Objective To analyze molecular evolution and binding free energies of cephalosporinase ADC-57.Methods Minimum Evolution method in MEGA 5.0 was used to analyze molecular evolution of cephalosporinase ADC-57 and other 19 kinds of beta-lactamases.Tertiary structure of ADC-57 was predicted by homology modeling referring to tertiary structure of CMY-2.The molecular docking of ADC-57 to 11kinds of beta-lactams substrates was performed using DOCK module in ArgusLab 4.1and the binding free energies (△G) was calculated.Results ADC-57,CMY-2,DHA-1,ADC-7,ADC-56 were all belong to class C beta-lactamase,and molecular evolution between ADC-57 and ADC-56 was closest.The top three antibiotics with declining binding free energy of beta-lactams were ertapenem,cefoxitin and ceftazidine,while the last two were clavulanic acid and aztreonam.Conclusions Catalytic activities of cephalosporinase ADC-57 to ertapenem,cefoxitin and ceftazidine are high,while to clavulanic acid and aztreonam are low. Hydrolytic activities of enzyme to beta-lactams (substrates) can be analyzed by molecular docking.

Three female patients admitted with elevated creatine kinase,impaired muscle on electromyogram,and positive repetitive nerve stimulation and neostigmine tests were diagnosed as polymyositis (PM) with myasthenia gravis (MG).Twenty five more cases were retrieved by literature search,and the clinical data of total 28 cases were analyzed.There were 10 males and 18 females with an average age of 56 years.The clinical manifestations include dyspnea(43％),dysphagia(43％),ptosis (43％),dysarthria(29％),diplopia(18％),cough after drinking(14％),myalgia(11％).Thirteen out of 26 cases (50％) had positive results in repetitive nerve stimulation (RNS) and 10/11 showed positive reaction in neostigmine test.Serum positive anti-acetylcholine receptor was detected in 21 out 23 patients (91％).

Objective To explore the clinical value of plasma(1,3)-β-D-glucan detection(G test)in the diagnosis of invasive fun-gal infections(IFI).Methods The plasma samples were collected in 67 cases of IFI,61 cases of non-IFI and 48 healthy controls from January to September 2013.The level of(1,3)-D-glucan in plasma was detected by the kinetic turbidimetric assay and the opti-mal critical value of the G test was determined by receiver operating characteristic curve(ROC).Results The levels of(1,3)-β-D glucan in the IFI,non-IFI and healthy control groups showed the non-normal distribution.However,the median level of plasma(1, 3)-β-D glucan in the IFI group was 208.00pg/mL,which was significantly higher than 61.30 pg/mL(Z =-5.083,P <0.01)in the non-IFI group and 31.16 pg/mL(Z =-8.288,P <0.01)in the healthy control group.The area under ROC of the G test for diag-nosing IFI was 0.846 and the optimal critical value was 90.49pg/mL.The corresponding sensitivity,specificity,positive and nega-tive predictive values were 86.6%,77.1%,69.9% and 90.3%,respectively;at the same time,which of the fungal culture for diag-nosing IFI were 53.7%,94.5%,85.7% and 61.9% respectively.Conclusion Plasma(1,3)-β-D-glucan detection exhibits the high sensitivity and the better negative predictive value for the diagnosis of IFI.But the false positive results occur at times.It is sugges-ted that the G test can be dynamically conducted combined with the fungal culture for improving the efficiency of IFI diagnosis.

Objective : To learn the regulatory effect of Lactobacillus plantarum JX025073.1 on intestinal flora and blood lipid in mice, so as to provide the basis for the nutritional intervention of probiotics in hyperlipidemia population. Methods : Thirty male ICR mice were randomly divided into a control group, a model group and a intervention group. The mice in the control group were fed with basic diet, and in the other two groups were fed with high fat diet. The mice in the intervention group was given 0.4 mL of Lactobacillus plantarum JX025073.1 fermentation liquid by gavage every day, and in the other two groups were given 0.4 mL of normal saline. The body weight of mice, the mass of heart, liver, spleen and kidney organs were weighed, and the organ index was calculated. The contents of total cholesterol (TC), triacylglycerol/triglyceride ( TG ), low density lipoprotein cholesterol ( LDL-C ) in serum, TC, TG in liver and in feces were determined by biochemical analyzer. Bifidobacterium, Lactobacillus and Escherichia coli in feces were cultured and counted. Results : After 42 days, compared with the control group, The mice in the model group had higher body weights, higher levels of TC, TG and LDL-C in serum, higher levels of TC, TG in liver and in feces, more Escherichia coli, less Bifidobacterium and less Lactobacillus ( P<0.05 ). Compared with the model group, the mice in the intervention group had lower body weight, lower levels of TC, TG and LDL-C in serum, lower levels of TC in liver, less Escherichia coli, higher levels of TC in feces, more Bifidobacterium and more Lactobacillus ( P<0.05 ). Conclusion Lactobacillus plantarum JX025073.1 can effectively regulate the blood lipid and intestinal flora of mice fed with high fat diet.

To investigate the characteristics of traditional Chinese medicine (TCM) syndromes and their elements in people with subhealth fatigue.

