Nicotinic acid could increase high density lipoprotein and reduce serum total cholesterol, low density lipoprotein cholesterol and triglycerides in human bodies, thus is frequently applied in treating low high-density lipoprotein cholesterol and hypertriglyceridemia in clinic. However, according to the findings, nicotinic acid could also cause adverse effects, such as skin flush, beside its curative effects. In this study, bioisosterism, fragment-based search and Lipinski's Rule of Five were used to preliminarily screen out potential TCM ingredients that may have similar pharmacological effects with nicotinic acid from Traditional Chinese medicine database (TCMD). Afterwards, homology modeling and flexible docking were used to further screen out potential nicotinic acid receptor agonists. As a result, eleven candidate compounds were derived from eight commonly used traditional Chinese medicines. Specifically, all of the candidate compounds' interaction with nicotinic acid receptor was similar to nicotinic acid, and their docking scores were all higher than that of nicotinic acid, but their druggability remained to be further studied. Some of the eight source traditional Chinese medicines were used to lower lipid according to literature studies, implying that they may show effect through above means. In summary, this study provides basis and reference for extracting new nicotinic acid receptor agonists from traditional Chinese medicines and improving the medication status of hyperlipidemia.
Drug Evaluation, Preclinical ; Drugs, Chinese Herbal ; chemistry ; Humans ; Models, Molecular ; Molecular Structure ; Nicotinic Acids ; chemistry ; Nicotinic Agonists ; chemistry ; Protein Binding ; Receptors, G-Protein-Coupled ; agonists ; chemistry ; Receptors, Nicotinic ; chemistry

Traditional Chinese medicine (TCM) has definitely clinical effect in treating hyperlipidemia, but the action mechanism still need to be explored. Based on consulting Chinese Pharmacopoeia (2010), all the lipid-lowering Chinese patent medicines were analyzed by associated rules data mining method to explore high frequency herb pairs. The top three couplet medicines with high support degree were Puerariae Lobatae Radix-Crataegi Fructus, Salviae Miltiorrhizae Radix et Rhizoma-Crataegi Fructus, and Polygoni Multiflori Radix-Crataegi Fructus. The 20 main ingredients were selected from the herb pairs and docked with 3 key hyperlipidemia targets, namely 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase), peroxisome proliferator activated receptor-α (PPAR-α ) and niemann-pick C1 like 1 (NPC1L1) to further discuss the molecular mechanism of the high frequency herb pairs, by using the docking program, LibDock. To construct evaluation rules for the ingredients of herb pairs, the root-mean-square deviation (RMSD) value between computed and initial complexes was first calculated to validate the fitness of LibDock models. Then, the key residues were also confirmed by analyzing the interactions of those 3 proteins and corresponding marketed drugs. The docking results showed that hyperin, puerarin, salvianolic acid A and polydatin can interact with two targets, and the other five compounds may be potent for at least one of the three targets. In this study, the multi-target effect of high frequency herb pairs for lipid-lowering was discussed on the molecular level, which can help further researching new multi-target anti-hyperlipidemia drug.
Asteraceae ; chemistry ; Drugs, Chinese Herbal ; chemistry ; metabolism ; Humans ; Hydroxymethylglutaryl CoA Reductases ; chemistry ; genetics ; metabolism ; Hyperlipidemias ; drug therapy ; enzymology ; genetics ; metabolism ; Hypolipidemic Agents ; chemistry ; metabolism ; Membrane Proteins ; chemistry ; genetics ; metabolism ; Molecular Docking Simulation ; PPAR alpha ; chemistry ; genetics ; metabolism ; Protein Binding ; Pueraria ; chemistry

