OBJECTIVE: To investigate the association of various polycyclic aromatic hydrocarbon (PAH) metabolites with diverse subtypes of cardiovascular disease (CVD) risk. METHODS: A novel predicting risk of cardiovascular disease EVENTs PREVENT equation was used to estimate the 10-year diverse subtypes of CVD risk, and their associations with PAH metabolites were analyzed using multiple logistic regression models, the weighted quantile sum (WQS) model, the quantile g-computation (qgcomp) model, and a stratified analysis of subgroups. RESULTS: For this study, six thousand seven hundred and forty-five participants were selected, and significant positive associations were observed between PAHs, naphthalene (NAP), and fluorene (FLU), and the risks of total CVD, atherosclerotic cardiovascular disease (ASCVD), and heart failure (HF). NAP and FLU were the primary contributors to the effects of PAH mixtures, and their associations with total CVD, ASCVD, and HF risk were significant in younger participants (30 ≤ age < 50 years); however, the associations of phenanthrene (PHEN) with ASCVD, HF, coronary heart disease (CHD), and stroke were dominant in aging participants (age ≥ 50 years). Notably, pyrene (PYR) was negatively associated with the risk of ASCVD, HF, CHD, and stroke. Similarly, negative associations of PYR with the four CVD subtypes were noticeable in aging participants. CONCLUSION Different PAHs metabolites had different impacts on each CVD subtype among different age groups. Notably, the protective effects of PYR on ASCVD, HF, CHD, and stroke were noticeable in aging individuals.
Humans ; Cardiovascular Diseases/chemically induced* ; Middle Aged ; Polycyclic Aromatic Hydrocarbons/metabolism* ; Male ; Female ; Adult ; Aged ; Risk Factors ; China/epidemiology*

Objective: To investigate the association of the levels of high sensitivity C-reactive protein (hs-CRP) with frailty and its components among the elderly over 65 years old in 9 longevity areas of China. Methods: Cross-sectional data from the Health Ageing and Biomarkers Cohort Study (HABCS, 2017-2018) were used and the elderly over 65 years old were included in this study. Through questionnaire interview and physical examination, the information including demographic characteristics, behavior, diet, daily activity, cognitive function, and health status was collected. The association between hs-CRP and frailty and its components in the participants was analyzed by multivariate logistic regression model and restrictive cubic spline. Results: A total of 2 453 participants were finally included, the age was (84.8±19.8) years old. The median hs-CRP level was 1.13 mg/L and the prevalence of frailty was 24.4%. Compared with the low-level group (hs-CRP<1.0 mg/L), the OR (95%CI) value of the high-level group (hs-CRP>3.0 mg/L) was 1.79 (1.35-2.36) mg/L. As for the components, the hs-CRP level was also positively associated with ADL disability, IADL disability, functional limitation and multimorbidity. After adjusting for confounding factors, compared with the low-level group, the OR (95%CI) values of the high-level group for the four components were 1.68 (1.25-2.27), 1.88 (1.42-2.50), 1.68 (1.31-2.14) and 1.39 (1.12-1.72), respectively. Conclusion: There is a positive association between the levels of hs-CRP and the risk of frailty among the elderly over 65 years old in 9 longevity areas of China. The higher hs-CRP level may increase the risk of frailty by elevating the risk of four physical functional disabilities, namely ADL disability, IADL disability, functional limitation and multimorbidity.
Humans ; Aged ; Aged, 80 and over ; C-Reactive Protein/analysis* ; Frailty/epidemiology* ; Cohort Studies ; Cross-Sectional Studies ; China/epidemiology*

