Objective To compare the effect of Devine surgery with different fixed positions in the treatment of concealed penis.Methods According to the different fixed positions,45 patients with concealed penis in our hospital from January 2010 to February 2015 were divided into two groups:20 patients were treated with the method that fixing the scapus penis to dermis of the penis' root (group A);the other 25 patients were treated with the method that fixing the scapus penis to pectineal fascia (group B).The surgical success rate,the penile length,and the edema time after surgery between two groups were compared.Results There was no significant difference in surgical success rate and edema time between two groups (P ＞ 0.05).But the penile length of group B was longer than that of group A after surgery (P ＜ 0.05).Conclusion In the treatment of concealed penis with Devine surgery,comparing to the method which fixing scapus penis to dermis of penis'root,the method which fixing scapus penis to fascia pectinea is much better in penile length and penile appearance.

【Objective】To investigate the role of mycophenolate mofetil (MMF) in the prevention of acute rejection in renal transplantation.【Methods】A total of 106 patients were randomized into two groups.One group received MMF (n=56),the other received azathioprine (Aza) (n=50).The time of the following study was within the first 6 months after transplantation.【Results】The rate of acute rejection of group receiving MMF was 20%,it′s lower than that of the group receiving Aza 44% (P<0.01).The recovery rate of acute rejection treated by methylprednisolone (MP),in MMF group 82% was higher than Aza group 55%.(P<0.05).Meanwhile the hepatotoxicity as well as cytomegalovirus (CMV) infection were lower in MMF group than those in Aza group.【Conclusion】MMF as a new anti-rejection drug could more effectively prevent acute rejection than Aza after renal transplantation,and has lower toxicity and side effect.

Objective To clone the full-length CDS sequence of LOC 401296 , an undefined gene that we found recently, and to obtain both its expression in eukaryotic cells or E.coli and antiserum to LOC401296 protein.Methods The full-length CDS sequence of LOC401296 was amplified by polymerase chain reaction (PCR).Then we established the expression vectors pET28B-LOC401296 and pCMV-Myc-LOC401296 by cloning the full-length CDS sequence into vector PET28B and vector pCMV-Myc respectively.Isopropyl Thiogalactoside (IPTG) was used to induce LOC401296 expression in E.coli.Furthermore,the protein purified and refolded was used to immunize BALB /c mice.The titer of the antiserum collected from immunized mice was identified by ELISA assay and Western blot .Results We cloned the full-length CDS sequence of LOC401296 was successfully .Protein LOC401296 was expressed as was expected and the mouse anti-human LOC401296 antiserum was obtained .The antiserum titer reaching 1∶64 000 was identified by ELISA .Besides, Western blot analysis showed that the antiserum could be used to detect protein LOC 401296 .Conclusion The full-length sequence of LOC401296 is obtained and the mouse anti-human LOC401296 antiserum becomes available .This study can contribut to further research on the undefined gene LOC 401296 .

Objective To investigate the expression of matrixmetalloprotein -9(MMP-9)and E-cad-herin in triple negative breast cancer ( TNBC) and its relationship with the clinicopathologic features of TNBC .To analyze the function of MMP -9 and E-cadherin in TNBC .Methods Immunohistochemical method was used to detect the expression of MMP -9 and E-cadherin in 127 cases of TNBC.Results The MMP-9 positive rate was 53.54%and E-cadherin positive grade was 32.28%in TNBC.Expression of MMP-9 was correlated with tumor size(P=0.007),histological grade(P=0.006),TNM stage(P=0.003),lymph node metastasis(P=0.000)and lymph duct invasive(P=0.000).Expression of E-cadherin was correlated with lymph node metasta-sis(P=0.016)and lymph duct invasive(P=0.015).However,they were not correlated with other factors .Con-clusion The expression of MMP -9 and E -cadherin was correlated with invasion and metastasis in TNBC , which could be an important research topic in the future studies .

