Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

OBJECTIVE: To explore the relationship between drug treatment and outcomes in patients with late-onset severe pneumonia (LOSP) after allogeneic stem cell transplantation (allo-SCT). METHODS: We retrospectively analyzed the effects of the initiation time of treatment drugs, especially antiviral drugs and glucocorticoids on the clinical outcomes in 82 patients between January 2016 and August 2021 who developed LOSP after allo-SCT in Peking University People's Hospital. Univariate analysis was performed by Mann-Whitney U test and χ² test, and multivariate analysis was performed by Logistic regression. When multiple groups (n>2) were involved in the χ² test, Bonferroni correction was used for the level of significance test. RESULTS: Of all 82 patients in this study, the median onset time of LOSP was 220 d (93-813 d) after transplantation, and the 60-day survival rate was 58.5% (48/82). The median improvement time of the survival patients was 18 d (7-44 d), while the median death time of the died patients was 22 d (2-53 d). Multivariate analysis showed that the initiation time of antiviral drugs from the onset of LOSP (< 10 d vs. ≥10 d, P=0.012), and the initiation time of glucocorticoids from antiviral drugs (< 10 d vs. ≥10 d, P=0.027) were the factors affecting the final outcome of the patients with LOSP at the end of 60 d. According to the above results, LOSP patients were divided into four subgroups: group A (antiviral drugs < 10 d, glucocorticoids ≥10 d), group B (antiviral drugs < 10 d, glucocorticoids < 10 d), group C (antiviral drugs ≥10 d, glucocorticoids ≥10 d) and group D (antiviral drugs ≥10 d, glucocorticoids < 10 d), the 60-day survival rates were 91.7%, 56.8%, 50.0% and 21.4%, respectively. CONCLUSION Our study demonstrated that in patients who developed LOSP after allo-SCT, the initiation time of antiviral drugs and glucocorticoids were associated with the prognosis of LOSP, and the survival rate was highest in patients who received antiviral drugs early and glucocorticoids later. It suggested that for patients with LOSP of unknown etiology should be highly suspicious of the possibility of a secondary hyperimmune response to viral infection.
Antiviral Agents/therapeutic use* ; Glucocorticoids/therapeutic use* ; Hematopoietic Stem Cell Transplantation/methods* ; Humans ; Pneumonia/etiology* ; Prognosis ; Retrospective Studies ; Transplantation, Homologous/adverse effects*

OBJECTIVE: To estimate the univariate heritability of resting heart rate and common chronic disease such as hypertension, diabetes, and dyslipidemia based on extended pedigrees in Fujian Tulou area and to explore bivariate heritability to test for the genetic correlation between resting heart rate and other relative phenotypes. METHODS: The study was conducted in Tulou area of Nanjing County, Fujian Province from August 2015 to December 2017. The participants were residents with Zhang surname and their relatives from Taxia Village, Qujiang Village, and Nanou Village or residents with Chen surname and their relatives from Caoban Village, Tumei Village, and Beiling Village. The baseline survey recruited 1 563 family members from 452 extended pedigrees. The pedigree reconstruction was based on the family information registration and the genealogy booklet. Univariate and bivariate heritability was estimated using variance component models for continuous variables, and susceptibility-threshold model for binary variables. RESULTS: The pedigree reconstruction identified 1 seven-generation pedigree, 2 five-generation pedigrees, 23 four-generation pedigrees, 186 three-generation pedigrees, and 240 two-generation pedigrees. The mean age of the participants was 57.2 years and the males accounted for 39.4%. The prevalence of hypertension, diabetes, dyslipidemia in this population was 49.2%, 10.0%, and 45.2%, respectively. The univariate heritability estimation of resting heart rate, hypertension, and dyslipidemia was 0.263 (95%CI: 0.120－0.407), 0.404 (95%CI: 0.135－0.673), and 0.799 (95%CI: 0.590－1), respectively. The heritability of systolic blood pressure, diastolic blood pressure, fasting glucose, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol was 0.379, 0.306, 0.393, 0.452, 0.568, 0.852, and 0.387, respectively. In bivariate analysis, there were phenotypic correlations between resting heart rate with hypertension, diabetes, diastolic blood pressure, fasting glucose, and triglyceride. After taking resting heart rate into account, there were strong genetic correlations between resting heart rate with fasting glucose (genetic correlation 0.485, 95%CI: 0.120－1, P<0.05) and diabetes (genetic correlation 0.795, 95%CI: 0.181－0.788, P<0.05). CONCLUSION Resting heart rate was a heritable trait and correlated with several common chronic diseases and related traits. There was strong genetic correlation between resting heart rate with fasting glucose and diabetes, suggesting that they may share common genetic risk factors.
Blood Pressure ; Chronic Disease ; Female ; Heart Rate ; Humans ; Hypertension ; Male ; Middle Aged ; Pedigree

