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Traumatic brain injury (TBI) can result in poor functional outcomes and death, and overall outcomes are varied. Growth factors, such as angiopoietin-1 (Ang-1), vascular endothelial growth factor (VEGF), and granulocyte-colony stimulating factor (G-CSF), play important roles in the neurological functions. This study investigated the relationship between serum growth factor levels and long-term outcomes after TBI. Blood samples from 55 patients were collected at 1, 3 and 7 days after TBI. Blood samples from 39 healthy controls were collected as a control group. Serum Ang-1, G-CSF, and VEGF levels were measured using ELISA. Patients were monitored for 3 months using the Glasgow Outcome Scale-Extended (GOSE). Patients having a GOSE score of > 5 at 3 months were categorized as a good outcome, and patients with a GOSE score of 1-5 were categorized as a bad outcome. Our data demonstrated that TBI patients showed significantly increased growth factor levels within 7 days compared with healthy controls. Serum levels of Ang-1 at 1 and 7 days and G-CSF levels at 7 days were significantly higher in patients with good outcomes than in patients with poor outcomes. VEGF levels at 7 days were remarkably higher in patients with poor outcomes than in patients with good outcomes. Receiver operating characteristic analysis showed that the best cut-off points of serum growth factor levels at 7 days to predict functional outcome were 1,333 pg/mL for VEGF, 447.2 pg/mL for G-CSF, and 90.6 ng/mL for Ang-1. These data suggest that patients with elevated levels of serum Ang-1, G-CSF, and decreased VEGF levels had a better prognosis in the acute phase of TBI (within 7 days). This study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1800018251) on September 7, 2018.

This study assesses the long-term outcomes in Han Chinese patients with clinical stage I non-seminomatous germ cell testicular cancer （CSI NSGCT） treated with surveillance, retroperitoneal lymph node dissection （RPLND） and adjuvant chemotherapy. We retrospectively evaluated 89 patients with a mean age of 26.5 years. After orchiectomy, 37 patients were treated with surveillance, 34 underwent RPLND and 18 were managed with chemotherapy. The overall survival rate, the recurrence-free survival rate and the risk factors were evaluated. The median follow-up length was 92 months （range： 6-149 months）. Thirteen of the 89 patients （14.6%） had relapses, and one died by the evaluation date. The overall survival rate was 98.9%. The cumulative 4-year recurrence-free rates were 80.2%, 92.0% and 100% for the surveillance, RPLND and chemotherapy groups, respectively. The disease-free period tended to be briefer in patients with a history of cryptorchidism and those with stage Is. Therefore, surveillance, RPLND and adjuvant chemotherapy might be reliable strategies in compliant patients with CSI NSGCT. Surveillance should be recommended for patients with the lowest recurrence rate, especially those without lymphovascular invasion. This study might aid the establishment of a standard therapy for CSI NSGCT in China.

Aim： To investigate whether the insulin-like growth factor 2 mRNA-binding protein 2 （IGF2BP2） rs1470579 and rs4402960 polymorphisms are associated with the development of type 2 diabetes mellitus （T2DM） and the repaglinide therapeutic efficacy in Chinese T2DM patients. Methods： A case-control study of a total of 350 patients with T2DM and 207 healthy volunteers was conducted to identify their genotypes for the IGF2BP2 rs1470579 and rs4402960 polymorphisms using a polymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP） assay. Forty-two patients were randomly selected to undergo an 8-week repaglinide treatment （3 mg/d）. Fast- ing plasma glucose （FPG）, postprandial plasma glucose （PPG）, glycated hemoglobin （HbAIc）, fasting serum insulin （FINS）, postprandial serum insulin （PINS）, homeostasis model assessment for insulin resistance （HOMA-IR）, serum triglyceride, total cholesterol （TC）, low- density lipoprotein-cholesterol （LDL-c）, and high-density lipoprotein-cholesterol （HDL-c） were determined before and after repaglinide treatment. Results： The frequencies of the IGF2BP2 rs1470579 C allele and the rs4402960 T allele were higher in T2DM patients than in healthy controls （P〈0.05 and P〈0.001, respectively）. The effects of the repaglinide treatment on FPG （P〈0.05） and PPG （P〈0.05） were reduced in patients with the rs1470579 AC＋CC genotypes compared with AA genotype carriers. Patients with the rs4402960 GT＋TT genotypes exhibited an enhanced effect of repaglinide treatment on PINS （P〈0.01） compared with GG genotype subjects. Conclusion： The IGF2BP2 rs1470579 and rs4402960 polymorphisms may be associated with the development of T2DM, and these polymorphisms may affect the therapeutic efficacy of repaglinide in Chinese T2DM patients.

