Unraveling the draft genome and phylogenomic analysis of a multidrug-resistant Planococcus sp. NCCP-2050T: a promising novel bacteria from Pakistan.

Planococcus is a genus of Gram-positive bacteria known for potential industrial and agricultural applications. Here, we report the first draft genome sequence and phylogenomic analysis of a CRISPR-carrying, multidrug-resistant, novel candidate Planococcus sp. NCCP-2050T isolated from agricultural soil in Pakistan. The strain NCCP-2050T exhibited significant resistance to various classes of antibiotics, including fluoroquinolones (i.e., ciprofloxacin, levofloxacin, ofloxacin, moxifloxacin, and bacitracin), cephalosporins (cefotaxime, ceftazidime, cefoperazone), rifamycins (rifampicin), macrolides (erythromycin), and glycopeptides (vancomycin). Planococcus sp. NCCP-2050T consists of genome size of 3,463,905 bp, comprised of 3639 annotated genes, including 82 carbohydrate-active enzyme genes and 39 secondary metabolite genes. The genome also contained 80 antibiotic resistance, 162 virulence, and 305 pathogen-host interaction genes along with two CRISPR arrays. Based on phylogenomic analysis, digital DNA-DNA hybridization, and average nucleotide identity values (i.e., 35.4 and 88.5%, respectively) it was suggested that strain NCCP-2050T might represent a potential new species within the genus Planococcus. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03748-z.

Risk stratification for worsening renal function and renal decline in heart failure patients with reduced ejection fraction after sacubitril/valsartan treatment.

BACKGROUND: In the real-world setting, data regarding renal decline following sacubitril/valsartan treatment are lacking. This study aimed to develop a scoring system to predict renal outcome in sacubitril/valsartan-treated patients. METHODS: Between 2017 and 2018, a total of 1505 heart failure patients with reduced ejection fraction (HFrEF) undergoing sacubitril/valsartan treatment were consecutively enrolled from 10 hospitals to serve as the derivation cohort. Another 1620 HFrEF patients receiving sacubitril/valsartan were included as the validation cohort. Worsening renal function (WRF) was defined as a serum creatinine increase of >0.3 mg/dL and/or >25 % at 8 months of sacubitril/valsartan treatment. The derivation cohort was used to identify independent predictive factors for WRF through multivariate analysis, which were then used to develop the risk score system. RESULTS: Among the 3125 HFrEF patients, 689 (22.0 %) patients had WRF at 8 months following sacubitril/valsartan treatment. In the derivation cohort, six prognostic factors (age, functional class, history of peripheral arterial disease, diabetes mellitus, gout or hyperuricemia, and serum albumin level) were independently associated with WRF, and were combined into a risk predicting score. This score showed accurate discrimination in the derivation and validation cohorts (Harrell's concordance indexes 0.74 and 0.71, 95 % confidence intervals 0.71-0.78 and 0.69-0.74, respectively). Patients with a higher risk score experienced a more rapid decline in renal function, poorer clinical outcomes, and a higher rate of discontinuation of sacubitril/valsartan treatment. CONCLUSIONS: This study developed a score for WRF after sacubitril/valsartan treatment, which may assist clinicians with risk stratification and therapeutic decision-making.

Effects of Ivabradine on Patients with Depressed Left Ventricular Function after Cardiac Resynchronization Therapy.

Background: The potential synergistic effect of ivabradine and cardiac resynchronization therapy (CRT) in heart failure (HF) patients has rarely been studied. We aimed to evaluate the clinical benefits of ivabradine in patients with left ventricular dysfunction following CRT implantation. Methods: Two hundred and thirty-one patients receiving CRT were consecutively enrolled between January 2014 and December 2018 from two HF centers. A total of 123 patients had left ventricular ejection fraction (LVEF) < 40% and resting sinus heart rate (HR) ≥ 75 bpm after six months of CRT implantation. Among these patients, 45 were treated with ivabradine (Group 1), and 78 did not receive ivabradine treatment (Group 2). Results: Baseline characteristics and prescription rates of HF medications other than ivabradine were similar between the two groups. In Group 1, the mean HR decreased from 82.2 ± 11.4 bpm to 76.3 ± 10.5 bpm (p = 0.012), and the mean LVEF increased from 29.9 ± 6.5% to 38.8 ± 12.4% (p < 0.001). Atrial pacing percentage, biventricular pacing percentage, and burden of atrial fibrillation (AF) were not significantly different between the two groups during the study period. The patients' daily physical activity increased significantly in Group 1 compared to Group 2 (Δ daily activity 0.4 ± 0.7 hours/day vs. -0.1 ± 7.2 hours/day, p < 0.001). Conclusions: Ivabradine could effectively reduce HR and improve physical activity. It was safe to use and did not increase AF burden or affect biventricular pacing percentage in CRT recipients.