Objective To explore the clinical features of respiratory syncytial virus(RSV) pneumonia in full-term neonatal patients.Methods All 422 full-term newborns diagnosed as pneumonia in NICU of Shenzhen Children's Hospital during January 2014 to January 2015 were included in this study.They had been detected for RSV in the way of direct immunofluorescence assay.According to the detection results, they were divided into RSV positive group and RSV negative group, the clinical data in two groups were analyzed.Results Forty-five cases were RSV positive,377 cases were RSV negative.The proportion of breast feeding was 42.22％ vs.65.25％ ,the proportion of cesarean section was 20.00％ vs.76.12％ in two groups,there were significant differences between the two groups.Hospitalization time, birth weight, gestational age, the age of admission showed no difference between two groups.The incidencs of cough (100％), shormess of breath (88.89％), three depressions (48.89 ％), fine rales (66.67 ％), wheezing (22.22％) in RSV positive group were higher than those in the RSV negative group(84.88％ ,42.44％, 13.26％, 13.53％ ,3.98％ respectively), there were significant differences between the two groups.The incidences of fever, saliva, nasal showed no significant difference between the two groups.There was significant difference in the X-ray chest film performance between two groups,RSV positive group was more emhrysema(71.11％ vs.6.9％) ,and less patch shadow(88.89％ vs.93.10％).The laboratory examination of blood routine test, C-reactive protein,respiratory failure, the positive rate of sputum culture, pneumothorax, pleural effusion were without differences.Conclusion RSV is an important pathogen of full-term neonates with infectious pneumonia.Breastfeeding and eutocia can reduce the incidence of RSV infection.Cough, shortness of breath, pulmonary rales, and emphysema in X-ray were common in RSV pneumonia.

AIM: To assess the relative agreement of GAT and NCT in IOP measurement by comparing the differences between Goldmann applanation tonometer (GAT) and non-contact tonometer (NCT) in intraocular pressure (IOP) detection.METHODS: IOP of 529 eyes of 265 volunteers were measured with both NCT and GAT, respectively.RESULTS: The measurement results of NCT were lower than that of GAT, there was significant difference between the IOP measured with NCT and GAT (19.13 vs23.43, t=22.644, P＜0.05). With the increasing of IOP values, the difference magnitude was greater, especially in IOP group that was more than 30mmHg, but the correlation coefficient became lower.CONCLUSION: The measurement results with NCT are lower than that of GAT. When the IOP with the NCT is in borderline value, it need be corrected with GAT, in order to discover the pathologically elevated IOP and avoid the misdiagnosis and mistreatment of glaucoma.

Simvastatin is a hypolipidemic drug that inhibits hydroxymethylglutaryl coenzyme A (HMGCoA) reductase to control elevated cholesterol,or hypercholesterolemia.Previous studies have shown that simvastatin may attenuate inflammation in ischemia-reperfusion injury and sepsis.Herein,we hypothesized that simvastatin may prevent rats from lipopolysaccharide (LPS)-induced septic shock.In our study,rats were divided into a saline group,an LPS group and an LPS plus simvastatin group.Male Sprague-Dawley (SD) rats were pretreated with simvastatin (1 mg/kg) for 30 min before the addition of LPS (8 mg/kg),with variations in left ventricular pressure recorded throughout.Ninety min after LPS injection,whole blood was collected from the inferior vena cava,and neutrophils were separated from the whole blood using separating medium.The neutrophils were then lysed for Western blotting to detect the levels of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1).In addition,mesentery microcirculations of inlet diameter,outlet diameter and blood flow rate were measured in all three groups.The results indicated that simvastatin significantly promoted heart systolic function and increased the level ofuPA while simultaneously inhibited the expression of PAI-1 as compared with LPS group.Moreover,simvastatin reversed the LPS-induced inhibition of mesentery microcirculation.Taken together,it was suggested that simvastatin can effectively protect the rats from LPS-induced septic shock.

