1.The characterization on the site of vindoline binding to human serum albumin
Wenying HE ; Zhenfan SUN ; Xiaojun YAO ; Guangying CHEN
Acta Pharmaceutica Sinica 2010;45(5):608-14
In this paper, the fluorogenic property of vindoline was exploited and, as a probe, used to analyze the interaction of vindoline with HSA by fluorescence and absorption spectra in combination with molecular modeling under a simulated physiological conditions. The evidences from synchronous fluorescence and absorption spectroscopes showed the effect of vindoline on the microenvironment around HSA in aqueous solution. Data obtained by the fluorescence spectroscopy indicated that binding of vindoline with HSA leads to dramatic enhancement of the fluorescence emission intensity. The binding constants and the number of binding sites between vindoline and HSA at different temperatures (303, 310 and 317 K) were calculated according to the data obtained from fluorescence titration. Molecular docking was performed to reveal the possible binding mode or mechanism and suggested that vindoline can bind strongly to HSA. It is considered that vindoline binds to HSA mainly by a hydrophobic interaction and there are four hydrogen bonds interactions between the drug and the residues Ala291, Arg222, Arg218 and Lys195, separately. Fluorescent displacement measurements confirmed that vindoline bind HSA on site II. The thermodynamic parameters obtained (the enthalpy change deltaH0 and the entropy change deltaS0 were calculated to be -10.30 kJ x mol(-1) and 79.98 J x mol(-1) x K(-1), respectively, according to the Van't Hoff equation) suggested that hydrophobic and electrostatic interaction is the predominant intermolecular forces stabilizing the complex.
2.Prevalence of nonalcoholic fatty liver disease in taxi drivers in Shenzhen, China
Haiyan HUANG ; Rongxin WEI ; Guangying HE
Journal of Clinical Hepatology 2020;36(3):612-615
ObjectiveTo investigate the prevalence of nonalcoholic fatty liver disease (NAFLD) and related abnormal indicators among taxi drivers in Shenzhen, China, and to provide a basis for scientific prevention and treatment of fatty liver disease. MethodsA total of 1752 taxi drivers who underwent physical examination in Shenzhen Longhua District People’s Hospital from May 2018 to June 2019 were selected, and related indicators were measured, including body mass index (BMI), blood pressure, fasting plasma glucose (FPG), total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and uric acid (UA). Liver ultrasound examination was also performed. The association between the prevalence rate of NAFLD and various biochemical parameters was analyzed. The t-test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. ResultsThe prevalence rate of NAFLD among the taxi drivers was 51.66% (905/1752), and male drivers had a significantly higher prevalence rate than female drivers[57.94% (770/1329) vs 31.91% (135/423), χ2=9.209, P=0.027]. The taxi drivers with NAFLD had significantly higher abnormal rates of BMI, blood lipids, blood pressure, FPG, and UA than those without NAFLD (χ2=5.894, 7.126, 8.045, 8.909, and 10.373, P=0.047, 0.035, 0.030, 0.028, and 0.018). The taxi drivers with a BMI of ≥28 kg/m2 had a significantly higher prevalence rate of NAFLD than those with a BMI of 24.0-27.9 kg/m2 or a BMI of <24 kg/m2 (male: χ2=7.904 and 18.624, P=0.035 and 0.008; female: χ2=8.613 and 31.635, P=0.029 and 0.006). The taxi drivers with working years of >15 years had a significantly higher prevalence rate of NAFLD than those with working years of 11-15 years, 5-10 years, and <5 years (male: χ2=9.781, 13.546, and 18.052, P=0.024, 0.012, and 0.008; female: χ2=7.052, 9.847, and 12.157, P=0.036, 0.023, and 0.016). ConclusionThere is a high prevalence rate of NAFLD among taxi drivers in Shenzhen, and male drivers have a higher prevalence rate than female drivers. The prevalence rate of NAFLD is associated with the abnormal rates of hyperlipidemia, obesity, hyperglycemia, and hyperuricemia and the working years in driving.
