Minimally invasive surgery role in central squamous lung cancer after neoadjuvant chemoimmunotherapy.

Background: The present body of literature provides restricted evidence concerning the application of video-assisted thoracoscopic surgery (VATS) in individuals diagnosed with centrally located, locally advanced, and initially surgically challenging squamous cell lung carcinoma (SqCLC) following neoadjuvant chemoimmunotherapy (CIT). Further research is warranted to elucidate the role and potential benefits of VATS in this particular patient population. Methods: We performed a retrospective analysis on individuals diagnosed with centrally located and locally advanced SqCLC who received preoperative CIT at a single institution. The study evaluated the percentage of VATS performed, conversion rates, and perioperative outcomes. Furthermore, survival outcomes related to the resection extent were compared between patients who underwent standard lobectomy (SL) and extended lobectomy (EL, e.g., sleeve, bilobectomy or pneumonectomy) after neoadjuvant CIT. Results: A total of 27 cases of centrally located SqCLC underwent neoadjuvant CIT followed by VATS, with one case requiring conversion to thoracotomy due to adhesions. Comparison of perioperative outcomes and long-term cancer-specific mortality between the VATS group (N=24) and the thoracotomy group (N=13) did not yield any statistically significant differences. However, the VATS group exhibited a significantly higher frequency of SL (66.7% vs. 30.8%, P=0.046). Notably, within the VATS group, all three patients who experienced tumor relapse or died due to tumor recurrence were from the SL subgroup. Conclusions: This study contributes valuable real-world evidence demonstrating the feasibility and safety of utilizing VATS in the management of patients with centrally located and locally advanced SqCLC following neoadjuvant CIT. However, careful consideration might be given to the extent of resection to optimize patient long-term outcomes.

Effectiveness comparison of third-generation EGFR-TKI as initial and sequential therapy in adjuvant treatment for EGFR mutation-sensitive stage IIIA non-small cell lung cancer after surgery.

Introduction: Although third-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) Osimertinib has been approved as adjuvant therapy for resected stage IIIA non-small cell lung cancer (NSCLC) with EGFR-sensitive mutations, the optimal treatment sequencing of EGFR-TKIs, particularly whether Osimertinib should be the initial or sequential therapy following the first-generation EGFR-TKIs remains uncertain. Methods: A retrospective analysis was conducted on a cohort of patients with EGFR-mutated stage IIIA NSCLC who received treatment with either first-generation EGFR-TKIs or Osimertinib (third-generation) alone, or in sequential combination, at a single institution. The data analysis involved using the Kaplan-Meier method, log-rank test, and Cox regression. Results: Out of the total 148 patients with stage IIIA NSCLC included in the study, 76 individuals underwent treatment with either first-generation EGFR-TKIs (referred to as subgroup "1″) or exclusively Osimertinib (subgroup "0 + 3″), or a sequential combination of the two (subgroup "1 + 3″) following surgery. Both univariate and multivariate analyses demonstrated that there were no discernible disparities in terms of disease-free survival and overall survival between subgroup " 1″ and " 1 + 3," nor between subgroup " 0 + 3″ and "1 + 3". Conclusion: The findings from this study indicate that the introduction of third-generation EGFR-TKI Osimertinib did not yield enhanced survival benefits when compared to the first-generation drug in patients with stage IIIA completely resected NSCLC who were administered EGFR-TKIs as part of their postoperative adjuvant treatment. Additionally, within the observed sample size of this cohort, the sequential use of Osimertinib alongside first-generation EGFR-TKI did not demonstrate superiority over using either the first-generation EGFR-TKI or Osimertinib alone in terms of postoperative survival.

LINC00299 polymorphisms rs891058, rs13395467, and rs13398375 reduce the risk of allergic rhinitis among the Chinese Han population.

