Examining Road Traffic Mortality Status in China: A Simulation Study

Background Data from the Chinese police service suggest substantial reductions in road traffic injuries since 2002, but critics have questioned the accuracy of those data, especially considering conflicting data reported by the health department. Methods To address the gap between police and health department data and to determine which may be more accurate, we conducted a simulation study based on the modified Smeed equation, which delineates a non-linear relation between road traffic mortality and the level of motorization in a country or region. Our goal was to simulate trends in road traffic mortality in China and compare performances in road traffic safety management between China and 13 other countries. Results Chinese police data indicate a peak in road traffic mortalities in 2002 and a significant and a gradual decrease in population-based road traffic mortality since 2002. Health department data show the road traffic mortality peaked in 2012. In addition, police data suggest China’s road traffic mortality peaked at a much lower motorization level (0.061 motor vehicles per person) in 2002, followed by a reduction in mortality to a level comparable to that of developed countries. Simulation results based on health department data suggest high road traffic mortality, with a mortality peak in 2012 at a moderate motorization level (0.174 motor vehicles per person). Comparisons to the other 13 countries suggest the health data from China may be more valid than the police data. Conclusion Our simulation data indicate China is still at a stage of high road traffic mortality, as suggested by health data, rather than a stage of low road traffic mortality, as suggested by police data. More efforts are needed to integrate safety into road design, improve road traffic management, improve data quality, and alter unsafe behaviors of pedestrians, drivers and passengers in China

A Synergistic Therapeutic Scheme for Hyperglycemia and Nephrotic Disorders in Diabetes

We previously demonstrated that the utilization of an electrospun scaffold could boost functional outputs of transplanted islets. In this study, we aim to develop a drug-eluting scaffold with a payload of pioglitazone to simultaneously rein in hyperglycemia and recoup lost renal functions in diabetic mice that underwent islet transplantation. The in vivo proliferation of islets was measured by a non-invasive bio-imaging technology whereas the blood insulin, blood glucose and renal proteins were assayed. The local stimulation of transplanted islets by pioglitazone saw an accelerated in vivo proliferation without apoptosis caused by the drug-eluting scaffold. In addition, pioglitazone contributed to an increased secretion of insulin and C-peptide 2, giving rise to an accelerated rein-in of hyperglycemia and enhanced tolerance of sudden oral glucose challenge. Moreover, the accelerated decrease of blood creatinine, urine creatinine and blood urea nitrogen suggested that pioglitazone contributed to the recovery of renal functions compromised by diabetes. Our bioengineering strategy effectively ameliorated hyperglycemia and associated nephrotic disorders, and shed a new light on an engineering approach to combat diabetes

Genetic variants in the vitamin D pathway genes VDBP and RXRA modulate cutaneous melanoma disease-specific survival

Single nucleotide polymorphisms (SNPs) in the vitamin D pathway genes have been implicated in cutaneous melanoma (CM) risk, but their role in CM disease-specific survival (DSS) remains obscure. We comprehensively analyzed the prognostic roles of 2669 common SNPs in the vitamin D pathway genes using data from a published genome-wide association study (GWAS) at The University of Texas M.D. Anderson Cancer Center (MDACC) and then validated the SNPs of interest in another GWAS from the Nurses' Health Study and Health Professionals Follow-up Study. Among the 2669 SNPs, 203 were significantly associated with DSS in MDACC dataset (P C was associated with a better DSS [combined hazards ratio (HR) = 0.66]; and the same for RXRA rs7850212 C > A (combined HR = 0.38), which were further confirmed by the Fine and Gray competing-risks regression model. Further bioinformatics analyses indicated that these loci may modulate corresponding gene methylation status

Genetic variants in the PIWI-piRNA pathway gene DCP1A predict melanoma disease-specific survival

