BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER NCT02063100 on ClinicalTrials.gov.

BACKGROUND: Metabolic syndrome (MetS) is relatively common worldwide and an important risk factor for cardiovascular diseases. It is closely linked to arterial stiffness of the carotid artery. However, the association of MetS with the safety of carotid revascularization has been rarely studied. The aim of this study was to observe the current status of MetS and its components in Chinese carotid revascularized patients, and investigate the impact on major adverse clinical events (MACEs) after carotid endarterectomy (CEA) or carotid artery stenting (CAS). METHODS: From January 2013 to December 2017, patients undergoing CEA or CAS in the Neurosurgery Department of Xuanwu Hospital were retrospectively recruited. The changes in prevalence of MetS and each component with time were investigated. The primary outcome was 30-day post-operative MACEs. Univariable and multivariable analyses were performed to identify the impact of MetS on CEA or CAS. RESULTS: A total of 2068 patients who underwent CEA (766 cases) or CAS (1302 cases) were included. The rate of MetS was 17.9%; the prevalence rate of MetS increased with time. The occurrence rate of MACEs in CEA was 3.4% (26 cases) and in CAS, 3.1% (40 cases). There was no statistical difference between the two groups (3.4% vs. 3.1%, P = 0.600). For CEA patients, univariate analysis showed that the MACE (+) group had increased diabetes history (53.8% vs. 30.9%, P = 0.014) and MetS (34.6% vs. 15.8%, P = 0.023). For CAS patients, univariate analysis showed that the MACE (+) group had increased coronary artery disease history (40.0% vs. 21.6%, P = 0.006) and internal carotid artery tortuosity (67.5%% vs. 37.6%, P < 0.001). Furthermore, the MACE (+) group had higher systolic blood pressure (143.38 ± 22.74 vs. 135.42 ± 17.17 mmHg, P = 0.004). Multivariable analysis showed that the influencing factors for MACEs in CEA included history of diabetes (odds ratio [OR] = 2.345; 95% confidence interval [CI] = 1.057-5.205; P = 0.036) and MetS (OR = 2.476; 95% CI = 1.065-5.757; P = 0.035). The influencing factors for MACEs in CAS included systolic blood pressure (OR = 1.023; 95% CI = 1.005-1.040; P = 0.010), coronary artery disease (OR = 2.382; 95% CI = 1.237-4.587; P = 0.009) and internal carotid artery tortuosity (OR = 3.221; 95% CI = 1.637-6.337; P = 0.001). CONCLUSIONS The prevalence rate of MetS increased with time in carotid revascularized patients. MetS is a risk for short-term MACEs after CEA, but not CAS.
Carotid Arteries/surgery* ; Carotid Stenosis/surgery* ; China/epidemiology* ; Endarterectomy, Carotid/adverse effects* ; Humans ; Metabolic Syndrome/epidemiology* ; Retrospective Studies ; Risk Factors ; Sample Size ; Stents/adverse effects* ; Stroke ; Time Factors ; Treatment Outcome

OBJECTIVE: To investigate the current status of antibiotic use for very and extremely low birth weight (VLBW/ELBW) infants in neonatal intensive care units (NICUs) of Hunan Province. METHODS: The use of antibiotics was investigated in multiple level 3 NICUs of Hunan Province for VLBW and ELBW infants born between January, 2017 and December, 2017. RESULTS: The clinical data of 1 442 VLBW/ELBW infants were collected from 24 NICUs in 2017. The median antibiotic use duration was 17 days (range: 0-86 days), accounting for 53.0% of the total length of hospital stay. The highest duration of antibiotic use was up to 91.4% of the total length of hospital stay, with the lowest at 14.6%. In 16 out of 24 NICUs, the antibiotic use duration was accounted for more than 50.0% of the hospitalization days. There were 113 cases with positive bacterial culture grown in blood or cerebrospinal fluid, making the positive rate of overall bacterial culture as 7.84%. The positive rate of bacterial culture in different NICUs was significantly different from 0% to 14.9%. The common isolated bacterial pathogens Klebsiella pneumoniae was 29 cases (25.7%); Escherichia coli 12 cases (10.6%); Staphylococcus aureus 3 cases (2.7%). The most commonly used antibiotics were third-generation of cephalosporins, accounting for 41.00% of the total antibiotics, followed by penicillins, accounting for 32.10%, and followed by carbapenems, accounting for 13.15%. The proportion of antibiotic use time was negatively correlated with birth weight Z-score and the change in weight Z-score between birth and hospital discharge (r=-0.095, -0.151 respectively, P<0.01), positively correlated with death/withdrawal of care (r=0.196, P<0.01). CONCLUSIONS Antibiotics used for VLBW/ELBW infants in NICUs of Hunan Province are obviously prolonged in many NICUs. The proportion of routine use of third-generation of cephalosporins and carbapenems antibiotics is high among the NICUs.
Anti-Bacterial Agents ; Birth Weight ; Humans ; Infant ; Infant, Extremely Low Birth Weight ; Infant, Newborn ; Intensive Care Units, Neonatal ; Surveys and Questionnaires

