Risk factors for progression of Urolith Associated with Obstructive Urosepsis to severe sepsis or septic shock.

INTRODUCTION: To analyze the risk factors for progression of urolith associated with obstructive urosepsis to severe sepsis or septic shock, we had done the retrospective cross-sectional study, which would facilitate the early identification of high-risk patients. MATERIALS AND METHODS: Datas were retrospectively reviewed from 160 patients, suffering from obstructive urosepsis associated with urolith between December 2013 and December 2019. There were 49 patients complicating by severe sepsis (severe sepsis group), 12 patients complicating by septic shock (septic shock group), and 99 patients without progressing to severe sepsis or septic shock (sepsis group). The data covered age, gender, BMI (body mass index), time interval from ED (emergency department) to admission, WBC count (white blood cell count), NLR (neutrophil/lymphocyte ratio), HGB (hemoglobin), etc. Datas were analyzed by univariate analyses and multivariate logistic regression analysis. The corresponding nomogram prediction model was drawn according to the regression coefficients. RESULTS: Univariate analysis showed that the differences of age, the time interval from ED to admission, history of diabetes mellitus, history of CKI (chronic kidney disease), NLR, HGB, platelet count, TBil (total bilirubin), SCr (serum creatinine), ALB (albumin), PT (prothrombin time), APTT (activated partial thromboplastin time), INR (international normalized ratio), PCT (procalcitonin), and positive rate of pathogens in blood culture were statistically significant (P < 0.05). Multivariatelogistic regression analysis showed that age, SCr, and history of CKI were independent risk factors for progression to severe sepsis, or septic shock (P < 0.05). CONCLUSIONS: Aged ≥ 65 years, SCr ≥ 248 mol/L, and history of CKI were independent risk factors for progression of urolith associated with obstructive urosepsis to severe sepsis or septic shock. We need to pay more attention to these aspects, when coming across the patients with urolithic sepsis.

Effects of compound porcine cerebroside and ganglioside on neurotoxicity caused by oxaliplatin chemotherapy: preliminary results.

OBJECTIVE: Oxaliplatin has shown good anti-tumour activity in the treatment of tumours involving the digestive system. However, its application is limited because of severe neurotoxicity in some patients. The purpose of this study was to evaluate whether compound porcine cerebroside and ganglioside (CPCG) can reduce or prevent oxaliplatin-induced neurotoxicity. PATIENTS AND METHODS: Patients with digestive system tumour who received oxaliplatin-based chemotherapy were retrospectively divided into experimental and control groups according to the receipt of CPCG during chemotherapy. Adverse events at the end of each chemotherapy cycle were recorded. We compared the incidence of neurotoxicity between the two groups and graded the neurotoxicity symptoms using the Common Terminology Criteria for Adverse Events v5.0. RESULTS: The study included 115 patients (experimental group, 57; control group, 58). The number of chemotherapy cycles (6.65 vs. 6.41, p=0.540) and oxaliplatin dose (775.92 mg/m2 vs. 724.20 mg/m2, p=0.250) were comparable between the two groups. All patients developed grade 1 to 3 neurotoxicity; grade 4-5 neurotoxicity was not observed. The incidence of neurotoxicity and the probability of advanced neurotoxicity were significantly lower in the experimental group than in the control group (p<0.05). After a 6 to 18 months follow-up, the two groups showed no significant differences in the chemotherapy response and recurrence rate (p=0.846). CONCLUSIONS: CPCG reduces oxaliplatin-induced neurotoxicity without reducing the efficacy of oxaliplatin-based regimens; thus, it can be used for preventing oxaliplatin-induced neurotoxicity in patients with cancer.

Expression of RNF8 on cochlear apoptosis and aging in mice of different ages.

