A series of new pleuromutilins derivatives were designed and synthesized through coupling 2-aminothiazole ring of WL001 with different nitrogen-containing substituted heterocycles in the side chain. Their biological activities were evaluated against both Gram-positive and Gram-negative clinical bacteria in vitro Most new compounds displayed specificity to certain strain of bacteria. Particularly, compounds with saturated nitrogen-containing heterocycles exhibited significant antibacterial activities (0.062 5-8 µg · mL(-1)) superior or similar to those of amoxicillin, tiamulin and levofloxcin. Furthermore, treatment with 15a and 15b having piperidine or morpholine residues also could effectively inhibit Gram-negative bacteria. Therefore, our novel findings may provide a new insight into the design of novel pleuromutilin derivatives and lay the basis for further studies on the treatment of drug-resistance of pathogenic bacteria.

Objective Knowing the BRCA gene mutational condition of high risk triple negative breast cancer (TNBC) in Xinjiang Uygur Autonomous and acquiring the differences of clinical and pathologic characteristics between person with BRCA gene mutation and person without it by means of BRCA gene mutation testing for 30 cases of TNBC in Xinjiang Uygur Autonomous.Methods The objects of this study were 30 cases of high risk TNBC from Xinjiang.All the coded sequences of BRCA1/2 gene were amplified by means of extracting genomic DNA from peripheral venous blood.BRCA1/2 gene mutation analysis were prescreened through DHPLC.Then,the result was verified by DNA sequencing.The clinical and pathologic characteristics between person with BRCA gene mutation and person without it of 30 high risk TNBC cases were contrastively analysed.Results In all the 30 cases of BRCA gene mutation testing for TNBC in Xinjiang Uygur Autonomous,there were 5 cases of pathogenic mutations of BRCA gene (5/30,16.7 ％); 4 cases of BRCA 1 mutation (4/30,13.3 ％); 1 case of BRCA 2 mutation (1/30,3.3 ％); and there was no mutation to be found in 25 cases of BRCA gene of TNBC (25/30,83.3 ％).As compared with person without gene mutation,who with it had the characteristics of earlier of TNM,the difference was statistically significant (P =0.040).Conclusion Since the rate of BRCA1 gene mutation of high risk TNBC is higher.It is suggested that the BRCA gene of every patients with high risk TNBC should be tested.Comparing with person with BRCA gene mutation and person without it,there might have differences on clinical pathological characteristics features.Therefor,individualized treatment should be taken into consideration.

A series of new pleuromutilins derivatives were designed and synthesized through coupling 2-aminothiazole ring of WL001 with different nitrogen-containing substituted heterocycles in the side chain. Their biological activities were evaluated against both Gram-positive and Gram-negative clinical bacteria in vitro Most new compounds displayed specificity to certain strain of bacteria. Particularly, compounds with saturated nitrogen-containing heterocycles exhibited significant antibacterial activities (0.062 5-8 µg · mL(-1)) superior or similar to those of amoxicillin, tiamulin and levofloxcin. Furthermore, treatment with 15a and 15b having piperidine or morpholine residues also could effectively inhibit Gram-negative bacteria. Therefore, our novel findings may provide a new insight into the design of novel pleuromutilin derivatives and lay the basis for further studies on the treatment of drug-resistance of pathogenic bacteria.
Amoxicillin ; Anti-Bacterial Agents ; chemical synthesis ; chemistry ; Diterpenes ; chemical synthesis ; chemistry ; Gram-Negative Bacteria ; drug effects ; Levofloxacin ; Microbial Sensitivity Tests ; Nitrogen ; Structure-Activity Relationship

OBJECTIVE To observe the clinical effects of the combination of Duhuo Bugu decoction and zoledronic acid in the treatment of malignant bone metastasis.METHODS Fifty patients with bone metastases of malignant tumor were selected from the Department of oncology,Chongqing Hospital of traditional Chinese medicine from September 2014 to February 2016, and were randomly divided into the observation group and the control group.Two groups were both treated by zoledronic acid, and the observation group was also treated by adding Duhuo Bugu Decoction.Changes of the analgesic effects,analgesic dosa-ges and life quality scores(KPS)of two groups were observed before and after treatment.Urinary type I collagen amino termi-nal peptide(uNTX)and bone alkaline phosphatase(BALP)were measured via ELISA method before and after treatment.RE-SULTS Compared with the control group,the analgesic medicinal amount of the observation group reduced significantly(P<0.05),and KPS improved significantly(P<0.05).After the treatment,numerical pain scores(NRS) of two groups had no significant changes(P>0.05).After the treatment,uNTX and sBALP level of the treatment group decreased compared with that before treatment(P<0.01).While compared with the control group,the difference was not significant(P>0.05).CON-CLUSION The combination of Chinese herbs and zoledronic acid is an effective therapy for bone metastasis malignant tumors. Chinese herbs can effectively improve the analgesic effect,reduce the analgesic medicinal amount,improve the patients'life quality,and have a tendency of synergy in improving the bone destruction caused by tumor.