The Piwi-piRNA pathway is important for germ cell maintenance, genome integrity, DNA methylation and retrotransposon control and thus may be involved in cancer development. In this study, we comprehensively analyzed prognostic roles of 3,116 common SNPs in PIWI-piRNA pathway genes in melanoma disease-specific survival. A published genome-wide association study (GWAS) by The University of Texas M.D. Anderson Cancer Center was used to identify associated SNPs, which were later validated by another GWAS from the Harvard Nurses' Health Study and Health Professionals Follow-up Study. After multiple testing correction, we found that there were 27 common SNPs in two genes (PIWIL4 and DCP1A) with false discovery rate < 0.2 in the discovery dataset. Three tagSNPs (i.e., rs7933369 and rs508485 in PIWIL4; rs11551405 in DCP1A) were replicated. The rs11551405 A allele, located at the 3' UTR microRNA binding site of DCP1A, was associated with an increased risk of melanoma disease-specific death in both discovery dataset [adjusted Hazards ratio (HR) = 1.66, 95% confidence interval (CI) = 1.21-2.27, p =1.50 × 10-3 ] and validation dataset (HR = 1.55, 95% CI = 1.03-2.34, p = 0.038), compared with the C allele, and their meta-analysis showed an HR of 1.62 (95% CI, 1.26-2.08, p =1.55 × 10-4 ). Using RNA-seq data from the 1000 Genomes Project, we found that DCP1A mRNA expression levels increased significantly with the A allele number of rs11551405. Additional large, prospective studies are needed to validate these findings

Serum Cytokines Th1, Th2, and Th17 Expression Profiling in Active Lupus Nephritis-IV: From a Southern Chinese Han Population

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by aberrant T cell immune response. Diffuse proliferative lupus nephritis (LN-IV) is the most common, severe, and active form of lupus nephritis. In this study, we investigated the production of Th1, Th2, and Th17 cytokines in prediction of active form of LN-IV. ProcartaPlex multiplex immunoassays panels were used for detection of serum Th1, Th2, and Th17 cytokines profiling. Th1 and Th17 cytokines (IL-18, IFN-γ, IL-12p70, IL-6, and IL-17A) were considerably expressed in the serum of lupus nephritis IV patients in comparison to the healthy control. However, only IL18 and IL6 were higher in class IV versus class III lupus nephritis. Importantly, the ratios of Th1/Th2 (IL-18/IL-4) and Th17/Th2 (IL-17A/IL-4) were significantly elevated in LN-IV when compared with LN-III, LN-V, and healthy controls. Consistently, the serum cytokines IL-18, IL-17A, and IFN-γ were markedly expressed in LN-IV patient glomeruli and interstitial tissue compared to other classes of LN by IHC. ROC further suggests that IL-18 was a potential marker for LN-IV. The data from our study suggests that the early detection and quantification of these cytokines may help in prediction of active form of LN-IV

Evaluating active versus passive sources of human brucellosis in Jining City, China

Human brucellosis (HB) remains a serious public health concern owing to its resurgence across the globe and specifically in China. The timely detection of this disease is the key to its prevention and control. We sought to describe the differences in the demographics of high-risk populations with detected cases of HB contracted from active versus passive sources. We collected data from a large sample population from January to December 2018, in Jining City, China. We recruited patients that were at high-risk for brucellosis from three hospitals and Centers of Disease Control and Prevention (CDCs). These patients were classified into two groups: the active detection group was composed of individuals receiving brucellosis counseling at the CDCs; the passive detection group came from hospitals and high-risk HB groups. We tested a total of 2,247 subjects and 13.3% (299) presented as positive for HB. The positive rates for active and passive detection groups were 20.5% (256/1,249) and 4.3% (43/998), respectively (p < 0.001). The detection rate of confirmed HB cases varied among all groups but was higher in the active detection group than in the passive detection group when controlled for age, sex, ethnicity, education, career, and contact history with sheep or cattle (p < 0.05). Males, farmers, those with four types of contact history with sheep or cattle, and those presenting fever, hyperhidrosis and muscle pain were independent factors associated with confirmed HB cases in multivariate analysis of the active detection group. Active detection is the most common method used to detect brucellosis cases and should be applied to detect HB cases early and avoid misdiagnosis. We need to improve our understanding of brucellosis for high-risk populations. Passive HB detection can be supplemented with active detection when the cognitive changes resulting from brucellosis are low. It is important that healthcare providers understand and emphasis the timely diagnosis of HB

Genotypes and haplotypes of the VEGF gene and survival in locally advanced non-small cell lung cancer patients treated with chemoradiotherapy