This study aimed to investigate the role of RNF8 (RING finger protein 8) in DNA damage repair in mice of different ages, and to provide new insight into the pathology and treatment of senile deafness. Sixteen C57BL/6J mice aged 8 weeks, 16 weeks and 32 weeks were obtained by paired reproduction. The mice of three age groups were equally divided into two groups, named experimental group (RNF8 gene knockout) and control group (no knockout). The cochlear hair cells, stria vascularis and spiral ganglion cells were observed by HE (hematoxylin-eosin) staining. The degree of DNA damage and the related expressions were observed by immunofluorescence γ-H2AX staining and 8-OH immunohistochemical staining, and the aging of damaged cells was detected by lipofuscin and ß-galactosidase staining. HE staining showed that the changes of cochlear hair cells, stria vascularis and spiral ganglion cells were obvious in the same group of mice at different ages. Compared with the control group, the aging changes of cochlear hair cells, stria vascularis and spiral ganglion cells were more significant in the experimental group. Immunofluorescence γ-H2AX staining showed H2AX phosphorylation in injured cells. The aging of cochlea in mice changed, and staining of ß-galactosidase in the experimental group suggested that the striae of blood vessels were changed with age at 32 weeks old and staining of lipofuscin showed dark brown staining around the nucleus (P < 0.05). In conclusion, the deletion of RNF8 is an important cause of morphological changes in the cochlea of mice. The deletion of RNF8 accelerates the aging of the cochlea of mice, suggesting that the apoptosis of the cochlea could contribute to aging in RNF8 gene-deficient mice.

MRFAP1 plays a protective role in neddylation inhibitor MLN4924-mediated gastric cancer cell death.

OBJECTIVE: MLN4924 is a second-generation small molecule inhibitor with anti-cancer activity that inhibits neddylation activation enzyme (NAE), subsequently blocking the neddylation-dependent activation of Cullin-RING E3 ligases (CRLs). Mof4 family associated protein 1 (MRFAP1) is a highly conserved, short half-life protein and one of the most up-regulated proteins in response to MLN4924 treatment. MRFAP1 has been identified as a novel cell cycle-related protein and a regulatory component monitoring and preventing genomic instability. However, whether MRFAP1 plays a role in MLN4924-mediated cancer cell death remains elusive. PATIENTS AND METHODS: The expression of MRFAP1 in gastric cancer clinic samples was detected by Real-time PCR and Western blot. CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 system was used to knockout MRFAP1 gene in both AGS and SGC-7901 cells. The proliferation of GC cells was measured by CCK8 assay. The cell cycle distribution of GC cells was determined by fluorescence-activated cell sorting (FACS) assay. Co-immunoprecipitation assay was used to determine the interaction between MRFAP1 and P27. RESULTS: MRFAP1 was downregulated in clinic gastric cancer samples at post-translational level. Overexpression of MRFAP1 decreased gastric cancer cells proliferation. CRISPR-mediated knockout of MRFAP1 increased the cytotoxicity of MLN4924 by augmenting MLN4924-induced G2/M arrest and apoptosis against gastric cancer cells. At the molecular level, we found that MLN4924 induced the interaction between P27 and MRFAP1, the latter associated with P27, which was further stabilized in response to MLN4924 treatment. CONCLUSIONS: We showed a protective role of MRFAP1 in gastric cancer cells with MLN4924 treatment and suggested the potential possibility to combine MLN4924 with MRFAP1 inhibition to treat gastric cancer.

[Detection and clinical significance of circulating tumor cells in patients with colorectal carcinoma].

Objective: To detect circulating tumor cells (CTC) in patients with colorectal carcinoma and to evaluate the relationship among CTC, clinic-pathological characteristics and prognosis of colorectal carcinoma. Methods: Peripheral blood samples were obtained from 109 patients with colorectal carcinoma in Department of General Surgery, Beijing Friendship Hospital, Capital Medical University from April 2014 to October 2016. There were 60 male and 49 female patients, aging from 33 to 86 years with a mean age of (65±10) years.CTC were detected using density-gradient centrifugation and immunofluorescence staining. χ(2) test, Fisher exact test and rank-sum test were used to analyze the relation between positive rate of CTC and clinical characteristic, respectively. The correlation analysis of CTC and common tumor markers was detected by χ(2) test and Spearman test. The overall survival of patients was analyzed by Kaplan-Meier curve and Cox proportional hazard model. Results: CTC were found in 71 of the 109 patients with colorectal carcinoma. The presence of CTC was significantly correlated with N stage (Z=4.422, P=0.035) and M stage (χ(2)=4.424, P=0.049). However, CTC was not significantly correlated with age, sex, tumor location, tumor size, differentiation, T stage, Ki-67 and TNM stage (P>0.05). Meanwhile, there was significant correlation between CTC and carcino-embryonic antigen (CEA) (χ(2)=4.897, P=0.027; r=0.212, P=0.027) indicated by χ(2) test and Spearman correlations analysis. The positive rate of CTC was higher than that of CEA (χ(2)=15.45, P=0.000). Survival analysis suggested that positive CTC was poor for overall survival in colorectal cancer with adjusted HR as 3.023(95%CI: 1.330 to 6.872, P=0.008). Conclusions: CTC is helpful to early diagnosis tumor recurrence and metastasis. Hence, combined multiple tumor markers, including the CTC as common indicators of tumor diagnosis, relapse and metastasis could effectively improve the accuracy of diagnosis.

