OBJECTIVE: Preliminary assessment of rabies virus neutralizing activity, safety and immunogenicity of a recombinant human rabies antibody (NM57) compared with human rabies immunoglobulin (HRIG) in Chinese healthy adults. METHODS: Subjects were randomly (1:1:1) allocated to Groups A (20 IU/kg NM57), B (40 IU/kg NM57), or C (20 IU/kg HRIG). One injection was given on the day of enrollment. Blood samples were collected on days -7 to 0 (pre-injection), 3, 7, 14, 28, and 42. Adverse events (AEs) and serious AEs (SAEs) were recorded over a period of 42 days after injection. RESULTS: All 60 subjects developed detectable rabies virus neutralizing antibodies (RVNAs) (> 0.05 IU/mL) on days 3, 7, 14, 28, and 42. The RVNA levels peaked on day 3 in all three groups, with a geometric mean concentration (GMC) of 0.2139 IU/mL in Group A, 0.3660 IU/mL in Group B, and 0.1994 IU/mL in Group C. At each follow-up point, the GMC in Group B was significantly higher than that in Groups A and C. The areas under the antibody concentration curve over 0-14 days and 0-42 days in Group B were significantly larger than those in Groups A and C. Fifteen AEs were reported. Except for one grade 2 myalgia in Group C, the other 14 were all grade 1. No SAEs were observed. CONCLUSION The rabies virus neutralizing activity of 40 IU/kg NM57 was superior to that of 20 IU/kg NM57 and 20 IU/kg HRIG, and the rabies virus neutralizing activity of 20 IU/kg NM57 and 20 IU/kg HRIG were similar. Safety was comparable between NM57 and HRIG.
Adult ; Antibodies, Neutralizing ; Antibodies, Viral ; Data Collection ; Humans ; Rabies/prevention & control* ; Rabies Vaccines/adverse effects* ; Rabies virus/genetics*

Background::Accurate prediction of ischemic stroke is required for deciding anticoagulation use in patients with atrial fibrillation (AF). Even though only 6% to 8% of AF patients die from stroke, about 90% are indicated for anticoagulants according to the current AF management guidelines. Therefore, we aimed to develop an accurate and easy-to-use new risk model for 1-year thromboembolic events (TEs) in Chinese AF patients.Methods::From the prospective China Atrial Fibrillation Registry cohort study, we identified 6601 AF patients who were not treated with anticoagulation or ablation at baseline. We selected the most important variables by the extreme gradient boosting (XGBoost) algorithm and developed a simplified risk model for predicting 1-year TEs. The novel risk score was internally validated using bootstrapping with 1000 replicates and compared with the CHA 2DS 2-VA score (excluding female sex from the CHA 2DS 2-VASc score). Results::Up to the follow-up of 1 year, 163 TEs (ischemic stroke or systemic embolism) occurred. Using the XGBoost algorithm, we selected the three most important variables (congestive heart failure or left ventricular dysfunction, age, and prior stroke, abbreviated as CAS model) to predict 1-year TE risk. We trained a multivariate Cox regression model and assigned point scores proportional to model coefficients. The CAS scheme classified 30.8% (2033/6601) of the patients as low risk for TE (CAS score = 0), with a corresponding 1-year TE risk of 0.81% (95% confidence interval [CI]: 0.41%-1.19%). In our cohort, the C-statistic of CAS model was 0.69 (95% CI: 0.65-0.73), higher than that of CHA 2DS 2-VA score (0.66, 95% CI: 0.62-0.70, Z = 2.01, P = 0.045). The overall net reclassification improvement from CHA 2DS 2-VA categories (low = 0/high ≥1) to CAS categories (low = 0/high ≥1) was 12.2% (95% CI: 8.7%-15.7%). Conclusion::In Chinese AF patients, a novel and simple CAS risk model better predicted 1-year TEs than the widely-used CHA 2DS 2- VA risk score and identified a large proportion of patients with low risk of TEs, which could potentially improve anticoagulation decision-making. Trial Registration::www.chictr.org.cn (Unique identifier No. ChiCTR-OCH-13003729).

