The prevalence, diagnostic accuracy and genotype-phenotype correlation of GNAS mutations in fibrous dysplasia: a meta-analysis.

Background: There is inconsistent evidence regarding the accuracy of GNAS mutations identification for the diagnosis of FD/MAS. This study was performed to estimate the prevalence and diagnostic accuracy of GNAS mutations detection and to preliminarily investigate the genotype-phenotype correlation in FD patients. Methods: Five electronic databases were searched from 1995 to 2024 using search terms related to GNAS and fibrous dysplasia. Observational studies of FD patients undergoing GNAS mutation detection in FD were included. Results: A total of 878 FD patients were included. The pooled prevalence of GNAS mutations in FD based on the random effects model was 74% (95% CI = 64%-83%). Regarding diagnostic accuracy, a sensitivity of 0.83 (95% CI, 0.65-0.96), specificity of 0.99 (95% CI, 0.98-1.00) and the area under the receiver operating characteristic curve of 98.38% were found. Additionally, meta-analysis and Fisher's test showed the GNAS mutation types were significantly associated with FD types (OR = 3.51, 95% CI = 1.05 to 11.72; p < 0.05). Conclusion: A high detection rate of GNAS mutations occurred in FD, and its detection is reliable for diagnosing FD. Additionally, GNAS mutation type was types were significantly associated with FD type. Systematic Review Registration: Identifier CRD42024553469.

Association between angiotensin-converting enzyme inhibitor-induced cough and the risk of lung cancer: a Mendelian randomization study.

Background: Observational studies and meta-analyses have demonstrated a positive correlation between the use of angiotensin-converting enzyme inhibitors (ACEIs) and lung cancer. However, the findings remain controversial; furthermore, the relationship between ACEI-induced cough and lung cancer development remains unknown. We used Mendelian randomization (MR) to verify the association between ACEI use, ACEI-induced cough, and the risk of lung cancer. Methods: We performed a two-sample MR analysis to determine the unconfounded relationships between ACE inhibition, which mimics the effects of ACEIs, and genetic proxies for ACEI-induced cough and lung cancer. Single nucleotide polymorphisms that imitate ACE receptors and ACEI-induced cough were collected and integrated into a meta-analysis of existing genome-wide association studies for various lung cancers. The relationship was quantified using inverse variance weighting, weighted median, and MR-Egger methods. Results: A statistically significant association was observed between ACE inhibition and the risk of small cell lung cancer for Europeans (excluding rs118121655/rs80311894). Associations were identified between ACEI-induced cough and the risk of lung cancer for Europeans, although not for Asians, and between ACEI-induced cough and lung adenocarcinoma (excluding rs360206). Conclusion: Our findings reveal a relationship between ACE inhibition and lung cancer development, as well as a significant association between ACEI-induced cough and a higher risk of lung cancer for Europeans. Patients with hypertension who experience dry cough as a side effect of ACEI use should consider switching to an alternative antihypertensive treatment.

Siderophore-mediated iron partition promotes dynamical coexistence between cooperators and cheaters.

Microbes shape their habitats by consuming resources and producing a diverse array of chemicals that can serve as public goods. Despite the risk of exploitation by cheaters, genes encoding sharable molecules like siderophores are widely found in nature, prompting investigations into the mechanisms that allow producers to resist invasion by cheaters. In this work, we presented the chemostat-typed "resource partition model" to demonstrate that dividing the iron resource between private and public siderophores can promote stable or dynamic coexistence between producers and cheaters in a well-mixed environment. Moreover, our analysis shows that when microbes not only consume but also produce resources, chemical innovation leads to stability criteria that differ from those of classical consumer resource models, resulting in more complex dynamics. Our work sheds light on the role of chemical innovations in microbial communities and the potential for resource partition to facilitate dynamical coexistence between cooperative and cheating organisms.

Association between angiotensin-converting enzyme inhibitors and the risk of lung cancer: a systematic review and meta-analysis.