Preliminary practice in the postoperative cardiopulmonary exercise testing for children with congenital heart disease / 中华心血管病杂志

Objective: To investigate the postoperative cardiopulmonary fitness of children with congenital heart diseases (CHD). Methods: This is a retrospective study. A total of 136 children after cardiac correction undergoing cardiopulmonary exercise test (CPET) in Shanghai Children's Medical Center from March 1 to June 30, 2021 were selected. According to the surgical procedure, the children were divided into two groups: the biventricular correction group (BV group) (n=75) and single ventricular correction group (SV group) (n=61). The BV group was divided into two subgroups: simple congenital heart disease (S-CHD) group (n=35) and complex congenital heart disease (C-CHD) group (n=40). CPET parameters, including VO2 max, VO2/kg max, VO2/kg@AT, O2/HR max, HRR, PetCO2 max, CI, HRR at 1 min, VE/VCO2 slope, OUES/kg and EOV, were analyzed. CPET parameters of patients underwent different procedure were compared. In the subgroup analysis, CPET parameters of patients in S-CHD group and C-CHD group were compared. The parameters of the BV group were compared with the normal value. Linear correlation analysis was used to identify the correlation between the CPET parameters. Results: A total of 136 children with CHD after surgery were enrolled. The age was (9.4±3.1) (ranged 6.2-16.0) years, and there was 84 (61.8%) male. All the children completed CPET examination safely without experiencing serious circulation abnormalities. Compared with the SV group, the VO2/kg max ((32.6±6.9) ml·kg-1·min-1 vs. (23.5±5.9) ml·kg-1·min-1, P<0.001), O2/HR max ((7.24±2.93) ml/beat vs. (6.35±2.17)ml/beat, P=0.030), HRR at 1 min ((32.5±13.9) beat/min vs. (26.3±12.5) beat/min, P=0.036), OUES/kg (36.9±8.8 vs. 29.7±11.8, P=0.001) were significantly higher, VE/VCO2 slope (29.1±5.20 vs. 35.1±8.0, P<0.001) and incidence of EOV (32.0%(24/75) vs. 57.4%(31/61), P=0.027) were significantly lower in BV group. Compared with the simple CHD subgroup, VE/VCO2 slope and the incidence of EOV were higher, VO2/kg max, O2/HR max, HRR at 1 min and OUES/kg were lower in the complex CHD subgroup (all P<0.05). Cardiopulmonary function parameters of the BV group were lower than the normal value. Linear correlation analysis showed that VO2/kg@AT was strongly correlated with VO2/kg max (r=0.86, P<0.001), VO2/kg max was strongly correlated with OUES/kg (r=0.63, P<0.001), HRR was strongly correlated with CI (r=0.91, P<0.001), and VO2/kg max was strongly correlated with OUES/kg (r=0.63, P<0.001). VE/VCO2 slope was strongly correlated with PetCO2 max (r=1.00, P<0.001). Conclusions: The exercise cardiopulmonary function of children after single ventricular correction is weaker than that of biventricular correction, and the exercise tolerance of children after biventricular correction is lower than that of normal children. Among the children after biventricular correction, the exercise tolerance of children with complex CHD is lower than that of children with simple CHD. Postoperative CPET is of important realistic significance for CHD children.

The Characteristics and Outcomes of Patients with Heart Failure and Reduced Ejection Fraction: The Eligibility of Novel Heart Failure Medications.

