Development and validation of a risk prediction model for early diabetic peripheral neuropathy based on a systematic review and meta-analysis.

Background: Early identification and intervention of diabetic peripheral neuropathy is beneficial to improve clinical outcome. Objective: To establish a risk prediction model for diabetic peripheral neuropathy (DPN) in patients with type 2 diabetes mellitus (T2DM). Methods: The derivation cohort was from a meta-analysis. Risk factors and the corresponding risk ratio (RR) were extracted. Only risk factors with statistical significance were included in the model and were scored by their weightings. An external cohort were used to validate this model. The outcome was the occurrence of DPN. Results: A total of 95,604 patients with T2DM from 18 cohorts were included. Age, smoking, body mass index, duration of diabetes, hemoglobin A1c, low HDL-c, high triglyceride, hypertension, diabetic retinopathy, diabetic kidney disease, and cardiovascular disease were enrolled in the final model. The highest score was 52.0. The median follow-up of validation cohort was 4.29 years. The optimal cut-off point was 17.0, with a sensitivity of 0.846 and a specificity of 0.668, respectively. According to the total scores, patients from the validation cohort were divided into low-, moderate-, high- and very high-risk groups. The risk of developing DPN was significantly increased in moderate- (RR 3.3, 95% CI 1.5-7.2, P = 0.020), high- (RR 15.5, 95% CI 7.6-31.6, P < 0.001), and very high-risk groups (RR 45.0, 95% CI 20.5-98.8, P < 0.001) compared with the low-risk group. Conclusion: A risk prediction model for DPN including 11 common clinical indicators were established. It is a simple and reliable tool for early prevention and intervention of DPN in patients with T2DM.

Wilms' tumor gene 1 is an independent prognostic factor for pediatric acute myeloid leukemia following allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Sequential monitoring of Wilms' tumor gene 1 (WT1) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) could predict relapse in adult acute myeloid leukemia (AML). However, the prognostic role of WT1 in pediatric AML after allo-HSCT is unclear. Thus, we determined to see whether sequential monitoring of WT1 after allo-HSCT could predict relapse in AML children. METHODS: Pediatric AML patients receiving allo-HSCT from January 21, 2012 to December 20, 2018 at the Peking University Institute of Hematology were included in this study. WT1 expression level was determined by TaqMan-based reverse transcription-polymerase chain reaction. WT1 sequential monitoring was performed 1, 2, 3, 4.5, 6, 9, and 12 months post-transplantation and at 6-month intervals thereafter. The primary end point was relapse. The secondary end points included disease-free survival (DFS), overall survival (OS), and non-relapse mortality (NRM). Kaplan-Meier analysis was used for DFS and OS estimates, while competing risk analysis was used for estimating relapse and NRM. RESULTS: Of the 151 consecutive patients included, the median age was 10 years (range, 1-17). The optimal cutoff value of WT1 within 1 year after allo-HSCT to predict relapse was 0.8% (80 WT1 copies/104 ABL copies), with a sensitivity of 60% and specificity of 79%. Compared with WT1 expression < 0.8%, WT1 expression ≥0.8% indicated significantly higher 5-year cumulative incidence of relapse (CIR, 35.1% vs. 11.3%; P = 0.001), lower 5-year disease-free survival (DFS, 60.4% vs. 80.8%; P = 0.009), and lower 5-year overall survival (OS, 64.9% vs. 81.6%; P = 0.038) rates. Multivariate analyses showed that WT1 was an independent risk factor for relapse (HR 2.89; 95% confidence interval (CI), 1.25-6.71; P = 0.014). Both the CIR (5-year CIR: 8.3% vs. 11.3%; P = 0.513) and DFS (5-year DFS: 91.7% vs. 80.8%; P = 0.208) were comparable between patients achieving minimal residual disease (MRD) negativity after preemptive interferon-α (IFN-α) treatment and those without MRD after allo-HSCT, which were better than those of MRD-positive patients without preemptive therapies. CONCLUSIONS: Sequential monitoring of WT1 could predict relapse in pediatric AML after allo-HSCT. WT1-directed immunotherapy may have the potential to prevent relapse and improve survival.

[Lymphocytic Clonal Expansion in Adult Patients with Epstein-Barr Virus-Associated Lymphoproliferative Disease].