Objective: This study explored the thromboembolism risk of low-risk atrial fibrillation (AF) patients (CHA₂DS₂-VASc score of 0 or 1 for male and 1 or 2 for female) with different clinical characteristics to provide the basis for anticoagulation decision-making in these patients. Methods: We prospectively enrolled consecutive 2 862 nonvalvular low-risk AF patients between August 2011 to December 2018 in China-AF (China Atrial Fibrillation Registry) Study, their CHA₂DS₂-VASc score was 0 or 1 for male and 1 or 2 for female. According to their age, sex, presence or absence of hypertension, diabetes mellitus, congestive heart failure, and vascular disease at the time of enrolling, patients were divided into CHA₂DS₂-VASc score 0 score group, 1 score group, and 2 score group. Patients were followed up every 6 months by outpatient clinic visit or telephone interview. The outcome was a thromboembolic event, including ischemic stroke and systemic embolism. Univariate Cox regression analysis was used to compare the thromboembolism risk between the patients with different risk factors and CHA₂DS₂-VASc score 0 group. Results: A total of 2 862 low-risk atrial fibrillation patients were enrolled in this study. 915 patients (32.0%) were female, and age was (55.0±10.7) years old. There were 933 patients (32.6%) in CHA₂DS₂-VASc score 0 group, 1 401 patients (49.0%) in score 1 group and 528 patients (18.5%) in score 2 group. During follow-up (median 1.5 years, 5 811.82 person-years), 33 cases of thromboembolic events were recorded, the annual rate of thromboembolism was 0.57% (95%CI 0.40%~0.80%). The number of thromboembolic events in patients with CHA₂DS₂-VASc score 0, 1 and 2 were 8, 11 and 14, respectively, and the annual thromboembolism event rates were 0.40% (95%CI 0.20%-0.81%), 0.39% (95%CI 0.22%-0.71%) and 1.34% (95%CI 0.80%-2.27%), respectively. The risk of thromboembolism of CHA₂DS₂-VASc score 2 group (HR=3.53, 95%CI 1.48-8.44; P=0.005), especially female patients aged 65-74 years in CHA₂DS₂-VASc score 2 group (HR=2.67, 95%CI 1.63-4.38; P<0.000) was significantly higher than that in patients of CHA₂DS₂-VASc score 0 group. Conclusion: Low-Risk Atrial Fibrillation patients with CHA₂DS₂-VASc score 2, especially female patients aged 65-74 years old with CHA₂DS₂-VASc score 2 are at higher risk of thromboembolism in low-risk AF patients. For such patients, intensified oral anticoagulant therapy might be helpful to reduce the risk of thrombolism.
Adult ; Aged ; Anticoagulants ; Atrial Fibrillation ; China ; Female ; Humans ; Male ; Middle Aged ; Risk Assessment ; Risk Factors ; Stroke ; Thromboembolism

We aim to reassess the safety of the monopolar transurethral resection of the prostate (M-TURP) without suprapubic cystostomy at our institution over the past decade. This retrospective study was conducted in patients who underwent M-TURP at Peking University First Hospital between 2003 and 2013. A total of 1680 patients who had undergone M-TURP were identified, including 539 patients in the noncystostomy group and 1141 patients in the cystostomy group. After propensity score matching, the number of patients in each group was 456. Smaller reductions in hemoglobin and hematocrit (10.9 g vs 17.6 g and 3.6% vs 4.7%, respectively) were found in the noncystostomy group. In addition, patients undergoing surgery without cystostomy had their catheters removed earlier (4.6 days vs 5.2 days), required shorter postoperative stays in the hospital (5.1 days vs 6.0 days), and were at lower risk of operative complications (5.7% vs 9.2%), especially bleeding requiring blood transfusion (2.9% vs 6.1%). Similar findings were observed in cohorts of prostates of 30-80 ml and prostates >80 ml. Furthermore, among patients with a resection weight >42.5 g or surgical time >90 min, or even propensity-matched patients based on surgical time, those with cystostomy seemed to be at a higher risk of operative complications. These results suggest that M-TURP without suprapubic cystostomy is a safe and effective method, even among patients with larger prostates, heavier estimated resection weights, and longer surgical times.
Aged ; Blood Transfusion ; Cystostomy/methods* ; Hematocrit ; Hemoglobins/analysis* ; Hemorrhage/epidemiology* ; Humans ; Intraoperative Complications/epidemiology* ; Male ; Middle Aged ; Postoperative Complications/epidemiology* ; Propensity Score ; Prostatectomy/methods* ; Prostatic Neoplasms/surgery* ; Retrospective Studies ; Transurethral Resection of Prostate/methods* ; Treatment Outcome

