[Genomic characterization and cluster analysis of Carbapenem-resistant Klebsiella pneumoniae].

To investigate the genomic features and perform cluster analysis of Carbapenem-resistant Klebsiella pneumoniae (CRKP) to provide an experimental basis for guiding the prevention and treatment of CRKP infections.A retrospective case-cohort study was conducted on 19 non-redundant CRKP strains isolated from the Tenth Affiliated Hospital of Southern Medical University between January and June 2023. Whole genome sequencing (WGS) and multilocus sequence typing (MLST) were performed to compare genomic features and analyze the resistance genes and homology of the strains.The results showed that the 19 CRKP strains were isolated from 8 different clinical departments, mainly from respiratory specimens. The whole genome sequencing revealed that the genomic lengths of CRKP ranged from 4.90 to 5.85 Mbp, with contigs N50 values>20 kb for each genome. The median overall GC content was 57.0% (50.4%-57.1%). Comparative genomic analysis identified three regions with high genomic variability. WGS detected 32 resistance genes across 11 categories. All 19 strains carried carbapenem resistance genes (blaKPC-2 and blaOXA-48), blaTEM-1B extended-spectrum ß-lactamase resistance genes, qnrS1 quinolone resistance gene, and fosA fosfomycin resistance gene, with each strain carrying only one carbapenemase gene. The detection rate of blaKPC-2 was 94.7% (18/19). MLST identified three sequence types: ST11, ST437 and ST147, with ST11 being predominant (89.5%, 17/19). Clustering analysis based on acquired resistance genes revealed three clonal transmission patterns among strains 72 and 90, and strains 88, 84, 66 and 79.In conclusion, CRKP strains carry multiple resistance genes, and clustering analysis indicating that nosocomial clonal transmission is closely related to acquired resistance genes. The ST11-blaKPC-2 type strain is the predominant clone. Strengthened surveillance and effective control strategies are necessary to reduce nosocomial transmission of CRKP.

[Association between cardiometabolic diseases and quality of life and the mediation effect of perceived stress].

Objective: To explore the association between cardiometabolic diseases (CMD) and quality of life, the association between CMD and perceived stress, and the mediation effect of perceived stress on the association between CMD and quality of life, and to provide evidence for the prevention and treatment of CMD and the improvement of quality of life in these patients. Methods: This is a cross-sectional study. Data were collected by the employees' physical examination of a company in Xi'an in 2021. Multiple linear regression models were used to analyze the association between the status of CMD (divided into three categories: no CMD, presence of one kind of CMD, and with≥2 kinds of CMD (≥2 kinds of CMD were defined as cardiometabolic multimorbidity (CMM)), quality of life, and perceived stress. Mediation analysis with a multi-categorical independent variable was conducted to determine the mediation effect of perceived stress on the association between CMD and quality of life. Results: Among all 4 272 participants, 1 457 (34.1%) participants had one kind of CMD and 677 (15.8%) participants had CMM. The average scores for quality of life and perceived stress were (57.5±15.7) and (16.9±7.9), respectively. Compared with participants without CMD, after adjusting for demographic and lifestyle factors, no statistically significant associations were observed between one kind of CMD and perceived stress or quality of life (both P>0.05). Perceived stress did not mediate the association between one kind of CMD and quality of life. However, participants with CMM had lower quality of life and higher perceived stress than participants without CMD. The relative total effect coefficient c (95%CI) and the relative direct effect coefficient c' (95%CI) between CMM and quality of life were -3.71 (-5.04--2.37) and -2.52 (-3.81--1.24) (both P<0.05), respectively. The relative indirect effect coefficient a2b (95%CI) of perceived stress on the association between CMM and quality of life was -1.18 (-1.62--0.77) (P<0.05). The mediation effect size was 31.8%. Conclusions: CMM is negatively associated with quality of life and positively associated with perceived stress. Perceived stress partially mediates the association between CMM and quality of life. Our results suggest that, in addition to preventing and treating CMM actively, efforts should be taken to relieve the perceived stress of people with CMM to improve their quality of life.

