The combined application of statins that inhibit HMG-CoA reductase and fibrates that activate PPAR-α can produce a better lipid-lowering effect than the simple application, but with stronger adverse reactions at the same time. In the treatment of hyperlipidemia, the combined administration of TCMs and HMG-CoA reductase inhibitor in treating hyperlipidemia shows stable efficacy and less adverse reactions, and provides a new option for the combined application of drugs. In this article, the pharmacophore technology was used to search chemical components of TCMs, trace their source herbs, and determine the potential common TCMs that could activate PPAR-α. Because there is no hyperlipidemia-related medication reference in modern TCM classics, to ensure the high safety and efficacy of all selected TCMs, we selected TCMs that are proved to be combined with statins in the World Traditional/Natural Medicine Patent Database, analyzed corresponding drugs in pharmacophore results based on that, and finally obtained common TCMs that can be applied in PPAR-α and combined with statins. Specifically, the pharmacophore model was based on eight receptor-ligand complexes of PPAR-α. The Receptor-Ligand Pharmacophore Generation module in the DS program was used to build the model, optimize with the Screen Library module, and get the best sub-pharmacophore, which consisted of two hydrogen bond acceptor, three hydrophobic groups and 19 excluded volumes, with the identification effectiveness index value N of 2. 82 and the comprehensive evaluation index CAI value of 1. 84. The model was used to screen the TCMD database, hit 5,235 kinds of chemical components and 1 193 natural animals and plants, and finally determine 62 TCMs. Through patent retrieval, we found 38 TCMs; After comparing with the virtual screening results, we finally got seven TCMs.
Acyl Coenzyme A ; metabolism ; Animals ; Databases, Factual ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Hydrophobic and Hydrophilic Interactions ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; chemistry ; pharmacology ; Lipid Metabolism ; drug effects ; Lipids ; blood ; Medicine, Chinese Traditional ; Models, Molecular ; Quantitative Structure-Activity Relationship ; Technology

BACKGROUND: With mechanical ventilation widely used in intensive care unit, the ventilator associated pneumonia (VAP) has become a common and serious complication in critically ill patients. Compared with adults, the incidence of VAP and the mortality are higher in children in pediatric intensive care unit (PICU) because of immune deficiency, severe basic diseases, and increased use of artificial airway or mechanical ventilation. Hence it is of significance to study the epidemiology and changes of antibacterial susceptibility in order to reduce the incidence and mortality of VAP in children. METHODS: From January 2008 to June 2010, 2758 children were treated in PICU of Wuhan Children's Hospital. Among them, 171 received mechanical ventilation over 48 hours in PICU, and 46 developed VAP. The distribution and drug-resistance pattern of the pathogenic bacteria isolated from lower respiratory tract aspirations were analyzed. RESULTS: A total of 119 pathogenic microbial strains were isolated. Gram-negative bacilli (G-) were the most (65.55％), followed by fungi (21.01％) and gram-positive cocci (G+, 13.45％). Among them, the most common pathogens were Acinetobacter baummannii, Escherichia coli, Klebsiella pneumoniae, candida albicans and coagulase-negative staphylococci. Antibiotic susceptibility tests indicated that the multiple drug-resistances of G- and G+ to antibiotics were serious. Most of G- was sensitive to ciprofloxacin, amikacin, imipenem, meropenem, cefoperazone-sulbactam and piperacillin-tazobactam. The susceptibility of G+ to vancomycin, teicoplanin and linezolid were 100％. Fungi were almost sensitive to all the antifungal agents. The primary pathogens of VAP were G-, and their multiple drug-resistances were serious. CONCLUSION: In clinical practice we should choose the most sensitive drug for VAP according to pathogenic test.