Objective To construct BRCC3(BRCA1/BRCA2-containing complex subunit 3)gene knockout mice and preliminarily study the phenotypes.Methods Using the Cas9/sgRNA-Mediated genome Editing, the BRCC3 knockout mouse models were constructed.Genomic DNAs of mouse tail tissues were extracted and identified, the genotypes of mice were determined at the DNA level,and RNAs and proteins of tissues, such as the heart, liver, spleen, lung, kidney of mice were extracted and the expression of BRCC3 gene was detected by real-time-PCR and Western blotting(WB).The trend of relative body mass change and indexes that might affect the growth development and metabolism were observed. Major organs were hematoxylin-eosin(HE)stained and observed.The routine blood test of peripheral blood of mice was conducted.Results The mouse model of BRCC3 knockout was successfully constructed.BRCC3 knockout mouse survived and were fertile, indexes of blood lipid and liver function were normal, organs were not degenerative and indexes of peripheral blood in routine blood test were all in the normal range.The relative body mass of BRCC3 knockout mice was higher than that of wild type mice,and the level of serum cholesterol was increased.Conclusion BRCC3 may be involved in relative body mass regulation and cholesterol metabolism in mice.

Adult ; Female ; Fracture Fixation, Internal ; methods ; Humans ; Imaging, Three-Dimensional ; Male ; Maxillofacial Injuries ; diagnostic imaging ; surgery ; Middle Aged ; Otorhinolaryngologic Surgical Procedures ; methods ; Skull Fractures ; diagnostic imaging ; surgery ; Tomography, X-Ray Computed ; Treatment Outcome ; Young Adult

Objective To explore the imaging and clinical characteristics and related risk factors of patients with coronary artery stenosis located proximally to myocardial bridging.Methods This study enrolled 603 patients with angiography evidenced myocardial bridging-mural coronary artery between May 2004 to May 2009.Angiographic and clinic data were collected according to uniform protocol and standard questionnaires were used to obtain patients' demographic and clinical information.Univariate and multivariate analysis were performed to explore related risk factors.Results Chest pain was present in 247cases (41.0％).Dynamic ST-T changes were found in 229 cases (38％).A total of 644 myocardial bridging-mural coronary arteries were detected including 382 (62.4％) segments located proximally to myocardial bridging.Diastolic vessel diameters in the myocardial bridging segment were significantly smaller than reference segments (all P ＜ 0.01).Stepwise multiple regression analysis suggested that vascular bifurcation lesions,the degree of narrowing and the number of diseased coronary vessels of non-myocardial bridging-mural coronary arteries,age,LDL-C/HDL-C,male gender,diabetes,and systolic narrow rate of myocardial bridging-mural coronary arteries were positively related with the narrowing degree of the first coronary artery stenosis located proximally to myocardial bridging (P ＜ 0.05 or P ＜ 0.01).Vascular bifurcation lesions,the degree of narrowing and the number of diseased coronary vessels of non-myocardial bridging-mural coronary arteries,age,LDL-C/HDL-C,male,diabetes and dyslipidemia were positively related with the narrowing degree of the most severe coronary artery stenosis located proximally to myocardial bridging(P ＜ 0.05 or P ＜ 0.01).Conclusions Myocardial ischemia is common in patients with myocardial bridging and the artery segments located proximally to myocardial bridging are prone to stenosis.Systolic narrow rate of myocardial bridging-mural coronary arterics is one of major determinants of coronary artery stenosis located proximally to myocardial bridging.Whereas the other coronary heart disease risk factors are likely to play more important roles.