[Similarities and differences of myocardial metabolic characteristics between HFpEF and HFrEF mice based on LC-MS/MS metabolomics].

Objective: To reveal the similarities and differences in myocardial metabolic characteristics between heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) mice using metabolomics. Methods: The experimental mice were divided into 4 groups, including control, HFpEF, sham and HFrEF groups (10 mice in each group). High fat diet and Nω-nitroarginine methyl ester hydrochloride (L-NAME) were applied to construct a"two-hit"HFpEF mouse model. Transverse aortic constriction (TAC) surgery was used to construct the HFrEF mouse model. The differential expression of metabolites in the myocardium of HFpEF and HFrEF mice was detected by untargeted metabolomics (UHPLC-QE-MS). Variable importance in projection>1 and P<0.05 were used as criteria to screen and classify the differentially expressed metabolites between the mice models. KEGG functional enrichment and pathway impact analysis demonstrated significantly altered metabolic pathways in both HFpEF and HFrEF mice. Results: One hundred and nine differentially expressed metabolites were detected in HFpEF mice, and 270 differentially expressed metabolites were detected in HFrEF mice. Compared with the control group, the most significantly changed metabolite in HFpEF mice was glycerophospholipids, while HFrEF mice presented with the largest proportion of carboxylic acids and their derivatives. KEGG enrichment and pathway impact analysis showed that the differentially expressed metabolites in HFpEF mice were mainly enriched in pathways such as biosynthesis of unsaturated fatty acids, ether lipid metabolism, amino sugar and nucleotide sugar metabolism, glycerophospholipid metabolism, arachidonic acid metabolism and arginine and proline metabolism. The differentially expressed metabolites in HFrEF mice were mainly enriched in arginine and proline metabolism, glycine, serine and threonine metabolism, pantothenate and CoA biosynthesis, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism and arachidonic acid metabolism, etc. Conclusions: HFpEF mice have a significantly different myocardial metabolite expression profile compared with HFrEF mice. In addition, biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, glycerophospholipid metabolism and arginine and proline metabolism are significantly altered in both HFpEF and HFrEF mice, suggesting that these metabolic pathways may play an important role in disease progression in both types of heart failure.

[Efficacy and safety of various doses of hybutimibe monotherapy or in combination with atorvastatin for primary hypercholesterolemia: a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase â ¢ clinical trial].

Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.

[The current research status and thinking on the history of stomatology in modern China].

The research on the history of stomatology in modern China began in the middle of 20th century. The history of stomatology is a branch of medical history and stomatology education research. Most of researches on it were general historical researches, but problems on its medical knowledge dissemination and system, development process and social relations, etc. had not been drawn wider attentions at the moment. In order to innovate the research methods of stomatology history, and to promote the study of stomatology history from the perspective of empirical and cultural mutual corroboration, this article classifies and summarizes the research status, characteristics and trends of the stomatology history in modern China.

Development of explicit formulations of G45-based gas kinetic scheme for simulation of continuum and rarefied flows.

In this work, the explicit formulations of the Grad's distribution function for the 45 moments (G45)-based gas kinetic scheme (GKS) are presented. Similar to the G13 function-based gas kinetic scheme (G13-GKS), G45-GKS simulates flows from the continuum regime to the rarefied regime by solving the macroscopic governing equations based on the conservation laws, which are widely used in conventional Navier-Stokes solver. These macroscopic governing equations are discretized by the finite volume method, where the numerical fluxes are evaluated by the local solution to the Boltzmann equation. The initial distribution function is reconstructed by the G45 distribution function, which is a higher order truncation of the Hermite expansion of distribution function compared with the G13 distribution function. Such high order truncation of Hermite expansion helps the present solver to achieve a better accuracy than G13-GKS. Moreover, the reconstruction of distribution function makes the development of explicit formulations of numerical fluxes feasible, and the evolution of the distribution function, which is the main reason why the discrete velocity method is expensive, is avoided. Several numerical experiments are performed to examine the accuracy of G45-GKS. Results show that the accuracy of the present solver for almost all flow problems is much better than G13-GKS. Moreover, some typical rarefied effects, such as the direction of heat flux without temperature gradients and thermal creep flow, can be well captured by the present solver.