BACKGROUND: With beta-lactam drugs and immunosuppressants widely used, the infection caused byAcinetobacter baumannii (Ab) has become more and more serious with multidrug resistant Acinetobacter baumannii (MDRAb) emerging and worsening rapidly. Compared with other patients, the incidence and multidrug resistance of MDRAb are higher in children in pediatric intensive care unit (PICU) because of immune deficiency, severe basic diseases, prolonged hospitalization and invasive operations. Hence it is significant to study the epidemiology and changes of antibacterial susceptibility in order to reduce the incidence of MDRAb in children. METHODS: A total 115 patients with MDRAb pneumonia and 45 patients with negative MDRAb (NMDRAb) pneumonia who had been treated from January 2009 to August 2011 were studied retrospectively at the PICU of Wuhan Children's Hospital. Clinical data were analyzed with univariate and multivariate Logistic regression. RESULTS: In 176 clinical strains ofAcinetobacter baumannii isolated, there were 128 strains of MDRAb, accounting for 72.73％. Drug susceptibility tests showed that the resistance rates of β-lactam antibiotics were more than 70％ except for cefoperazone sulbactam. The rates to carbapenems were higher than 90％. They were significantly higher than those of NMDRAb. Amikacin, levofloxacin, ciprofloxacin and minocycline had the lowest drug-resistance rates (<20％). Multivariate Logistic regression revealed that ICU stay, the time of mechanical ventilation, anemia, hypoproteinemia and the use of carbapenems were independent risk factors for MDRAb pneumonia. CONCLUSIONS: MDRAb is an important opportunistic pathogen to pneumonia in PICU, and its drug-resistance is severe. It increases significantly the mortality of patients. It is important to take the effective prevention measures for controlling it.

The pertinent literature on application of traditional Chinese medicine (TCM) in hemopoietic stem cell transplantation was summarized, it indicated that the intervention of TCM could raise the mobilization effect, speed up the hemopoiesis and immunologic reconstruction after transplantation, decrease the incidence of complications, and prolong the life span of patients, showing a preliminary achievement.
Combined Modality Therapy ; Drugs, Chinese Herbal ; therapeutic use ; Graft vs Host Disease ; etiology ; prevention & control ; Hematopoietic Stem Cell Transplantation ; adverse effects ; methods ; Humans ; Medicine, Chinese Traditional ; methods ; Phytotherapy ; Postoperative Complications ; etiology ; prevention & control

OBJECTIVETo compare the clinical safety and efficacy of laparoscopic versus open colorectal resection in octogenarians. Methods Studies comparing laparoscopic colorectal resection with open colorectal resection in octogenarians were identified from the Medline, Embase, Ovid, and Cochrane databases from 1990 to 2012. The methodological quality of the selected studies was assessed to determine studies suitable for inclusion. Meta-analysis was performed by fixed or random effects model.

RESULTSFive observational studies with a total of 685 patients (330 laparoscopic colorectal resections and 355 open colorectal resections) were identified. Laparoscopic colorectal resection was associated with a prolonged operative time (WMD=27.89, P<0.01) and a lower rate of overall complications (OR=0.58, P<0.01), wound infection (OR=0.50, P<0.05), cardiovascular complication(OR=0.53, P<0.05), quicker bowel function return (WMD=-0.83, P<0.01), and shorter length of hospital stay (WMD=-3.60, P<0.05). No differences were found with regard to anastomotic leak (OR=1.13, P>0.05), prolonged ileus (OR=0.71, P>0.05), respiratory complication (OR=0.59, P>0.05),mortality (OR=0.67, P>0.05), and reoperation (OR=0.85, P>0.05).

CONCLUSIONLaparoscopic colorectal resection is as safe as open colorectal resection, and is more favorable in terms of length of hospital stay and bowel function return in octogenarians.

Aged, 80 and over ; Anastomotic Leak ; Colectomy ; methods ; Humans ; Laparoscopy ; Length of Stay ; Operative Time ; Treatment Outcome

OBJECTIVETo analyze the clinicopathologic characteristics and the prognostic factors of breast cancer patients with skip metastases in the axilla.

