AIM To establish an UPLC-MS/MS method for simultaneous content determination of protocatechuic acid,epicatechin,chlorogenic acid,quercitrin,gaultherin and gaultheroside A in Gaultheria leucocarpa var.yunnanensis.METHODS The analysis was performed on a 40℃thermostatic Waters BEH C18 column(100 mm×2.1 mm,1.7 μm),with the mobile phase comprising of water(containing 0.1%formic acid)-acetonitrile(containing 0.1%formic acid)flowing at 0.3 mL/min in a gradient elution manner,and electron spray inoization source was adopted in positive and negative ion scanning with multiple reaction monitoring(MRM)mode.Hierarchical cluster analysis(HCA)and principal component analysis(PCA)was used to screen important components that affect the quality of medicinal materials.RESULTS Six constituents showed good linear relationships within their own ranges(R2≥0.998 2),whose average recoveries were 98.76%-101.88%with the RSDs of 1.0%-2.5%.The constituents of G.leucocarpa in the roots and aerial parts were quite different.Gaultherin,epicatechin and protocatechuic acid may be the quality mark constituents of G.leucocarpa.CONCLUSION This accurate and efficient method can be used for the quality control of G.leucocarpa.

Male ; Humans ; Germ-Line Mutation ; Prostatic Neoplasms/genetics* ; BRCA2 Protein/genetics* ; Genetic Predisposition to Disease

Objective:To evaluate the consistency of the Gleason scores of PCa patients based on preoperative biopsy with those from postoperative pathology,identify the possible factors influencing results of scoring,and construct a risk scoring model.Meth-ods:We collected the demographic and clinical data on the patients with PCa confirmed by preoperative prostate biopsy or postoperative pathology and treated by radical prostatectomy within 6 months after diagnosis.Using paired sample t-test,we identified the difference between the Gleason scores based on preoperative biopsy and those from postoperative pathology,analyzed the demographic and clinical data on the patients for relevant factors affecting the consistency of the Gleason scores,and calculated and visualized the relative risk values of the factors through Poisson regression.From the continuous variables with statistical significance,we screened independent risk factors for the difference in the Gleason scores by Lasso regression analysis,established a risk scoring model,generated risk coeffi-cients,and evaluated the predictive ability of the model using the ROC curve.Based on the results of imaging examination with statisti-cally significant differences,we constructed a column chart by logistic regression and evaluated the predictive validity of the chart using calibration curves,decision curves and ROC curves.Results:The results of paired sample t-test for 210 PCa patients showed statisti-cally significant differences between the Gleason scores from preoperative biopsy and those from postoperative pathology(P＜0.001).There were significant differences in the body weight,BMI and PSA level as well as in all other factors but prostate calcification be-tween the patients with consistent and those with inconsistent Gleason scores(all P＜0.05).An 8-factor prediction model was suc-cessfully constructed,which could predict the consistency of Gleason scores,with a better predicting performance than the single indi-cator within the model.The nomogram exhibited a C-index value of 0.85,with the calibration curve similar to the standard one,the threshold of the decision curve 0.10-0.92,and the area under the ROC curve higher than other predictive indicators.Conclusion:Based on the demographic and clinical data on PCa patients,a risk prediction model and a column chart were successfully constructed,which could effectively predict the difference between the Gleason scores from preoperative prostate biopsy and those from postoperative pathology.