Variant of gas kinetic flux solver for flows beyond Navier-Stokes level.

In this paper, a variant of gas kinetic flux solver (GKFS) is presented for simulation of flows beyond the Navier-Stokes (NS) level. The method retains the framework of GKFS and reconstructs the numerical fluxes by the moments of distribution function at the cell interface, which is given from the local solution of the Boltzmann equation. In the conventional GKFS, the first-order Chapman-Enskog (CE) expansion is utilized to approximate the initial distribution function. By using the differential chain rule, it was found that the CE expansion form could be linked to the stress tensor and the heat flux. For flows in the NS level, the stress tensor and heat flux can be simply calculated from the linearized constitutive relationship and Fourier's law, respectively. However, for flows beyond the NS level, due to the strong nonequilibrium effect, the linearized constitutive relationship and Fourier's law are insufficient to predict the stress tensor and the heat flux. To overcome this difficulty, this paper introduces correction terms to the stress tensor and heat flux in the initial distribution function. These correction terms will take effect in the strong nonequilibrium region for flows beyond the NS level. To avoid finding complex expressions or solving complicated partial differential equations for the correction terms, a simple and iterative procedure is proposed to update the correction terms based on the framework of GKFS. The proposed method is validated by three benchmark cases which cover the flow from the continuum regime to the transition regime. Numerical results show that the present solver can provide accurate solution in the continuum regime. It is indeed the correction terms that take effect in the strong nonequilibrium region for flows beyond the NS level, which enables the present solver to capture the nonequilibrium phenomenon with reasonable accuracy for rarefied flows at moderate Knudsen number.

[Clinical features and treatment outcome of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract].

Objective: To investigate the clinical features and prognosis of extranodal nasal-type NK/T-cell lymphoma of the extra-upper aerodigestive tract (extra-UADT NKTCL). Methods: The clinical data of 159 patients with extra-UADT NKTCL from the China Lymphoma Collaborative Group (CLCG) database between November 2001 and December 2015 were retrospectively analyzed. Kaplan-Meier survival analysis and Log-rank test were used to evaluate the prognosis. The Cox regression model is used for multi-factor analysis. Results: Extra-UADT NKTCL commonly occurs in skin and soft tissues (106/159, 66.7%) and gastrointestinal tract (31/159, 19.5%). The incidences of elevated lactate dehydrogenase (LDH) and Ann Arbor Ⅲ~Ⅳ stage were 47.8% (76/159) and 64.2% (102/159), respectively. The 3-year overall survival (OS) and progression-free survival (PFS) rates were 43.6% and 27.9%, respectively. The corresponding OS rates of primary skin/soft tissue site and gastrointestinal tract site were 41.0% and 59.4% (P=0.281), while the PFS rates were 24.8% and 48.3%, respectively (P=0.109). Combined modality treatment improved the 3-year OS of all the patients (58.4% vs 33.9%, P=0.001) and 3-year PFS (40.7% vs 20.7%, P=0.008) when compared with chemotherapy alone. LDH elevation, Ann Arbor synthesising and ≥2 junction external bits were intrusive as independent risk factors for total survival (P<0.05), LDH elevation and ≥2 junction outer bits were intrusive as independent risk factors for progressionless survival(P<0.05). The distant extranodal dissemination was the primary failure patterns. Conclusions: Extra-UADT NKTCL appears to have distinct clinical characteristics and poor outcome. Compared with chemotherapy alone, combined modality treatment may improve the prognosis of patients with extra-UADT NKTCL.

[Cost-effectiveness of primary prophylaxis with PEG-rhG-CSF in early-stage breast cancer patients receiving chemotherapy in China].

