A functional polymorphism in the SPINK5 gene is associated with asthma in a Chinese Han Population

<p>Abstract</p> <p>Background</p> <p>Mutation in <it>SPINK5 </it>causes Netherton syndrome, a rare recessive skin disease that is accompanied by severe atopic manifestations including atopic dermatitis, allergic rhinitis, asthma, high serum IgE and hypereosinophilia. Recently, single nucleotide polymorphism (SNP) of the <it>SPINK5 </it>was shown to be significantly associated with atopy, atopic dermatitis, asthma, and total serum IgE. In order to determine the role of the <it>SPINK5 </it>in the development of asthma, a case-control study including 669 asthma patients and 711 healthy controls in Han Chinese was conducted.</p> <p>Methods</p> <p>Using PCR-RFLP assay, we genotyped one promoter SNP, -206G>A, and four nonsynonymous SNPs, 1103A>G (Asn368Ser), 1156G>A (Asp386Asn), 1258G>A (Glu420Lys), and 2475G>T (Glu825Asp). Also, we analyzed the functional significance of -206G>A using the luciferase reporter assay and electrophoresis mobility shift assay.</p> <p>Results</p> <p>we found that the G allele at SNP -206G>A was associated with increased asthma susceptibility in our study population (p = 0.002, odds ratio 1.34, 95% confidence interval 1.11–1.60). There was no significant association between any of four nonsynonymous SNPs and asthma. The A allele at -206G>A has a significantly higher transcriptional activity than the G allele. Electrophoresis mobility shift assay also showed a significantly higher binding efficiency of nuclear protein to the A allele compared with the G allele.</p> <p>Conclusion</p> <p>Our findings indicate that the -206G>A polymorphism in the <it>SPINK5 </it>is associated with asthma susceptibility in a Chinese Han population.</p

Twice evasions of Omicron variants explain the temporal patterns in six Asian and Oceanic countries

Abstract Background The ongoing coronavirus 2019 (COVID-19) pandemic has emerged and caused multiple pandemic waves in the following six countries: India, Indonesia, Nepal, Malaysia, Bangladesh and Myanmar. Some of the countries have been much less studied in this devastating pandemic. This study aims to assess the impact of the Omicron variant in these six countries and estimate the infection fatality rate (IFR) and the reproduction number $${R}_{0}$$ R 0 in these six South Asia, Southeast Asia and Oceania countries. Methods We propose a Susceptible-Vaccinated-Exposed-Infectious-Hospitalized-Death-Recovered model with a time-varying transmission rate $$\beta (t)$$ β ( t ) to fit the multiple waves of the COVID-19 pandemic and to estimate the IFR and $${R}_{0}(t)$$ R 0 ( t ) in the aforementioned six countries. The level of immune evasion and the intrinsic transmissibility advantage of the Omicron variant are also considered in this model. Results We fit our model to the reported deaths well. We estimate the IFR (in the range of 0.016 to 0.136%) and the reproduction number $${R}_{0}(t)$$ R 0 ( t ) (in the range of 0 to 9) in the six countries. Multiple pandemic waves in each country were observed in our simulation results. Conclusions The invasion of the Omicron variant caused the new pandemic waves in the six countries. The higher $${R}_{0}(t)$$ R 0 ( t ) suggests the intrinsic transmissibility advantage of the Omicron variant. Our model simulation forecast implies that the Omicron pandemic wave may be mitigated due to the increasing immunized population and vaccine coverage

Identifying optimal first-line immune checkpoint inhibitors based regiments for advanced non-small cell lung cancer without oncogenic driver mutations: A systematic review and network meta-analysis.