OBJECTIVE: To explore the lymphocytic clonal expansion in adult patients with Epstein-Barr virus-associated lymphoproliferative diseases (EBV+LPD), and to investigate the experimental methods for EBV+LPD cells so as to provide a more objective measure for the diagnosis, classification and prognosis in the early stage of this disease. METHODS: Peripheral blood samples from 5 patients with EBV+LPD, 4 patients with adult infectious mononucleosis(IM) as negative control and 3 patients with acute NK-cell leukemia(ANKL) as positive control were collected. Prior to immunochemotherapy, viral loads and clonality were analysed by flow cytometry (FCM), T cell receptor gene rearrangement (TCR) was detected by real-time polymerase chain reaction (RT-PCR), and diversity of EB virus terminal repeat (EBV-TR) was detected by Southern blot. RESULTS: FCM showed only 1 case with clonal TCRVß in 5 patients with EBV+LPD, TCR clonal expansion could be detected both in patients with IM(4 of 4) and 4 patients with EBV+LPD(4 of 5), Out of patients with EBV+LPD, 1 patient displayed a monoclonal band and 2 patients showed oligoclonal bands when detecting EBV-TR by southen blot. CONCLUSION: Detecting the diversity of EBV-TR by Southern blot may be the most objective way to reflex clonal transformation of EBV+LPD, which is of great benefit to the diagnosis, classification and prognosis in the early stage of this disease.

Probiotics in 14-day triple therapy for Asian pediatric patients with Helicobacter pylori infection: a network meta-analysis.

Although 14-day triple therapy has been widely administrated for eradicating Helicobacter pylori (H. pylori) in Asia, its antibiotic-associated side effects restrict the effectivity of eradication therapy in pediatric patients. Therefore, a network meta-analysis (NMA) was conducted to compare the efficacy and safety of probiotics supplemented in 14-day triple therapy in Asian pediatric patients. MATERIALS AND METHODS: Randomized controlled trials (RCTs) were retrieved comprehensively in electronic databases (such as PubMed, Cochrane library, Embase, CNKI, Wan fang database, VIP database and CBM) until April 2017. Additional references were obtained from reviewed articles. NMA was performed using a random-effects model under a frequentist framework. RESULTS: Seventeen RCTs were included. NMA indicated that Bifidobacterium infantis+Clostridium butyricum was most beneficial for H. pylori eradication rates (P-score = 0.82) and Bacillus mesentericus+Clostridium butyricum+Streptococcus faecalis for total side effects (P-score = 0.77). Taken together, Bacillus mesentericus+Clostridium butyricum+Streptococcus faecalis was the best one to supplement in 14-day triple therapy due to its efficacy (P-score = 0.72) and safety (P-score = 0.77). Additionally, pairwise meta-analysis indicated that probiotics supplemented 14-day triple therapy significantly increased H. pylori eradication rates (RR: 1.16, 95%CI: 1.07-1.26) and reduced the incidence of total side effects (RR: 0.40, 95%CI: 0.34-0.48) compared with placebo. CONCLUSIONS: Bacillus mesentericus+Clostridium butyricum+Streptococcus faecalis is the optimal probiotic regime of reducing total side effects and improving eradication rates when supplemented 14-day triple therapy. Further direct evidence is needed to warrant it.

Dysregulation of microRNA biosynthesis enzyme Dicer plays an important role in gastric cancer progression.

BACKGROUND AND AIM: Dicer is one of the most important components in microRNA biogenesis. Although studies have revealed the aberrantly expression of Dicer in types of cancer, the results were greatly controversial. Here we aimed to study the expression of Dicer in gastric cancer (GC) and further explored the possible roles of Dicer in cancer progression. METHODS: The alteration of Dicer-expression in GC and its clinical significance was retrospectively studied with immunohistochemical analyses on 377 cases of cancer tissues using tissue microarray (TMA). Dicer mRNA and protein levels were also examined in 8 paired of GC tissues and non-neoplastic surrounding gastric epithelium with real time RT-PCR and western blot. RESULTS: We found that Dicer was reduced in GC tissues in both mRNA and protein levels. Moreover, down-regulation of Dicer was correlated highly with tumor differentiation (P<0.05) and lymph node invasion (P<0.05) in GC tissues, which suggested an essential role of Dicer in cancer invasion. CONCLUSIONS: Considering that Dicer might be closely related to progression of GC, we proposed that Dicer might offer a promising target for prevention of metastatic progression in GC.