BACKGROUND: A few studies have reported that allergic rhinitis (AR) pathogenesis is related to genetic factors. And the most important genetic factor is single nucleotide polymorphism (SNP). The study aimed to investigate the effects of LINC00299 SNPs (rs891058, rs13395467 and rs13398375) on AR risk in the Chinese Han population. METHODS: Independent sample t-test was carried out for statistical analyses of the distribution of age and BMI in AR cases and healthy controls, and χ2 test was used for statistical analyses of gender and different regions. The Agena MassARRAY platform was applied for LINC00299 SNP genotyping. Further, the association between SNPs and AR risk was evaluated by odds ratios (ORs) as well as 95% confidence intervals (CIs). RESULTS: Our study found that LINC00299 rs891058, rs13395467, and rs13398375 were associated with a decreased risk of AR in the Chinese Han population. More precisely, rs891058 and rs13398375 were associated with a reduced risk of AR in subjects aged ≤ 43 years. In males, subjects with BMI ≤ 24 kg/m2, and from loess hills region, rs891058, rs13395467, and rs13398375 played a protective role against AR. The study on SNP-SNP interactions suggested that rs891058, rs13395467 and rs13398375 were related. CONCLUSIONS: LINC00299 polymorphisms rs891058, rs13395467, and rs13398375 are associated with a reduced risk of AR in the Chinese Han population, and these SNPs can be used as potential targets to assess AR risk.

The Assessment of TLR1 Gene Polymorphism Association with the Risk of Allergic Rhinitis in the Chinese Han Population from Northern China.

Background: Environmental factors and genetic predisposition can influence the occurrence and development of AR. Toll-like receptor 1 (TLR1) belongs to the TLR receptor family, which plays a fundamental role in the activation of innate immunity. This study aimed to explore the association between TLR1 genetic loci and AR susceptibility in the Han Chinese from northern China. Methods: Genotyping of three SNPs in the TLR1 has proceeded using the Agena MassARRAY platform. Odds ratio (OR) and 95% confidence interval (CI) were used to assess the correlation between candidate SNPs and AR susceptibility. Using FPRP (false-positive report probability analysis) to detect whether the positive results are noteworthy findings. The SNP-SNP interactions were detected by multifactor dimensionality reduction (MDR). Results: TLR1-rs72493538 (Allele "G": OR=0.77, p = 0.034) and -rs76600635 (Allele "G": OR=0.75, p = 0.024) were associated with reducing the risk of AR among Han Chinese in northern China. In addition, we found evidence that TLR1-rs72493538 (males, participants with aging > 43 years, or coming from the wind-blown sand region) and -rs76600635 (males, participants with BMI ≤ 24 kg/m2, or coming from the wind-blown sand region) were associated with AR risk in stratified analyses. FPRP showed that all positive results are noteworthy findings. MDR analysis showed that a two-loci genetic model composed of rs72493538 and rs76600635 can be chosen as the best genetic model to predict the risk of AR. Conclusion: TLR1-rs72493538 and -rs76600635 have a close association with reducing the risk of AR.

LPP polymorphisms are risk factors for allergic rhinitis in the Chinese Han population.

BACKGROUND: Lipoma preferred partner (LPP) polymorphisms are related to immune diseases, but the role of LPP gene in the pathogenesis of allergic rhinitis (AR) is unclear. The current study aimed to explore the contribution of LPP variants to AR susceptibility in the Chinese Han population. METHODS: A total of 992 healthy controls and 992 patients with AR were recruited. Agena MassARRAY system was applied for genotyping. Odds ratios (OR) and 95% confidence intervals (CI) adjusted by age, sex, and body mass index (BMI) were calculated to conduct the risk assessment of LPP variants in people with a predisposition to AR. Additionally, multifactor dimensionality reduction (MDR) was applied to identify high-order interaction models for AR risk. RESULTS: We found that rs2030519-G (p = 0.027, OR: 1.15, 95% CI: 1.02-1.31), rs6780858-G (p = 0.019, OR: 1.16, 95% CI: 1.03-1.32), and rs60946162-T (p = 0.014, OR: 1.18, 95% CI: 1.03-1.34) were associated with increased susceptibility to AR. Subgroup analyses indicated the interaction of LPP polymorphisms in terms of age, gender, and BMI with AR susceptibility (p < 0.05, OR > 1). MDR analysis revealed that rs60946162 had the information gain (0.40%) of individual attribute regarding AR. CONCLUSION: Our results first determined that rs2030519, rs6780858, and rs60946162 were correlated with increased susceptibility to AR in the Chinese Han population, which add to our understanding of the impact of LPP gene variants on AR development.

The role of immunoglobulin E and mast cells in hypertension.