METHODSThe clinical data of 1502 breast cancer patients who underwent complete axillary lymph node dissection were retrospectively reviewed. The patterns of skip metastases, clinical features and prognostic factors were analyzed.

RESULTSOf the 1502 patients, lymph node metastases were found in 814, of whom skip metastases in 119 (14.6%, 119/814). The Clinicopathologic factors such as age, tumor size, tumor location, clinical stage, hormonal receptor status and involved interpectoral lymph nodes were not correlated with skip metastases (P > 0.05). The disease free survival rate was lower in clinical stage I and II patients with skip metastases than that in those without (P = 0.003), while no significant difference was observed in clinical stage III patients (P = 0.457). Multivariate analysis showed that the tumor size, number of metastatic lymph nodes, extracapsular invasion of the lymph nodes and skip metastases in the axilla were significantly correlated with survival rate.

CONCLUSIONSkip metastasis in the axilla cannot be accurately predicted by clinicopathologic factors. Early breast cancer patients with skip metastases should be treated properly due to poor prognosis.

Adult ; Aged ; Axilla ; Breast Neoplasms ; pathology ; surgery ; Carcinoma, Ductal, Breast ; pathology ; surgery ; Female ; Follow-Up Studies ; Humans ; Lymph Node Excision ; Lymph Nodes ; pathology ; surgery ; Lymphatic Metastasis ; pathology ; Middle Aged ; Neoplasm Staging ; Proportional Hazards Models ; Retrospective Studies ; Survival Rate ; Tumor Burden ; Young Adult

Background:The preferred treatment for uncomplicated type B dissection (thoracic endovascular aortic repair [TEVAR] or medical) is still under debate.Since 2001,our center has performed TEVAR for uncomplicated type B dissection.Based on our data,5-and 10-year survival rates among patients with uncomplicated type B dissection after TEVAR were 96.5％ and 83.0％,respectively.We,therefore,believe that TEVAR is preferable for uncomplicated type B dissections.This study analyzed the impact of a pre-operative smoking history on long-term survival after TEVAR in patients with uncomplicated type B dissections.Methods:From May 2001 to December 2013,data from 751 patients with type B dissections were collected and analyzed.Patients were divided into two groups (337 smoking patients and 414 non-smoking patients).The Kaplan-Meier method and log-rank test were used to compare survival curves of the two groups.Multivariable analyses using the Cox proportional hazards model were used to estimate the effects of smoking on survival rates.Results:The 5-and 10-year survival rates of non-smokers were 97.6％ (95％ confidence interval [CI],96.0％-99.2％) and 87.0％ (95％ CI,81.6％-92.7％),respectively,and 94.9％ (95％ CI,92.2％-97.7％) and 73.8％ (95％ CI,62.3％-87.5％) for smokers,respectively (Log-rank test,P =0.006).Multivariable analyses showed that smoking increased the risk of death during follow-up,2.1-fold when compared to non-smokers (P =0.039).Conclusion:A pre-operative smoking history increases long-term mortality rates after TEVAR in patients with uncomplicated type B dissections.

Objective: To observe the clinical effect of guava leaf (GL) in treating infantile rotaviral enteritis.Methods: Sixty-two patients of rotaviral enteritis were randomly divided into the treated group treated with GL and the control group treated with Gegen Qinlian Decoction. The time for ceasing diarrhea, content of Na+ in blood, content of Na+ and glucose in stool, and the rate of negative conversion of human rotavirus antigen (HRVA) were observed.Results: The 3-day recovery rate in the treated group (87.1%) was significantly higher than that in the control group (58.1%, P<0.05). The time of ceasing diarrhea in the treated group (25.1±9.5 hrs) was significantly shorter than that in the control group (38.7±15.2 hrs, P<0.01). Moreover, content of Na+ and glucose in stool were reduced obviously in the treated group but not in the control group; and negative conversion rate of HRVA in the former group also got better than that in the latter group (87.1% vs 58.1%, P<0.05). Consequently, the effect of GL was superior to that of the control significantly.Conclusion: GL has good curative effect on infantile rotaviral enteritis.