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

Objective To investigate the influencing factors of the formation of intracranial collateral circulation in patients with anterior circulation chronic occlusion. Methods From January 2015 to December 2017,181 consecutive patients with unilateral internal carotid artery or middle cerebral artery chronic occlusion diagnosed by DSA and admitted to the Department of Neurology,Chinese People′s Liberation Army General Hospital were enrolled retrospectively. According to the American society for interventional and therapeutic neuroradiology/society of interventional radiology ( ASITN/SIR ) collateral circulation grading system, 68 patients were divided into poor collateral circulation group (grade 0-2) and 113 were divided into good collateral circulation group (grade 3-4). After admission,the patients completed the relevant examinations, including blood routine,blood uric acid,blood lipids,and DSA examination. The age,gender,basic diseases (hypertension,diabetes,hyperlipidemia, coronary heart disease, history of previous ischemic stroke) and history of smoking/alcohol of the patients were recorded. The formation of collateral circulation was used as the dependent variable. The factor of P<0. 05 in the univariate analysis was included in the multivariate logistic regression analysis. Results (1) The patients of the poor collateral circulation group were older than those of the good collateral circulation group (61 ± 9 years vs. 56 ± 12 years),and the proportion of hyperlipidemia was higher than that of the good collateral circulation group (26. 5%[18/68] vs. 13. 3%[15/113]). The differences were statistically significant between the groups (all P<0. 05). There were no significant differences in the proportions of gender,hypertension,diabetes,coronary heart disease,ischemic stroke,tobacco and alcohol history between the two groups ( all P>0. 05) . (2) Compared with the good collateral circulation group,the level of high density lipoprotein ( HDL) in the poor collateral circulation group was lower. The differences were statistically significant between the groups (1. 0 ± 0. 2 mmol/L vs. 1. 1 ±0. 3 mmol/L,P<0. 05). There were no significant differences in blood uric acid,triglyceride,cholesterol, low-density lipoprotein,and platelet count levels between the two groups (all P>0. 05). (3) After variable selection,age (from young to old) and HDL (from low to high) as independent variables and the formation of collateral circulation as dependent variables, they were included in multivariate logistic regression analysis. The results showed that increasing age increases the risk of poor collateral circulation (OR,1. 053, 95%CI 1.021-1.085,P <0.05);the elevated HDL level was a protective factor of the formation of collateral circulation (OR,0. 265,95% CI 0. 085-0. 825,P<0. 05). Conclusion With the increase of age,the risk of intracranial poor collateral circulation increases,and the increased HDL level is beneficial to the formation of collateral circulation.

BACKGROUND: Dermal fibroblasts are widely used and demanded, and there are various isolation methods, but no comparative studies on enzyme digestion methods are reported. OBJECTIVE: To compare the cell count, morphology, migration and proliferation of human dermal fibroblasts isolated by two enzyme digestion methods. METHODS: Human dermal fibroblasts were isolated using either dispase-collagenase or trypsin, and their cell yield and viability were assessed by morphology, cell count and proliferation curve by cell counting-kit 8 assay. The ability of migration was observed by cell scratch test. RESULTS AND CONCLUSION: The fibroblasts digested with dispase-collagenase were fused at 6-7 days after inoculation, and the cells isolated by trypsin digestion were fused at 8-9 days after inoculation. Fibroblasts could be obtained by both two digestion methods. The production in the dispase-collagenase group was significantly higher than that in the trypsin group. The migration rate in the dispase-collagenase group was significantly faster than that in the trypsin group. The growth cures of the human dermal fibroblasts in the two groups revealed that the cell count was positively correlated with time, and the absorbance values of the dermal fibroblasts in the dispase-collagenase group were significantly higher than those in the trypsin group at 3, 4 and 5 days after incubation. To conclude, the cell yields, migration and proliferation of dermal fibroblasts digested with dispase-collagenase are significantly higher than those of the cells digested by trypsin, indicating that dispase-collagenase digestion results in better isolation and viability of dermal fibroblasts from the dermis.

Objective To investigate the risk assessment,guiding role,and clinical value of Vaso CT image features for recanalization of vertebrobasilar junction occlusion. Methods From January 2016 to May 2017,14 patients with vertebrobasilar junction occlusion admitted to the Department of Neurology, Chinese PLA General Hospital were analyzed retrospectively. Preoperative cerebral angiography confirmed vertebrobasilar junction occlusion. Vaso CT was used to measure the length of the occluded vessels and vascular direction at both ends. According to these results, the operative risks were evaluated and the recanalization of vertebrobasilar junction occlusion were guided. Results The length of vertebrobasilar junction occlusion was 2. 56-19. 09 mm (mean 4. 5 ± 2. 1 mm) in 14 patients,and 13 of them were treated with the recanalization of vertebrobasilar artery occlusion,the blood vessels of 12 cases were successfully recanalized and stent placement was performed after the recanalization,among them,8 Solitaire stents and 4 Wingspan stents were implanted;One patient did not perform recanalization because of longer length of occlusion (19. 09 mm). All patients operated did not have any perioperative complications, and the neurological symptoms were significantly improved after procedure. Conclusion Vaso CT can accurately determine the surgical risk of the recanalization of vertebrobasilar junction occlusion,and can guide the surgical pathways,reduce the incidence of perioperative complications,and improve the success rate of the operation.