Cholesterol ester transfer protein (CETP) is a key regulator of high density lipoprotein (HDL). Owing to its important role in the reverse of cholesterol transport, CETP has become a hotspot target in modulating lipid drug design. In this paper, structure based pharmacophore (SBP) models for CETP inhibitors were built based on the protein structure 4F2A from Protein Database (PDB). The best pharmacophore contained six hydrophobic features, one hydrogen bond acceptor feature and nine excluded volume features, with the N and CAI value was 3.33 and 2.31 respectively. Then the model was used to search the traditional Chinese medicine database (TCMD) and 629 compounds originated from 315 TCM herbs were obtained. Molecular docking was also used to validate SBP by analyzing the critical amino acid residue and the interaction between potential active compounds and receptor. In this study, several TCM herbs, like Lycii Frutus and Schisandrae chinensis fructus, which contained more optimal SBP based screening results, have been reported hypolipidemic effect, and need to be studied deeply in a more focused research on herbal active constituents. Therefore, this study could provide reliable fundamental data for exploring the action mechanisms of TCM, and be applicable to identify lead candidates, which can be utilized as starting scaffolds for natural CETP inhibitors.
Cholesterol Ester Transfer Proteins ; antagonists & inhibitors ; Drug Evaluation, Preclinical ; methods ; Medicine, Chinese Traditional ; Molecular Docking Simulation

Objective:To analyze the epidemiological characteristics of novel coronavirus positive cases including confirmed cases with clinical symptoms and asymptomatic infected cases in Guangzhou.Methods:Epidemiological data were collected on the nucleic acid positive cases of COVID-19 in Guangzhou from January to September 2020. The epidemiological characteristics, the distribution of time intervals between the confirmed/isolation date and the date of the first positive detection were analyzed, at last the influencing factors for the confirmed cases and asymptomatic infected persons were discussed.Results:From January 7 to September 4 in 2020, a total of 1 097 nucleic acid positive cases were identified, including 658 confirmed cases (59.98%) and 439 asymptomatic infected cases (40.02%). Among the 658 confirmed cases, the median age was 42 years old, the cases indicated two significant peaks. one of the peaks was related to the imported and associated cases from Hubei province, and the other peak was connected with individuals from overseas. In terms of 439 asymptomatic infected cases, the median age was 32 years old. There were two stages in these cases. The first stage followed the second peak of confirmed cases, and the second stage overlapped with the confirmed cases in Guangzhou when the epidemic was in a period of normal prevention and control, mainly related to imported cases from abroad. The asymptomatic infected persons accounted for 57.32% in all the imported infected cases. In both of asymptomatic and symptomatic cases, the positive rate of pharyngeal swabs was higher than that of nasopharyngeal swabs and anal swabs. There were statistically significant differences in age, source of infection and gender composition between confirmed cases and asymptomatic infected persons ( P<0.05). Older age groups were more likely to have clinical symptoms, with ≥40 years being the risk factor for confirmed cases (OR=2.334, P=0.001), and 20-39 years less likely to have clinical symptoms (OR=0.620, P=0.047), compared with the 0-19 years old group. Compared with those infected in China, those infected abroad were less likely to develop clinical symptoms and became confirmed cases (OR=0.723, P=0.013). Women were more likely to have clinical symptoms than men (OR=1.574, P=0.001). Conclusions:At present, asymptomatic infected persons and confirmed patients with clinical symptoms co-existed, and the number of asymptomatic infected patients was higher than that of confirmed cases in Guangzhou. High age, domestic infection and female may be risk factors for confirmed cases. It was of great value to further explore these underlying mechanisms for the prevention and treatment of the COVID-19.

Objective To understand the clinical features of patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) complicated by cytomegalovirus (CMV)viremia.Methods The clinical data of 249 cases of HIV/AIDS patients hospitalized in Beijing Ditan Hospital from Oct 2008 to Nov 2009 were analyzed retrospectively,in which 43 HIV/AIDS patients were diagnosed with CMV viremia.The symptoms and signs,cerebrospinal fluid (CSF)tests,and pathological detections by bronchoscope,gastroscope and fibercoloscope were collected.The database was set up using Excel software.The association between cellular immunity and CMV DNA level was determined by SPSS12.0 software.Results Forty-three patients (17.3%)were diagnosed with CMV viremia by positive results of CMV pp65 antigen and CMV DNA tests; 14 patients manifested retinal bleeding or infiltration and 4 patients displayed retinal fibrosis; 1 patient was diagnosed with CMV pneumonitis by pathological results of bronchoalveolar lavage fluid.Low level of CD4+ T lymphocytes and CMV DNA levels were positively correlated.Conclusions CMV pp65 antigen and CMV DNA should be detected in HIV/AIDS patients with CD4+ T lymphocytes less than 100 × 106/L and anti-CMV treatment should be given according to the results.Ophthalmologic examination and bronchoalveolar lavage fluid pathological detection are effective methods in diagnose of CMV retinitis and pneumonitis.

