Germline mutations in 40 cancer susceptibility genes among Chinese patients with high hereditary risk breast cancer.

Multigene panel testing of breast cancer predisposition genes have been extensively conducted in Europe and America, which is relatively rare in Asia however. In this study, we assessed the frequency of germline mutations in 40 cancer predisposition genes, including BRCA1 and BRCA2, among a large cohort of Chinese patients with high hereditary risk of BC. From 2015 to 2016, consecutive BC patients from 26 centers of China with high hereditary risk were recruited (n = 937). Clinical information was collected and next-generation sequencing (NGS) was performed using blood samples of participants to identify germline mutations. In total, we acquired 223 patients with putative germline mutations, including 159 in BRCA1/2, 61 in 15 other BC susceptibility genes and 3 in both BRCA1/2 and non-BRCA1/2 gene. Major mutant non-BRCA1/2 genes were TP53 (n = 18), PALB2 (n = 11), CHEK2 (n = 6), ATM (n = 6) and BARD1 (n = 5). No factors predicted pathologic mutations in non-BRCA1/2 genes when treated as a whole. TP53 mutations were associated with HER-2 positive BC and younger age at diagnosis; and CHEK2 and PALB2 mutations were enriched in patients with luminal BC. Among high hereditary risk Chinese BC patients, 23.8% contained germline mutations, including 6.8% in non-BRCA1/2 genes. TP53 and PALB2 had a relatively high mutation rate (1.9 and 1.2%). Although no factors predicted for detrimental mutations in non-BRCA1/2 genes, some clinical features were associated with mutations of several particular genes.

Integration of evidence-based medicine concept into the training of thyroid specialist residency / 中华医学教育探索杂志

The standardization training of residents playsan important role in cultivating high and comprehensive quality of specialists.How to carry out the standardized training of thyroid specialist residency effectively and speed up the training of high-quality thyroid specialist are the key problems to be solved.Breast and Thyroid Diseases Center of Southwest Hospital integrated the concepts of evidence-based medicine into the training of thyroid specialist residencies,using the assessment,diagnosis,treatment and follow-up of thyroid nodules as example,and successfully establish the training system of thyroid specialist residency.

Comparation of the prognoses in pregnancy women receiving routine perineal shaving and non perineal shaving before vaginal delivery : a Meta analysis / 重庆医学

Objective To compare the prognoses in pregnancy women receiving routine perineal shaving and non perineal shaving before vaginal delivery through meta analysis.Methods The randomized controlled trials or non-randomized controlled trials for comparing the prognoses in pregnancy women receiving routine perineal shaving and non perineal shaving before vaginal delivery were retrieved from databases,including Cochrane Library,PubMed,EMbase,SCI,Ovid,CBM,Wanfang,VIP and CNKI,till December 2015.The studies were selected according to the inclusion and exclusion criteria,and the data were extracted and evaluated by two reviewers independently.The Meta-analysis was conducted via RevMan 5.2.6 software.Results A total of 6 studies (including three articles in English and three ones in Chinese) including 1 924 delivery women were included,1 083 cases in the perineal shaving group and 841 cases in the non perineal shaving group.No statistically significant difference was found in the incidence rate of fever after delivery between the perineal shaving group and the non perineal shaving group[Z=0.57,P=0.57,RR=1.14,95 ％ CI(0.73,1.76)],and there was no statistically significant difference in post-operative wound infection between the two groups [Z=0.43,P=0.66,RR=1.11,95％CI(0.69,1.78)].Conclusion Perineal shaving may be not an essential nursing intervention before vaginal delivery.