Long non-coding RNA NEAT1 overexpression is associated with unfavorable prognosis in patients with hepatocellular carcinoma after hepatectomy: A Chinese population-based study.

AIM: To identify the association between the expression of lncRNA NEAT1 and clinicopathological characteristics of patients with HCC, and to explore the prognostic significance of lncRNA NEAT1 in predicting prognosis of HCC. METHODS: We retrospectively reviewed 86 patients with HCC (35 female, 51 male) managed in our institution between 2009 and 2014. The expression level of lncRNA NEAT1 was detected by real-time PCR. Prognostic factors were evaluated using Kaplan-Meier curves and Cox proportional hazards models. RESULTS: For the entire cohort of 86 patients, we showed that the expression level of NEAT1 was significantly higher in HCC tissues compared with non-tumorous tissues and NEAT1 was increased obviously in the HCC cell lines including SMMC-7721, Huh-7 and Hep3B (P < 0.001). MTT assay showed that si-NEAT1 remarkably inhibited the cell proliferation in three HCC cell lines. Moreover, over-expression of lncRNA NEAT1 was closely related to liver cirrhosis (P = 0.026), microvascular invasion (MVI) (P = 0.023), and TNM stage (P = 0.017). After adjusting for competing risk factors, we identified that expression level of lncRNA NEAT1 was an independently risk factor associated with the prognosis of patients with HCC (P = 0.031). CONCLUSIONS: In this study, we found NEAT1 expressed significantly higher in HCC tissues compared with non-tumorous tissues. Overexpression of lncRNA NEAT1 was an independently risk factor associated with the prognosis of patients with HCC.

Association of thymidylate synthase polymorphisms with the tumor response to preoperative chemoradiotherapy in rectal cancer: a systematic review and meta-analysis.

Preoperative chemoradiotherapy (pCRT) followed by surgery is currently the standard therapy for patients with locally advanced rectal cancer. It is very important to develop biomarkers to prior identify the patients who have a higher likelihood of responding to pCRT. Recently, a series of studies have been conducted to investigate the association of thymidylate synthase (TYMS) polymorphisms with the tumor response to pCRT in rectal cancer, but the results were not consistent and conclusive. In the present study, we performed a systematic literature search for relevant studies up to 30 March 2015 and conducted a meta-analysis to summarize and clarify the association between the TYMS polymorphisms and the tumor response to pCRT in rectal cancer. Finally, 7 studies containing 892 cases for TYMS 2R/3R polymorphism, 7 studies involving 715 cases for TYMS 1494del6 polymorphism and 6 studies containing 616 cases for TYMS 5' untranslated region (UTR) expression allele polymorphism were analyzed in the meta-analysis. The results suggested that TYMS 2R/3R was associated with the response and the patients with 2R/2R or 2R/3R genotype with rectal cancer might benefit more from pCRT than others. On the contrary, neither 1494del6 nor 5'UTR expression allele polymorphisms was associated with the response to pCRT.

A systematic review and meta-analysis of music therapy for the older adults with depression.

OBJECTIVES: To determine the efficacy of music therapy in the management of depression in the elderly. METHOD: We conducted a systematic review and meta-analysis of randomized controlled trials. Change in depressive symptoms was measured with various scales. Standardized mean differences were calculated for each therapy-control contrast. RESULTS: A comprehensive search yielded 2,692 citations; 19 articles met inclusion criteria. Meta-analysis suggests that music therapy plus standard treatment has statistical significance in reducing depressive symptoms among older adults (standardized mean differences = 1.02; 95% CI = 0.87, 1.17). CONCLUSIONS: This systematic review and meta-analysis suggests that music therapy has an effect on reducing depressive symptoms to some extent. However, high-quality trials evaluating the effects of music therapy on depression are required. Copyright © 2016 John Wiley & Sons, Ltd.

Learning curve and outcome of laparoscopic transcystic common bile duct exploration for choledocholithiasis.

