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.

OBJECTIVE: To develop and validate a user-friendly risk score for older mitral regurgitation (MR) patients, referred to as the Elder-MR score. METHODS: The China Senile Valvular Heart Disease (China-DVD) Cohort Study functioned as the development cohort, while the China Valvular Heart Disease (China-VHD) Study was employed for external validation. We included patients aged 60 years and above receiving medical treatment for moderate or severe MR (2274 patients in the development cohort and 1929 patients in the validation cohort). Candidate predictors were chosen using Cox's proportional hazards model and stepwise selection with Akaike's information criterion. RESULTS: Eight predictors were identified: age ≥ 75 years, body mass index < 20 kg/m², NYHA class III/IV, secondary MR, anemia, estimated glomerular filtration rate < 60 mL/min per 1.73 m², albumin < 35 g/L, and left ventricular ejection fraction < 60%. The model displayed satisfactory performance in predicting one-year mortality in both the development cohort (C-statistic = 0.73, 95% CI: 0.69-0.77, Brier score = 0.06) and the validation cohort (C-statistic = 0.73, 95% CI: 0.68-0.78, Brier score = 0.06). The Elder-MR score ranges from 0 to 15 points. At a one-year follow-up, each point increase in the Elder-MR score represents a 1.27-fold risk of death (HR = 1.27, 95% CI: 1.21-1.34, P < 0.001) in the development cohort and a 1.24-fold risk of death (HR = 1.24, 95% CI: 1.17-1.30, P < 0.001) in the validation cohort. Compared to EuroSCORE II, the Elder-MR score demonstrated superior predictive accuracy for one-year mortality in the validation cohort (C-statistic = 0.71 vs. 0.70, net reclassification improvement = 0.320, P < 0.01; integrated discrimination improvement = 0.029, P < 0.01). CONCLUSIONS The Elder-MR score may serve as an effective risk stratification tool to assist clinical decision-making in older MR patients.

Dengue virus ( DENV ) perpetuates in an alternating cycle replication in arthropod and vertebrate hosts. It is particularly important to gain comprehensive understanding of host-virus interactions and the relationship between genetic variation and virulence. To simulate the transmit of DENN between human hosts and mosquito vectors, DENV was repeatedly passaged between human hepatocellular carcinoma cell line ( Huh-7) and mosquito cell line ( C6/36) . After 10 and 18 passages, the fitness of viral populations was measured with one-step growth curves and their virulence to mice and vector transmissibility were evaluated. Mutations in each population were determined by nucleotide sequencing. Viral fitness of DENV-2 decreased following alternating passages but increased after serial passages. Analysis of the amino acid sequences revealed that DENV that underwent continuous passage in C6/36 cells accumulated fewer mutations than virus passaged in Huh-7 cells or transferred between both cell types. Furthermore, the increased virulence that observed in serial passages might be due to the amino acid changes at positions 155 and 186 of protein E and the decreased virulence that observed in alternate passages might be due to the mutation at position 307. These results explored relationship between pathogenicity and genomic mutations of DENN and are valuable to guide the monitoring of future outbreaks.

Objective To investigate the clinical features of patients with acute ST-segment elevation myocardial infarction (STEMI) comorbid with diabetes mellitus (DM) and to analyze the prognosis within 12 months after primary percutaneous coronary intervention (pre-PCI). Methods A total of 375 STEMI patients were divided into the diabetes group (n=140) and the normal blood glucose group(n=235) according to whether they met the diagnostic criteria of DH. The clinical data,characteristics of coronary artery lesions,type of stent implant,rate of coronary slow flow or no-reflow after pre-PCI, and the prognosis within 12 months after PCI of the two groups were investigated.Results Patient in the diabetes group presented with higher mean age ,higher comorbid rates of hypertension , hyperlipidemia and heart function of Killip class Ш and above than patients in the normal blood glucose group (all P<0.05). patients in the diabetes group had higher rates of slow reflow /no-reflow after PCI(12.9% vs.5.5%,P=0.013),higher percentages of 3-ressel disease(40.7% vs. 28.9%,P=0.019)and lef t main lesions(13.6% vs. 7.2%,P=0.044). The in-hospital mortality rates(6.4% vs.1.7%,P=0.020),revascularization rates within 12 months(7.9% vs.0.9%,P=0.001)and incidence of heart failure(7.9% vs. 2.6%,P=0.017)were all higher in the diabetes group. Conclusions STEMI patients comorbid with DM were relatively older, had higher comorbidities of hypertension,hyperlipidemia, three-vessel disease, left main coronary lesions and higher mortality during hospitalization. No significant increase in cardiac death and recurrent myocardial infarction were deserved during the follow-up period. These patients may benefit more from early intervention.