BACKGROUND: Renin-angiotensin system inhibitors and beta-blockers are the initial treatment of choice for heart failure with reduced ejection fraction (HFrEF), whereas sacubitril/valsartan (SAC/VAL) and ivabradine are considered to second-line therapies. The eligibility of SAC/VAL and ivabradine according to the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA) labels, Taiwan National Health Insurance (TNHI) reimbursement regulations, and European Society of Cardiology (ESC) heart failure (HF) guidelines are diverse, and they may not fulfill the needs of real-world HFrEF patients. METHODS: Patients hospitalized for HF with left ventricular ejection fraction (LVEF) ≤ 40% were recruited from 21 hospitals in Taiwan between 2013 and 2014. The criteria for SAC/VAL and ivabradine according to the different regulations were applied. RESULTS: Of 1,474 patients, 86.8%, 29.4%, and 9.5% met the EMA/FDA label criteria, TNHI-regulation, and ESC guidelines for SAC/VAL, compared to 47.1%, 37.2%, and 45.6% for ivabradine, respectively. Ineligible reasons for the TNHI regulations included LVEF > 35% (19.9%, for SAC/VAL and ivabradine) and sinus rate < 75 beats per minute (bpm) (29.9%, for ivabradine). Although not meeting the TNHI regulations, patients with LVEF 35-40% had a similar 1-year mortality rate (15.6% vs. 15.8%, p = 0.876) to those with LVEF ≤ 35%, whereas patients with a sinus rate 70-74 bpm had a similar 1-year mortality rate (15.3% vs. 16.1%, p = 0.805) to those with a sinus rate ≥ 75 bpm. CONCLUSIONS: Approximately 70% and 63% of TSOC-HFrEF registry patients were ineligible for SAC/VAL and ivabradine, respectively, according to current TNHI regulations. Regardless of the eligibility for novel HFrEF medications, the high incidence of adverse events suggests that all patients should be treated cautiously.

Prescription patterns of diabetes medications influencing clinical outcomes of heart failure patients with reduced ejection fraction.

AIMS: We collected the different prescription patterns of diabetes medications in a cohort of patients with heart failure with reduced ejection fraction (HFrEF) and analysed the impact of different prescription patterns on clinical outcomes. METHODS AND RESULTS: Consecutive diabetic patients with HFrEF from a heart failure referral centre were retrospectively analysed between 2015 and 2016. Exclusion criteria include being lost to follow-up, not receiving diabetes medications, and having severe renal impairment with a glomerular filtration rate < 30 mL/min/1.73 m2 . Prescription of diabetes medications and the respective clinical outcomes were collected between 2016 and 2018. Among 381 patients (mean age, 64.8 ± 12.8 years; 71.9% male; mean left ventricular ejection fraction, 27.6 ± 7.0%; mean body mass index, 26.1 ± 4.7 kg/m2 ), the prescription rates of sodium-glucose co-transporter 2 inhibitor (SGLT2i) increased from 10.3% in 2016 to 17.6% in 2017 and 26.5% in 2018 (P < 0.001); the prescription rates of metformin, sulfonylurea, insulin, and dipeptidyl peptidase-4 inhibitors did not change significantly over time. The prescription rates of metformin and SGLT2i were significantly higher in patients managed by cardiologists than non-cardiologists (in 2018, 71.1% vs. 44.2% for metformin, 45.4% vs. 9.9% for SGLT2i, both P < 0.001). During the study period, annualized event rates of cardiovascular death or first unplanned HF hospitalization were 19.0 per 100 patient-years. After a multivariate analysis, prescriptions of metformin {odds ratio (OR): 0.49 [95% confidence interval (CI) 0.27-0.51], P < 0.001} and SGLT2i [OR: 0.52 (95% CI 0.28-0.98), P = 0.042] were independently associated with lower annualized event rates of cardiovascular death or unplanned HF hospitalization. CONCLUSIONS: Prescription patterns of diabetes medications in diabetics with HFrEF were diverse among different specialists. Prescriptions of metformin and SGLT2i were associated with favourable clinical outcomes. Our finding indicates the importance of awareness of beneficial effect of different classes of diabetes medications and collaboration between specialists in the management of diabetic HFrEF patients.

Recovery of left ventricular dysfunction after sacubitril/valsartan: predictors and management.

