Malignant transformation of ovarian endometriosis is known as endometriosis associated ovarian cancer (EAOC). However, the carcinogenic pathways by which EAOC develops remained poorly understood, and numerous studies found the risk factors of malignant transformation. Recent studies have provided evidence that estrogen receptor-β(ER-β) can influence the proliferation, motility and apoptosis of ovarian cancer cells. The signal pathway of tyrosine kinase receptor-B (TrkB)/brain-derived neurotrophic factor (BDNF) has a direct relation with the endometriosis, and its anti-anoikis plays a prerequisite role in proliferation of cancer. In the nervous system, estradiol and estrogen receptor can be combined through a variety of ways to promote BDNF/TrkB high expression and activity enhancement. Therefore,the relationship between high-risk factors of malignant transformation and ER-β expression and ER-β and TrkB/BDNF signal pathways need to be explored in EAOC.

Background:Myopathy due to smooth muscle cells( SMC)abnormalities is involved in the pathogenesis of diabetic gastroparesis(DGP),however,the relationship between myopathy and advanced glycation end products(AGEs)is not fully clarified. Aims:To investigate the ultrastructural changes of gastric SMC in patients with diabetes mellitus( DM)and the relationship between expressions of contractile proteins and AGEs. Methods:Full-thickness gastric specimens from 30 gastric neoplasm patients undergoing gastrectomy from July 2012 to December 2012 at the First Affiliated Hospital with Nanjing Medical University were collected. Of them 15 patients had DM( DM group)and the other 15 patients without ( control group). Ultrastructure of SMC was observed by transmission electron microscopy. Expressions of three contractile proteins[ myosin heavy chains( MHC),α-actin and calponin]and Nε-carboxymethyllysine( CML),the key component of AGEs in gastric muscular layer were determined by Western blotting,and expressions of MHC,α-actin and calponin mRNA were determined by real-time PCR. Correlations of mRNA expressions of three contractile proteins with protein expression of CML were analyzed by Pearson correlation coefficient. Results:In DM group,significant ultrastructural changes were found in gastric SMC,including disruption of gap junction,swelling of mitochondria,occurring of lipofuscin in cytoplasm,increase in cell membrane alveolae,and thickening of basal lamina. Protein and mRNA expressions of muscular MHC,α-actin and calponin were significantly lower in DM group than in control group(P all ﹤0. 01),while protein expression of CML was significantly higher in DM group(P ﹤0. 01). In gastric muscular layer of DM group, negative correlations were found between expressions of MHC,calponin mRNA and CML protein(r= -0. 59,P=0. 02;r= -0. 63,P=0. 01),but no correlation was seen between α-actin mRNA and CML protein(r= -0. 49,P=0. 06). Conclusions:Disruption of SMC ultrastructure,decrease in contractile proteins and increase in AGEs are existed in gastric muscular layer of DM patients,and there is a negative correlation between contractile proteins and AGEs. These changes may cause impaired contractility of SMC,and subsequently lead to gastric motility disorders in diabetic patients.

BacKground:The mechanism of diabetic gastrointestinaI dysmotiIity is stiII uncIear. More and more studies showed that gastrointestinaI smooth muscIe derived factors pIay an important roIe in gastrointestinaI dysmotiIity. RecentIy,the roIe of RhoA/ROCK signaIing pathway in diabetic compIications become a research hotspot. Aims:To investigate the possibIe roIe of RhoA/ROCK signaIing pathway in diabetic coIon dysmotiIity by examining the expressions of major signaIing moIecuIes in diabetic coIon muscIe. Methods:NormaI coIon tissue sampIes taken from patients undergoing radicaI surgery for coIonic cancer from Sept. 2012 to Dec. 2013 at the First AffiIiated HospitaI of Nanjing MedicaI University were coIIected. According to gIycated hemogIobin IeveI,the patients were divided into diabetes meIIitus( DM)group and controI group. The expressions of major signaIing moIecuIes in RhoA/ROCK1 signaIing pathway incIuding RhoA,ROCK1,MYPT1 and p-MYPT1 were determined by immunohistochemistry or Western bIotting. Results:Immunohistochemistry showed that expression of RhoA protein in DM group was significantIy Iower than that in controI group(P<0. 05). Western bIotting showed that expression IeveIs of RhoA,ROCK1 and p-MYPT1 proteins were significantIy Iower in DM group than in controI group(0. 62 ± 0. 42 vs. 1. 15 ± 0. 69,0. 54 ± 0. 09 vs. 0. 75 ± 0. 05,0. 70 ± 0. 28 vs. 1. 04 ± 0. 47;P<0. 05),whereas no significant difference in expression IeveI of MYPT1 protein was found between DM group and controI group(0. 94 ± 0. 50 vs. 1. 21 ± 0. 80,P>0. 05). Conclusions:The inhibition of RhoA/ROCK signaIing pathway in diabetic coIon muscIe may have some correIation with diabetic coIon dysmotiIity.