<p>Abstract</p> <p>Background</p> <p>Vascular endothelial growth factor (VEGF) is a major mediator of angiogenesis involving in carcinogenesis, including lung cancer. We hypothesized that <it>VEGF </it>polymorphisms may affect survival outcomes among locally advanced non-small cell lung cancer (LA-NSCLC) patients.</p> <p>Methods</p> <p>We genotyped three potentially functional <it>VEGF </it>variants [-460 T > C (rs833061), -634 G > C (rs2010963), and +936 C > T (rs3025039)] and estimated haplotypes in 124 Caucasian patients with LA-NSCLC treated with definitive radiotherapy. We used Kaplan-Meier log-rank tests, and Cox proportional hazard models to evaluate the association between <it>VEGF </it>variants and overall survival (OS).</p> <p>Results</p> <p>Gender, Karnofsky's performance scores (KPS) and clinical stage seemed to influence the OS. The variant C genotypes were independently associated with significantly improved OS (CT+CC vs. TT: adjusted hazard ratio [HR] = 0.58; 95% confidence interval [CI] = 0.37-0.92, <it>P </it>= 0.022), compared with the <it>VEGF </it>-460 TT genotype.</p> <p>Conclusions</p> <p>Our study suggests that <it>VEGF </it>-460 C genotypes may be associated with a better survival of LA-NSCLC patients after chemoradiotherapy. Large studies are needed to confirm our findings.</p

Whole exome sequencing identifies frequent somatic mutations in cell-cell adhesion genes in chinese patients with lung squamous cell carcinoma

Lung squamous cell carcinoma (SQCC) accounts for about 30% of all lung cancer cases. Understanding of mutational landscape for this subtype of lung cancer in Chinese patients is currently limited. We performed whole exome sequencing in samples from 100 patients with lung SQCCs to search for somatic mutations and the subsequent target capture sequencing in another 98 samples for validation. We identified 20 significantly mutated genes, including TP53, CDH10, NFE2L2 and PTEN. Pathways with frequently mutated genes included those of cell-cell adhesion/Wnt/Hippo in 76%, oxidative stress response in 21%, and phosphatidylinositol-3-OH kinase in 36% of the tested tumor samples. Mutations of Chromatin regulatory factor genes were identified at a lower frequency. In functional assays, we observed that knockdown of CDH10 promoted cell proliferation, soft-agar colony formation, cell migration and cell invasion, and overexpression of CDH10 inhibited cell proliferation. This mutational landscape of lung SQCC in Chinese patients improves our current understanding of lung carcinogenesis, early diagnosis and personalized therapy

Polymorphisms of Homologous Recombination Genes and Clinical Outcomes of Non-Small Cell Lung Cancer Patients Treated with Definitive Radiotherapy

The repair of DNA double-strand breaks (DSBs) is the major mechanism to maintain genomic stability in response to irradiation. We hypothesized that genetic polymorphisms in DSB repair genes may affect clinical outcomes among non-small cell lung cancer (NSCLC) patients treated with definitive radio(chemo)therapy. We genotyped six potentially functional single nucleotide polymorphisms (SNPs) (i.e., RAD51 −135G>C/rs1801320 and −172G>T/rs1801321, XRCC2 4234G>C/rs3218384 and R188H/rs3218536 G>A, XRCC3 T241M/rs861539 and NBN E185Q/rs1805794) and estimated their associations with overall survival (OS) and radiation pneumonitis (RP) in 228 NSCLC patients. We found a predictive role of RAD51 −135G>C SNP in RP development (adjusted hazard ratio [HR] = 0.52, 95% confidence interval [CI], 0.31–0.86, P = 0.010 for CG/CC vs. GG). We also found that RAD51 −135G>C and XRCC2 R188H SNPs were independent prognostic factors for overall survival (adjusted HR = 1.70, 95% CI, 1.14–2.62, P = 0.009 for CG/CC vs. GG; and adjusted HR = 1.70; 95% CI, 1.02–2.85, P = 0.043 for AG vs. GG, respectively) and that the SNP-survival association was most pronounced in the presence of RP. Our study suggests that HR genetic polymorphisms, particularly RAD51 −135G>C, may influence overall survival and radiation pneumonitis in NSCLC patients treated with definitive radio(chemo)therapy. Large studies are needed to confirm our findings