BACKGROUND: Literature describing recovery of left ventricular (LV) function post sacubitril/valsartan treatment and the optimal management of heart failure (HF) patients receiving sacubitril/valsartan remain sparse. METHODS: We recruited 437 consecutive chronic HF patients with baseline left ventricular ejection fraction (LVEF) less than 40%, who were treated with sacubitril/valsartan. All patients underwent routine echocardiographic measurement. RESULTS: During treatment period, recovery of LVEF to 50% or greater was observed in 77 (17.6%) patients. After multivariate analysis, recovery of LV dysfunction was associated with non-ischemic etiology of HF, smaller baseline LV end-diastolic diameter (LVEDD), and higher initial dosage of sacubitril/valsartan. Compared to those without recovery of LV dysfunction, death from cardiovascular causes or first unplanned hospitalization for HF (CVD/HFH) were significantly lower in patients with LVEF recovery [11.7% vs. 24.4%, hazard ratio (HR) 0.42, p = 0.014]. Among patients with recovery of LVEF, 51 patients continued to receive the same dosage of sacubitril/valsartan had higher LVEF and were less likely to have deterioration of LVEF than the other 26 patients who received either tapering dose of sacubitril/valsartan or switching from sacubitril/valsartan to renin-angiotensin-system blockers (LVEF 56.4 ± 5.3% vs. 45.0 ± 12.8%, p < 0.001; ΔLVEF 1.2 ± 5.1% vs. -9.3 ± 12.0%, p < 0.001). CVD/HFH occurred more frequently in the taper group than the maintenance group (23.1% vs. 5.9%, HR 0.22, p = 0.035). CONCLUSIONS: Non-ischemic etiology of HF, smaller baseline LVEDD, and higher initial dosage of sacubitril/valsartan could predict better recovery of LV function. Among patients with functional recovery, tapering sacubitril/valsartan dose was associated with deterioration of recovered heart function and had less favorable prognosis during follow-up.

Elective Splenectomy Combined with Modified Hassab's or Sugiura Procedure for Portal Hypertension in Decompensated Cirrhosis.

Objective: Portal hypertension is a major complication of decompensated cirrhosis. In China, modified Hassab's and Sugiura procedure are the two major methods of nonshunting surgery. This study aims to compare the efficacy and safety of the two procedures for portal hypertension. Method: Between January 1994 and December 2009, 172 elective patients diagnosed with decompensated cirrhosis with significant hypersplenism adopted elective splenectomy for hypersplenism, and also modified Hassab's (n = 91) or Sugiura (n = 81) procedure was additionally performed to reduce the risk of variceal bleeding. Postoperative mortality and morbidity data were collected, and a retrospectively comparative analysis was conducted. Results: All of the patients were treated successfully without death during operation, and no variceal bleeding occurred during hospitalization. There were 4 (4.4%) deaths in Hassab's group and 3 (3.7%) deaths in Sugiura group postoperatively (P > 0.05). During follow-up, the survival rate was 90.2%, 82.42%, and 71.43% in Hassab's group and 96.29%, 81.48%, and 75.31% in Sugiura group in 1, 3, and 5 years (P > 0.05). There were 22/71 and 12/63 patients in each groups who suffered no deadly variceal bleeding (P = 0.11). Bleeding related death and no bleeding related death occurred in 7/23 and 3/13 patients in each group (P = 0.26 and 0.14, respectively). Conclusion: Elective splenectomy combined with modified Sugiura procedure seemed to be associated with a reduced trend of no deadly variceal bleeding compared with Hassab's procedure. As statistical significance was not found, further large scale and prospective study was warranted.

Sacubitril/valsartan in heart failure with reduced ejection fraction patients: Real world experience on advanced chronic kidney disease, hypotension, and dose escalation.

BACKGROUND: Angiotensin receptor and neprilysin inhibition (ARNI) has been shown to reduce cardiovascular mortality by 20% as compared with enalapril in a randomized controlled trial. However, there is a paucity of real-world data on the effects of ARNI in heart failure patients with reduced ejection fraction (HFrEF), especially those with concurrent renal impairment or hypotension. METHODS: Between 2016 and 2017, we recruited 466 HFrEF patients treated with sacubitril/valsartan (Group A) and 466 patients managed with standard HF treatment without ARNI (Group B) in a HF referral center. Baseline characteristics and clinical outcomes were collected between both groups. RESULTS: Baseline characteristics were comparable between the two groups. During a follow-up period of 15 months, death from cardiovascular causes or first unplanned hospitalization for HF occurred in 100 patients in Group A (21.5%) and 144 in Group B (30.9%, hazard ratio 0.66; 95% CI 0.51-0.85; p=0.001). The incidences of deaths from any causes, cardiovascular death, sudden death, and HF re-hospitalization were all significantly lower in Group A than Group B patients. Among patients with different chronic kidney disease stages and normotensive patients, treatment with sacubitril/valsartan showed more favorable outcomes than treatment with standard HF care without ARNI. However, in patients with baseline systolic blood pressure lower than 100mmHg, there were no significant differences of outcomes in both groups. Among Group A patients, escalation of sacubitril/valsartan was associated with better outcomes. CONCLUSIONS: Our study demonstrated the effectiveness of sacubitril/valsartan on HFrEF patients in real world practice, including those with advanced renal impairment.