BackgroundImmune checkpoint inhibitors (ICIs) have changed the treatment pattern of advanced and metastatic NSCLC. A series of ICI based therapies have emerged in the first-line treatment field, but the comparative efficacy was unclear.MethodWe searched multiple databases and abstracts of major conference proceedings up to Apri1, 2022 for phase III randomised trials of advanced driver-gene wild type NSCLC patients receiving first-line therapy. Outcomes analyzed included progression free survival (PFS), overall survival (OS), and et al.ResultsThirty-two double-blind RCTs were included, involving 18,656 patients assigned to 22 ICI-based first-line regimens. A series of ICI regiments (including ICI plus chemotherapy), ICI monotherapy, doublet ICIs, doublet ICIs plus chemotherapy) emerged, and showed significant PFS and OS benefit than chemotherapy and chemotherapy + bevacizumab (BEV) for advanced wild-type NSCLC. In comprehensive terms of PFS, chemoimmunotherapy (CIT) were significantly more effective than ICI monotherapy and doublet ICIs. In terms of OS for patients with non-squamous NSCLC, pembrolizumab containing CIT was associated with a median rank of the best regimens, and followed by Atezolizumab+BEV based CIT; while for OS in patients with squamous NSCLC, Cemiplimab and sintilimab based CIT were the most effective regimens. For more than 2 years follow-up, the atezolizumab, pembrolizumab, nivolumab and durvalumab containing ICI therapy all provide a durable long-term OS benefit over chemotherapy and BEV + chemotherapy.ConclusionsThe findings of the present NMA represent the most comprehensive evidence, which might suggest or provide basis for first-line ICI therapy decision for advanced NSCLC patients without oncogenic driver mutations

Association study between vitamin D receptor gene polymorphisms and asthma in the chinese han population: a case-control study

Abstract Background Modulation of the immune system is one of the principal roles of Vitamin D, for which the effects are exerted via the vitamin D receptor (VDR). Importantly, variants in the VDR gene have been susceptible in the past to raise the risk of asthma in several populations. These effects of VDR allelic markers remain speculative in the Chinese Han population. Results A case-control study of 1090 individuals including 567 asthmatic patients was realized on five SNPs within the VDR gene. Only rs7975232 (ApaI) marker showed a significant association with asthma (P = 0.009). Haplotype analysis of the five VDR polymorphisms showed a significant association with asthma (global-p value = 0.012). Conclusion Although the susceptibility of VDR gene variants with asthma could not be confirmed for all SNPs tested in this study, the significant association obtained for rs7975232 provides evidence for a previously unknown report about the Chinese Han population and may raise the susceptibility of VDR to be a candidate gene for asthma.</p

The impact of outdoor air pollutants on outpatient visits for respiratory diseases during 2012–2016 in Jinan, China

Abstract Background Few studies have investigated the associations between outdoor air pollution and outpatient visits for respiratory diseases (RDs) in general population. Methods We collected daily outpatient data of primary RDs from five hospitals in Jinan during January 2012 and December 2016, as well as daily measurements of air pollutants from the Jinan Environmental Monitoring Center and daily meteorological variables from the China Meteorological Data Sharing Service System. A generalized additive model (GAM) with quasi-Poisson regression was constructed to estimate the associations between daily average concentrations of outdoor air pollutants (PM2.5,PM10, SO2, NO2, CO and O3) and daily outpatient visits of RDs after adjusting for long-time trends, seasonality, the “day of the week” effect, and weather conditions. Subgroup analysis stratified by gender, age group and the type of RDs was conducted. Results A total of 1,373,658 outpatient visits for RDs were identified. Increases of 10 μg/m3 in PM2.5, PM10, NO2, CO and O3 were associated with0.168% (95% CI, 0.072–0.265%), 0.149% (95% CI, 0.082–0.215%), 0.527% (95% CI, 0.211–0.843%), 0.013% (95% CI, 0.003–0.023%), and 0.189% (95% CI, 0.032–0.347%) increases in daily outpatient visits for RDs, respectively. PM2.5 and PM10 showed instant and continuous effects, while NO2, CO and O3 showed delayed effects on outpatient visits for RDs. In stratification analysis, PM2.5 and PM10 were associated with acute RDs only. Conclusions Exposure to outdoor air pollutants including PM2.5, PM10, NO2, CO and O3 associated with increased risk of outpatient visits for RDs

Network meta-analysis (NMA) of immunotherapy compared with chemotherapy for PFS and OS for PD-L1 TPS 1–49% cohort.

Summary estimates represent Hazard-Radio (HR) and 95% credibility intervals for PFS and OS. Interventions are ranked by Surface Under the Cumulative Ranking curve values. (TIF)</p

ORR comparative profiles for overall study cohort according to network meta-analysis (NMA).

Each cell contains the Mean difference (MD) and 95% credibility intervals for PFS and OS; significant results are emboldened. (TIF)</p