Objective: To investigate the drug resistance and positive virulence genes of Acinetobacter baumannii (A.baumannii) and analyze the correlation between drug resistance and the positive pattern of virulence genes. Methods: A total of 67 strains of A.baumannii were collected and identified by matrix assisted laser desorption ionization time of flight mass spectrometry technology (MALDI-TOF MS). Drug susceptibility tests were carried out by turbidimetric and redox indicator method. The homology of A.baumannii stains was explored by cluster analysis. The 8 virulence genes including bacterial outer membrane protein (ompA), biofilm formation (adeH, csuA, pgaA), iron uptake system (basJ), phospholipase D (plcD), capsular positive phenotype (ptk) and regulation of quorum sensing system (abaI) were amplified by PCR and sequenced. The correlation between virulence genes and drug resistance in the 67 strains of A. baumannii was investigated. Results: The positive rates of virulence genes ompA, adeH, csuA, pgaA, abaI, basJ, ptk and plcD were 94%, 100%, 94%, 99%, 93%, 96%, 82% and 99%, respectively. Among the 67 strains of A. baumannii, 3 genes were simultaneously detectable in 1 strain (1.5%), 5 genes were positive in 2 strains (3.0%), 6 genes were positive in 2 strains (3.0%), 7 genes were positive in 14 strains (20.9%) and all the 8 genes were positive in 48 strains (71.6%). Among the 48 strains with 8 positive virulence genes, the drug resistance rate of polymyxin was only 2.1%, but tetracycline was 58.2%, piperacillin and other 13 antibiotics was more than 80%. The 14 strains with 7 positive virulence genes showed more than 78% of resistance rate for all the tested antibiotics except for tetracycline and polymyxin. Cluster analysis showed that the 67 strains of A. baumannii were divided into 2 genotypes: A (41 strains) and B (26 strains). The 41 strains of A type were divided into A1 (27 strains) and A2 (14 strains) subtypes. The strains of A1 subtype were mainly from neurosurgery department (7 strains), ICU (5 strains) and pneumology department (3 strains). The strains of A2 subtype were mainly from pneumology department (3 strains), cardiothoracic surgery department (3 strains), ICU (2 strains) and neurosurgery department (2 strains). The 26 strains of B type were divided into B1 (19 strains) and B2 (7 strains). The strains of B1 type were mainly from ICU (7 strains), neurosurgery department (4 strains) and respiratory department (3 strains). The strains of B2 type were mainly from ICU (2 strains) and respiratory department (3 strains). Conclusion The cross infection from A. baumannii may present in our hospital. There was no correlation between drug resistance and positive pattern of virulence gene in Acinetobacter baumannii.

Objective To explore the effect of sorafenib on HeLa cell proliferation by inducing cell apoptosis and autophagy and its impact on drug resistance.Methods The drug-resistant cell strains were constructed through in-termittent induction method,with concentrations of 0,2.5,5.0,7.5,10.0,15.0,20.0 μmol/L.HeLa cells were incubated with increasing concentrations of sorafenib with each concentration for 1 week.The drug-resistant cell strains with stable passages were collected.MTT assay was used to detect the effect of sorafenib on cell prolifer-ation.Cell cycle distribution was analyzed by flow cytometry.The change in the expression of drug-resistant and ap-optotic genes in the parents and drug-resistant cell strains under different drug concentrations was examined by semi-quantitative PCR.The changes of apoptotic related marker proteins LC3-Ⅰ and LC3-Ⅱ were detected by Westernblot.Results Stable drug-resistant strains were successfully obtained;Drug-treated cells were more blocked in the G1 phase.In drug-resistant cells,the expression of apoptosis suppressor gene Bcl-2 was significantly decreased and the apoptotic gene Bax as well as the drug-resistant genes were all significantly increased(P＜0.05).The LC3-Ⅱ/LC3-Ⅰ ratio of drug-resistant cells was significantly higher than that of parent cells(P＜0.05).Conclusions Sorafenib may block the cell cycle,suppress malignant cell proliferation and promote autophage.On one hand,autophagy participates in the development of cell drug resistance and promotes cell survival.On the other hand,drug-induced autophagy may activate some of apoptotic signaling pathway in drug-resistant cells and promote the reversal of cell drug resistance.

The hospital introduced a multi-department synergy in management of the rational use of carbapenems. Specifically,the medical affairs department conducts training and appraisal of doctors along with a monthly checkup of medical records. The pharmaceutical affairs division conducts prior prescriptions checkup and follow-up comment. The clinical microbiology laboratory and the hospital-acquired infection management department monitors and releases such infection and bacterial resistance information of the whole hospital in real time. The results showed increased prescriptions of imipenem and cilastatin sodium, and decreased prescriptions of biapenem for injection. Drug resistance analysis showed that carbapenem resistant strains increased by 28%,but the total number of patients reduced by 10% and total number of patients with multidrug resistance remained unchanged. It is proposed to further antimicrobial stewardship in the hospital to achieve rational drug use and curb bacterial resistance.

Transdermal drug delivery systems (TDDs) avoid gastrointestinal degradation and hepatic first-pass metabolism, providing good drug bioavailability and patient compliance. One emerging type of TDDs is the wearable patch worn on the skin surface to deliver medication through the skin. They can generally be grouped into passive and active types, depending on the properties of materials, design principles and integrated devices. This review describes the latest advancement in the development of wearable patches, focusing on the integration of stimulus-responsive materials and electronics. This development is deemed to provide a dosage, temporal, and spatial control of therapeutics delivery.