Managements and outcomes of hospitalized heart failure patients with paroxysmal vs nonparoxysmal atrial fibrillation in Taiwan.

BACKGROUND: The prognostic significance and the optimal treatment strategy for patients with atrial fibrillation (AF) and heart failure (HF) remain controversial. METHODS: We extracted data from a large prospective national database involving Taiwanese patients with AF who were hospitalized for acute HF with reduced ejection fraction. Baseline characteristics, AF types, medications, and 1-year outcomes of the patients were analyzed. RESULTS: At baseline, 393 (26%) patients had AF, including 117 (29.8%) patients with paroxysmal AF (PAF) and 276 (70.2%) with nonparoxysmal AF (N-PAF). Patients with PAF were more likely to have ischemic cardiomyopathy (47.3% vs 29.7%, p = 0.021), chronic kidney disease (46.2% vs 29.0%, p = 0.001), and higher CHA2DS2-VASc score (4.0 vs 3.6, p = 0.033) compared with patients with N-PAF; however, patients with N-PAF had larger left atrial diameter (50.5 vs 47.3 mm, p = 0.004) than patients with PAF. Patients with PAF were more likely to receive treatment with amiodarone (31.6% vs 13.8%, p < 0.001) and antiplatelet agents (54.1% vs 42.5%, p = 0.041) but less likely to receive treatment with renin-angiotensin system blockers (52.3% vs 64.9%, p = 0.021) and anticoagulants (33.3% vs 50%, p = 0.003) compared with patients with N-PAF at discharge. The 1-year mortality (26.2% vs 16.5%, p = 0.024) and non-HF-related death rates (13.1% vs 5%, p = 0.005) were significantly higher in patients with PAF, whereas HF and arrhythmic death rates were similar in both groups (13.1% vs 11.5%). CONCLUSION: Among patients with HF complicated with AF, those with PAF were more likely to receive antiarrhythmic agents, less likely to receive guideline-recommended therapy, but developed worse 1-year outcome compared with patients with N-PAF. These findings further emphasize the importance of optimal guideline-recommended medical therapy in patients with HF.

Construction and anti-tumor efficacy of a peptide vaccine that targets calcium-binding protein S100A9 / 药学学报

Calcium-binding protein S100A9 is closely related to inflammation and tumor invasion, and is one of the specific markers of myeloid-derived suppressor cells (MDSC). In this study, a recombinant polypeptide vaccine CTB-S100A9 targeting mouse calcium-binding protein S100A9 was constructed by fusion cholera toxin B subunit (CTB) with S100A9 gene. The CTB-S100A9 fusion protein was expressed in E coli. and purified by Ni+ affinity chromatography. Vaccinate the purified recombinant CTB-S100A9 protein supplemented with aluminum hydroxide adjuvant can break the autoimmune tolerance and produce high titer of S100A9 antibody in mice. Moreover, the S100A9 antibody produced by CTB-S100A9 vaccination is more specific and does not cross-react with S100A8. In the mouse 4T1 breast cancer model, CTB-S100A9 vaccination not only has significant tumor prevention effects, but also has significant tumor therapeutic effects. In addition, CTB-S100A9 significantly inhibited lung metastasis in 4T1 mice breast cancer model. Further analysis by flow cytometry showed that CTB-S100A9 vaccination can significantly reduce the tumor induced Treg cells and granulocyte-derived MDSC in 4T1 mice model, and reverse the tumor immunosuppressive environment, thereby promote the anti-tumor efficacy. The animal experiments in this study were carried out under the animal care guidelines approved by the Animal Ethics Committee of the Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine. This study shows that CTB-S100A9 is a good recombinant vaccine that targets the tumor immune-suppression environment and has great potential for the future clinical application.

PRISMA-efficacy and safety of lixisenatide for type 2 diabetes mellitus: A meta-analysis of randomized controlled trials.