Objective To investigate effects of new nursing experimental teaching mode on professional ability of nursing students. Methods Traditional experimental teaching mode was used in control group (402 nursing students of 2006 grade) and experimental teaching model was used in experimental group (564 nursing students of 2007 grade). Questionnaires survey was conducted among clinical teachers to evaluate 8 abilities (service consciousness, knowledge application, practical abil-ity, communication ability. etc) of nursing students after 3 months' clinical practice. Satisfaction de-gree of experimental teaching and the first time employment rate of nursing students were recorded. All data were sorted out and analyzed by Epidata 3.1 and SPSS 13.0. Total score of students' profes-sional capacity was compared by independent t test. Score of the scale item was compared by rank sum test. Satisfaction rating for experimental teaching, passing rate of nurse practicing qualification examination and the first time employment rate were compared by chi-square test. All statistical tests were two-sided and P<0.05 was considered statistically significant different. Results Students' scores of communication ability, innovation capacity, capability to identify problems, practical ability, knowl-edge application, ability of organization and independent learning ability were 2.86±0.23, 2.86±0.17, 2.85±0.19, 2.84±0.24, 2.79±0.20, 2.78±0.19, 2.65±0.19 in experimental group, higher than those in control group. Satisfaction degree of experimental teaching and the first employment rate of students in experimental group were 94.5%(536/567) and 84.5%(479/567), higher than those in con-trol group with statistically significant differences(P<0.05). Conclusion New teaching mode of nurs-ing experiment can improve the professional ability of nursing students.

Objective To investigate the micminnammatory state and its relationship with atherosclerosis and cardiac function in patients on continuous ambulatory peritoneal dialysis(CAPD). Methods Sixty-seven CAPD patients,27 non-dialytic stage 5 chronic kidney disease(CKD 5)patients and 27 gender and age matched healthy controls wore enrolled in this cross-sectional study.Clinical data and biochemical parameters were collected.Serum interleukin-6(IL-6)and IL-10 levels were measured by enzyme-linked immunosorbent assay(ELISA).High-sensitivity C-reactive protein(hs-CRP)was measured by immunoturbidimetry.Prevalence of atherosclerosis was detected by carotid uhrasonography while cardiac function was detected by echocardiography. Results Serum levels of inflammatory biomarkers were elevated significantly in CAPI)and CKD 5 patients as compared with healthy controls[IL-6(ng/L):2.400,1.515 vs 0.698;IL-10(ng/L):1.988,1.958 vs 0.277;hs-CRP(mg/L):1.090,1.345 vs 0].Left ventricular mass index(LVMI),myocardial performance index(Tei index 0.75±0.31,0.66±O.27 vs 0.52±0.23)in CAPD and CKD 5 patients increased significantly.The prevalence of carotid artery atherosclerosis and left ventricular hypertrophy(LVH)in CAPD and CKD 5 patients was significantly higher than that in healthy controls.No significant difference of the ultrasonic parameters was found between CAPD and CKD 5 patients.In CAPD patients,IL-6 was positively correlated with Tei index,whereas IL-10 was negatively correlated with INMI and was positively correlaled with ejection fraction(EF).In a multiple regression model,IL-6,self-rating depressive scale(SDS)score and pulse pressure were independent predictors of carotid artery atherosclerosis.Similarly,IL-6 and primary hypertension were independent correlates of Tei index in CAPD patients. Conclusions Microinflammatory state exists in either non-dialytic CKD 5 patients or CAPD patients and it is associated with atherosclerosis and cardiac distunetion.IL-6 is an independent risk factor of atherosclerosis and increased Tei index in CAPD patients.

Objective To investigate the impact of peritoneal albumin leakage on malnutrition-inflammation-atherosclerosis (MIA) syndrome in continuous ambulatory peritoneal dialysis (CAPD) patients. Methods A cross-sectional study of a cohort of 130 CAPD patients without edema or active infection was performed. In order to identify peritoneal transport characteristics in CAPD patients, a standard peritoneal equilibration test (PET) was carried out. For malnutrition and inflammation, serum albumin and high-sensitivity C-reactive protein (hs-CRP) levels were measured. Mean-carotid artery intima media thickness (IMT) was used to determine atherosclerosis. Residual glomerular filtration rate (rGFR) was defined as the average of 24-hour urinary urea and creatinine clearances. Results Pearson and Spearman correlation analysis showed that peritoneal albumin leakage amount was positively correlated with age, body mass index, night dwell time, blood glucose, 4 h D/P creatinine levels and hs-CRP levels (r=0.204, P<0.05 ;r=0.314, P<0.01; r=0.265, P<0.01; r=0.212, P<0.05; r=0.401, P<0.01; r=0.216, P<0.05); whereas it was negatively correlated with diastolic perssure, serum albumin levels, glucose level of dialyzate and peritoneal Kt/V (r=-0.209, P<0.05; r=-0.123, P<0.05; r=-0.271, P<0.01; r=-0.212, P<0.01). Overall, there was no correlation between peritoneal albumin leakage and IMT. Patients was significantly greater (P<0.01), and there was a positive correlation between peritoneal albumin leakage amount and IMT (r=0.650, P<0.01). Conclusions Peritoneal albumin leakage is significantly associated with peritoneal transport characteristics, malnutrition and inflammatory state in CAPD patients. High peritoneal albumin leakage amount is a risk factor for atherosclerosis in patients with rGFR less than 1 ml·min-1(1.73 m2)-1.