OBJECTIVETo evaluate the effect of sustained-release alpha-lipoic acid tablets (SRLA) on blood lipid, glucose and insulin levels in hyperlipidemic New Zealand rabbits.

METHODSTwenty-four New Zealand rabbits were randomized into normal diet group, high-fat diet group, and high-fat diet + SRLA (300 mg/tablet) group with corresponding feed. At the beginning and 4 weeks after the feeding, the serum levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), blood glucose, and serum insulin were measured, and insulin sensitivity index (ISI) was calculated.

RESULTSFour weeks after feeding with high-fat diet, the insulin levels was elevated and the ISI lowered in the New Zealand rabbits, indicating successful establishment of the animal model of hyperlipidemia. Compared with the high-fat diet group, the serum levels of TG, TC, LDL-C and insulin were significantly reduced (P<0.05), and the ISI was significantly increased (P<0.05) in high fat diet + SRLA group. But no statistically significant difference was found in the blood glucose among the 3 groups.

CONCLUSIONSRLA can significantly correct blood lipid and insulin disorders in hyperlipidemic New Zealand rabbits and prevent the occurrence of insulin resistance and hyperlipidemia.

Animals ; Blood Glucose ; metabolism ; Delayed-Action Preparations ; Hyperlipidemias ; blood ; drug therapy ; metabolism ; Insulin ; metabolism ; Lipids ; blood ; Male ; Rabbits ; Tablets ; Thioctic Acid ; administration & dosage ; pharmacology ; therapeutic use

OBJECTIVETo investigate the effects of insulin-like growth factor II (IGF-II) on promoting cell proliferation, regulating levels of cellular nitric oxide (NO) and mRNA transcriptions of inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS) in mouse osteoblast-like cells.

METHODSMouse osteoblastic cell line MC3T3-E1 was selected as the effective cell of IGF-II. After the cells were treated with IGF-II at different concentrations for different time duration, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) colorimetric assay was used to examine cell proliferation, and nitrate reductase method was applied to detect NO concentrations in cell culture supernatants and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) was employed to determine transcription levels of cellular iNOS and eNOS mRNAs.

RESULTSAfter the MC3T3-E1 cells were treated with IGF-II at concentration of 1 ng/ml for 72 h, 10 and 100 ng/ml for 24, 48 and 72 h respectively, all the MTT values increased (P<0.05 or P<0.01) with obvious dosage-time dependent pattern. NO levels of the MC3T3-E1 cells treated with 100 ng/ml IGF-II for 48 h, and with 1, 10 and 100 ng/ml IGF-II for 72 h were remarkably lower than that of the normal control, respectively (P<0.05 or P<0.01). After the cells were treated with 100 ng/ml IGF-II for 48 h cellular iNOS mRNA levels were significantly decreased (P<0.01). But the levels of eNOS mRNA in the cells treated with each of the used IGF-II dosages for different time duration did not show any differences compared with the normal control (P>0.05).

CONCLUSIONIGF-II at different concentrations could promote proliferation of mouse MC3T3-E1 cell. This cell proliferation promotion was associated with the low NO levels maintained by IGF-II. Higher concentration of IGF-II could down-regulate iNOS gene expression at the level of transcription but not affect transcription of eNOS mRNA, which might be one of the mechanisms for IGF-II maintenance of the low NO levels in MC3T3-E1 cells.

3T3 Cells ; Animals ; Cell Proliferation ; drug effects ; Dose-Response Relationship, Drug ; Gene Expression Regulation, Enzymologic ; drug effects ; physiology ; Insulin-Like Growth Factor II ; administration & dosage ; Mice ; Osteoblasts ; cytology ; drug effects ; physiology