Effects of carbon nanoparticles-epirubicin suspension on cell proliferation and apoptosis in breast cancer MCF-7 cells / 中华内分泌外科杂志

Objective To explore the effect of carbon nanoparticles-epirubicin suspension on proliferation and apoptosis in human breast cancer MCF-7 cells.Methods MCF-7 cells were cultured with different concentrations of CNP-EPI in vitro.CCK-8 assay was used for determinate inhibition effect of CNP-EPI on the proliferation of MCF-7 cells at different concentration and different time.According to the determination of IC90,5 μg/ml CNP-EPI was selected,and cell morphology and cell apoptosis rates were observed after 24 h.Results The inhibition effect of the CNP-EPI was stronger significantly in CNP-EPI group than in normal control group within 24 h,48 h,72 h when the concentration was from 1 μg/ml to 200 μg/ml (P＜0.01).The inhibition of CNP-EPI on the proliferation of MCF-7 cells was gradually strengthened in a dose-dependent relation within the same time,and the inhibition effect is reduced in the same concentration of drugs with the time extension,but it still has a strong inhibitory effect in 72 h,and the inhibition effect of different concentration of CNP was not obvious on MCF-7 cells.Obvious changes of cell morphology were observed under inverted microscope such as:a lot of dead cells,cell adherent growth poor,cell morphology became round and karyopycnosis etc,in 5 μg/ml CNP-EPI group after 24 h.However,no obvious abnormity of cell norphology was observed in normal control group and corresponding CNP group.Late apoptosis rate was (14.57±2.41) ％,the mortality rate could reach (78.63±-20.55)％ in 5 μg/ml CNP-EPI group after 24 h.The mortality rate and apoptosis rate of cells was higher significantly in CNP-EPI group than in CNP group and normal control group (P＜0.05).Conclusion CNP-EPI can obviously inhibit the proliferation or kill human breast cancer MCF-7cells,and the inhibition effect of CNP-EPI on proliferation of breast cancer cells might be the result of delayed releasing of EPI.

The Expression and Significance of CXCR5 and MMP-13 in Colorectal Cancer.

The objective of the study is to investigate the CXCR5 and MMP-13 expression in colorectal cancer and explore its correlation between the clinicopathological characteristics and prognosis. The expressions of CXCR5 and MMP-13 proteins in 236 paired specimens of colorectal cancer and incisal edge normal tissues as well as 62 samples of colorectal adenoma tissues were analyzed by immunohistochemistry. The CXCR5 and MMP-13 positive expression rate in colorectal cancer tissues was 43.6 and 80.5 %, respectively. Both rates were higher than those in the incisal edge healthy intestinal mucosal tissues (4.2 and 13.1 %) and colorectal adenoma tissues (24.2 and 64.5 %), P < 0. 05 in both cases. The expressions of the CXCR5 and MMP-13 proteins were positively related to the lymph node and distal metastasis, tumor stage and relapse, P < 0. 05. The expression of the CXCR5 protein was positively related to MMP-13, P < 0. 05. The median and overall survival in the patients with positive CXCR5 and MMP-13 expression were significantly shorter than those with negative expression: median survival, 20.5 months (CXCR5 +) versus 30.8 months (CXCR5 -), 20.3 months (MMP-13 +) versus 24.6 months; overall survival, 26.5 months (CXCR5 +) versus 47.5 months (CXCR5 -), 22.7 months (MMP-13 +) versus 29.3 months. The expression of CXCR5 and MMP-13 could promote the pathogenesis, development, metastasis, and relapse of colorectal cancer. It could also serve as a valuable indicator for the prediction of metastasis and relapse of colorectal cancer.

Correlation of expression of Oct-4 and tumorigenesis and prognosis of colorectal cancer / 国际肿瘤学杂志