Objective: To investigate the incidence and trend of short-term outcomes among preterm infants born <34 weeks' gestation. Methods: A secondary analysis of data from the standardized database established by a multicenter cluster-randomized controlled study "reduction of infection in neonatal intensive care units (NICU) using the evidence-based practice for improving quality (REIN-EPIQ) study". This study was conducted in 25 tertiary NICU. A total of 27 192 infants with gestational age <34 weeks at birth and admitted to NICU within the first 7 days of life from May 2015 to April 2018 were enrolled. Infants with severe congenital malformation were excluded. Descriptive analyses were used to describe the mortality and major morbidities of preterm infants by gestational age groups and different admission year groups. Cochran-Armitage test and Jonckheere-Terpstra test were used to analyze the trend of incidences of mortality and morbidities in 3 study-years. Multiple Logistic regression model was constructed to analyze the differences of outcomes in 3 study-years adjusting for confounders. Results: A total of 27 192 preterm infants were enrolled with gestational age of (31.3±2.0) weeks at birth and weight of (1 617±415) g at birth. Overall, 9.5% (2 594/27 192) of infants were discharged against medical advice, and the overall mortality rate was 10.7% (2 907/27 192). Mortality for infants who received complete care was 4.7% (1 147/24 598), and mortality or any major morbidity was 26.2% (6 452/24 598). The incidences of moderate to severe bronchopulmonary dysplasia, sepsis, severe intraventricular hemorrhage or periventricular leukomalacia, proven necrotizing enterocolitis, and severe retinopathy of prematurity were 16.0% (4 342/27 192), 11.9% (3 225/27 192), 6.8% (1 641/24 206), 3.6% (939/25 762) and 1.5% (214/13 868), respectively. There was a decreasing of the overall mortality (P<0.001) during the 3 years. Also, the incidences for sepsis and severe retinopathy of prematurity both decreased (both P<0.001). However, there were no significant differences in the major morbidity in preterm infants who received complete care during the 3-year study period (P=0.230). After adjusting for confounders, infants admitted during the third study year showed significantly lower risk of overall mortality (adjust OR=0.62, 95%CI 0.55-0.69, P<0.001), mortality or major morbidity, moderate to severe bronchopulmonary dysplasia, sepsis and severe retinopathy of prematurity, compared to those admitted in the first study year (all P<0.05). Conclusions: From 2015 to 2018, the mortality and major morbidities among preterm infants in Chinese NICU decreased, but there is still space for further efforts. Further targeted quality improvement is needed to improve the overall outcome of preterm infants.
Bronchopulmonary Dysplasia/epidemiology* ; Gestational Age ; Humans ; Infant ; Infant Mortality/trends* ; Infant, Newborn ; Infant, Premature ; Infant, Premature, Diseases/epidemiology* ; Patient Discharge ; Retinopathy of Prematurity/epidemiology* ; Sepsis/epidemiology*

Objective: To evaluate the effects of antiretrovirals on cardiovascular function and some biochemical indexes in gestational female rats. Methods: Nineteen 9-week-old female and six 10-week-old male SD rats were divided into normal control group (CON) and highly active antiretroviral therapy group (HARRT), 9/10 female rats and 3 male rats were combined into one cage, totally 2 cages. Female rats in CON group were intragastrically given with normal saline (NS, 10 ml/kg) every morning and evening, while female rats in HARRT group were treated with equal volume antiretrovirals (AZT 31.25 mg/kg + 3TC 15.63 mg/kg + LPV/r (41.67/10.42) mg/kg) for 3 months. The body weight and survival rate of female rats were recorded. Echocardiography and multichannel physiological recorder were used to detect arterial blood pressure and cardiac hemodynamic parameters. The levels of blood glucose, blood lipids, myocardial enzymes and liver enzymes were detected by corresponding kits. Myocardial collagen fibers were observed by Masson staining and the ultrastructure of myocardial cells were observed by transmission electron microscopy. Results: All female rats in CON group survived (9/9), while only 6 rats in HARRT group survived (6/10). Compared with CON group, the body weight of female rats in HAART group was decreased significantly(P＜0.01); the levels of left ventricular end diastolic diameter (LVDd), interventricular septal thickness (IVST), thickness of left ventricular posterior wall (LVPWT) , left atrial diameter (LAD) and arterial diastolic pressure were increased significantly (P＜0.05); the level of LVP+dP/dtmax was decreased (P＜0.01). The levels of triglyceride, creatine kinase, and glutamic oxaloacetic transaminase were decreased (P＜0.05 or P＜0.01), while the level of glucose was increased (P＜0.05). The collagen fibers were increased in myocardial tissue, and ultrastructure of myocardial cells was abnormal. Conclusion: Antiretrovirals during gestation can cause cardiovascular diseases in female rats.
Animals ; Anti-Retroviral Agents/adverse effects* ; Body Weight ; Cardiotoxicity ; Collagen ; Female ; Myocytes, Cardiac/ultrastructure* ; Pregnancy ; Rats ; Rats, Sprague-Dawley