Aim： To evaluate retrospectively the association of cytochrome P450 3A （CYP3A） and ATP-binding cassette sub-family B member 1 （ABCB1） gene polymorphisms with the pharmacokinetics of cyclosporine A （CsA） in Chinese renal transplant patients. Methods： One hundred and twenty-six renal transplant patients were recruited. Blood samples were collected, and corresponding clini- cal indices were recorded on the seventh day after the procedure. The patients were genotyped for CYP3A4＊IG, CYP3A5＊3C, ABCB1 1236 C〉T, ABCB1 2677 G〉T/A, and ABCB1 3435 C〉T polymorphisms. Whole blood trough concentrations of CsA at time zero （Co） were measured before the drug administration. A multiple regression model was developed to analyze the effects of genetic factors on the CsA dose-adjusted Co （Co/dose） based on several clinical indices. Results： The CYP3A5＊3C polymorphism influenced the Co and Co/dose of CsA, which were significantly higher in patients with the GG genotype than in patients with the AA or GA genotypes. No significant differences were detected for other SNPs （CYP3A4＊IG, ABCB1 1236 C〉T, ABCB1 2677 G〉T/A, and ABCB1 3435 C〉T）. In a univariate analysis using Pearson＇s correlation test, age, hemoglobin, blood urea nitrogen and blood creatinine levels were significantly correlated with the log-transformed CsA Co/dose. In the multiple regression model, CYP3A5＊3C, age, hemoglobin and blood creatinine level were associated with the log-transformed CsA Co/dose. Conclusion： CYP3A5＊3C correlates with the Co/dose of CsA on the seventh day after renal transplantation. The allele is a putative indi- cator for the optimal CsA dosage in the early phase of renal transplantation in the Chinese population.

Yinghao Sun and colleagues report a genome-wide association study for prostate cancer in Han Chinese men. They identify two new risk-associated loci at chromosomes 9q31 and 19q13. Prostate cancer risk–associated variants have been reported in populations of European descent, African-Americans and Japanese using genome-wide association studies (GWAS). To systematically investigate prostate cancer risk–associated variants in Chinese men, we performed the first GWAS in Han Chinese. In addition to confirming several associations reported in other ancestry groups, this study identified two new risk-associated loci for prostate cancer on chromosomes 9q31.2 (rs817826, P = 5.45 × 10 −14 ) and 19q13.4 (rs103294, P = 5.34 × 10 −16 ) in 4,484 prostate cancer cases and 8,934 controls. The rs103294 marker at 19q13.4 is in strong linkage equilibrium with a 6.7-kb germline deletion that removes the first six of seven exons in LILRA3 , a gene regulating inflammatory response, and was significantly associated with the mRNA expression of LILRA3 in T cells ( P < 1 × 10 −4 ). These findings may advance the understanding of genetic susceptibility to prostate cancer.

Recent evidence indicates that microRNAs (miRNAs) can function as tumor suppressors and oncogenes. Single nucleotide polymorphisms (SNPs) at miRNA genes can influence the maturation of miRNAs or miRNA-mediated transcriptional regulation. Our objective was to investigate the association of SNPs in deregulated miRNAs with clinical outcome in patients with non-small cell lung cancer (NSCLC) in a Chinese population. Deregulated miRNAs in NSCLC and their SNPs were identified through public databases. A single SNP, rs895819 in pre-miR-27a, was found suitable for selection. TaqMan assays were performed for genotyping and to assess the effect on the overall survival (OS) and chemotherapy response in 576 NSCLC patients. Log-rank test and Cox regression analysis indicated that the G allele of rs895819 was associated with shorter survival and increased risk of death in NSCLC [dominant model: 22.0 vs. 46.0 months, P<0.001; adjusted hazard ratio (HR) = 1.71, 95% confidential interval (CI): 1.12-2.26]. Further stepwise regression analysis suggested that this SNP was an independently unfavorable factor for the prognosis of NSCLC and the effect remained significant in subgroup analysis stratified by clinical parameters and treatment status. Moreover, multivariate logistic regression analysis showed that the subjects with AG/GG genotypes of rs895819 had significantly decreased response rate to platinum-based chemotherapy compared to those with the AA genotype. Our results suggest that the pre-miR-27a rs895819 polymorphism may influence NSCLC patients' clinical outcome. Further large sample studies should be used to validate our findings.

The process of preadipocytes differentiation plays a vital role in adipose tissue expansion and many factors are involved in this event. Cathepsin B (CTSB), secreted from lysosome, has been reported in regulating a variety of physiological processes. In this study, we demonstrated CTSB promotes lipid accumulation and adipogenic genes expression in porcine primary preadipocytes by degrading fibronectin (Fn), a key component of extracellular matrix. Lithium chloride (LiCl) is an activator of Wnt/β-catenin signaling through stabilizing β-catenin. We found that CTSB can relieve the anti-adipogenic effects of LiCl, indicating that CTSB could impact Wnt/β-catenin signaling pathway. Interestingly, Fn is an important target gene of Wnt/β-catenin. So we considered that CTSB promote preadipocytes differentiation by suppressing these two pathways.