Objective: To study the effects of ganoderma lucidum A on the proliferation and apoptosis of human inflammatory breast cancer SUM149 cells in vitro, and to clarify their mechanisms. Methods: The human inflammatory breast cancer SUM149 cells were divided into control group and different concentrations (0. 1, 0. 5, 1.0, 5. 0 and 10. 0 μmol · L-1) of ganoderma lucidum A groups; four holes were set up, and the samples were taken at 24, 48 and 72 h after culture. MTT assay was used to detect the inhibitory rate of proliferation of SUM149 cells. Flow cytometry was used to detect the apoptotic rate and cell cycle of SUM149 cells. The expression levels of Ki67 and Livin proteins in SUM149 cells were detected by immunocytochemical staining. Results: Compared with 0. 1 μmol · L-1 ganoderma lucidum A group, the inhibitory rates of proliferation of SUM149 cells in other concentrations of ganoderma lucidum A groups were significantly increased detectde by MTT method (P<0. 05 or P<0. 01) in a concentration- and time-dependent manner. The flow cytometry results showed that the apoptotic rates of SUM149 cells in different conventrations of ganoderma lucidum A groups were significantly higher than that in control group (P<0. 05 or P<0. 01) in a concentration- and time-dependent manner; at the same time, the cell cycle changed significantly. With the increase of ganoderma lucidum A of the concentration of ganoderma lucidum A, the pencentages of cells at G1 phase in different concentrations of ganoderma lucidum A groups were increased (P<0. 05), and the percentages of cells at S phase were decreased compared with control group (P<0. 05 or P<0. 01). The expression levels of Ki67 and Livin proteins in different concentrations of ganoderma lucidum A groups were decreased compared with control group (P<0. 05). Conclusion: Ganoderma lucidum A can inhibit the proliferation of human inflammatory breast cancer SUM149 cells through induction of apoptosis.

Objective To analyze the adverse drug reactions (ADR) during the standardized treatment of multidrug-resistant pulmonary tuberculosis (MDR-PTB), and to evaluate its impact on treatment outcomes.Methods A retrospective study was carried out on 305 MDR-PTB patients.Medical records of clinical treatment and laboratory examinations were collected, and the ADR data were analyzed.Chi-square test or Fisher exact test was used for discontinuous variables, and t test or non-parametric test was used for continuous variables.Results Among 305 MDR-PTB patients , 282 (92.5%) had at least one ADR.The major ADR were gastrointestinal reaction (46.9%), thyroid dysfunction (41.3%), hypokalemia (34.1%), renal injury (29.8%), hematological system impairment (21.6%), hepatotoxicity (19.0%), arthralgia or courbature (11.1%), and ototoxicity and vestibular dysfunction (8.5%).Sex, age, native place, the history of using second-line TB drugs or the history of diabetes mellitus had no significant effect on the incidence of ADR (all P>0.05).As per the Naranjo causality assessment of ADR, 34 patients had definite, 236 had probable, 12 had possible and 0 had doubtful causal relations.Among the 282 cases with ADR, 175 (62.1%) patients continued the original treatment regimen, 89 (31.6%) patients changed or stopped ADR-related drugs, only 18 (6.4%) cases stopped MDR-PTB treatment.The episodes of ADR had no significant effect on the treatment outcomes (P>0.05).Conclusions Although ADR are common in MDR-PTB patients during the treatment course, most of the ADR can be managed.Through timely monitoring and appropriate treatment of ADR, most of the patients could continue MDR-PTB treatment.