OBJECTIVETo investigate the presence of leukemia stem cells (LSC) in acute myeloid leukemia (AML) and find out the relative position of leukemia cells in the figures of flow cytometry, and to analyze the relationship between minimal residual diseases (MRD) and the level of LSC, so as to explore the correlation of LSC changes with the curative effect and the prognosis during chemical therapy.

METHODSA total of 85 samples were collected from 50 AML (except M3) patients, including 50 samples from the newly diagnosed patients, 7 samples of AML patients with non-remission and 28 samples of AML patients with complete remission. All samples were used for detection of LSC from immune phenotype of CD34/CD38/CD123 by flow cytometry. The detection of immune phenotypic of leukemia cells was performed in the newly diagnosed patients. The detection of leukemia- associated immune phenotypes (LAIP) was implemented in the non-newly diagnosed patients.

RESULTSThe LSC was identified in the CD34/ CD38/ CD123 in AML and consistent with the relative position of the leukemia cell in flow cytometry figures. Statistical analysis showed significant difference in LSC content between the newly diagnosed AML group and the post-chemotherapy complete remission group(P<0.01),but did not between the newly diagnosed AML group and the post-chemotherapy non-remission group(P>0.05).There was significant positive correlation between the LSC content and MRD level in 28 AML patients with complete remission (r=0.680,P<0.01).

CONCLUSIONLSC exist in AML and the relative position are consistent with the leukemia cells in flow cytometry figures, the size characteristics and weak expression of CD45 are also similar to leukemia cells. The proportion of LSC decreases after chemotherapy. Detecting and tracking the LSC changes in bone marrow and combination with detecting minimal resident disease(MRD) may contribute to evaluate the theraputic efficacy and prognosis of leukemia patients.

Flow Cytometry ; Humans ; Interleukin-3 Receptor alpha Subunit ; Leukemia, Myeloid, Acute ; Neoplasm, Residual ; Neoplastic Stem Cells ; Prognosis

Objective: To explore the risk predictive value of lipoprotein-associated phospholipase A2 (Lp-PLA2) on acute coronary syndrome(ACS) and to study the relationship between Lp-PLA2 and the severity of coronary stenosis in ACS patients. Methods:A total of 155 ACS patients admitted in our hospital were enrolled. The patient were divided into 2 groups:AMI (acute myocardial infarction) group, n=49 and UA (unstable angina)group, n=106; in addition, there was a Control group, n=44 subjects with normal coronary angiography (CAG).Blood levels of Lp-PLA2 were examined, CAG was conducted and GRACE score, SYNTAX score,Gensini score were calculated. Based on Grace score, ACS patients were divided into 3 subgroups: Low risk subgroup, Grace score≤108, Mid risk subgroup,Grace score 109-140 and High risk subgroup,Grace score≥140.The above parameters were comparedamong different groups. Results: Compared with UA group and Control group, AMI group had increased blood level of Lp-PLA2, P<0.05. Compared with Low risk subgroup, High risk subgroup had much higher Lp-PLA2, P<0.05. Correlation analysis showed that Lp-PLA2 level was positively related to Gracescore (r=0.301, P<0.001). By SYNTAX score and Gensini score evaluation,Lp-PLA2 levels were similar among different subgroups. Conclusion:Blood level of Lp-PLA2 had certain risk predictive value in ACS patients; while it was not related to the severity of coronary stenosis.

OBJECTIVETo construct a breast cancer gene-drug network model for extracting and predicting the correlations between breast cancer-related genes and drugs.

METHODSWe developed an algorithm based on the ABC principle and the association rules to obtain the correlations between the biological entities. For breast cancer, we constructed 3 different correlations (gene-gene, drug-drug and gene-drug) and used the R language to implement the associated network model. The reliability of the algorithm was verified by ROC curve.

RESULTSWe identified 185 breast cancer-associated genes and 98 associations between them, 97 drugs and 170 associations between them. The breast cancer genes-drugs network contained 127 genes and 77 drugs with 384 associations between them.

CONCLUSIONSWe identified a large number of different correlations between the breast cancer-related genes and drugs and close correlations between some biological entity pairs that have not yet been reported, which may provide a new strategy for experimental design for testing personalized breast cancer treatment.