AIMS: Hypertension is the major cause of cardiovascular diseases and global mortality. Immunoglobulin E (IgE), which plays crucial roles in allergic diseases, has been implicated in the pathogenesis of vascular and cardiac remodelling via its receptor (FcεR1). In this study, we aimed to reveal the role of IgE and FcεR1 in hypertension. METHODS AND RESULTS: Herein, we reported that IgE levels were significantly increased in hypertensive patients as well as in hypertensive mice induced by angiotensin II (Ang II). Ang II-induced vascular remodelling and hypertension were significantly alleviated in FcεR1 genetic knockout mice or in mice treated with anti-IgE monoclonal antibody. Similarly, treatment with omalizumab (a clinical IgE antagonist) also markedly inhibited Ang II-induced hypertension. Furthermore, the cellular contribution of IgE-FcεR1 in hypertension was evaluated in mice with FcεR1 conditional knockout in mast cell (MC), smooth muscle cell (SMC), or endothelial cell (EC). Our data revealed that IgE-mediated hypertension is largely dependent on FcεR1 in MCs but not SMCs and ECs. Finally, RNA-seq and signalling pathway analyses of mouse bone marrow-derived MCs suggested that interleukin 6 (IL-6) is one of critical mediators in IgE-mediated hypertension. IL-6 derived from IgE-stimulated MCs promoted reactive oxygen species production and decreased the levels of phosphorylated endothelial nitric oxide synthase in ECs, leading to endothelial dysfunction. CONCLUSION: Our findings reveal that IgE contributes to the pathogenesis of hypertension, at least partially through activating the IgE-FcεR1 signalling in MCs. Thus, IgE may represent a new therapeutic target for IgE-mediated hypertension.

CLEC16A variants conferred a decreased risk to allergic rhinitis in the Chinese population.

Background: Allergic rhinitis (AR) is a chronic respiratory disease. Hereditary factors played a key role in the pathogenesis of the AR. This study investigated the association between CLEC16A variants and AR risk in the Chinese population. Methods: We applied Agena MassARRAY technology platform to genotype five single nucleotide polymorphisms (SNPs) located in CLEC16A in 1004 controls and 995 cases. The association between CLEC16A SNPs (rs2286973, rs887864, rs12935657, rs11645657 and rs36045143) and AR risk were calculated by logistic regression analysis, with odds ratio (OR) and 95% confidence interval (CI). False-positive report probability (FPRP) was also used to assess the significant results to reduce false positives. Multifactor dimensionality reduction (MDR) was completed to assess the interaction between CLEC16A variants to predict AR risk. Results: Totally, CLEC16A (rs887864, rs12935657, rs2286973, rs11645657 and rs36045143) were significantly associated with AR risk. Therein, rs2286973, rs11645657 and rs36045143 were related to a decreased risk of AR in the people ≤ 43 years old, females and the people with BMI≤24, respectively. And rs887864 and rs12935657 were also associated with a decreased susceptibility of AR in the people >43 years old. Meanwhile, in the results of region stratification, rs887864 conferred a reduced risk to AR in the people from loess hilly area. Conclusion: CLEC16A variants conferred a decreased risk to AR in the Chinese population.

Sensitization Profiles of Timothy Grass Pollen in Northern China.

PURPOSE: Grass pollen is an important cause of IgE-mediated allergy in countries worldwide, especially within Europe. However, there has been no research on grass pollen allergy in northern China. We aimed to determine the status of grass pollen allergy and the sensitization patterns to Phleum pratense (P. pratense) in northern China. PATIENTS AND METHODS: Pollen data were collected for three geographic areas (Beijing, Shenmu, Shizuishan) in northern China. The study enrolled 101 patients (62 men; age range, 1-64 years; median age, 10 years) who had allergic rhinoconjunctivitis and/or asthma during the grass pollen season and positive skin prick test results positive to P. pratense. Serum-specific IgE (sIgE) against Phl p 1, Phl p 2, Phl p 5, Phl p 6, Phl p 7, Phl p 12 was measured by ImmunoCAP. RESULTS: The pollen season of P. pratense was from June to September in Beijing, May to September in Shenmu and July to August in Shizuishan. P. pratense pollen accounted for 2-3% of the annual pollen index of total pollen counts. Among 101 patients with positive skin prick test results to P. pratense, 72% had detectable sIgE to P. pratense. Phl p 12 was the most frequently recognized component (45%), followed by Phl p 1 (22%), Phl p 5 (14%), Phl p 6 (8%) and Phl p 7 (3%). No patients had sIgE to Phl p 2. Ten sensitization patterns to the six components were observed. High rate of sIgE to Phl p 12 was positively correlated with co-sensitization to weed or tree pollen. CONCLUSION: Considering the pollen concentration, P. pratense was a minor pollen allergen in northern China and its pollen season overlapped with that of weed pollen. IgE sensitization to P. pratense was likely to be induced by cross-reactivity between grass pollen allergy and weed/tree pollen allergy.