OBJECTIVETo investigate the feasibility of real-time fluorescent quantitative (qPCR) assay in detecting mycobacterium tuberculosis complex (MTB) in paraffin embedded tissues for diagnostic purpose.

METHODSUsing qPCR assay, 1000 consecutive formalin-fixed and paraffin embedded (FFPE) tissues (from 2011 to 2012) suspected of MTB infection were tested by amplifying the MTB specific insertion sequence 6110 (IS6110). The specificity of the PCR product was confirmed by Sanger sequencing as compared with the MTB genomic DNA of the IS6110 sequence. Tissues with Ziehl-Neelsen acid-fast staining were used as control.

RESULTSIn the 1000 samples, 513 were positive for mycobacterium by Ziehl-Neelsen acid-fast staining (detection rate 51.3%); whereas 546 were MTB positive by qPCR assay (detection rate 54.6%). Concordance rate for both assays was 73.1%. The diagnosis rate increased by 14.4% by combinination of Ziehl-Neelsen acid-fast staining and qPCR results. More interestingly, by analyzing the Ziehl-Neelsen acid-fast staining and qPCR results three cases of M.leprae infection and four cases of non-tuberculous Mycobacterium (NTM) infection were identified.

CONCLUSIONSqPCR detection of MTB in FFPE tissue is more sensitive than Ziehl-Neelsen acid-fast staining assay. Combination of these two assays can increase the detection rate and also identify some rare cases of NTM infection.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; DNA, Bacterial ; genetics ; Female ; Humans ; Male ; Middle Aged ; Mycobacterium tuberculosis ; genetics ; isolation & purification ; Paraffin Embedding ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, DNA ; Staining and Labeling ; methods ; Tuberculosis ; diagnosis ; microbiology ; Tuberculosis, Gastrointestinal ; diagnosis ; microbiology ; Tuberculosis, Lymph Node ; diagnosis ; microbiology ; Tuberculosis, Pulmonary ; diagnosis ; microbiology ; Young Adult

OBJECTIVETo investigate the complications of surgical treatments for femoral intertrochateric fractures using dynamic hip screw (DHS).

METHODSFrom Jan. 2002 to Dec. 2007, sixty-nine patients with intertrochanteric fractures were treated by dynamic hip screw fixation included 27 males and 42 females,with an average age of 72.9 years ranging from 53 to 96 years. According to Evans classification there were 10 cases in type I ,21 in type II, 22 in type III, and 16 in type IV, of which 51 patients (73.9%) suffered from systematic diseases preoperatively.

RESULTSFifty-seven patients were followed up for 8 to 70 months (41 months on average). Four patients died, 17 cases occurrenced systematic complications postoperatively. Internal fixation related complications occurred in 12 patients. There were 8 cases with mechanical failure of DHS including 4 of screw loosen,3 of cutting-out of device through femoral head and neck and 1 of plate breakage. Five patients had a coxa vara, and delayed union occurred in 4 patients.

CONCLUSIONUnstable fracture pattern produced high percentage of mechanical failure. In such cases DHS should not be the first choice for treatment. The appropriate treatment should be in relation to pre-operative fracture stability and osteoporosis.

Aged ; Aged, 80 and over ; Bone Screws ; Female ; Fracture Fixation, Internal ; adverse effects ; Hip Fractures ; surgery ; Humans ; Male ; Middle Aged ; Postoperative Complications ; etiology ; Retrospective Studies