Objective To investigate the relationship between nutritional risk status and implementation of nutrition therapy in mechanical ventilated (MV) chronic obstructive pulmonary disease (COPD) patients, so as to provide evidence for individualized nutrition therapy. Methods A prospective multicenter observational study was conducted. MV COPD patients admitted to Department of Intensive Care Units (ICU) of 10 County Hospitals in Zhejiang Province from January 2015 to January 2016 were enrolled, and according to nutrition risk screening 2002 (NRS2002) score, they were divided into nutritional high risk group (NRS2002 3-5) and nutritional extremely high risk group (NRS2002 6-7). Nutrition therapy situation and hospital mortality were compared between the two groups; multivariate Cox regression analysis was used to analyze the risk factors affecting the prognosis of patients with COPD under mechanical ventilation. Kaplan-Meier curve was used to analyze the prognosis at 30 days; receiver operating characteristic (ROC) curve was used to test the robustness of multivariable regression analysis. Results ① One hundred and six COPD patients with MV were analyzed; among them, 90 patients were in the nutritional high risk group, and 16 were in the nutritional extremely high risk group. There were no significant differences in age, gender and body mass index (BMI) between the two groups (all P > 0.05); the acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, NRS2002 score in patients of nutrition risk extremely high group were obviously higher than that in patients with nutrition high risk group (APACHEⅡ: 24.9±6.1 vs. 20.3±5.8, NRS2002 score: 6.3±0.5 vs. 4.2±0.8, both P < 0.05). ② Patients in both groups received early enteral nutrition (EN) therapy, the proportion of patients in nutritional extremely high risk group received early EN was lower than that of patients in the nutritional high risk group [12.5% (2/16) vs. 17.7% (16/90)], along with the prolongation of hospital stay, the proportions of patients beginning to receive the EN were gradually increased in the nutrition extremely high risk group and high risk group, after 2 days the EN increased significantly, and reached the highest value on day 6 after entering ICU [100.0% (16/16), 98.9% (89/90), respectively]; within 3 days after admission into ICU, the proportion of EN in nutrition extremely high risk group was obviously lower than that in nutrition high risk group, and from day 4, there was no statistical significant difference in proportion of EN between the two groups (all P > 0.05). The time to start parenteral nutrition (PN) treatment was relatively early admission to the ICU on day 1 and the proportion of this therapy was high in the two groups [56.2% (9/16), 27.7% (25/90), respectively], the PN proportion did not decrease with the length of hospitalization and the increase of EN. The proportion of patients in the nutrition extremely high risk group who started PN treatment was higher, which reached 56.2% admission to the ICU on day 1.③ With extension of hospital stay, the calories of EN were gradually increased in the nutritional high risk group, the highest calories in nutritional high risk groups was 4 318 (3 912, 4 812) kJ/d at day 7; while the highest calories in nutritional extremely high risk groups was 3 602 (2 167, 4 615) kJ/d at day 6 and a slight decreased at day 7; the difference of calories within the first week between the two groups had no significance (all P > 0.05). The calorific value of PN therapy remained at a constant level during hospitalization within 7 days, and after admission into ICU for 4-5 days, the target range of calories was achieved. ④ Kaplan-Meier survival curve analysis showed that the mortality at 30 days in the extremely high risk group was significantly higher than that in the high risk group [62.5% (10/16) vs. 11.1% (10/90), χ2 = 15.4, P < 0.01]. ⑤ Multiple cox-regression analysis showed that NRS2002 scoring was the independent risk factor affecting the mortality of patients in hospital [odds ratio (OR) = 2.08, 95% confidence interval (95%CI) = 1.39-3.12, P = 0.005]. ⑥ ROC curve analysis: according to ROC curve analysis of the effectiveness of multi-factor regression model, area under ROC curve (AUC) was 0.79, sensitivity was 70.00%, specificity was 74.42%, positive likelihood ratio was 2.74, negative likelihood ratio was 0.40, 95% confidence interval (95%CI) was 0.702-0.864, P = 0.001, and it showed that the regression model had a good prediction effect. Conclusions MV COPD patients have significant nutritional risk and all receive early EN therapy. The proportion of beginning to use PN treatment in patients with nutritional extremely high risk is relatively high. Initial nutritional status is the independent risk factor of poor prognosis in MV patients with COPD.