OBJECTIVE: We aimed to systematically evaluate the efficacy and safety of lixisenatide in patients with type 2 diabetes mellitus. METHODS: PubMed, EMBASE, Cochrane Library, ClinicalTrials.gov, Google, Web of Science and the Chinese Science Citation Database were searched up to March 2018. Randomized controlled trials determining the efficacy and safety of lixisenatide in patients with type 2 diabetes mellitus were eligible for inclusion. Two authors independently extracted the data in a prespecified Microsoft Excel spreadsheet. A meta-analysis was performed using Review Manager 5.3 software. Weighted mean difference (WMD) and relative risk (RR) together with their corresponding 95% confidence intervals (CIs) were estimated, and only the random effects model was used in order to achieve a more conservative estimate of the efficacy and safety. RESULTS: Fourteen multicenter randomized controlled trials involving 11,947 patients were eligible for inclusion. Compared to placebo, lixisenatide could more significantly reduce the level of HbA1c (WMD=-0.44; 95% confidence interval [CI] [-0.55,-0.33]), and a higher proportion of lixisenatide-treated patients achieved the HbA1c level of < 7.0% (RR = 1.89, 95% CI [1.75-2.03]) and < 6.5% (RR = 3.03, 95% CI [2.54-3.63]) than the placebo-treated patients. Lixisenatide was also associated with a significant reduction in fasting plasma glucose and 2-hour postprandial plasma glucose levels. The risks for any adverse events, gastrointestinal adverse events, and symptomatic hypoglycemia significantly increased in the lixisenatide-treatedment group compared to those in the placebo group. However, lixisenatideit did not increase the risks of serious adverse events, death, or severe hypoglycemia. CONCLUSIONS: Lixisenatide was more effective than placebo in patients with type 2 diabetes mellitus, and the mild-to-moderate adverse events were found to be tolerated during the follow-up.

Impact of Renal Denervation on Atrial Arrhythmogenic Substrate in Ischemic Model of Heart Failure.

BACKGROUND: Myocardial infarction increases the risk of heart failure (HF) and atrial fibrillation. Renal denervation (RDN) might suppress the development of atrial remodeling. This study aimed to elucidate the molecular mechanism of RDN in the suppression of atrial fibrillation in a HF model after myocardial infarction. METHODS AND RESULTS: HF rabbits were created 4 weeks after coronary ligation. Rabbits were classified into 3 groups: normal control (n=10), HF (n=10), and HF-RDN (n=6). Surgical and chemical RDN were approached through midabdominal incisions in HF-RDN. Left anterior descending coronary artery in HF and HF-RDN was ligated to create myocardial infarction. After electrophysiological study, the rabbits were euthanized and the left atrial appendage was harvested for real-time polymerase chain reaction analysis and Trichrome stain. Left atrial dimension and left ventricular mass were smaller in HF-RDN by echocardiography compared with HF. Attenuated atrial fibrosis and tyrosine hydroxylase levels were observed in HF-RDN compared with HF. The mRNA expressions of Cav1.2, Nav1.5, Kir2.1, KvLQT1, phosphoinositide 3-kinase, AKT, and endothelial nitric oxide synthase in HF-RDN were significantly higher compared with HF. The effective refractory period and action potential duration of HF-RDN were significantly shorter compared with HF. Decreased atrial fibrillation inducibility was noted in HF-RDN compared with HF (50% versus 100%, P<0.05). CONCLUSIONS: RDN reversed atrial electrical and structural remodeling, and suppressed the atrial fibrillation inducibility in an ischemic HF model. The beneficial effect of RDN may be related to prevention of the downregulation of the phosphoinositide 3-kinase/AKT/endothelial nitric oxide synthase signaling pathway.

Probiotics Reduce Postoperative Infections in Patients Undergoing Colorectal Surgery: A Systematic Review and Meta-Analysis.

Background. We performed this meta-analysis to investigate the efficacy of probiotics on prevention of infection-related complications following colorectal resection. Method. PubMed, EMBASE, Cochrane Library, and the Web of Science were searched up to January 2016. According to the results, only randomized controlled trials that compared the efficacy of probiotics on patients with colorectal resection were included for meta-analysis. Results. Nine studies including a total of 1146 patients met the criteria (556 received multistrain probiotic bacteria, 590 with non-multistrain probiotic bacteria). The combination of multistrain probiotics was beneficial in the reduction of total infections (OR = 0.30, 95%CI: 0.15-0.61, p = 0.0009), including surgical site infections (SSI) (OR = 0.48, 95%CI: 0.25-0.89, p = 0.02) and nonsurgical site infections (NSSI) (OR = 0.36, 95%CI: 0.23-0.56, p < 0.00001). However, there was no significant reduction in total infections (OR = 0.74, 95%CI: 0.50-1.09, p = 0.13) or SSI (OR = 0.77, 95%CI: 0.52-1.12, p = 0.17) with the application of non-multistrains of probiotics. Conclusion. Combinations of multistrain probiotic bacteria showed promise in preventing the incidence of infections following colorectal surgery. However, the efficacy of one or two strains of probiotics remains undetermined.