Gastrectomy with D2 lymphadenectomy is a standard procedure of curative resection for gastric cancer (GC). The aim of this study was to develop a simple and reliable prognostic scoring system for GC treated with D2 gastrectomy combined with adjuvant chemotherapy. A prognostic scoring system was established based on clinical and laboratory data from 579 patients with localized GC without distant metastasis treated with D2 gastrectomy and adjuvant chemotherapy. From the multivariate model for overall survival (OS), five factors were selected for the scoring system: ≥50% metastatic lymph node rate, positive lymphovascular invasion, pathologic TNM Stage II or III, ≥5 ng/mL preoperative carcinoembryonic antigen level, and <110 g/L preoperative hemoglobin. Two models were derived using different methods. Model A identified low- and high-risk patients for OS (P<0.001), while Model B differentiated low-, intermediate-, and high-risk patients for OS (P<0.001). Stage III patients in the low-risk group had higher survival probabilities than Stage II patients. Both Model A (area under the curve [AUC]: 0.74, 95% confidence interval [CI]: 0.69-0.78) and Model B (AUC: 0.79, 95% CI: 0.72-0.83) were better predictors compared with the pathologic TNM classification (AUC: 0.62, 95% CI: 0.59-0.71, P<0.001). Adjuvant paclitaxel- or oxaliplatin-based or triple chemotherapy showed significantly better outcomes in patients classified as high risk, but not in those with low and intermediate risk. A clinical three-tier prognostic risk scoring system was established to predict OS of GC treated with D2 gastrectomy and adjuvant chemotherapy. The potential advantage of this scoring system is that it can identify high-risk patients in Stage II or III who may benefit from paclitaxel- or oxaliplatin-based regimens. Prospective studies are needed to confirm these results before they are applied clinically.

Background. Syphilis has made a rapid resurgence in China, especially among high-risk groups including female sex workers (FSWs). Methods. Two cities in each of 3 provinces in South China were chosen and allocated to intervention or control arms. The intervention consisted of enhancing community-based syphilis screening outreach intervention with comprehensive sexually transmitted infection services at designated clinics while the control maintained routine intervention activities. Generalized linear modeling was used to examine effect of the intervention on incident syphilis infection. Results. A total of 8275 women were eligible, and 3597 women enrolled (n = 2011 in control arm, n = 1586 in intervention arm, in the study. The median follow-up duration was 375 days (interquartile range, 267-475). Syphilis incidence density in the intervention group was reduced by 70% (95% confidence interval, 53%-81%) compared with the incidence in the control arm. The syphilis prevention intervention benefits were robust among FSWs at low-tier venues, individuals with less than high school education, migrants, and women who did not report condom use during the last episode of sex. Conclusions. Integrated sexually transmitted infection and human immunodeficiency virus prevention strategies substantially reduce syphilis incidence among FSWs, especially among those at low-tier venues. This intervention suggests the need for scaling up comprehensive FSW programs in China.

Melanoma differentiation-associated gene-7 (mda-7)/interleukin-24 (IL-24) has shown potent tumor cell apoptosis inducing capacity in multiple cancers. However, the apoptosis induction capacity of mda-7/IL-24 was low and directly correlated with the adhesion to tumor cells.Cell adhesion molecule integrin αvβ3 expressed on the surface of several types of solid tumor cells, and they bind to arginine-glycine-aspartic acid (RGD) which enhanced the adhesion to tumor cells. This rout was exploited to construct a tumor-targeting gene RGD-IL-24 which can express RGD-MDA-7/IL-24 protein that includes the cell adhesive sequence 164Arg-165Gly-166Asp (A Glycine residue was inserted into the recombinant MDA-7/IL-24 between Arg164 and Asp165 to form a RGD motif). We successfully got the MDA-7/IL-24 mutant by overlapping polymerase chain reaction (PCR) and evaluated its therapeutic efficacy for tumor cell lines MCF-7, HeLa, HepG2, and normal human lung fibroblast (NHLF) line. And we found that the expression of pCDNA3.1/RGD-IL-24 was same to the expression of pCDNA3.1/IL-24. The RGD-IL-24 enhanced the apoptosis-inducing function in tumor cells, but not in normal cells. In tumor cell lines, the apoptosis-inducing activities of RGD-IL-24 was significantly higher than IL-24 detecting by MTT assay, Annexin V, and Hoechst 33258 analysis. Further, pCDNA3.1/RGD-IL-24 showed a significant increase in the ratio of pro-apoptotic (bax) to anti-apoptotic (bcl-2) proteins in tumor cell lines, but not in NHLF cell line. Together, these results suggest that RGD-IL-24 can enhance the apoptosis of tumor cells and may provide a promising drug in tumor therapy.