Objective To observe the effects of dopamine in different doses on hemodynamics and cerebral oxygen metabolism in the early stage of post-resuscitation in rabbit with cardiac arrest.Methods Healthy adult rabbits were randomly(random number) divided into 4 groups according to the different doses of dopamine administration:control group (CG),low dose group (LG),medium dose group (MG),high dose group (HG),(n=15 in each group).Ventricular fibrillation (VF) was induced by electricity and cardiopulmonary resuscitation (CPR) was performed subsequently as the experiment designed.When 10 rabbits with restoration of spontaneous circulation (ROSC) were got each group,it was enough for experiment carried out.Cardiac output (CO),mean arterial pressure (MAP),heart rate (HR),systemic vascular resistance index (SVRI) and the cerebral local tissue blood oxygen saturation (TOI) were observed at 0 min,15 min,30 min,60 min,120 min after ROSC.The animals were sacrificed at 120 min after ROSC,brain tissues were harvested for study by using HE staining.Repeated measure analysis of variance was used to determine the statistical significance among the four groups at different intervals.Multi-group quantitative data was analyzed by one way ANOVA and then further by LSD test for multiple comparisons.Chi-square test or Fisher's exact probabilities was applied for multi-group binomial classification variable.Log-rank test was used for comparisons of survival curves in four groups.A twotailed value of P＜0.05 was considered statistically significant.Results There were no differences in the rate of ROSC among groups.Compared with CG and LG,ROSC time was shorter in MG (277±15 vs.190±12,P＜0.01;252±16 vs.190±12,P=0.016) with higher 120 min survival rate (20％ vs.90％,x2=9.899,P=0.005;30％ vs.90％,x2=7.5,P=0.02).CO was higher in MG than that in other groups at all given intervals in the early stage of post-resuscitation(P＜0.05).MAP levels were significantly higher in MG and HG compared with CG and LG at given intervals 15 min after ROSC (P＜0.05).SVRI was significantly higher in HG than that in other groups at all given intervals after ROSC (P＜0.05).Compared with other groups,the TOI levels in MG were significantly higher than that in other groups at 15 min and 30 min after ROSC (P＜0.05).The median survival time in MG and HG was significantly longer than that in CG and LG.The number of cellular necrosis in MG (28.4±1.0) was significantly fewer than that in other groups (CG 41.2±1.5;LG 41.0±2.0;HG 39.6±1.9) (P＜0.01).Conclusion The moderate dose of dopamine might maintain MAP and CO at a higher level meeting the cerebral oxygen metabolism in the early stage of post-resuscitation from cardiac arrest in rabbits.

AIM:To observe the expression of microRNA-126-5p during myocardial injury and its role in myo-cardial cell injury induced by adriamycin(also called doxorubicin, DOX).METHODS: The BALB/c mouse model of DOX-induced acute and chronic myocardial injury was established via intraperitoneal injection of DOX.HE staining was applied to observe the morphological changes of myocardial tissues.Lactate dehydrogenase(LDH)in serum was detected and PowerLab system was used to detect the influence of DOX on the changes of ±dp/dtmax.The expression of microRNA-126-5p in injured myocardial tissues and the H 9c2 cells exposed to DOX was detected by real-time PCR.Gain-and loss-of-function experiments were conducted to detect the role of microRNA-126-5p in H9c2 cells treated with DOX on LDH release and caspase-3 activation.RESULTS:In acute and chronic DOX myocardial damage models in mice,HE staining showed disarranged myocardial fibers, dissolved myofibril and inflammatory cell infiltration.Higher serum LDH level and lower ±dp/dtmaxin DOX-treated mice than those in normal mice were found.Compared with the normal mice, the expression level of microRNA-126-5p was significant increased in the myocardium with DOX-induced injury.Similarly,the expression level of microRNA-126-5p was significant increased in the H9c2 cells treated with DOX.In addition, over-expression of microRNA-126-5p decreased cell viability and promoted apoptosis,while microRNA-126-5p ablation promoted the viability and inhibited the apoptosis of H9c2 cells.CONCLUSION:The microRNA-126-5p expression is up-regulated in myocar-dial injury induced by DOX,and microRNA-126-5p inhibits cell viability and promotes apoptosis induced by DOX.

Objective To understand the resistance, molecular charac-teristics of oxacillin susceptible methicillin-resistant Staphylococcus au-reus ( OS-MRSA) strains isolated 2011-2012 in China.Methods A total of 297 methicillin -resistant Staphylococcus aureus ( MRSA ) were collected in the Ministry of Health National Antimicrobial Resistance Sur-veillance Net program and the susceptibility test were performed by agar dilution method.All the oxacillin-susceptible MRSA strains were con-firmed to be Staphylococcus aureus by detecting nuc gene.The molecular typing methods included SCCmec and spa typing.Results A total of 14 isolates ( 4.9%) were oxacillin susceptible methicillin-resistant Staphy-lococcus aureus among 288 MRSA isolates and most of them were from se-cretion (50%, 7/14) and blood (28.6%, 4/14).The susceptibility rate to gentamicin, amikacin, rifampicin and trimethroprim/sulfamethox-azole was more than 90% and the rate to quinolones, tetracycline and chloramphenicol was about 80%, 28.6%, 28.6%, respectively.Moreo-ver, the resistance rate to erythromycin, azithromycin and clindamycin was more than 90%.PCR revealed that 14 isolates were Staphylococcus aureus and mecA positive and the most predominant clone was SCCmecⅤ-spat437 (42.9%,6/14).Conclusion The most predominant clone of the OS-MRSA isolates in China was SCCmecⅤ-spat437; most of OS-MRSA isolates were susceptible to the majority of antibacterial agents except macrolides, tetracycline and chloramphenicol.