In order to study the influence of trichosanthin (TCS) on apoptosis and growth inhibition of human NB4 cells in vitro, the expression of annexin V and the change of DeltaPsim of NB4 cells induced by TCS was analyzed by FACS, and MTT assay was adopted to measure the growth inhibition ratio of NB4 cells treated with TCS. Apoptosis was assayed by agarose gel electrophoresis. The results showed the higher concentration of TCS and the longer the acting time, the stronger growth inhibition of NB4 cells. The expression of annexin V was positive, and the positive ratio was greatly enhanced with prolongation of acting time. DeltaPsim reduced gradually while the apoptosis cells increasing. DNA agarose gel electrophoresis showed a gradient, which confirmed that TCS could induce NB4 cells apoptosis. In conclusion, taken together, data show that TCS can inhibit NB4 growth in vitro, and induce apoptosis. Experiment provides an important evidence for application of TCS in clinical treatment of acute promyelocytic leukemia.
Antineoplastic Agents, Phytogenic ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; DNA Fragmentation ; drug effects ; Dose-Response Relationship, Drug ; Flow Cytometry ; Humans ; Trichosanthin ; pharmacology

To explore the role of intrapulmonary neuropeptides in the development of airway hyperresponsiveness, we established an animal model of airway hyperresponsiveness (AHR) in rabbits by using ozone exposure. With the model, after test of the mechanics of respiration and bronchoalveolar lavage assay, the levels of vasoactive intestinal peptide (VIP) and calcitonin gene-related peptide (CGRP) in the lungs were determined by radioimmunoassay, and the expression of mRNA coding receptors of these two neuropeptides was evaluated by reverse transcriptional-polymerase chain reaction (RT-PCR). At the same time, the distribution of VIP receptor-1 (VIPR1) and CGRP receptor-1 (CGRPR1) in lung tissues and its time-course were examined by in situ hybridization. The results showed: (1) in ozone-stressing groups, airway resistance increased significantly and typical inflammatory pathological changes were observed in pulmonary tissue slides, including neutrophil and eosinophil infiltration, mucus exudation and bronchial epithelial cells (BECs) shedding; (2) with elongation of ozone exposure, the levels of VIP and CGRP in the lungs increased at first, reaching a peak on d 2 to 4, then decreased slowly, and CGRP peaked somewhat earlier than VIP; (3) mRNA expression of the two neuropeptide receptors in the lungs changed in a similar manner like VIP and CGRP, but the high level of mRNA expression of VIPR1 lasted longer than that of CGRPR1; and (4) in situ hybridization for neuropeptide receptors demonstrated that, in unstressed control, VIPR1 and CGRPR1 positive cells appeared in the airway epithelium, pulmonary interstitial and focal areas of airway and vascular smooth muscles. With the elongation of ozone exposure, hybridization stained deeper and the majority of positive cells were located around the vessels and bronchus except a few in the alveoli. At 8 d, only a small number of positive cells were seen in the lungs. From the results, it is concluded that ozone-stressing can induce the development of AHR, in which VIP and CGRP may play important roles. That implies, through binding to CGRPR1, CGRP stimulates an early inflammation response which contributes in cleaning up of irritants, while VIP exerts a later dampening of pulmonary inflammation response. These two neuropeptides may play sequential and complementary roles in the development of AHR.
Animals ; Bronchi ; pathology ; Bronchial Hyperreactivity ; chemically induced ; metabolism ; Bronchoalveolar Lavage Fluid ; Calcitonin Gene-Related Peptide ; metabolism ; Epithelium ; metabolism ; Lung ; metabolism ; Ozone ; Rabbits ; Receptors, Calcitonin Gene-Related Peptide ; metabolism ; Receptors, Vasoactive Intestinal Peptide ; metabolism ; Vasoactive Intestinal Peptide ; metabolism

AIMTo establish new methods for the chiral separation and preparation of three new drugs, alfuzosin, terazosin and doxazosin.

METHODSBy optimizing factors which affect the chiral separation, modifier of solvent, chiral additive, pH of mobile phase, modifier of organic base and stationary phase, the optimum condition for chiral separation were selected. The preparation of enantiomers was carried out on semi-preparative reverse phase column (7.8 mm x 250 mm C4 5 microns). Acetonitrile-water modified by the addition of carboxymethyl-beta-cyclodextrin (2%-5%, w/v) was applied as chiral mobile phase.

RESULTSThe enantiomers of three new drugs were base-line-separated and milligram-scale samples of enantiomer were obtained.

CONCLUSIONThe newly established method can be used in research and development of the enantiomers of three new drugs.

Adrenergic alpha-1 Receptor Antagonists ; Adrenergic alpha-Antagonists ; isolation & purification ; Chromatography, High Pressure Liquid ; methods ; Doxazosin ; isolation & purification ; Molecular Structure ; Prazosin ; analogs & derivatives ; isolation & purification ; Quinazolines ; isolation & purification