The rearranged during transfection (RET) is a receptor protein tyrosine kinase. Oncogenic RET fusions or mutations are found most often in non-small cell lung cancer (NSCLC) and in thyroid cancer, but also increasingly in various types of cancers at low rates. In the last few years, two potent and selective RET protein tyrosine kinase inhibitors (TKIs), pralsetinib (BLU-667) and selpercatinib (LOXO-292, LY3527723) were developed and received regulatory approval. Although pralsetinib and selpercatinib gave high overall response rates (ORRs), < 10% of patients achieved a complete response (CR). The RET TKI-tolerated residual tumors inevitably develop resistance by secondary target mutations, acquired alternative oncogenes, or MET amplification. RET G810 mutations located at the kinase solvent front site were identified as the major on-target mechanism of acquired resistance to both selpercatinib and pralsetinib. Several next-generation of RET TKIs capable of inhibiting the selpercatinib/pralsetinib-resistant RET mutants have progressed to clinical trials. However, it is likely that new TKI-adapted RET mutations will emerge to cause resistance to these next-generation of RET TKIs. Solving the problem requires a better understanding of the multiple mechanisms that support the RET TKI-tolerated persisters to identify a converging point of vulnerability to devise an effective co-treatment to eliminate the residual tumors.
Humans ; Carcinoma, Non-Small-Cell Lung/genetics* ; Neoplasm, Residual ; Lung Neoplasms/genetics* ; Mutation ; Protein Kinase Inhibitors/therapeutic use* ; Proto-Oncogene Proteins c-ret/genetics*

Hereditary gingival fibromatosis (HGF) is a rare inherited condition with fibromatoid hyperplasia of the gingival tissue that exhibits great genetic heterogeneity. Five distinct loci related to non-syndromic HGF have been identified; however, only two disease-causing genes, SOS1 and REST, inducing HGF have been identified at two loci, GINGF1 and GINGF5, respectively. Here, based on a family pedigree with 26 members, including nine patients with HGF, we identified double heterozygous pathogenic mutations in the ZNF513 (c.C748T, p.R250W) and KIF3C (c.G1229A, p.R410H) genes within the GINGF3 locus related to HGF. Functional studies demonstrated that the ZNF513 p.R250W and KIF3C p.R410H variants significantly increased the expression of ZNF513 and KIF3C in vitro and in vivo. ZNF513, a transcription factor, binds to KIF3C exon 1 and participates in the positive regulation of KIF3C expression in gingival fibroblasts. Furthermore, a knock-in mouse model confirmed that heterozygous or homozygous mutations within Zfp513 (p.R250W) or Kif3c (p.R412H) alone do not led to clear phenotypes with gingival fibromatosis, whereas the double mutations led to gingival hyperplasia phenotypes. In addition, we found that ZNF513 binds to the SOS1 promoter and plays an important positive role in regulating the expression of SOS1. Moreover, the KIF3C p.R410H mutation could activate the PI3K and KCNQ1 potassium channels. ZNF513 combined with KIF3C regulates gingival fibroblast proliferation, migration, and fibrosis response via the PI3K/AKT/mTOR and Ras/Raf/MEK/ERK pathways. In summary, these results demonstrate ZNF513 + KIF3C as an important genetic combination in HGF manifestation and suggest that ZNF513 mutation may be a major risk factor for HGF.
Animals ; Humans ; Mice ; Fibromatosis, Gingival/pathology* ; Gingiva ; Kinesins/genetics* ; Mutation/genetics* ; Phosphatidylinositol 3-Kinases/genetics*