve myocardial ischemia-reperfusion injury(MIRI) through the regulation of gut microbiota and their metabolites, specifically short-chain fatty acids(SCFAs). Rats were randomly divided based on body weight into the sham operation group, model group, low-dose Xintong Granules group(1.43 g·kg~(-1)·d~(-1)), medium-dose Xintong Granules group(2.86 g·kg~(-1)·d~(-1)), high-dose Xintong Granules group(5.72 g·kg~(-1)·d~(-1)), and metoprolol group(10 mg·kg~(-1)·d~(-1)). After 14 days of pre-administration, the MIRI rat model was established by ligating the left anterior descending coronary artery. The myocardial infarction area was assessed using the 2,3,5-triphenyltetrazolium chloride(TTC) staining method. Apoptosis in tissue cells was detected by the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL) assay. Pathological changes in myocardial cells and colonic tissue were observed using hematoxylin-eosin(HE) staining. The levels of tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β), interleukin-6(IL-6), creatine kinase MB isoenzyme(CK-MB), and cardiac troponin T(cTnT) in rat serum were quantitatively measured using enzyme-linked immunosorbent assay(ELISA) kits. The activities of lactate dehydrogenase(LDH), creatine kinase(CK), and superoxide dismutase(SOD) in myocardial tissue, as well as the level of malondialdehyde(MDA), were determined using colorimetric assays. Gut microbiota composition was analyzed by 16S rDNA sequencing, and fecal SCFAs were quantified using gas chromatography-mass spectrometry(GC-MS). The results show that Xintong Granules significantly reduced the myocardial infarction area, suppressed cardiomyocyte apoptosis, and decreased serum levels of pro-inflammatory cytokines(TNF-α, IL-1β, and IL-6), myocardial injury markers(CK-MB, cTnT, LDH, and CK), and oxidative stress marker MDA. Additionally, Xintong Granules significantly improved intestinal inflammation in MIRI rats, regulated gut microbiota composition and diversity, and increased the levels of SCFAs(acetate, propionate, isobutyrate, etc.). In summary, Xintong Granules effectively alleviate MIRI symptoms. This study preliminarily confirms that Xintong Granules exert their inhibitory effects on MIRI by regulating gut microbiota imbalance and increasing SCFA levels.
Animals ; Gastrointestinal Microbiome/drug effects* ; Rats ; Male ; Myocardial Reperfusion Injury/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Rats, Sprague-Dawley ; Apoptosis/drug effects* ; Humans ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/genetics* ; Malondialdehyde/metabolism*