Objective To investigate and analysis the correlation between immune dysfunction and inflammation in patients with sepsis.Methods From February 2013 to May 2017,80 cases of sepsis patients in our hospital intensive care unit were selected as the treatment group,and the other 80 healthy people were enrolled as control group.The inflammatory factors,such as interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α)were deternied by enzyme linked immunosorbent assay.The immune function index (CD4 + and CD8 +) were detected by flow cytometry.The correlation were analyzed.Results The contents of serum IL-6 and TNF-α in the treatment group were (85.73 ± 15.34),(58.04 ± 9.11) pg · mL-1,respectively,which were significantly higher than (12.33 ± 8.24),(17.49 ± 8.76) pg · mL-1 in the control group with significantly(all P ＜ 0.05).The CD4 + and CD8 + values in the treatment group were (48.71 ± 11.16)％ and (22.11 ± 11.09)％,and the control group were (35.75 ± 11.31)％ and(28.83 ± 11.36)％ respectively.The difference comparison between the two groups were statistically significant (all P ＜ 0.05).Among the 80 patients in the treatment group,Pearson correlation analysis showed that IL-6 and TNF-α were positively correlated with CD4 + (all P ＜0.05),but negatively correlated with CD8 + (P ＜ 0.05).Logistic regression analysis showed that IL-6,TNF-α,CD4 + and CD8 + were the major independent risk factors for affecting Acute Physiology and Chronic Health Evaluation (APAHCE) Ⅱ score (all P ＜ 0.05).Conclusion There are inflammatory reaction and immune dysfunction in sepsis patients that they can interact with each other and affect the APAHCE Ⅱ score.

BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.

METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.

RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).

CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications

In the present study, the safety of Haemophilus influenza type b conjugate vaccines inoculated in the upper arm deltoid and vastus lateralis muscle was evaluated. 680 infants aged 2-5 months and 6-12 months were selected to be the research subjects in whom the Hib conjugate vaccines were inoculated by injection in the upper arm deltoid and vastus lateralis muscle, respectively. The safety analysis indicated that there were no statistic differences in the incidence rates of adverse reactions when the Hib conjugate vaccines were inoculated at different sites. So we concluded that the safety of inoculation injection of Hib conjugate vaccines in vastus lateralis muscle was the same as that inoculated in the upper arm deltoid.
Bacterial Capsules ; China ; Haemophilus Vaccines ; administration & dosage ; adverse effects ; Humans ; Incidence ; Infant

Effects of the effective components group of Xiaoshuantongluo formula (XECG) on rat acute blood stasis model were studied under the guidance of the concept of effective components group. Rat acute blood stasis model was induced by subcutaneous injection of epinephrine combined with ice water bath. Hemorheology indices such as whole blood viscosity, plasma viscosity, erythrocyte aggregation index and platelet aggregation rate; coagulation parameters including PT, APTT, TT and FIB; 6-keto-PGF1alpha, TXB2 and D-dimer levels were determined to evaluate the effects of XECG. The results showed that XECG significantly reduced ADP-induced platelet aggregation, but showed little influence on the whole blood viscosity, plasma viscosity and erythrocyte aggregation rate. XECG extended PT and TT slightly, but had no effects on APTT and FIB content. D-dimer levels significantly decreased after administration of XECG with a little decrease of TXB2, but the content of 6-keto-PGF1alpha did not change significantly. The results suggest that the role of XECG of anti-aggregation is more prominent.
6-Ketoprostaglandin F1 alpha ; blood ; Animals ; Blood Coagulation ; drug effects ; Blood Coagulation Disorders ; blood ; Blood Viscosity ; drug effects ; Drug Combinations ; Drugs, Chinese Herbal ; isolation & purification ; pharmacology ; Erythrocyte Aggregation ; drug effects ; Fibrin Fibrinogen Degradation Products ; metabolism ; Hemorheology ; drug effects ; Male ; Partial Thromboplastin Time ; Plants, Medicinal ; chemistry ; Platelet Aggregation ; drug effects ; Prothrombin Time ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Thrombin Time ; Thromboxane B2 ; blood