BACKGROUND: The association between the use of angiotensin-converting enzyme inhibitors (ACEIs) and lung cancer risk remains controversial. This study evaluated the association between the use of ACEIs and lung cancer risk. METHODS: Records from five databases were searched from inception to 26 January 2022. Clinical studies involving persons aged ≥18 years with at least one year of follow-up and reporting adverse events, including lung cancer, were recorded with separate outcome reports supplied for the ACEIs and control groups. Data were extracted independently by three authors and pooled using a random-effects model. The primary outcome was lung cancer development. Odds ratios (ORs) with 95% confidence intervals (CIs) and lung cancer-related morbidity were calculated. RESULTS: Of 2400 records screened, 13,061,226 patients were included from seven cohort studies and four case-control studies. Pooled results showed that ACEIs use was linked to increased lung cancer risk (OR 1.19, 95% CI 1.05-1.36; P = 0.008), with high heterogeneity (I2 = 98%). CONCLUSIONS: ACEI usage is a greater risk factor for lung carcinogenesis than angiotensin receptor blocker use, especially in Asian patients. Further randomised controlled trials are needed to confirm the causal association between the use of ACEIs and lung cancer risk.

A zero-sum game or an interactive frame? Iron competition between bacteria and humans in infection war.

ABSTRACT: Iron is an essential trace element for both humans and bacteria. It plays a vital role in life, such as in redox reactions and electron transport. Strict regulatory mechanisms are necessary to maintain iron homeostasis because both excess and insufficient iron are harmful to life. Competition for iron is a war between humans and bacteria. To grow, reproduce, colonize, and successfully cause infection, pathogens have evolved various mechanisms for iron uptake from humans, principally Fe 3+ -siderophore and Fe 2+ -heme transport systems. Humans have many innate immune mechanisms that regulate the distribution of iron and inhibit bacterial iron uptake to help resist bacterial invasion and colonization. Meanwhile, researchers have invented detection test strips and coupled antibiotics with siderophores to create tools that take advantage of this battle for iron, to help eliminate pathogens. In this review, we summarize bacterial and human iron metabolism, competition for iron between humans and bacteria, siderophore sensors, antibiotics coupled with siderophores, and related phenomena. We also discuss how competition for iron can be used for diagnosis and treatment of infection in the future.

Nasal nitric oxide testing for allergic rhinitis patients: Systematic review and meta-analysis.

BACKGROUND: Nasal nitric oxide (nNO) levels in allergic rhinitis (AR), healthy people or nonallergic rhinitis (NAR) have shown contradicting results in previous studies. By meta-analysis, we reviewed studies that measured nNO in AR patients to assess nNO's ability to discriminate AR from healthy people or NAR. METHODS: We systematically searched PubMed, Cochrane, Embase, Ovid, Web of Science, Wanfang Data, CNKI until December 15, 2020. Differences were expressed as standardized mean differences (SMD) with 95% confidence interval (CI), by random-effects method. RESULTS: A total of 10 original studies with 561 AR patients, 327 healthy controls, 123 NAR patients were included in the narrative synthesis and 9 studies in the meta-analysis. nNO in AR was significantly increased compared with healthy controls (SMD: 0.989; 95% CI: 0.402, 1.576; p = .001) or NAR (SMD: 0.680; 95% CI: 0.101, 1.259; p = 0.021). However, subgroup analysis based on measuring process and patient characteristics showed that no significant differences were detected in nNO between AR patients with nasal polyps or sinusitis or marked ostial obstruction and healthy controls. CONCLUSIONS: nNO is a potential indicator for recognizing AR. Nasal polyps, sinusitis and marked ostial obstruction should be considered before nNO is applied to detect AR.

Small airway remodeling in diabetic and smoking chronic obstructive pulmonary disease patients.

Diabetes mellitus can reinforce the small airway dysfunction of chronic obstructive pulmonary disease (COPD) patients. The epithelial-mesenchymal transition (EMT) that is associated with small airway remodeling is activated in the airway epithelial cells (AECs) of both COPD patients and diabetic patients. Transforming growth factor ß (TGF-ß) can induce EMT via the TGF-ß/Smad pathway. We found that the small airway dysfunction and airflow limitations were worse in COPD patients with a history of smoking or diabetes than in simple COPD patients, and were even worse in COPD patients with both histories. Pulmonary ventilation tests in rats confirmed these findings. EMT and the TGF-ß/Smad pathway were activated in the AECs of rats with COPD or diabetes, and the combination of COPD and diabetes amplified those effects, as indicated by downregulation of Zo1 and upregulation of vimentin, TGF-ß and Smad4 in immunohistochemical experiments. Twenty-four-hour treatment with 25 mM glucose and/or 1% cigarette smoke extract upregulated vimentin, TGF-ß, Smad2/3/4 and p-Smad2/3, but downregulated Zo1 in AECs. Suppressing the TGF-ß/Smad pathway prevented EMT activation and small airway remodeling following cigarette smoke exposure and hyperglycemia. Thus, cigarette smoke and high glucose exposure induces EMT via the TGF-ß/Smad pathway in AECs.