Objective To investigate the antimicrobial resistance of Enterobacteriaceae isolated from patients of first class hospitals in China in 2012.Methods All the clinical isolates of Enterobacteriaceae were collected and the susceptibility tests of the isolates were performed by 557 first class hospitals around China from 1st Jan.2012 to 31st Dec.2012.The susceptibilities of isolates to antimicrobial agents were determined by using CLSI (2010) guideline and the susceptibility data were processed with Whonet 5.6 software.Results A total of 372052 clinical isolates were collected.Among all the strains Escherichia coli ( 161211starins, 43.3%) outnumbered the other bacteria, followed by Klebsiella pneu-moniae (112600 strains, 30.3%), Enterobacter clacaer (31887strains, 8.6 %).The most effective antimicrobials were carbapenems.The re-sistant rates of Escherichia coli to imipenem and meropenem were both be-low 12.5%, and the rates in other Enterobacteriaceae were below 10%.Besides this, piperacillin/tazobactam, cefoperazone/sulbactam and ami-kacin demonstrated good antibacterial activity against Enterobacteriaceae in vitro.Overall, little difference was observed in the resistant rates of Enterobacteriaceae isolated from first class hospi-tals in different parts of China.Conclusion Enterobacteriaceae from firs class hospital were of different degree resis-tance to various antimicrobial agents.Carbapenems remained very high activity against Enterobacteriaceae,but the car-bapenem resistance strains has appeared and the issue should be attracted attention.

Background As one of the most common microvascular complication of diabetes in eyes,diabetic retinopathy (DR) is one of the most important cause of blindness.Nuclear factor-kappa B (NF-κB) is involved in the occurrence and development of the disease through the activation of a series of inflammatory cytokines.Objective The present study was to investigate the effects of peroxisome proliferator-activated receptor-gamma (PPAR-γ) excitomotor,rosiglitazone,on NF-κB expression and apoptosis of the retinal ganglion cells (RGCs) in the retina with diabetes mellitus. Methods Ninety SPF male Wistar rats were randomized into normal control group,diabetic control group and rosiglitazone group.Diabetes mellitus was induced by intraperitoneal injection of 50 mg/kg streptozotocin(STZ).Then 3 mg/kg rosiglitazone was intragastricly administered once per day in the rosiglitazonegroup,and the same volume of saline solution was used at the same way in the normal control group and diabetic control group from 3 days after modeling.The rats were sacrificed and the eye cups specimen was made at 4,8 and 12 weeks after usage of drugs.Retinal histopathological examination was performed by hematine-eosin staining,and expression of NF-κB p65 protein in retina and apoptotic index(AI) of RGCs were detected by immunohistochemistry and TUNEL assay,respectively in different time points mentioned above.The use of the animals complied with the Regulations for the Administration of Affairs Concerning Experimental Animals by State and Technology Commission.Results The blood glucose level was significantly elevated at various time points in the diabetic control group and rosiglitazone group compared with normal control group (P＜0.01 ),and that of the rosiglitazone group was significantly declined in comparison to the diabetic control group (q =0.81,0.82,1.23,P＞ 0.05 ).Normal retinal structure was seen in the normal control group,and edema retinal cell and disorder of retinal layers were exhibited in the diabetic control group.Retinal structure was almost normal in the rosiglitazone group.The NF-κB p65 was expressed weakly in the retina of normal control group,but the expression of NF-κB p65 was significantly elevated in the diabetic control group and rosiglitazone group compared with the normal control group(P＜0.01 ).However,the expression of NF-κB p65(A value)was significantly decreased in the rosiglitazone group compared with diabetic control group at 8 weeks and 12 weeks( q=17.77,15.30,P＜0.01 ).There were a few apoptotic cells in rat retina of the normal control group.Compared with the normal control group,the AI of the diabetic control group and rosiglitazone group was significantly reduced(P＜0.01 ).However,the AI of RGCs in the rosiglitazone group was significantly lower than that of diabetic control group in various time points (q =19.28,27.39,49.92,P＜0.01 ). Conclusions As one of the PPAR-γexcitomotors,rosiglitazone can inhibit apoptosis of RGCs through downregulating the expression of NF-κB in rat retina with diabetes mellitus,indicating a protective effect of rosiglitazone on retina in diabetic rat.