Imatinib and the second generation tyrosine kinase inhibitors(TKI) not only have revolutionized the management of patients with CML,but also become a model for the development of novel targeting agents in treating malignancies. Under IM treatment.more than 90%CML-CP patients could achieve complete hematologic remission,and more than 80% patients could achieve CCyR/MMoR.,the event free survival at 6-7 years were around 80%.resulting in a major change in the natural history of CML.Nevetherless, TKI cannot eliminate the bcr-abl fusion gene or CML stem cells.the patients have to take the medicine continuously or for life long,More than 10%patients developing resistance Or intolerance are also problematic.The available TKI are preferable choice for treatment of CML

Objective To screen specific mutations on extracellular regions of membrane proteins ( extracellular membrane protein mutations ) in tumor cells and provide the reference information for target searching in cancer precision medicine .Methods Somatic mutations on extracellular regions of membrane proteins of 7042 tumor samples were collected to screen all specific extracellular membrane protein mutations, and the overall distribution of these mutations were obtained by statistical analysis.Genes, gene site and cancer types occured high frequency of extracellular membrane protein mutations were identified.Results 97193 specific extracellular membrane protein mutations were obtained from 4938362 somatic mutations in 7042 tumor samples (30 cancer types), the statistical analysis showed that 4347 genes and 65532 sites were involved in these specific mutations.The study further analyzed five genes (MUC16、LRP1B、CSMD3、RYR2、USH2A), one site (17:37868208) and six cancer types (including colorectal cancer, melanoma, uterine cancer, brain lower grade glioma, lung adenocarcinoma and stomach adenocarcinoma) which occured high frequency of extracellular membrane protein mutations.Conclusion An information library of specific mutations on extracellular regions of membrane proteins was established and the distribution of these specific mutations was obtained which can provide reference information for target detection in targeted cancer therapy and immunological therapy.

Objective To analyze the risk factors and prognosis of Clostridium difficile infection (CDI) among hospitalized patients with inflammatory bowel disease (IBD).Methods From March 2014 to February 2015,216 first-time hospitalized patients with IBD were enrolled.Once hospitalized,stool samples were obtained for Clostridium difficile culture immediately,and at the same time toxins of Clostridium difficile (tcd) A and tcdB were detected by polymerase chain reaction(PCR).The incidence and risk factors of CDI in enrolled patients were analyzed.Chi square test and nonparametric test were performed for statistical analysis.Results Among the 216 IBD patients,there were 73 patients with ulcerative colitis(UC) and 143 patients with Crohn's disease(CD).The positive rate of CDI was 13.9 ％ (30/216) in IBD patients.The positive rate of CDI was 24.7 ％ (18/73) in UC patients,which was higher than that of CD patients (8.4％,12/143),and the difference was statistically significant (x2 =10.690,P＜0.01).As the severity of the disease increased,the rate of CDI positive patients in UC patients increased.Among three patients at remission period,17 patients at mild active stage,23 patients at moderate active stage and 30 patients at severe active stage,the CDI positive patients were zero,two,five,11,respectively,and the difference was statistically significant (x2 =4.820,P=0.028).In UC patients,the incidences of patients with hospitalization history in other hospitals within three months before admission in CDI positive group and negative group were 6/18 and 7.3％ (4/55),respectively,and the difference was statistically significant (x2 =5.740,P=0.020).In 30 days before admission,the rates of patients with proton pump inhibitor (PPI) taking history of two groups were 7/18 and 7.3％ (4/55),and the difference was statistically significant (x2=8.270,P=0.004).The length of hospital stay in CDI negative UC patients was 7.0 d (5.0 d,12.0 d),which was shorter than that of CDI positive patients (10.5 d (8.8 d,18.2 d)),and the difference was statistically significant (U=277.000,P=0.005).The rate of patients underwent intestinal operation in CDI negative CD patients within three months after CDI examination was 10.7 ％ (14/131),which was significantly lower than that of CDI positive patients (5/12) (x2 =4.520,P=0.010).Conclusions The incidence of CDI in hospitalized IBD patients was high,especially in UC patients;the risk factors included disease severity,prior hospitalization history within three months before admission and PPI taking history within 30 days before admission.CDI was correlated with poor prognosis.

Studies demonstrate that the serum level of cytokeratin 19 fragment antigen 21-1 ( CYFRA21-1 ) is high in various cancer types.As a novel epithelial cells derived tumor marker,detection of the serum level of CYFRA21-1 is of great clinical significance for screening and diagnosis,curative effect evaluation,recurrent monitoring and prognosis assessment for cancer patients.

Numerous studies found that the content of peripheral blood circulating RNA in various cancer types is aberrant increased,which could be a potential biological diagnostic marker and therapeutic target.Detecting the peripheral blood circulating RNA through the molecular biology technology will provide a sensitive and efficient,convenient,specific,noninvasive and minimally invasive therapy for the early diagnosis and detection,prognosis and therapeutic monitoring of malignant tumor.

An 18-year-old woman was admitted to the hospital for swelling of the right lower limb and vulva with milky-white vesicles for 3 years.Skin examination revealed swollen and enlarged right lower limb and labium,numerous clustered or scattered pinhead-to millet-sized whitish thick-walled vesicles over the right labium majus,bilateral labium minus,vaginal orifice,and right thigh,with milky-white chylous fluid draining from the vagina.Magnetic resonance imaging revealed obvious lymphangiectasia in the lower abdominal cavity and right side of the pelvis,dilation and distortion of lymphatic vessels in the skin and subcutaneous tissue of the right inner thigh,the vaginal wall and at the medial side of the right labium majus,but no abnormality in the uterus.Histopathological examination of the milky-white vesicles showed cystic dilation of lymphatic vessels in the superficial dermis,and fibrous hyperplasia of the middle and lower dermis.A diagnosis of primary chylous reflux syndrome Ⅰ was made.