Overexpression of ß-catenin and cyclinD1 predicts a poor prognosis in ovarian serous carcinomas.

UNLABELLED: Ovarian serous cancer is the most common subtype of epithelial ovarian cancer, and is the leading cause of death from gynecologic cancer. There is an important need for exploration of diagnostic and prognostic markers for this disease. ß-catenin and cyclinD1 play central roles in the tumorigenesis for certain cancers. The role of ß-catenin and cyclinD1 in diagnosis and prognosis of ovarian serous carcinoma is uncertain. In the present study, the expression of ß-catenin and cyclinD1 was examined in 60 ovarian serous carcinomas patients with immunohistochemical staining. The relationship between expression of ß-catenin and cyclinD1 and FIGO stage, pathological grade was analyzed. Kaplan-Meier survival function was used to analyze the prognosis. Overexpression of ß-catenin is more often detected in patients with FIGO stage III and IV than in those with stage I, and II (P=0.003). No significant relationship was found between expression of ß-catenin and pathological grade (P=0.817). Positive expression of ß-catenin related to lower survival rate (P=0.034). The expression of cyclinD1 had no relationship with FIGO stage (P=0.829). Overexpression of cyclinD1 was positively to pathological grade (P=0.017) and survival rate (P=0.009). There is a significantly positive relationship between expression of ß-catenin and cyclinD1 (P=0.014). No statistical significance was found between expression of ß-catenin and cyclinD1 and other pathological parameters. CONCLUSIONS: Expression of ß-catenin and cyclinD1 may be used as predict markers for poor prognosis.

Loss of expression of EphB1 protein in serous carcinoma of ovary associated with metastasis and poor survival.

Aberrant expression of receptors tyrosine kinase of Eph gene in human cancers is extensively documented. We previously found that EphB1 subtype is down-regulated in gastric cancer and colorectal cancer. Fore the more, decreased expression of EphB1 is related to invasion and metastasis in cancers. There is no published data regarding the role of EphB1 in ovarian cancer, which is the focus of the present study. The expression of EphB1 protein was determined in tissues from 74 patients with serous ovarian carcinoma and 12 normal ovarian epithelial tissues. The expression level of EphB1 protein in serous ovarian carcinoma was analyzed with respect to clinicopathological parameters and survival. EphB1 protein was positively stained in 12 normal ovarian epithelial samples, and negatively stained in 32 out of 74 (43.2%) serous ovarian cancers. Loss of expression of EphB1 protein was associated with higher tumor grade (P=0.006), metastasis (P=0.049) and high proliferative index Ki67 expression (P=0.022), but not with FIGO stage (P=0.0937), age at diagnosis (P=0.624), and diameter of carcinoma (P=0.108). In addition, loss of EphB1 protein in serous ovarian carcinoma was associated with a significantly worse overall survival (P=0.015). Our data indicate that loss of EphB1 protein is associated with metastasis and poorer survival in patients with serous ovarian cancer. EphB1 may be used as a prognostic marker and a therapeutic target in serous ovarian carcinoma.

Increased expression of EphA1 protein in prostate cancers correlates with high Gleason score.

The erythropoietin-producing hepatocellular (Eph) family of receptor tyrosine kinases regulates a multitude of physiological and pathological processes. EphA1 is the first member of Eph superfamily and is involved in carcinogenesis. The aim of this study was to investigate the expression of EphA1 in prostate cancers cell lines and the tissues, then explore the correlation with the clinicopathologic parameters. The EphA1 transcript expression in prostate cancer cell lines was detected by Quantitative real-time PCR. The expression of EphA1 protein in 138 prostate cancer tissue samples and 21 benign prostate hyperplasia samples were checked by using immunohistochemical staining. EphA1 mRNA was high expressed in LNCap, moderately expressed in 22RV1 and Du145, and lost in PC3. Loss of expression of EphA1 transcript was related to hypermethylation of CpG island around the translation start site. EphA1 protein was differentially expressed in prostate cancers and hyperplasia. Increased expression of EphA1 protein was more frequently detected in prostate cancers than in hyperplasia (P = 0.02), and more often detected in prostate cancer with high Gleason score (P < 0.001). Our data indicate that EphA1 receptor may have roles in carcinogenesis and progression of prostate cancer, and can be a potentially useful target for prognostic and therapeutic application.