There are growing evidences that pinocembrin has better neuroprotective effect. In the present study, the effect of pinocembrin on mitochondrial respiratory function was evaluated in global brain ischemia/ reperfusion (4-vessel occlusion, 4-VO) rats. The results showed that pinocembrin improved the respiratory activity of 4-VO brain mitochondria, through increasing ADP/O, state 3 respiration state (V3), respiration control rate index (RCI) and oxidative phosphorylation rate (OPR). And then, the effect of pinocembrin on brain mitochondria was verified in vitro. The results showed that pinocembrin increased ADP/O, state 3 respiration state, respiration control rate index, oxidative phosphorylation rate in NADH/FADH2 dependent respiratory chain and decreased state 4 respiration state (V4) in NADH dependent respiratory chain. Pinocembrin improved ATP content in brain mitochondria in vitro and in SH-SY5Y cells.
Adenosine Diphosphate ; metabolism ; Adenosine Triphosphate ; biosynthesis ; Animals ; Brain Ischemia ; pathology ; physiopathology ; Cell Line, Tumor ; Cell Respiration ; drug effects ; Flavanones ; pharmacology ; Hippocampus ; pathology ; Male ; Mitochondria ; drug effects ; physiology ; Neuroblastoma ; metabolism ; pathology ; Neurons ; drug effects ; Neuroprotective Agents ; pharmacology ; Oxygen ; metabolism ; Rats ; Rats, Sprague-Dawley

The aim of this study is to investigate the effects of the metformin on the formation of hepatic fibrosis in type 2 diabetic rats and discuss its mechanism of liver-protecting activity. After SD rats were fed with high-fat and high-sucrose diet for four weeks, low-dose streptozotocin (STZ) was injected intraperitoneally to make the animal mode of type 2 diabetes. Then, all diabetic rats was fed with the high-fat diet and metformin (ig, 100 mg x kg(-1)) was given orally to metformin group for four months. After the last administration, fasting blood glucose was determined. The livers were removed to calculate the hepatic coefficient and to make HE and Picro acid-Sirius red staining, immunohistochemistry (alpha-SMA and TGFbeta1) and TUNEL staining in order to evaluate the effect of metformin on the hepatic fibrosis. The animal model of type 2 diabetes with hepatic fibrosis was successfully made. Metformin can significantly alleviate the lesions of hepatic steatosis and fibrosis, markedly reduce the expressions of alpha-SMA and TGFbeta1 in liver tissue of type 2 diabetic rats. However, TUNEL staining result suggested that metformin could not reduce apoptosis of hepatocytes. The results suggest that metformin can inhibit the formation of hepatic fibrosis in type 2 diabetes.
Actins ; metabolism ; Animals ; Apoptosis ; drug effects ; Blood Glucose ; metabolism ; Body Weight ; drug effects ; Diabetes Mellitus, Experimental ; drug therapy ; etiology ; metabolism ; pathology ; Diabetes Mellitus, Type 2 ; drug therapy ; etiology ; metabolism ; pathology ; Diet, High-Fat ; Female ; Hepatocytes ; pathology ; Hypoglycemic Agents ; pharmacology ; therapeutic use ; Liver ; metabolism ; pathology ; Liver Cirrhosis, Experimental ; drug therapy ; metabolism ; pathology ; Male ; Metformin ; pharmacology ; therapeutic use ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Streptozocin ; Transforming Growth Factor beta1 ; metabolism