Several studies have shown that the tumor endothelial cells are different from the normal tissue endothelial cells. These tumor endothelial cells may contribute to tumor neo-vasculogenesis. This study was purposed to analyze the biologic features and determine the expression level of CD133 and BCR/ABL fusion gene in circulating endothelial cells (CEC) isolated from peripheral blood of CML patients, as well as to investigate the role of CEC in disease progression. Mononuclear cells were isolated from peripheral blood by density gradient centrifugation; CEC were sorted by MACS and harvested in the endothelial growth medium. The morphologic features of CEC were observed by microscopy, the cell growth rate was calculated by cell counting, and the cells were identified by immunofluorescence staining for the expression of CD31,CD34,VWF and CD133. The expression of BCR/ABL fusion gene was examined by FISH in 12 CML patients. The results indicated that the isolated CEC displayed the typical cobble-stone morphology. These cells could be identified by the positive immunofluorescence staining for CD31, CD34 and VWF, and showed more increased proliferative potential as compared to that of healthy donors. It was found that the positive rate of CD133 was 31.29% in CML patients, which was significantly different from that of healthy donors (P < 0.05). In 12 CML patients, CEC carried the same chromosome aberration as the leukemia cells (10.77%). Higher expression level of CD133 and BCR/ABL fusion gene positively correlated with progression of disease. It is concluded that the CEC may participate in invasion and angiogenesis in patients with CML and possibly correlate to the spreading and progression of the disease.
AC133 Antigen ; Adult ; Antigens, CD ; metabolism ; Cell Proliferation ; Endothelial Cells ; metabolism ; Female ; Fusion Proteins, bcr-abl ; genetics ; metabolism ; Glycoproteins ; metabolism ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; metabolism ; pathology ; Male ; Middle Aged ; Neovascularization, Pathologic ; Peptides ; metabolism ; Young Adult

OBJECTIVETo construct a short hairpin (sh)RNA targeting aquaglyceroporin 9 (AQP9) that effectively silences gene expression in liver cells in order to investigate of the role of AQP9 in nonalcoholic fatty liver disease (NAFLD) pathogenesis using an in vitro cell model system.

METHODSSmall interfering (si)RNAs were designed against the human gene sequences encoding AQP9 (NCBI GenBank Accession No. AB008775) and unrelated control sequences, synthesized, annealed to form double-strands, and inserted into the pGenesil- 1 shRNA-expression plasmid. The silencing effects of the four pshRNA-AQP9 constructs (a-d) and the pshRNA-negative control construct were investigated by transfecting into the L02 human normal liver cell line and detecting expression of AQP9 mRNA and protein (relative to beta-actin) by reverse transcription-PCR and western blotting. The NAFLD cell model was established by treating L02 cells with oleic acid to induce fatty degeneration. After transfecting the NAFLD cell model with various constructs, the effects on NAFLD-related features were investigated by staining with Oil Red O (to detect lipid droplets) and performing enzymatic assays (to quantitate triglyceride (TG), free fatty acid (FFA) and glycerol content). The significance of intergroup differences was assessed by analysis of variance test.

RESULTSOf the four pshRNA-AQP9 constructs, pshRNA-AQP9a produced the most robust silencing effect on AQP9 mRNA (25.1 - 1.2% vs. untransfected: 39.3 +/- 1.7% and pshRNA-negative control: 39.4 +/- 1.5%, P < 0.01) and protein (25.4 - 2.0% vs. untransfected: 35.1 +/- 1.9% and psh-RNA-negative control: 35.6 +/- 2.3%, P < 0.01). Oleic acid-induced L02 cells showed enhanced AQP9 mRNA and protein expression, and increased intracellular content of lipid, TG, FFA, and glycerol, which were significantly reduced by pshRNA-AQP9a transfection (all P <0.05).