Rhodiola Inhibits Atrial Arrhythmogenesis in a Heart Failure Model.

INTRODUCTION: Rhodiola, a popular plant in Tibet, has been proven to decrease arrhythmia. The aim of this study was to elucidate the molecular mechanism and electrophysiological properties of rhodiola in the suppression of atrial fibrillation. METHODS: This study consisted of 3 groups as follows: Group 1: normal control rabbits (n = 5); Group 2: rabbits with heart failure (HF) created by coronary ligation and who received 2 weeks of water orally as a placebo (n = 5); and Group 3: rabbits with HF who received 2 weeks of a rhodiola 270 mg/kg/day treatment orally (n = 5). The monophasic action potential, histology, and real-time polymerase chain reaction (RT-PCR) analysis of ionic channels and PI3K/AKT/eNOS were examined. RESULTS: Compared with the HF group, attenuated atrial fibrosis (35.4 ± 17.4% vs. 16.9 ± 8.4%, P = 0.05) and improved left ventricular (LV) ejection fraction (51.6 ± 3.4% vs. 68.0 ± 0.5%, P = 0.001) were observed in the rhodiola group. The rhodiola group had a shorter ERP (85.3 ± 6.8 vs. 94.3 ± 1.2, P = 0.002), APD90 (89.3 ± 1.5 vs. 112.7 ± 0.7, P < 0.001) in the left atrium (LA), and decreased AF inducibility (0.90 ± 0.04 vs. 0.42 ± 0.04, P < 0.001) compared with the HF group. The mRNA expressions of Kv1.4, Kv1.5, Kv4.3, KvLQT1, Cav1.2, and SERCA2a in the HF LA were up-regulated after rhodiola treatment. The rhodiola-treated HF LA demonstrated higher mRNA expression of PI3K-AKT compared with the HF group. CONCLUSIONS: Rhodiola reversed LA electrical remodeling, attenuated atrial fibrosis and suppressed AF in rabbits with HF. The beneficial electrophysiological effect of rhodiola may be related to upregulation of Kv1.4, Kv1.5, Kv4.3, KvLQT1, Cav1.2, SERCA2a, and activation of PI3K/AKT signaling.

Hemodynamics and vasoactive substance levels during renal congestion that occurs in the anhepatic phase of liver transplantation.

AIM: To explore hemodynamics and vasoactive substance levels during renal vein congestion that occurs in the anhepatic phase of liver transplantation. METHODS: New Zealand rabbits received ligation of the hepatic pedicle, supra-hepatic vena cava and infra-hepatic vena cava [anhepatic phase group (APH); n = 8], the renal veins (RVL; n = 8), renal veins and hepatic pedicle [with the inferior vena cava left open) (RVHP; n = 8)], or a sham operation (SOP; n = 8). Hemodynamic parameters (systolic, diastolic, and mean arterial blood pressures) and the levels of serum bradykinin (BK) and angiotensin II (ANGII) were measured at baseline (0 min), and 10 min, 20 min, 30 min, and 45 min after the surgery. Correlation analyses were performed to evaluate the associations between hemodynamic parameters and levels of vasoactive substances. RESULTS: All experimental groups (APH, RVL, and RVHP) showed significant decreases in hemodynamic parameters (systolic, diastolic, and mean arterial blood pressures) compared to baseline levels, as well as compared to the SOP controls (P < 0.05 for all). In contrast, BK levels were significantly increased compared to baseline in the APH, RVL, and RVHP groups at all time points measured (P < 0.05 for all), whereas no change was observed in the SOP controls. There were no significant differences among the experimental groups for any measure at any time point. Further analyses revealed that systolic, diastolic, and mean arterial blood pressures were all negatively correlated with BK levels, and positively correlated with ANGII levels in the APH, RVL, and RVHP groups (P < 0.05 for all). CONCLUSION: In the anhepatic phase of orthotopic liver transplantation, renal vein congestion significantly impacts hemodynamic parameters, which correlate with serum BK and ANGII levels.

Laparoscopic Roux-en-Y gastric bypass versus sleeve gastrectomy for obese patients with Type 2 diabetes: a meta-analysis of randomized controlled trials.