Background/Aims: Direct‐acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients with end-stage renal disease (ESRD) on hemodialysis. Nevertheless, the complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit clinical practice in this special population. Methods: The number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan. Results: Of 2,015 hemodialysis patients screened in 2019, 169 patients seropositive for HCV RNA were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were ESRD-associated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%). ESRD-associated medications were excluded from DDI analysis. Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency of potential contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potentially significant DDIs (orange, requiring close monitoring or dose adjustments), sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red-category DDIs to all DAA regimens (n=62), followed by cardiovascular agents (n=15), and central nervous system agents (n=10). Conclusions HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest potential DDIs, and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs.

Background/Aims: Obstacles exist in facilitating hepatitis C virus (HCV) care cascade. To increase timely and accurate diagnosis, disease awareness and accessibility, in-hospital HCV reflex testing followed by automatic appointments and a late call-back strategy (R.N.A. model) was applied. We aimed to compare the HCV treatment rate of patients treated with this strategy compared to those without. Methods: One hundred and twenty-five anti-HCV seropositive patients who adopted the R.N.A. model in 2020 and another 1,396 controls treated in 2019 were enrolled to compare the gaps in accurate HCV RNA diagnosis to final treatment allocation. Results: The HCV RNA testing rate was significantly higher in patients who received reflex testing than in those without reflex testing (100% vs. 84.8%, P<0.001). When patients were stratified according to the referring outpatient department, a significant improvement in the HCV RNA testing rate was particularly noted in patients from non-hepatology departments (100% vs. 23.3%, P<0.001). The treatment rate in HCV RNA seropositive patients was 83% (83/100) after the adoption of the R.N.A. model, among whom 96.1% and 73.9% of patients were from the hepatology and non-hepatology departments, respectively. Compared to subjects without R.N.A. model application, a significant improvement in the treatment rate was observed for patients from non-hepatology departments (73.9% vs. 27.8%, P=0.001). The application of the R.N.A. model significantly increased the in-hospital HCV treatment uptake from 6.4% to 73.9% for patients from non-hepatology departments (P<0.001). Conclusions The care cascade increased the treatment uptake and set up a model for enhancing in-hospital HCV elimination.

【Objective】 The purpose of this study was to investigate puberty development in β-TM patients and to analyze its clinical characteristics and influencing factors. 【Methods】 A total of 42 β-TM patients aged ≥10 years old were evaluated for their stages of puberty development by reviewing follow-up data(using the REDCAP system, the thalassemia follow-up database), questionnaire, physical examination and laboratory tests. To investigate The correlations between multiple factors, such as age, beginning age of iron chelation, iron overload and so on, and abnormal puberty development in β-TM patients, were investigated. 【Results】 Twenty-four cases of β-TM patients were diagnosed as abnormal puberty development, including 11 girls and 13 boys. The common clinical manifestations of β-TM patients with abnormal puberty development were delayed puberty development and primary amenorrhea for girls and short penis and small testicles for boys. The prevalence rate of abnormal puberty development was significantly higher in β-TM patients who had older beginning age of iron chelation, β0β0 genotype, a history of splenectomy, vitamin D deficiency and diabetes(χ² = 3.966, 5.196, 5.567, 4.714, P = 0.046, 0.023, 0.018, 0.030). The result of logistic regression analysis indicated that cardiac MRT2* < 20 ms was an independent risk factor for abnormal puberty development in β-TM patients. 【Conclusions】 Abnormal puberty development in β-TM patients is very common. Influencing factors include beginning age of iron chelation, β0β0 genotype, vitamin D deficiency, diabetes and cardiac iron deposition. Moreover, hypogonadotropic hypogonadism may be an important pathogenesis of abnormal puberty development in β-TM patients.