CONCLUSIONThe new pshRNA-AQP9a construct can efficiently reduce AQP9 expression in cultured human liver cells and relieve steatosis-related features in an NAFLD cell model, pshRNA-AQP9a represents a novel tool for studying the role ofAQP9 in NAFLD pathogenesis and its potential as a gene therapy strategy.

Aquaporins ; genetics ; Cell Line ; Fatty Liver ; genetics ; Gene Expression ; Genetic Vectors ; Hepatocytes ; metabolism ; Humans ; Non-alcoholic Fatty Liver Disease ; Plasmids ; RNA Interference ; RNA, Messenger ; RNA, Small Interfering

Objective To improve the knowledge of Kaposi sarcoma and the relationship between Kaposi sarcoma and human immunodeficiency virus (HIV) infection,and to improve the ability to diagnose and treat Kaposi sarcoma and acquired immune deficiency syndrome (AIDS).Methods Symptoms,signs and results of 121 patients encountered in the department of otorhinolaryngology head and neck surgery in Tanzania,who was diagnosed as Kaposi sarcoma actually with HIV infection and AIDS,were retrospectively analyzed in this study.Results There were 46 males and 75 females with age ranged from 5 to 65 years,medium 30 year.The mucous membranes and skin lesions was the most commonly seen clinical manifestation in 121 cases,these lesions appeared as raised blotches or lumps that might be purple,brown,or red,early stages typical lesions began as flat or slightly raised colored spots.Among the cases reported here,25 patients(20.66％)showed progressive nose blockage and nose bleeding and the purple-red new-grows were found in the nose of these patients.Fifteen patients (12.40％) had fiat or slightly raised colored spots in their mucous membrane of mouth (palate or tongue),and in other 7 patients,purple small lumps were found in the gums of the patients.There were same lesions in their pharynx in 9 cases.In 10 patients (8.26％),Kaposi sarcoma was found in tonsil looked like tonsillitis with enlarged tonsils by two to three degree.Twelve patients(9.92％) had masses in the neck with no pain.Thirty-five patients(28.92％)had lesions of purple black nodules,including 10 patients who had the same lesions with ulcer formation in the nodules.All patients had been followed-up for at least two-years.Eighty-five patients passed away in one year,survival rate of one year was 21.48％ (26/121),only 12 patients survived from the disease over two years,two years' survival rate was 9.92％ (12/121).Conclusions Kaposi sarcoma is the characteristic disease for AIDS,mainly found on the membranes and skin.These lesions appears as raised blotches or lumps that may be purple,brown,or red,early stages typical lesions begin as fiat or slightly raised colored spots.Patients who had kaposi sarcoma often died in a short-time without treatment.

Objective To identify the main etiologies of emergency room (ER) patients with chest pain or equivalent syndrome.Methods This was a prospective and cross-sectinal survey of ER patinets with chest pain or equivalent syndrome in 17 medical centre in Beijing,China from July to August 2009.Data was collected by structured interviews and medical record reviews.The mean follow up period was 30 days.Results A total of 5666 patients were enrolled in the study (2663 males and 3303 females) and the mean age was 58.1 ± 18.4years.Their final diagnoses were:coronary heart disease 1506 ( 27.4％ ),acute heart failure 149 ( 2.6％ ),pericarditis 4 ( 0.1％ ),pulmonary embolism 11 ( 0.2％ ),aortic dissection 8 ( 0.1％ ),acute cerebrovascular disease 431 ( 7.6％ ) and non-cardic chest pain 2538 ( 44.9％ ).Thirty-seven cased died and 275 cases hospitalized again 30 days later,4.9％ patients with cornary heart disease had symptoms at their presentation.Conclusion Special vigilance and thorough coronary artery evaluation are needed for all patients with chest discomfort or respiratory distress in the ER,even for patients without chest pain.