3.Clinical study on hyperbaric oxygen combined with cilostazol foot in treating diabetic foot
Guangying ZHANG ; Wenying LUO ; Tongwei HE ; Yonggang ZU ; Chengyu WANG ; Yinghui GUO
International Journal of Laboratory Medicine 2017;38(21):2958-2960,2963
Objective To study the clinicalvalue of hyperbaric oxygen combined with cilostazol in treating diabetic foot .Methods 90 patients with diabetic foot in our hospital from June 2014 to July 2016 were selected and randomly divided into the observation group and control group according to the random number table method ,45 cases in each group .The control group was given the cilostazol treatment on the basis of basic treatment ,while on the basis of control group treatment ,the observation group was added with the hyperbaric oxygen therapy .The clinical efficacy and the changes of hemorheology ,blood parameters and plasma fibrinolytic indicators of the two groups were observed .Results The total effective rate in the observation group was 91 .11% ,which was sig-nificantly higher than 71 .11% in the control group ,the difference was statistically significant(P<0 .05);the whole blood viscosity (high shear and low shear ) ,hematocrit after treatment in the observation group were significantly lower than those in the control group(P<0 .05);the levels of HbA1c ,homocysteine(Hcy) and plasma high-sensitivity C reactive protein(hs-CRP) after treatment in the observation group were significantly lower than those in the control group (P<0 .05) ,the levels of plasma fibrinogen andtis-sue-type plasminogen activator(TPA) after treatment in the observation group were significantly superior to those in the control group(P<0 .05) .Conclusion Hyperbaric oxygen combined with cilostazol can effectively improve the levels of HbA 1c ,Hcy and hs-CRP in thee patients with diabetic foot ,promotesthe wound healing and improves the clinical treatment effect .
4.Analysis of epidemiological characteristics and clinical features of 480 hospitalized patients with dengue fever in Guangdong Province in 2019
Changquan LIU ; Guoming ZHANG ; Guangying WEI ; Ping PENG ; Xi HE ; Fuchun ZHANG ; Wanting LAO ; Jindi HUANG ; Yongjia GUAN ; Huimin XU ; Yuejun PAN
Chinese Journal of Infectious Diseases 2021;39(4):209-213
Objective:To analyze the epidemiological and clinical characteristics of hospitalized patients with dengue fever in Guangdong Province in 2019, so as to provide reference for clinical diagnosis and treatment of dengue fever.Methods:The general data, laboratory examination data, clinical manifestations and prognosis data of 480 inpatients with dengue fever admitted to Eight People′s Hospital Affiliated to Guangzhou Medical University between January 4 and October 31, 2019 were analyzed retrospectively. The clinical and onset characteristics of patients with dengue fever were described.Results:Among 480 dengue patients, 442(92.1%) were dengue fever, 38(7.9%) were severe dengue, and 136(28.3%) had underlying diseases. The peak age of onset was mainly in young adults aged 20 to 49 years old, accounting for 66.0%(317/480) in total. The seasonal peak was mainly in August to October. There were 399(83.1%) local cases and 61(12.7%) imported cases. The most common clinical manifestations were fever (98.1%, 471/480), chills (72.9%, 350/480), headache (58.5%, 281/480) and bone/joint/muscle pain (67.1%, 322/480), followed by digestive tract symptoms and respiratory tract symptoms. Among 446 serum samples, 358 (80.3%) were dengue virus (DENV)-1, 54 (12.1%) were DENV-2, 34 (7.6%) were DENV-3. The main laboratory tests of the patients were leucopenia (65.8%, 316/480), low hematocrit (30.2%, 145/480), thrombocytopenia (48.3%, 232/480), neutropenia (44.8%, 215/480), elevated alanine aminotransferase (ALT) (37.7%, 181/480) and aspartate aminotransferase (AST) (59.4%, 285/480). Treatment mainly adopted symptomatic support treatment and active prevention of complications. The length of stay was (5.8±3.1) days (range 1.0-38.0 days). A total of 461(96.0%) patients were cured or improved.Conclusions:In 2019, the majority of dengue fever patients in Guangdong Province are young adults aged 20 to 49 years old, and the proportion of severe patients is high, with DENV-1 infection as the main type. After symptomatic support treatment and active prevention of complications, most of the dengue fever patients have a good prognosis.