Objective :To study influence of nicorandil on vascular endothelial function and serum inflammatory reac-tion in patients with coronary heart disease (CHD) undergoing percutaneous coronary intervention (PCI).Methods :A total of 118 CHD patients undergoing PCI in our hospital were randomly divided into routine treatment group (n＝58) and nicorandil group (n＝60 ,received nicorandil based on routine treatment ) ,both groups were treated for six months .Endothelial function ,levels of inflammatory factors and myocardial injury markers before and after treatment ,and incidence of major adverse cardiovascular events (MACE) were observed and compared between two groups.Results : Compared with routine treatment group after treatment ,there were significant rise in radial artery reactive hyperemia inner diameter [D1 ,(3-83 ± 0-37) mm vs.(4-01 ± 0-39) mm] ,flow-mediated dilation of bra-chial artery [FMD ,(14-33 ± 1-42 )% vs.(19-35 ± 1-95 )%] ,serum levels of nitric oxide [NO , (70-72 ± 7-82 ) μmol／L vs .(86-15 ± 8-52) μmol／L] and interleukin-10 [IL-10 ,(392-86 ± 40-19) ng／ml vs.(472-75 ± 48-62) ng／ml] ,and significant reductions in serum levels of endothelin-1 [ET-1 ,(70-29 ± 7-39) ng／L vs.(59-62 ± 6-02) ng／L ] ,intercellular adhesion molecule-1 [ICAM-1 ,(195-68 ± 20-48) μg／L vs.(146-72 ± 15-07) μg／L] ,cardiac tropo-nin I [cTnI ,(0-471 ± 0-071) ng／ml vs.(0-222 ± 0-052) ng／ml] ,creatine kinase isoenzyme MB [CK-MB ,(27-62 ± 3-72) U／L vs.(14-79 ± 1-52) U／L] ,mean platelet volume [MPV ,(10-26 ± 1-06) fl vs.(9-75 ± 0-95) fl] ,high sensitive C reactive protein [hsCRP , (5-36 ± 0-63 ) mg／L vs.(3-08 ± 0-27 ) mg／L ] , in-stent restenosis rate (20-69% vs.1-67%) and incidence rate of MACE (67-24% vs.10-00%) in nicorandil group ,P＜0-05 or ＜0-01-Conclusion : Nicorandil can improve postoperative endothelial function ,reduce inflammatory reaction ,protect myo-cardial cells with good prognosis in CHD patients undergoing PCI ,which is worth extending .

【Objective】Through summarizing the clinical manifestations and gene mutations of 5 types of RASopathies in childhood including Neurofibromatosis type1（NF1），Noonan syndrome（NS），Noonan syndrome with multiple lentigines（NSML），Costello syndrome（CS）and cardio-facio-cutaneous syndrome（CFC）and analyzing their commonalities and characteristics，to deepen the clinician′s understanding of the RASopathies and improve the domestic doctors′ diagnosis and treatment level of RASopathies.【Methods】The clinical data and gene mutation types of 11 patients of RASopathies who were diagnosed in Sun Yat- Sen Memorial Hospital from January 2015 to May 2018 were retrospectively analyzed. 【Results】The age of onset ranged from 6 months to 12 years and the main clinical manifestations of 11 patients included： short stature，craniofacial features，congenital heart defect，café-au-lait macules，developmental delay，thrombocytopenia， seizures and dystonia，cryptorchidism，etc. Five gene mutations were detected including NF1 gene，PTPN11 gene， RAF1 gene ，BRAF gene and HRAS gene.【Conclusions】The RASopathies are a clinically defined group of medical genetic syndromes caused by germline mutations in genes that encode components or regulators of the Ras/MAPK pathway. The RAS/MAPK pathway plays an important role in regulating growth development，promoting cell proliferation，differentiation，metabolism，and signal transduction of various hormones. Therefore，they share many overlapping characteristics，including craniofacial features，growth retardation，cardiac malformations，cutaneous and musculoskeletal abnormalities，neurocognitive impairment and tumor susceptibility. However ，each RASopathy exhibits different degree phenotypes because of mutations at different points in the pathway. In addition ，tumor susceptibility is one of the typical clinical features of RASopathies. Therefore，tumor monitoring is one of the most important contents in the follow-up process.