Objective To study dynamic expression of Oct-4 during development of colorectal cancer (CRC) and investigate the association between Oct-4 expression and prognosis of patients with CRC.Methods CRC tissues, matched non-tumor tissues and colonic polyp tissues were collected and Oct-4 expressions were analyzed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR), flow cytometry analysis (FCM) and immunohistochemistry (IHC).Medical records of patients with CRC were reviewed.Clinicopathological analysis was performed to assess the association between Oct-4 expression and certain chnicopathological parameters.Kaplane-Meier survival curve was conducted to evaluate association between Oct-4 expression and survival time of patients with CRC.Results The results of qRT-PCR showed that the relative expressions of Oct-4 mRNA in matched non-tumor, colonic polyp and CRC tissues were (0.23 ±0.16) × 10-5, (1.19 ± 0.76) × 10-5 and (3.79 ± 1.94) × 10-5 respectively, with a significant difference (F =8.633, P =0.001).IHC analysis displayed that the positive expression ratios of Oct-4 in matched non-tumor tissues, colonic polyp tissues and CRC tissues were 4.43％, 12.68％ and 40.51％ respectively, and a significant difference was discovered among them (x2 =66.311, P ＜ 0.001).Oct-4 expre-ssion in CRC was significantly correlated with pathological stage (x2 =7.248, P =0.007), lymph node metastasis (x2 =4.888, P =0.027), distant metastasis (x2 =5.732, P=0.017) and TNM stage (x2 =4.174, P=0.041).Kaplan-Meier survival curve analysis demonstrated that Oct-4 positive cases had a shorter median survival time (37.0 months) compared with Oct-4 negative cases (76.0 months), with a significant difference (x2 =14.050, P =0.001).Conclusion The expression of Oct-4 is step-wise increased during development of CRC.The abnormal expression of Oct-4 may play certain roles in the development of CRC.Oct-4 may be an important biomarker for the clinical diagnosis, assessment of disease and prognosis in CRC.

The value of peripheral blood circulating tumor cells in KRAS mutation testing of colorectal cancer patients / 国际肿瘤学杂志

Objective To explore the value of peripheral blood samples in KRAS mutation testing of colorectal cancer patients and the correlation between the number of circulating tumor cells and KRAS mutation testing.Methods We detected KRAS mutation using amplification refractory mutation system PCR method in paraffin embedded tissues and matched peripheral blood samples obtained from 112 colorectal cancer patients and 10 proctitic peripheral blood samples in Affiliated Hospital of Jiangnan University between 2013 and 2014.Meanwhile,immunofluorescence in situ hybridization method was used to count the circulating tumor cells in peripheral blood samples and proctitic control samples.Results Among the 112 colorectal cancer samples tested,25 cases of peripheral blood samples found KRAS mutation (41.1％) and which was 46 in formalin fixed paraffin embedded tissues testing (22.3 ％),with a significant difference (x2 =40.12,P ＜ 0.001).One case with KRAS wild type in formalin fixed paraffin embedded tissues was mutation type in peripheral samples.In another case,mutation site was different in different kinds of samples.The sensibility of KRAS mutation testing was 73.3％,41.9％ and 16.7％ when the number of circulating tumor cells was more than 15,5 to 15,and 1 to 5,respectively,with significant differences (x2 =23.70,P ＜ 0.001).No KRAS mutation and no circulating tumor cells were found in 10 proctitic control samples.Conclusion We find high specificity in KRAS mutation testing of peripheral blood samples.but the accurate rate is not satisfying.KRAS mutation testing in peripheral blood samples may be an optional choice to test KRAS mutations for colorectal cancer patients who were not subjected to surgery.The sensibility of KRAS mutation testing in peripheral blood samples has a corretion with the number of circulating tumor cells.

Significance of transbronchial needle aspiration and transbronchial biopsy in the diagnosis of central lung cancer / 中国综合临床

Objective To investigate the diagnostic value of transbronchial needle aspiration (TBNA) and transbronchial biopsy(TBB) in central lung cancer.Methods Retrospectively analyzed the diagnostic data of 150 patients with central lung cancer who underwent TBNA followed by TBB in our hospital from January 2011 to October 2012.Results Among 150 patients with central lung cancer,33 cases had intracavity mass.Thirtythree cases (100％) were confirmed by TBB and 32 cases (97.0％) confirmed by TBNA.There was no statistically significant difference between the diagnosis of TBB and TBNA(P =0.90).There were 26 cases with simple stenosis,among which 1 case(3.9％) confirmed by TBB and 26 cases(100％) confirmed by TBNA.And there was statistically significant difference was observed between the diagnosis by TBB and TBNA (P =0.01) Sixteen cases belonged to the lumen external pressure type with 2 cases(12.5％) were confirmed by TBB and 16 cases(100％) confirmed by TBNA.And there was statistically significant difference was observed between the diagnosis by TBB and TBNA (P =0.02).Forty-seven cases had luminal stenosis combined with mucosal diffuse lesions with 25 cases(53.2％) confirmed by TBB and 40 cases(85.1％) confirmed by TBNA.And there was statistical difference was observed between the diagnosis of TBB and TBNA(P =0.04).Twenty-eight cases had mixed type central lung cancer with 27 cases(96.4％) confirmed by TBB and 28 cases(100％) confirmed by TBNA.No statistically significant difference was observed between the diagnosis of TBB and TBNA (P =0.87).Conclusion According to endoscopic performance of central lung cancer,accurate and reasonable choice of biopsy method can minimize inspection costs on the basis of maintaining positive rate of diagnosis in order to achieve optimal titer.