OBJECTIVETo explore the effects of silencing HERC4 on the proliferation, apoptosis, and migration of cervical cancer cell line Hela and the possible molecular mechanisms.

METHODSThree HERC4-specific small interfering RNAs (siRNAs) were transfected into Hela cells, and HERC4 expression in the cells was examined with Western blotting. CCK-8 assay, annexin V-FITC/PI assay, and wound healing assay were used to assess the effect of HERC4 silencing on the proliferation, apoptosis and migration ability of Hela cells. The expression levels of cyclin D1 and Bcl-2 in the cells were detected using Western blotting.

RESULTSTransfection of siRNA-3 resulted in significantly decreased HERC4 protein expression (P<0.01). HERC4 silencing by siRNA-3 markedly suppressed the proliferation and migration of Hela cells, increased the apoptosis rate (P<0.01) and reduced the expression levels of cyclin D1 and Bcl-2 (P<0.01).

CONCLUSIONSilencing of HERC4 efficiently inhibits the proliferation, migration, and invasion of Hela cells in vitro, and the underlying mechanisms may involve the down-regulation of cyclin D1 and Bcl-2.

Apoptosis ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cyclin D1 ; metabolism ; Down-Regulation ; Female ; HeLa Cells ; Humans ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; RNA Interference ; RNA, Small Interfering ; genetics ; Transfection ; Ubiquitin-Protein Ligases ; genetics ; metabolism ; Uterine Cervical Neoplasms ; pathology

Objective To study the damage propagation and evolution mechanism of cartilage under compressive loads.Methods The fiber-reinforced porous elastic model of cartilage with micro-defect was established by using finite element method,and the process of damage evolution under compressive loads was simulated and analyzed with parameters.The patterns of stress and strain distributions on cartilage matrix and collagen fiber at different damage extension stages were obtained.Results The strain in the surface and forefront of cartilage damage increased significantly with the increase of compression displacement,and they were obviously in positive correlation;in the process of damage evolution,there was a trend that cartilage extended to the deep and both sides simultaneously;cracks and damage in cartilage extended preferentially along the fiber tangent direction.With the aggravation of cartilage damage,the lateral extension speed was significantly faster than the longitudinal extension speed.Conclusions The process of cartilage damage extension has a close relationship with the distribution of fibers.The damages in matrix and fiber promote each other.The evolution speed and degree of cartilage vary constantly in different layers and at different stages.These results can provide the qualitative reference for prediction and repair of cartilage damage,as well as the theoretical basis for explaining pathological phenomena of damage degeneration and its clinic treatment.

Objective To build a server to receive ECG data from the smart phone through remote network transmission,which has the functions of data storage,painting ECG waveform at real time,browsing historical waveform,preliminary ECG self-diagnosis and etc.Methods The development was executed with C# language in Visual Studio 2013,which used the socket for network transmission,GDI for waveform painting,Dataset/Datareader for data access as well as thread for multithreaded programming etc.Five-point smoothing filter was applied to ECG signal preliminary processing,and classical difference threshold algorithm was used to implement waveform analysis of ECG data.The main QRS waves were detected,and ECG features such as R-R interval were analyzed to form ECG self-diagnosis report.Results The server received and showed the ECG data transmitted by smart phone successfully,and then generated ECG waveform and self-diagnosis report.Conclusion This server has a great performance on receiving the data from portable facilities.In addition,it also performs well and stably in accessing and showing ECG data.