Objective Dickkopf-1 (DKK-1) is an antagonist of the Wnt signaling pathway of bone formation and it is the target gene of TNF.When DKK-1 is inhibited,osteoprotegerin (OPG) would increase,OPG can antagonize bone erosion caused by receptor activator of NF-κB ligand (RANKL).Detection the levelsof serum DKK-1,OPG,RANKL and TNF-α of patients with AS before and after applying TNF-α antagonist,the effects of anti-TNF-α treatment on signaling pathway of bone formation was explored.Methods Medical records and serum samples of 43 AS patients receiving TNF-α receptor-Ⅱ IgG Fc fusion protein for 12 weeks were collected and the levels of serum DKK-1,OPG,RANKL and TNF-α were detected by enzyme-linked immunosorbent assay.Paired t-test and Person's correlation analysis were used for data analysis.Results Disease activity indexes in AS patients with anti-TNF-α treatment,including VAS score,time of morning stiffness,BASDAI,BASFI,ESR and CRP,which were [(2.7±2.0) cm,(7±4) min,1.1±1.1,0.8±1.2,(10±9) mm/1 h and (16±26) mg/L] respectively,were reduced when compared with those before treatment,[(7.6±1.9) cm,(46±33) min,6.0±1.3,4.4±2.0,(39±29) mm/1 h and (76±43) mg/L] respectively,and the differences were statistically significant (P＜0.05).Serum levels of DKK-1,(3.3±1.5) μg/L vs (3.2±1.3) μg/L,OPG,(144±71) pg/ml vs (136±62) pg/ml,and RANKL,(71±37) pg/ml vs (68±30) pg/ml,were not changed (t=14.043,8.031,20.166,13.521,7.679,9.563,all P＞0.05).The levels of TNF-α increased from (1.9±1.3) pg/ml to (55.0±50.6) pg/ml (t=6.951,P＜0.05).There were no relations between DKK-1 and TNF-α,RANKUOPG,patient VAS,duration of morning stiffness,BASDAI,BASFI,ESR and CRP,allP＞0.05.Conclusion Clinical indicators are improved significantly by anti-TNF-α therapy; however,it should not be withdrawal suddenly.There is no relationship between serum levels of DKK-1 and level of inflammation in AS patients.

Objective To investigate neurological recovery effect and mechanisms of blood activating and phlegm removing decoction in the treatment of patients with hypertensive cerebral hemorrhage.Methods 68 patients with hypertensive cerebral hemorrhage in our hospital were divided into two groups.34 patients of the control group were given conventional western medicine,and 34 patients of the observation group were taken conventional western medicine combined with blood activating and phlegm removing decoction.The clinical outcomes, hematoma volume change and neurological recovery were compared,and analyzed its mechanism of action.Results The effective rate of the observation group(94.12%) was significantly higher than 73.53%of the control group (χ2 =5.31,P<0.05). After 7d,14d,21d treatment,NIHSS scores of the observation group [(12.87 ±1.43) points,(8.55 ±1.11) points and (5.67 ±0.76) points] were significantly lower than those of the control group [(20.43 ±2.57) points, (17.66 ±2.08)points,(14.54 ±1.44)points],and the differences were statistically significant (t=14.99,22.53, 31.76,all P<0.05).After treatment,hematoma volume of the observation group[(6.44 ±0.54)mL]was significant-ly lower than before treatment[(16.30 ±1.90)mL]and after treatment in the control group [(12.11 ±1.44)mL] (t=29.11,21.50,all P<0.05).After treatment,ALD score of the observation group [(66.34 ±5.22)points] was significantly lower than before treatment[(27.53 ±2.20)points]and after treatment in the control group[(47.55 ± 3.33)points],and the differences were statistically significant(t=39.95,17.70,all P<0.05).Conclusion The effect of blood activating and phlegm removing decoction in the treatment of patients with hypertensive cerebral hemor-rhage is significant,can significantly improve neurologic impairment and daily living skills,has no obvious conflict of interest and high application value,worthy of promotion and application.

HIV-related sensory neuropathy ( HIV-SN) mainly contains the HIV infection-related distal sensory polyneuropa-thy (DSP) and antiretroviral toxic neuropathies (ATN).HIV-DSP is associated with proinflammatory cytokines , chemokines, ros and which is induced by gp 120;and HIV-ATN may be related to mitochondrial toxicity which is induced by the application of anti retroviral drugs, such as ddC, and similar as the molecular mechanism of HIV-DSP, this means that the current conventional method for the treatment of neuropathic pain in AIDS may further aggravate the neuropathic pain of the patient .Therefore, developing the study on the neurochemical and pharmacological mechanisms of HIV-related neuropathic pain will provide novel targets for the new effective drugs .

MicroRNAS( miRNAs) are a class of single strand, small non-coding RNAs about 22 nucleotides, which have the function to regulate gene expression post-transcriptionally and control the biological processes,such as proliferation, differentiation and apoptosis. Recent studies indicate that miRNA plays an important role in tumor involved in invasion and metastasis. This article mainly reviews the feature of miRNA and its effect in metastasis or recurrence of breast cancer.