Algorithms ; Antineoplastic Agents ; pharmacology ; Breast Neoplasms ; genetics ; Female ; Gene Regulatory Networks ; Genes, Neoplasm ; Humans ; ROC Curve ; Reproducibility of Results

This study deals with morphological features on the male genitalia of Culex pipiens complex from China including 22 geographical strains collected.The results indicated that Cx.pipipens molestus was discovered in Manzhouli; Culex pipiens pipiens was discovered in Heixiazi island, Jiayuguan, Zhangye, Wuwei and Minqin.Through mathematical analysis, particularly linear and correlation analyses, the DV/D ratio showed a negative correlation with latitude of their locations, and regression equation were established.This analysis can be used to DV/D ratio of male Cx.pipiens complex decreased with the increase of latitude in China.

To probe and study the relationship between the species, genus or family of fleas and spatial distribution patterns in Hengduan Mountains of Yunnan Province.Based on investigation of fleas in Hengduan Mountains of Yunnan ( latitude:21°00′~29°00′N; east longitude: 97°30′~102°00′E), we applied the Pearson linear correlation analysis to compare and analyze the problems of species diversities and spatial distribution patterns of fleas in Hengduan Mountains in Yunnan Province.The results showed that the composition and distribution of fleas was significantly different along with altitude , latitude gradients and climate environment.In comparison, family, genus and species of flea richness were higher in northern latitude 25 °00′~27 °00′N; Family-genus of fleas species richness was the highest in between 2500-2900 meters, but species richness of fleas was the highest in between 2 500-3 800 meters.Distribution of 8 latitude gradients zones of fleas (latitude: 21°00′~29°00′N), species richness of genus, family and class strongly correlated with each other.Species richness of species-genus and family-genus was very significantly correlated, species richness of species was very correlated with that of family, the former is much larger than the latter; Distribution of 10 altitude gradients zones of fleas ( altitude:500 ~5 000 m ) , between the change of species-genus and family-genus has very significantly positive correlation respectively.there are not obvious of change of species-family; The relationship between the correlation of flea richness and species diversity in different peaks from Hengduan Mountains of Yunnan .There was a negative correlation between family-genus of fleas and species diversity, the between family-species and species diversity do, there was a positive correlation between genus-species of fleas and species diversity in 8 different locations from Hengduan Mountains of Yunnan Province.The composition and distribution of fleas was significantly different along with altitude , latitude gradients and climate environment.Relationship among family, genus and species in number of fleas display basic similar correlation coefficient along latitudinal and altitude gradients in Hengduan Mountains of Yunnan.The relationship was not significant between the correlation of flea richness and species diversity .The investigation showed up spatial distribution patterns of fleas species diversity, cooperative evolution trends, differences and effects of environment gradients.

OBJECTIVETo investigate the in vitro effect of caffeic acid phenethyl ester (CAPE), a NF-κB inhibitor, on the apoptosis of osteoarthritic (OA) chondrocytes and on the regulation of the gelatinases matrix metalloproteinase 2 (MMP-2) and matrix metalloproteinase 9 (MMP-9).

METHODSAnnexin V-FITC/propidium iodide (PI) labeling and western blotting were used to observe and determine the apoptosis in TNFα-stimulated primary cultured osteoarthritic chondrocytes. Also, gelatin zymography was applied to examine MMP-2 and MMP-9 activities in supernatants.

RESULTSIt was confirmed by both flow cytometry and western blotting that chondrocytes from OA patients have an apoptotic background. Use of CAPE in combination with 10 ng/mL of TNFα for 24 h facilitated the apoptosis. MMP-9 in the supernatant could be autoactivated (from proMMP-9 to active MMP-9), and the physiologic calcium concentration (2.5 mmol/L) could delay the autoactivation of MMP-9. The activities of MMP-2 and MMP-9 in the fresh supernatant increased significantly in response to stimulation by 10 ng/mL of TNFα for 24 h. The stimulatory effect of TNFα just on proMMP-9 was counteracted significantly by CAPE.

CONCLUSIONNF-κB could prevent chondrocytes apoptosis though its activation was attributed to the increase of proMMP-9 activity induced by TNFα (a pro-apoptotic factor). Therefore, therapeutic NF-κB inhibitor was a 'double-edged swords' to the apoptosis of chondrocytes and the secretion of MMP-9.

Aged ; Apoptosis ; drug effects ; Caffeic Acids ; pharmacology ; therapeutic use ; Calcium ; physiology ; Cells, Cultured ; Chondrocytes ; drug effects ; enzymology ; secretion ; Drug Evaluation, Preclinical ; Female ; Humans ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Middle Aged ; NF-kappa B ; antagonists & inhibitors ; Osteoarthritis ; drug therapy ; enzymology ; Phenylethyl Alcohol ; analogs & derivatives ; pharmacology ; therapeutic use ; Tumor Necrosis Factor-alpha ; pharmacology