Analysis of Prevalence and Risk Factors of Adult Self-Reported Allergic Rhinitis and Asthma in Plain Lands and Hilly Areas of Shenmu City, China.

Objective: The main aim of this study was to investigate the prevalence and risk factors of adult self-reported allergic rhinitis and asthma in plain lands and hilly areas of Shenmu City in China, and analyze the differences between regions. Methods: The multi-stage stratified random sampling was applied in a cross-sectional survey of adult residents in Shenmu City, from September to December 2019. The unconditional logistic regression analysis was used to screen the influence factors of allergic rhinitis and asthma. Results: 4,706 adults participated in the survey, and 99% (4,655 in 4,706) completed the questionnaires. The prevalence of allergic rhinitis was 25.4%, and the prevalence of asthma was 9.4%. The prevalence of the allergic rhinitis without asthma, asthma without allergic rhinitis, and the combined allergic rhinitis with asthma were 18.9, 2.9, and 6.5%, respectively. The prevalence of allergic rhinitis and asthma existed regional differences. The prevalence of adult self-reported allergic rhinitis was 41.5% in plain lands areas and 22.1% in hilly areas. The prevalence of adult self-reported asthma was 12.8% in plain lands and 8.8% in hilly areas. The prevalence of allergic rhinitis and asthma existed seasonal differences, with the highest prevalence from July to September. The analysis of risk factors showed that higher education [middle and high school (OR 1.72, 95%CI 1.42-2.07); college and above (OR 2.67, 95%CI 1.99-3.59)], comorbidities of other allergic diseases (OR 3.90, 95%CI 3.23-4.70), family history of allergies (OR 2.89, 95%CI 2.36-3.53), and plain lands areas (OR 2.51, 95%CI 2.06-3.05) were the risk factors for the allergic rhinitis without asthma. Aging [40-49 years old (OR 4.29, 95%CI 1.02-18.13); 50-59 years old (OR 5.89, 95%CI 1.40-24.76); ≥60 years old: (OR 6.14, 95%CI 1.41-26.71)], never-smokers (OR 1.66, 95%CI 0.99-2.80), comorbidities of other allergic disorders (OR 2.17, 95%CI 1.42-3.32), and family history of allergies (OR 2.20, 95%CI 1.40-3.47) were the risk factors for the asthma without allergic rhinitis. Advanced age [30-39 years (OR 2.16, 95%CI 1.23-3.82); 40-49 years (OR 2.86, 95%CI 1.56 to 5.25); 50-59 years (OR 2.95, 95%CI 1.58-5.51); ≥60 years old (OR 2.27, 95%CI 1.09-4.72)], higher education [middle and high school (OR 2.23, 95%CI 1.62-3.07); college and above (OR 4.28, 95%CI 2.72-6.74)], non-agricultural workers (OR 1.70, 95%CI 1.18-2.43),never-smokers (OR 2.26, 95%CI 1.51-3.39), comorbidities of other allergic diseases (OR 4.45, 95%CI 3.37-5.88), family history of allergies (OR 5.27, 95%CI 3.98-6.97), and plain lands areas (OR 2.07, 95%CI 1.51-2.86) were the risk factors for the combined allergic rhinitis with asthma. Conclusions: The prevalence of allergic rhinitis and asthma in Shenmu City was relatively high, with regional differences. Genetic and environmental factors were the important risk factors associated with allergic rhinitis and asthma. Our research would provide data support for preventing and controlling allergic rhinitis and asthma in this region in the future, and appropriate prevention and control programs should be formulated according to the characteristics of different regions.