Objective: To evaluate the cost effectiveness of primary prophylaxis (PP) with pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF), PP with recombinant human granulocyte colony stimulating factor (rhG-CSF) and no prophylaxis in women with early-stage breast cancer in China. Methods: Two phase Markov models were constructed for a hypothetical cohort of patients aged 45 with stage Ⅱ breast cancer. The first phase modelled costs and outcomes of 4 cycles docetaxel combined with cyclophosphamide [TC×4, febrile neutropenia (FN) risk>20%] chemotherapy, which assumptions based on literature reviews, including FN rates [base-case (deterministic sensitivity analysis range), 0.29 (0.24-0.35)] and related events [FN case-fatality, 3.4 (2.7-4.1)]. Second phase modelled the long term survival which was link with the relative dose intensity (RDI) [mortality hazard ratio (HR) of RDI < 85% vs ≥85%, 1.45 (1.00-2.32)]. Clinical effectiveness, therapeutic costs, and economic utilities were estimated from peer-reviewed publications and expert opinions in case of unavailability of published evidences. Results: Compared to rhG-CSF PP and no prophylaxis, the cost of PEG-rhG-CSF PP increased to 5 208.19 RMB and 5 222.73 RMB, respectively. The quality-adjusted life-years (QALYs) enhanced to 0.066 and 0.297, respectively. Accordingly, the incremental cost effectiveness ratios (ICERs) are 79 146.3 RMB and 17 558.77 RMB per QALY, which were both below the willingness to pay (WTP) threshold of three times GDP per capita (18, 000 RMB) recommended by the WHO. Sensitivity analysis suggested that the more clinically effective the primary prophylaxis with PEG-rhG-CSF is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. And the lower the mortality HR of RDI<85% vs ≥85% is, the more cost-effective primary prophylaxis with PEG-rhG-CSF will be. Conclusion: Although the cost of PP PEG-rhG-CSF is higher, considering the additional benefits, the administrating of PP PEG-rhG-CSF is likely to be a cost-effective alternative to PP rhG-CSF and no prophylaxis in patients with early stage breast cancer whose FN risks are more than 20% in China.

[Correlation of interleukin-4 gene methylation regulation with the pathogenesis of recurrent aphthous ulcer].

Objetive: To investigate whether the methylation patterns of the interleukin-4 (IL-4) gene promoter changed and whether environmental factors affected the methylation level of IL-4 gene in the peripheral blood of patients with recurrent aphthous ulcer (RAU). Methods: Totally 20 patients, who were diagnosed with RAU, were recruited from May 2018 to May 2019 in the Department of Stomatology， First Hospital of Shanxi Medical University in the study (RAU group), including 12 females and 8 males, with mean age of 16-35 years. During the same period, 20 healthy volunteers matching the age and gender of the RAU group were selected from the medical personnel of the same hospital as the healty control group, including 11 females and 9 males, with mean age of 15-35 years. Peripheral blood samples of two groups were collected and the methylation levels of the IL-4 promoter were detected by bisulfite sequencing PCR (BSP). The IL-4 promoter methylation level of each sample was analyzed by direct sequencing and the IL-4 mRNA level was detected by real-time quantitative PCR. The data obtained were statistically analyzed. Results: The IL-4 gene promoter fragment contained 10 CPG sites from -1400 to -1625 bp. The methylation rates of CPG(-1556), CPG(-1483), CPG(-1479)and 10 CPG sites were significantly higher in RAU group ï¼»(32.0±19.9)%, (53.0±13.4)%, (46.0±19.8)% and (39.3±12.4)%ï¼½ than in healthy control group ï¼»(20.0±3.2)%, (35.5±12.3)%, (28.0±14.4)% and (32.6±5.8)%ï¼½, with statistically significant differences (P<0.05). The relative expression of IL-4 mRNA in the peripheral blood of RAU patients (1.0±0.1) was significantly lower than that of the healthy control group (1.5±0.2) (P<0.01). There was a significant negative correlation between the overall methylation rate of IL-4 gene promoter and the relative expression level of IL-4 mRNA in RAU group (r=-0.494, P<0.05). In the multivariate analysis, smoking, vitamin B12 and folic acid in the RAU group were significantly correlated with the overall methylation rate of the IL-4 gene promoter (P<0.01). Conclusions: The hypermethylation of IL-4 promoter in RAU patients may be related to the reduction of IL-4 gene transcription. Vitamin B12, folic acid and smoking may affect IL-4 gene methylation in peripheral blood of RAU patients.