Clinical significance of transcranial Doppler and end-tidal carbon dioxide partial pressure on cerebrovascular reserve capacity in cerebral vessels stenosis patients / 中国医师进修杂志

Objective To study the clinical significance of cerebrovascular reserve (CVR) capacity in cerebral vessels stenosis (CVS) patients with transcranial Doppler (TCD) and end-tidal carbon dioxide partial pressure (PETCO2).Methods Fifty-two CVS patients were divided into two groups:one blood vessel stenosis group (22 cases) and multi blood vessels stenosis group (30 cases).Forty-five normal persons were selected as control group.All the groups were routinely examined with TCD and PETCO2.Hypercapnia was induced by inhaling the carbon dioxide who breathed himself,and hypocapnia was induced by voluntary hyperventilation to investigate the CVR capacity.Results (1)The vasodilator reserve of affected side of one blood vessel stenosis group [(3.16 ± 2.73)％/mm Hg,1 mm Hg =0.133 kPa],the heavier side of multi blood vessels stenosis group [(2.41 ± 1.25)％/mm Hg],and control group [(3.75 ± 1.77)％/mm Hg] had significant difference (F =3.866,P ＜ 0.05).The vasodilator reserve of heavier side of multi blood vessels stenosis group was significantly lower than that of control group (t =-2.657,P ＜ 0.05).The overall reserve of affected side of one blood vessel stenosis group [(3.13 ± 1.38)％/mm Hg],the heavier side of multi blood vessels stenosis group [(2.01 ± 1.89)％/mm Hg],and control group [(3.51 ±0.92)％/mm Hg] had significant difference (F =5.905,P ＜ 0.05).The overall reserve of heavier side of multi blood vesse stenosis group was significantly lower than that of control group and affected side of one blood vessels stenosis group (t =-3.468,2.582,P ＜ 0.05).(2) There was no significant difference among the 3 groups in PETCO2 when eupnea,hypocapnia and hypercapnia.(3) The extent of vascular disease correlated negatively with the vasodilator reserve and overall reserve (r =-0.433 and-0.475,P＜0.05).Conclusions TCD and PETCO2 are simple,economic and effective methods for assessing CVR capacity.The CVR capacity is reduced in patients with cerebral vessels changes.

A comparative study of four methods for establishing animal models of human breast cancer bone metastasis / 肿瘤研究与临床

Objective To investigate four methods for establishing animal models of human breast cancer bone metastasis. Methods Thirty-two female nude mice aged 4-6 weeks were divided randomly into four groups (n=8 in each group). 5×105 MDA-MB-231 cells were injected into the body via the left second mammary fat pads (group A), the tail veins (group B), the left heart ventricles (group C) and the left tibia marrow cavities (group D), respectively. Tumor formations in situ were recorded in group A. Deaths after the injection were recorded. The surviving nude mice 49 days after the injection were subjected to pathological examination to determine bone metastasis. Results The rate of tumor formation in situ of group A was87.5 %(7/8). One mouse in group C died after the injection of MDA-MB-231 cells. The bone metastasis rate in groups A, B, C and D was zero (0/8), 12.5 % (1/8), 71.4 % (5/7) and 100 % (8/8), respectively. There was statistically significant difference in the bone metastasis rate between group A and group C, group A and group D, group B and group C; and group B and group D. Conclusion Injections of tumor cells via the breast fat pads and tail veins were not suitablemethods to establish animal models of human breast cancer bone metastasis. The bone metastasis model could be established efficiently by injecting tumor cells into the left heart ventricles or the bone marrow cavity of nude mice.