We aimed to evaluate the efficacy and safety of laparoscopic Roux-en-Y gastric bypass versus sleeve gastrectomy for obese patients with Type 2 diabetes. We searched the Cochrane Library, PubMed, EMBASE, Google Scholar, and the Chinese Wan fang database up to October 2013. Randomized controlled trials regarding the efficacy and safety of laparoscopic gastric bypass versus sleeve gastrectomy for obese diabetic patients were included. Two review authors independently abstracted data and assessed the risk of bias. The mean difference and relative risk were estimated with 95 per cent confidence intervals. Four randomized controlled trials met inclusion criteria. There was no significant difference between gastric bypass and sleeve gastrectomy groups with regard to glycosylated hemoglobin (mean difference [MD], 0.41%; 95% confidence interval [CI], -0.09 to 0.91), fasting plasma glucose (standardized MD, 0.61 mg/mL; 95% CI, -0.10 to 1.32), the numbers of subjects using oral antihyperglycemic medications and insulin (relative rate [RR], 1.53; 95% CI, 0.45 to 5.24; RR, 1.44; 95% CI, 0.47 to 4.39, respectively), body weight (MD, 0.42 kg; 95% CI, -5.01 to 5.85), body mass index (MD, 0.85 kg/m(2); 95% CI, 0.13 to 1.58), or waist circumference (MD, 1.59 cm; 95% CI, -3.02 to 6.19). However, cardiovascular risk was more significantly lessened in the gastric bypass group. Our meta-analysis demonstrated that compared with laparoscopic sleeve gastrectomy, Roux-en-Y gastric bypass offers equal efficacy for treatment of diabetes in obese patients but is associated with a significantly decreased cardiovascular risk.

The role of death receptor 3 in the biological behavior of hepatocellular carcinoma cells.

Death receptor 3 (DR3) belongs to the tumor necrosis factor (TNF) receptor superfamily, primarily found in lymphoid tissues. Reports have determined that DR3 may also be distributed in numerous types of tumors. Therefore, it is thought that DR3 may have an important role in the process of tumorigenesis. The aim of the present study was to observe the effect of silencing DR3 expression on hepatocarcinoma cell growth, apoptosis and invasion in order to elucidate the role of DR3 in tumor development. The hepatocarcinoma cell lines (HepG2, Huh7, SMMC7721 and Bel­7402) and normal human liver cells (HL­7702) were transfected with three stealth RNA interference (RNAi) sequences that target the DR3 gene. Reverse transcription quantitative polymerase chain reaction was used to detect the expression levels of DR3 in hepatocarcinoma cell lines and normal liver HL­7702 cells. MTT assay and flow cytometry (FCM) were used to determine the rates of cell proliferation and apoptosis, respectively. Following silencing of the DR3 gene, western blot analysis was used to determine the protein expression of P53, Fas, Caspase8, nuclear factor kappa­light­chain­enhancer of activated B cells (NF­κB) and Caspase3. DR3 messenger RNA (mRNA) expression in hepatocarcinoma cell lines was significantly increased compared with that in the normal liver cell line. Three targeted DR3 gene small interfering RNAs significantly inhibited DR3 gene expression in Bel­7402 cells at the nucleic acid level. AF02670.1_stealth_883 and cocktail demonstrated the most efficient inhibition of DR3 gene expression at 48 and 72 h following transfection, with mRNA inhibition rates of 89.46 and 92.75%, and 90.53 and 94.25% (P<0.01), respectively. Cell viability was significantly reduced by AF02670.1_stealth_883 and RNAi cocktail at 24, 48 and 72 h following transfection. The inhibition rates of cell proliferation were 50.76 and 61.76% (P<0.05) at 72 h following transfection. FCM revealed that AF02670.1_stealth_883 and RNAi cocktail also induced apoptosis in Bel­7402 cells at 72 h following transfection. Reduction of NF­κB and P53 levels was observed (P<0.05) in Bel­7402 cells following DR3 silencing, whereas levels of Fas, Caspase3 and Caspase8 were markedly elevated (P<0.05). DR3 expression levels in hepatocellular carcinoma cells were significantly higher than those in normal cells. DR3 silencing effectively inhibited proliferation and invasion of hepatocellular carcinoma cells in vitro. However, silencing of the DR3 gene affect levels of apoptosis antigen­3 ligand in cells, therefore indicating that it may be involved with other pathways that regulate apoptosis in HCCs. In conclusion, the results of the present study indicated that DR3 may be a promising therapeutic target molecule for further study of hepatocellular carcinoma gene therapy.