[Research progress of the relationship between liver regeneration and tumor recurrence after hepatectomy].

Partial hepatectomy is still the preferred modality of treatment for hepatocellular carcinoma.In recent years, a substantial number of in vivo and in vitro tests have been carried out to study how to promote postoperative liver regeneration in order to prevent the occurrence of small-for-size liver syndrome and liver failure. However, several studies have shown that the process of liver regeneration after hepatectomy can actually promote the growth of tumor cells and activate occult micro-focal lesions leading to tumor recurrence. Moreover, cytokines and genes which play crucial roles in the 3 stages of liver regeneration, are involved in the formation, migration, infiltration and recurrence of liver cancer to varying degrees. Achieving a balance between promotion of postoperative liver regeneration and inhibition of tumor recurrence has become a major problem in liver surgery.

[Clinical significance of NS1-BP expression in esophageal squamous cell carcinoma].

Objective: To investigate the clinical significance of NS1-BP expression in patients with esophageal squamous cell carcinoma (ESCC), and to study the roles of NS1-BP in proliferation and apoptosis of ESCC cells. Methods: A total of 98 tumor tissues and 30 adjacent normal tissues from 98 ESCC patients were used as study group and control group, and these samples were collected in Sun Yat-Sen University Cancer Center between 2002 and 2008. In addition, 46 ESCC tissues which were collected in Cancer Institute and Hospital of Tianjin Medical University were used as validation group. Expression of mucosal NS1-BP was detected by immunohistochemistry. Kaplan-Meier curve and log-rank test were used to analyze the survival rate. Multivariate Cox proportional hazard model was used to analyze the prognostic factors. Furthermore, NS1-BP was over expressed or knocked down in ESCC cells by transient transfection. Protein levels of c-Myc were detected by western blot. Cell viability and apoptosis was analyzed by MTT assay and flow cytometry. Results: Among all of tested samples, NS1-BP were down-regulated in 9 out of 30 non-tumorous normal esophageal tissues (30.0%) and 85 out of 144 ESCC tissues (59.0%), respectively, showing a statistically significant difference (P=0.012). In the study group, three-year disease-free survival rate of NS1-BP high expression group (53.2%) was significantly higher than that of NS1-BP low expression group (27.6%; P=0.009). In the validation group, the three-year disease-free survival rates were 57.8% and 25.5% in NS1-BP high and low levels groups, respectively, showing a similar results (P=0.016). Importantly, multivariate analyses showed that low expression of NS1-BP was an independent predictor for chemoradiotherapy sensitivity and shorter disease-free survival time in ESCC patients(P<0.05 for all). Furthermore, overexpressed NS1-BP in TE-1 cells repressed c-Myc expression, inhibited cell proliferation and promoted apoptosis. In contrast, knockdown NS1-BP in KYSE510 cells induced c-Myc expression, increased cell proliferation and repressed apoptosis. Conclusions: NS1-BP is an independent favorable prognostic factor in ESCC. It inhibits cell proliferation and enhances cell apoptosis via repressing c-Myc. Targeting NS1-BP may be a new therapeutic strategy for ESCC patients.

Experimental and observational studies find contrasting responses of soil nutrients to climate change.