Objective To analyze the epidemic characteristics of tuberculosis (TB) cases in Zhejiang province from 2005 to 2014, and to identify the cluster spots.Methods TB notification data in Zhejiang province from 2005 to 2014 were analyzed at county and district level by using spatial scan statistic analysis method, which was showed on the digital map.Results In zhejiang province from 2005 to 2014, a total of 377 707 cases of patients with tuberculosis were reported.The average annual registration rates of the entire province was 72.61/100 000 (range: 28.85/100 000-182.90/100 000).Spatial analysis identified 14 clusters (RR=1.05-1.62) with statistical significance.Temporal analysis revealed that there were clusters between 2005 and 2009 in terms of the notification data on TB cases (RR=1.27,P=0.001).Spatio-temporal analysis identified 6 clusters (RR=1.19-3.55) with statistical significance.Counties and districts included in the first class cluster were similar by using the two different methods-spatial analysis and spatial-temporal analysis.Conclusions There is a descending trend of TB cases notification rates from western to eastern Zhejiang during the study period.The distribution of the TB case notified is not random at spatial, temporal and spatio-temporal levels.

OBJECTIVE:To establish a method for the simultaneous content determination of berberine hydrochloride,phello-dendrine hydrochloride and magnoflorine in Phellodendron amurense decoction piece,and to campare the contents of the 3 ingredi-ents in different grades of P. amurense decoction piece. METHODS:HPLC was performed on the column of Phenomenex Luna C18 with mobile phase of acetonitrile-0.05 mol/L KH2PO4 (gradient elution) at a flow rate of 1 ml/min,the detection wavelength was 280 nm,the column temperature was 30 ℃,and injection volume was 5 μl. RESULTS:The linear ranges were 0.387 0-7.740 μg for berberine hydrochloride(r=0.999 9),0.044 4-0.888 0 μg for phellodendrine hydrochloride(r=0.999 8)and 0.048 0-0.960 0 μg for magnoflorine(r=0.999 9);RSDs of precision, stability and reproducibility tests were lower than 3%, recoveries were 95.61%-103.22%(RSD=2.80%,n=6),96.18%-102.80%(RSD=1.84%,n=6) and 97.93%-102.78%(RSD=1.84%,n=6). CONCLUSIONS:The method is simple and accurate,and can be used for the contents determination of berberine hydrochloride, phellodendrine hydrochloride and magnoflonine in P. amurense. The contents of berbenine hydrochloride and phellodendrine hydro-chloride in the first-grade decation piece are higher than those in the second-grade decoction piece,and the content of magnoflorine in both decoction pieces shows no discernible differences.

Background Atrial electrical remodeling(AER)plays an important role in the pathogenesis and maintenance of atrialfibrillation.However,little is known about modulation of vagal activilty to AER.This study aimed to investigate the relationshipbetween vagal moduation and AER. Methods Twenty four adult mongrel dogs under general anesthesia were randomized into 3groups.Sympathetic activity was blocked by administration of metoprolol in 3 groups.The changes in vagal modulation to atria afterAER were observed in 10 dogs without vagal interruption in group A.The effects of vagal intervention on AER were investigated in 8dogs with administration of atropine in group B.The impact of aggressively vagal activity on AER was studied in 6 dogs with bilateralcervical vag sympathetic trunLks stimulation during AER in group C.Bilateral cervicall vagosympathetic trunks were decentralized.Multipolar catheters wereplaced into high right atria(RA),coronary sinus(CS)and rightventricle(RV).AER was induced by 600 bpmpacing through RA catheter for 30 minutes.Attial effective refractory period(ERP)and vulnerability window (VW)of atrial fibrillationwere measured with and without vagal stimulation before and after AER.Results In group A,ERP decreased significantly at baselineand during vagal stimulation after AER compared with that beforeAER(all P＜0.05).In group B,ERP remaind unchanged at baselineand vagal stimulation after AER compared with tbat before AER (all P＞0.05).In group C,ERP shortened significantly at baseline andvagal stimulation after AER compared with that before AER(all P＜0.05).ERP shortening after AER in Groups A and C increasedsignificantly than that in group B (all P＜0.05).Atrial fibrillation could not be induced at baseline(VW close to 0) before and after AERin three groups.VW became widen significantly during vagal stimulation after AER compared with that before AER in Groups A and C(all P＜0.05),while VW remained unchanged in group B (VW close to 0).Conclusions Short-term AER results in the decrease inERP.AER is accompanied by the increases in atrial vagal modulation.The increased vagal activity and vagal stimulation promote AER,thereby increase the susceptibility to atrial fibrillation.The interrupted vagal activity attenuates AER.thereby suppresses the atriaIfibrillation mediated by vagal stimutlation.