5.Clinical characteristics and CT imaging features of patients with different clinical types of coronavirus disease 2019
Changquan LIU ; Xilong DENG ; Yuejun PAN ; Zhoukun LING ; Guoming ZHANG ; Guangying WEI ; Ping PENG ; Xi HE ; Fuchun ZHANG
Chinese Critical Care Medicine 2020;32(5):548-553
Objective:To investigate the clinical characteristics and CT imaging features of patients with different clinical types of coronavirus disease 2019 (COVID-19), so as to provide a reference for the treatment and evaluation of COVID-19.Methods:The clinical data of 278 patients with COVID-19 admitted to Guangzhou Eighth People's Hospital from January 20th to February 10th in 2020 were collected. The patients were divided into mild, ordinary, severe and critical types. The differences of clinical symptoms and signs, laboratory examination indexes and CT image features of lung in different clinical types were analyzed and compared, and the relationship between clinical and imaging features and clinical types of diseases were analyzed.Results:Among the 278 patients with COVID-19, 130 were male (46.8%) and 148 were female (53.2%), of whom 88.8% (247/278) were 20 to 69 years old. 238 (85.6%) patients combined one or more basic diseases. The source of cases was mainly imported cases ( n = 201, 72.3%), of whom 89 cases were imported from Wuhan, accounting for 44.3% of all imported cases. With the aggravation of the disease, the male composition ratio, age and the number of basic diseases of patients gradually increased, and the incidences of fever, dry cough, chilly or chills, and fatigue in severe and critical patients were significantly higher than those in the mild and ordinary ones. The white blood cell count (WBC), neutrophil counts (NEU) and proportions (NEU%) of the severe and critical patients were higher than those of the mild and ordinary patients [WBC (×10 9/L): 5.7±3.1, 6.5±2.4 vs. 5.4±1.7, 4.9±1.6; NEU (×10 9/L): 4.4±3.1, 4.9±2.5 vs. 2.8±1.2, 2.9±1.3; NEU%: 0.72±0.13, 0.73±0.14 vs. 0.51±0.12, 0.59±0.11; all P < 0.01], while the lymphocyte count (LYM) and ratio (LYM%), platelet count (PLT) were lower than those in the mild and ordinary patients [LYM (×10 9/L): 1.0±0.4, 1.2±0.8 vs. 2.1±0.9, 1.5±0.6; LYM%: 0.21±0.11, 0.20±0.12 vs. 0.40±0.11, 0.32±0.11; PLT (×10 9/L): 177.1±47.8, 157.7±51.6 vs. 215.3±59.7, 191.8±64.3; all P < 0.05]. The level of albumin (Alb) was the lowest in the critical patients and the level of total bilirubin (TBil) was the highest, which was statistically significant as compared with the mild, ordinary and severe patients [Alb (g/L): 33.0±5.8 vs. 42.8±4.4, 39.6±5.1, 34.4±4.2; TBil (μmol/L): 20.1±12.8 vs. 12.0±8.7, 10.9±6.3, 12.2±8.3; both P < 0.01]. Lactate dehydration (LDH) and cardiac troponin I (cTnI) in the severe and critical patients were significantly higher than those in the mild and ordinary patients [LDH (μmol·s -1·L -1): 5.6±2.2, 5.0±2.9 vs. 2.8±0.9, 3.3±1.2; cTnI (μg/L): 0.010 (0.006, 0.012), 0.010 (0.006, 0.012) vs. 0.005 (0.003, 0.006), 0.005 (0.001, 0.008); both P < 0.05]. C-reactive protein (CRP) level of severe patients were higher than that in the mild, ordinary and critical patients [mg/L: 43.3 (33.2, 72.1) vs. 22.1 (16.2, 25.7), 29.7 (19.8, 43.1), 25.8 (23.0, 36.7), P < 0.01]. The level of procalcitonin (PCT) in the severe and critical patients was higher than that in the mild and ordinary patients [μg/L: 0.17 (0.12, 0.26), 0.13 (0.09, 0.24) vs. 0.06 (0.05, 0.08), 0.05 (0.04, 0.09), P < 0.01]. The typical CT imaging features were as follows: the ordinary type mainly showed the single or multiple ground glass shadows on the chest image; the severe type mainly showed the multiple ground glass shadows, infiltration shadows or solid transformation shadows. Compared with the ordinary patients, the lesions increase, and the scope of the lesion expanded to show double lungs. Critical type was mainly manifested as diffuse consolidation of both lungs with multiple patchy density increase shadows, multiple leafy patchy density increase shadows were seen on each leaf, most of them were ground glass-like density, and some were shown separately lung consolidation. Conclusions:Men, advanced aged, and combining multiple underlying diseases are high-risk populations of COVID-19, and they should pay close attention to the risk of progressing to severe or critical type. CT imaging features could be used as an important supplement when diagnosing severe and critical COVID-19.
6.Discovery of novel diarylamides as orally active diuretics targeting urea transporters.
Shun ZHANG ; Yan ZHAO ; Shuyuan WANG ; Min LI ; Yue XU ; Jianhua RAN ; Xiaoqiang GENG ; Jinzhao HE ; Jia MENG ; Guangying SHAO ; Hong ZHOU ; Zemei GE ; Guangping CHEN ; Runtao LI ; Baoxue YANG
Acta Pharmaceutica Sinica B 2021;11(1):181-202
Urea transporters (UT) play a vital role in the mechanism of urine concentration and are recognized as novel targets for the development of salt-sparing diuretics. Thus, UT inhibitors are promising for development as novel diuretics. In the present study, a novel UT inhibitor with a diarylamide scaffold was discovered by high-throughput screening. Optimization of the inhibitor led to the identification of a promising preclinical candidate,