Manipulative experiments and observations along environmental gradients, the two most common approaches to evaluate the impacts of climate change on nutrient cycling, are generally assumed to produce similar results, but this assumption has rarely been tested. We did so by conducting a meta-analysis and found that soil nutrients responded differentially to drivers of climate change depending on the approach considered. Soil carbon, nitrogen, and phosphorus concentrations generally decreased with water addition in manipulative experiments but increased with annual precipitation along environmental gradients. Different patterns were also observed between warming experiments and temperature gradients. Our findings provide evidence of inconsistent results and suggest that manipulative experiments may be better predictors of the causal impacts of short-term (months to years) climate change on soil nutrients but environmental gradients may provide better information for long-term correlations (centuries to millennia) between these nutrients and climatic features. Ecosystem models should consequently incorporate both experimental and observational data to properly assess the impacts of climate change on nutrient cycling.

[Efficacy and safety analysis of ivabradine hydrochloride treatment of Chinese patients with chronic heart failure: subgroup analysis of Chinese patients in the SHIFT study].

Objective: To evaluate the efficacy and safety of ivabradine for the treatment of Chinese patients with chronic heart failure based on the Chinese subgroup data of the systolic heart failure treatment with the I(f) inhibitor ivabradine trial (SHIFT). Method: A total of 6 558 stable outpatients who presented symptoms of heart failure, with a left ventricular ejection fraction (LVEF) ≤35%, sinus rhythms with a heart rate ≥70 bpm participated in the randomized, double-blind, placebo-controlled, international multicenter clinical study.The subset of Chinese patients with heart rate ≥75 bpm was enrolled in the post-hoc subgroup analyses.Patients were randomly allocated by computer-generated assignment through a telephone interactive voice response system to ivabradine group (starting dose 5 mg bid, which was then uptitrated to the maximum 7.5 mg bid) or matched placebo group.The clinical baseline characteristics of participants were obtained and analyzed.The primary outcome endpoint was a composite endpoint of cardiovascular death or hospitalization resulting from worsening HF.The primary safety endpoint included total incidence of adverse events during the study, bradycardia, and adverse visual reaction (phosphenes). Results: A total of 49 Chinese centers enrolled a total of 225 patients with chronic heart failure, of whom, 106 patients were randomized to the ivabradine group and the other 119 patients to the placebo group, and the mean follow-up time was (15.6±5.1) months.By the end of the study, mean heart rate (71.0 bpm vs. 80.3 bpm, P<0.05) and incidence of the primary endpoint events (18.9% (20/106) vs. 31.9%(38/119), HR=0.56, 95%CI 0.33-0.97, P=0.039) were significantly lower, while the percentage of patients with improvement in heart functional class NYHA (53.8% (56/106) vs. 34.5% (41/119), P=0.006 1) was significantly higher in the ivabradine group than in the placebo group.The total number of adverse events (129 events, 49.6% PY) in the ivabradine group was lower than that in the placebo group (203 events, 50.8% PY). In the ivabradine group and the placebo group, there were respectively 2 patients (1.9%) and 0 patients experienced bradycardia, 3 patients (2.9%) and 1 patient (0.8%) experienced adverse visual reaction (phosphenes). Conclusions: Ivabradine significantly reduced heart rate and improved the clinical outcomes and NYHA function class in Chinese patients with chronic heart failure, these beneficial effects are achieved without inducing remarkable adverse reactions.The results of Chinese subgroup analysis were thus consistent with the overall results of the SHIFT study. Clinical Trial Registry: International standard randomized controlled trials registry, ISRCTN 70429960.

[Clinical features and significance of cirrhosis-associated immune dysfunction].

Cirrhosis-associated immune dysfunction (CAID) refers to immunodeficiency and systemic inflammation in cirrhotic patients and is the characteristic pathophysiological change of liver cirrhosis of various causes. The phenotype of CAID changes dynamically with the progression of liver cirrhosis. In patients with stable cirrhotic ascites, CAID is manifested as "pro-inflammatory" state, and in patients with severe decompensated liver cirrhosis complicated by extrahepatic organ failure, it is manifested as "immunodeficiency". CAID affects the clinical manifestations and prognosis of liver cirrhosis, aggravates the condition of cirrhotic patients, and increases the risk of infection. This article briefly introduces the mechanism, features, and clinical significance of CAID.