Objective To compare the clinical effect of aripiprazole and risperidone in patients with schizophrenia and metabolic syndrome.Methods A retrospective analysis was performed on the case data of schizophrenia and metabolic syndrome.According to different treatment methods,they were divided into risperidone group(oral risperidone,2 mg once,twice a day)and aripiprazole group(oral aripiprazole,5 mg once,once a day).All were treated for 24 weeks and given lifestyle intervention.The clinical effect,scores of positive and negative symptom scale(PANSS),metabolic syndrome-related indexes[systolic blood pressure(SBP),diastolic blood pressure(DBP),body mass index(BMI),fasting blood glucose(FPG),triglyceride(TG)],cognitive function[MATRICS consensus cognitive battery(MCCB)],levels of serum brain-derived neurotrophic factor(BDNF),tyrosine kinase receptor B(TrkB)and glial cell line-derived neurotrophic factor(GDNF)were compared between the two groups.The adverse drug reactions were statistically analyzed in two groups.Results There were 60 cases in risperidone group and 60 cases in aripiprazole group.The total response rates of aripiprazole group and risperidone group were 91.67％and 76.67％,with significant difference(P＜0.05).After treatment,scores of positive symptoms in PANSS in aripiprazole group and risperidone group were(10.04±1.55)and(11.52±1.62)points;negative symptom scores were(12.74±2.38)and(14.38±2.25)points;general psychopathology scores were(16.53±4.39)and(19.76±4.10)points;total scores of PANSS were(39.31±6.25)and(45.66±6.71)points;total scores of MCCB were(43.61±8.50)and(40.55±8.16)points;BMI were(24.05±2.52)and(25.73±2.86)kg·m-2;SBP were(123.61±7.64)and(128.75±8.59)mmHg;FPG were(5.69±0.60)and(6.38±0.62)mmol·L-1;TG levels were(1.76±0.20)and(2.01±0.22)mmol·L-1;levels of serum BDNF were(32.41±5.81)and(28.65±4.87)pg·mL-1;TrkB levels were(43.88±5.92)and(41.73±5.63)ng·mL-1;GDNF levels were(587.47±36.12)and(468.23±35.68)pg·mL-1,the differences between the two groups were all statistically significant(all P＜0.05).There was no significant difference in the incidence of adverse drug reactions between aripiprazole group and risperidone group(15.00％vs.6.67％,P＞0.05).Conclusion Compared with risperidone,clinical effect of aripiprazole is better in patients with schizophrenia and metabolic syndrome,which has fewer effects on body weight,blood pressure and glycolipid metabolism,and it may improve cognitive function by increasing levels of serum BDNF,TrkB and GDNF.

Objective To understand the distribution,molecular characteristics and virulence genes of the O1 and O139 Vibrio cholerae isolates from the Pearl River Estuary water.Methods Vibrio cholerae isolates collected from the Pearl River estuary waters from January 2009 to December 2010,were tested by PCR for eight virulence-related genes,including cholera toxin(ctxA),zonula occludens toxin(zot),accessory cholera enterotoxin(ace),hemolysin(hlyA),toxin-coregulated pilus (tcpA),outer membrane protein(ompU),and the regulatory protein genes(tcpⅠ,toxR).Genetic relation was assessed by pulsed-field gel electrophoresis(PFGE)and the patterns were clustered by BioNumerics.Results From 1152 aquatic samples,69 isolates were identified,including 41 Inaba,18 Ogawa and 10 O139.All the isolates showed ctxA negative,while the hlyA and toxR genes were positive in all the isolates.34.15％(14/41)of the Inaba strains were hlyA + toxR + ompU + ace + zot + tcpI+,while 66.67％(12/18)belonged to Ogawa strains and 70％(7/10)of the O139 strains were hlyA + toxR+.Through PFGE analysis,the O1 isolates formed three clusters in this study.The patterns of O1 isolates differed widely,with the similarity as 72.8％-100.0％,while the patterns of O139 isolates having the similarity of 69.9％-95.5％.Conclusion The non-toxigenic O1 and O139 V.cholerae had a wide distribution in the environment of Pearl River estuary water during the nonepidemic period of cholera.All the aquatic isolates presented diversities on the related virulent genes.

OBJECTIVETo present the clinical application of composite graft of acellular allo-dermis matrix (ADM) with thin auto-microskin on burn wound.

METHODS8 inpatients with 18 full thickness skin burn wounds were transplanted with allo-ADM after eschar was excised, then the auto-microskin and allo-human skin were covered on the area of the matrix, the wound where no allo-ADM grafting were covered as control groups only with auto-microskin and allo-human skin. The area of donor to wound is 1:5 - 1:8.

RESULTSSurvived rate of 18 pieces composite skin that allo-ADM with auto-microskin were grafted were 94%. After following up for 3 to 13 months, the skins of complex grifting had well elastic and smooth texture compared to auto-microskin grafted, they appeared less cicatrisation and ulceration. 3 months after operation, it was indicated by histological examination that tightknit the epithelial-dermal conjunction and epidermal papilla structure could be identified in the allo-ADM skin and there were orderly collagenous fibres, but scar skin structure was observed in that auto-microskin grifted area.

CONCLUSIONThe graft effectiveness of allo-ADM and auto-microskin was better than that of auto-microskin, and this method could be used on major deep burn wound healing.

Adult ; Burns ; surgery ; Female ; Humans ; Male ; Middle Aged ; Skin Transplantation ; methods ; Tissue Donors ; Transplantation, Autologous ; Transplantation, Homologous ; Treatment Outcome