BACKGROUND: The best approach for cholecystocholedocholithiasis remains a matter of debate. The aim of this study was to evaluate the technical aspects, learning curve and outcome of laparoscopic transcystic common bile duct exploration (LTCBDE). METHODS: Patients who underwent laparoscopic cholecystectomy with LTCBDE between January 2007 and December 2012 were identified from an institutional database. Data on preoperative investigations, intraoperative and postoperative findings were retrieved retrospectively from the patients' hospital notes. RESULTS: There were 399 women (56·4 per cent) and 309 men (43·6 per cent), with a median age of 58 (range 18-87) years. Microincision (incision of the cystic duct at the confluence with the common bile duct (CBD) with extension of only 3-5 mm at the lateral margin of the CBD) and lithotripsy were used in the transcystic exploration in 119 patients, and increased the success rate of LTCBDE from 74·2 to 91·0 per cent. The median duration of operation was 85 (i.q.r. 65-120) min and the median postoperative hospital stay was 2 (1-3) days. Retained common bile duct stones were observed in 13 patients, and postoperative complications developed in 27 patients. The cumulative sum duration of operation learning curve comprised two phases; phase 1 included the first 250 patients and phase 2 the remaining 458 patients. Duration of operation and postoperative hospital stay decreased with increasing volume per surgeon. Recurrence of common bile duct stones was diagnosed in 26 patients during a median follow-up of 4 years. CONCLUSION: LTCBDE with or without microincision and/or lithotripsy is a safe and effective approach.

Efficacy and safety of ceftriaxone for uncomplicated gonorrhoea: a meta-analysis of randomized controlled trials.

We conducted a systematic review and meta-analysis of ceftriaxone for treatment of uncomplicated gonorrhoea compared with four other antibiotics. Thirteen randomized controlled trials (RCTs) totalling treatment of 2557 patients with uncomplicated gonorrhoea were included. Statistically significant differences were observed in side-effects, which were increased after ceftriaxone 250 mg versus cefotaxime 500 mg (odds ratio [OR] 1.87; 95% confidence interval [CI] 1.14-3.08). Cure rates of ceftriaxone 250 mg were significantly better than cefixime 400 mg (OR 1.77; 95% CI 1.11-2.80) as was ceftriaxone 125 mg versus spectinomycin 2 g (OR 3.44; 95% CI 1.08-10.90). There was no statistically significant difference between ceftriaxone 250 mg and cefixime 800 mg in cure rates (OR 1.39; 95% CI 0.92-2.10) or adverse effects (OR 1.29, 95% CI 0.58-2.84) for treating uncomplicated gonorrhoea. The cure rate after ceftriaxone 250 mg was not significantly different from that after spectinomycin 2 g (OR 1.96; 95% CI 1.00-3.87). In conclusion, this meta-analysis revealed that 250 mg ceftriaxone had a higher efficacy than 400 mg cefixime for uncomplicated gonorrhoea. Also, ceftriaxone 125 mg is a better choice than spectinomycin 2 g for patients with uncomplicated gonorrhoea, but ceftriaxone had higher side-effect rates than cefotaxime. In the current era further randomized controlled clinical trials of ceftriaxone for uncomplicated gonorrhoea are warranted.

Breast conservation therapy for stage I or stage II breast cancer: a meta-analysis of randomized controlled trials.

BACKGROUND: We carried out a meta-analysis to determine the effectiveness of breast conservation therapy (BCT) or mastectomy (MT) for stage I or stage II breast cancer. METHODS: A fully recursive literature search was conducted in the Cochrane Controlled Trials Register Databases, Medline, EMBASE and Chinese Biomedical Literature Database in any language. Randomized controlled trials (RCTs) were considered for inclusion. Analyses were carried out using RevMan software. RESULTS: In all, 18 RCTs including a total of 9388 patients were included. The meta-analysis showed that the overall survival in 3, 5, 10, 15 and 20 years and the locoregional recurrence rate in 3, 5, 15 and 20 years were not statistically significantly different between group BCT and group MT, but 10-year locoregional recurrence rate increased in group BCT. The sensitivity analysis indicated that both overall survival and locoregional recurrence rate were not statistically significant difference between group BCT and group MT. In the subgroup analysis, there was no significant difference in OS and locoregional recurrence rate between group BCT and group MT, but 20-year locoregional recurrence rate was statistically significantly higher in group BCT than group MT for women with tumors 2 cm or smaller. CONCLUSION: BCT was better choice than MT for women with stage I or stage II breast cancer.