Insulin in high concentration recede cigarette smoke extract induced cellular senescence of airway epithelial cell through autophagy pathway.

Recent clinical researches demonstrated "obesity paradox" in chronic obstructive pulmonary disease (COPD) patients. However, why obesity is beneficial to COPD development remains unclear. Obesity is distinguished by hyperinsulinemia, and cellular senescence of airway epithelial cells (AEC) is involved in COPD progression. In this study, we aim to investigate the roles of insulin in high concentration in AEC cellular senescence. Human bronchial epithelial cells (BEAS-2B) and small airway epithelial cells (HSAEpiC) were used for experiments and treated with insulin in indicated time period and concentration with or without 1% cigarette smoke extract (CSE) exposure, and autophagy activator (rapamycin) or inhibitor (chloroquine) after exposed to 1% CSE. The expression of senescence protein (p21), cell cycle related protein (cyclinE), and autophagy protein (LC3B, Beclin-1 and p62) were determined by western blot. Cellular senescence was detected by Senescence-ß-Galactosidase staining. Autophagy level was detected by GFP-LC3B fluorescent light. Results showed that insulin receded cellular senescence in different time and concentration, as indicated by decreased expression of p21, increased expression of cyclinE and down-regulated ratio of SA-ß-Gal stained cells in BEAS-2B and HSAEpiC under physiological or CSE exposure condition. 5 µg/ml insulin treated for 48 h up-regulated the ratio of LC3B II/I, Beclin-1 and number of spot dots of GFP-LC3B, and down-regulated the level of p62 in AEC cells after 1% CSE exposure, while 1% CSE showed an opposite effect. Activating autophagy receded cellular senescence, and vice versa. Meanwhile, the effect of 5 µg/ml insulin on receding cellular senescence could be alleviated by autophagy inhibitor chloroquine or reinforced by autophagy activator rapamycin. In conclusion, insulin in high concentration could reduce the CSE induced cellular senescence of human airway epithelial cells through autophagy pathway.

Body mass index of patients with chronic obstructive pulmonary disease is associated with pulmonary function and exacerbations: a retrospective real world research.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is prevalent in China. The role of body mass index (BMI) in COPD progression and prognosis is unclear. We analyzed the association between BMI and pulmonary function, inflammation levels and exacerbation in Chinese COPD patients. METHODS: Our retrospective real world research included 744 patients with COPD diagnosed by spirometry and hospitalized from January 1st, 2014 to December 31st, 2016. The indicators were gathered from hospital records database and frequency of exacerbation in the three years were followed up. All 744 patients were divided into four groups by BMI grades. We analyzed the association between BMI and pulmonary function, inflammation levels and exacerbation by Spearman bivariate correlations, Kruskal-Wallis test, Mann-Whitney U test and logistic regression. RESULTS: The singly proportion (median of BMI) of these patients in underweight, normal weight, overweight and obesity was 7.80% (17.54), 45.97% (22.12), 27.96% (27.00) and 18.28% (31.25) respectively. With increasing of BMI grades, the values of forced expiratory volume in 1 second (FEV1), peak expiratory flow (PEF), forced expiratory flow (FEF25/50/75) and diffusing capacity of carbon monoxide (DLCO) were correspondingly increasing; the percentage of neutrophils and C-reactive protein (CRP) presented significant declining trend while the trend of the percentage of eosinophils was negative; the dose of systemic corticosteroid and length of stay present decreasing tendency; the frequency of exacerbation and hospitalization were decreasing. These were similar results in gender, smoking status COPD subgroups. CONCLUSIONS: In our study, BMI was moderately correlated with pulmonary function positively and exacerbations negatively. To some extent, BMI might be a useful indicator to predict the prognosis of COPD patients and for long-term management.