Genetic variants in adiponectin and blood pressure responses to dietary sodium or potassium interventions: a family-based association study.

Previous studies have shown that genetic factors might have an important role in blood pressure (BP) responses to dietary salt or potassium intake. The aim of this study was to assess the association of common genetic variants of the adiponectin gene with BP responses to controlled dietary sodium or potassium interventions. Subjects (n=334) from 124 families in rural areas of Northern China were recruited. After a 3-day baseline observation, participants sequentially maintained a 7-day low-sodium diet (NaCl, 3 g per day; or sodium, 51.3 mmol per day), followed by a 7-day high-sodium diet (NaCl, 18 g per day; or sodium, 307.8 mmol per day) and a 7-day high-sodium plus potassium supplementation intervention (KCl, 4.5 g per day; or potassium, 60 mmol per day). A total of seven single nucleotide polymorphisms (SNPs) in the adiponectin gene were selected as the study sites. After adjustment for multiple testing, the adiponectin SNP rs16861205 was significantly associated with the diastolic BP (DBP) response to low-salt intervention, and the DBP and mean arterial pressure (MAP) responses to high-salt intervention (P=0.028, 0.023 and 0.027, respectively). SNP rs822394 was associated with the DBP and MAP responses to low-salt intervention and the DBP response to high-salt intervention (P=0.023, 0.030 and 0.033 respectively). Meanwhile, significant association also existed between SNP rs16861194 and the systolic BP response to potassium supplementation intervention (P=0.026). In addition, SNP rs822394 was significantly associated with basal DBP after adjustment for multiple testing (P=0.033). Our study indicated that the genetic polymorphisms in the adiponectin gene are significantly associated with BP responses to dietary sodium and potassium intake.

Anthropogenic disturbances are key to maintaining the biodiversity of grasslands.

Although anthropogenic disturbances are often perceived as detrimental to plant biodiversity, the relationship between biodiversity and disturbance remains unclear. Opinions diverge on how natural diversity is generated and maintained. We conducted a large-scale investigation of a temperate grassland system in Inner Mongolia and assessed the richness-disturbance relationship using grazing intensity, the primary anthropogenic disturbance in the region. Vascular plant-species richness peaked at an intermediate level of anthropogenic disturbance. Our results support the Intermediate Disturbance Hypothesis, which provides a valid and useful measure of biodiversity at a metacommunity scale, indicating that anthropogenic disturbances are necessary to conserve the biodiversity of grassland systems.

[Effect of radiation dose and dose rate on pulmonary fibrosis in mice].

OBJECTIVE: To study the effect of radiation dose and dose rate on radiation-induced pulmonary fibrosis in mice. METHODS: Twenty-four C57BL/6 mice were randomly divided into a control group (n=6) and an irradiation group(n=18). The irradiation group was further assigned to 3 subgroups according to the whole lung radiation with 15 Gy at 400 cGy/min, 20 Gy at 400 cGy/min and 20 Gy at 100 cGy/min, while the control group received sham-irradiation. All mice were scanned with computed tomograph (CT) 20 weeks post-irradiation, and then they were sacrificed and lung tissues were collected. H&E staining, sirius red staining, lung fibrosis scored and hydroxyproline content analysis were used to assess lung fibrosis and collagen deposition. Real time PCR was used to measure the mRNA expression of type Ⅰ collagen. Immunohistochemical staining was used to detect the activatin and distribution of a-SMA(+) -myofibroblasts. RESULTS: Compared to the control group, mice from irradiation groups exhibited significant pulmonary consolidation and collagen deposition.At the same dose rate, the higher irradiated dose used, the more severe pulmonary fibrosis was.On the other hand, with the same dose, the dose rate had less effect on pulmonary fibrosis. CONCLUSION: The effect of radiation dose on the degree of pulmonary fibrosis in mice is more than effect of the dose rate.