Associations between chronic obstructive pulmonary disease and ten common cancers: novel insights from Mendelian randomization analyses.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a significant global health issue, suspected to elevate the risk for various cancers. This study sought to discern whether COPD serves as a risk marker or a causative factor for prevalent cancers. METHODS: We employed univariable MR (UVMR) analyses to investigate the causal relationship between COPD and the top ten common cancers. Sensitivity analyses were performed to validate the main findings. Multivariable MR (MVMR) and two-step MR analyses were also conducted. False-discovery-rate (FDR) was used to correct multiple testing bias. RESULTS: The UVMR analysis demonstrated notable associations between COPD and lung cancer (odds ratio [OR] = 1.42, 95%CI 1.15-1.77, FDR = 6.37 × 10-3). This relationship extends to lung cancer subtypes such as squamous cell carcinoma (LUSC), adenocarcinoma (LUAD), and small cell lung cancer (SCLC). A tentative link was also identified between COPD and bladder cancer (OR = 1.53, 95%CI 1.03-2.28, FDR = 0.125). No significant associations were found between COPD and other types of cancer. The MVMR analysis that adjusted for smoking, alcohol drinking, and body mass index did not identify any significant causal relationships between COPD and either lung or bladder cancer. However, the two-step MR analysis indicates that COPD mediated 19.2% (95% CI 12.7-26.1%), 36.1% (24.9-33.2%), 35.9% (25.7-34.9%), and 35.5% (26.2-34.8%) of the association between smoking and overall lung cancer, as well as LUAD, LUSC, and SCLC, respectively. CONCLUSIONS: COPD appears to act more as a risk marker than a direct cause of prevalent cancers. Importantly, it partially mediates the connection between smoking and lung cancer, underscoring its role in lung cancer prevention strategies.

Synergistic Photoenzymatic Catalysis Enables Synthesis of a-Tertiary Amino Acids Using Threonine Aldolases.

a-Tertiary amino acids are essential components of drugs and agrochemicals, yet traditional syntheses are step-intensive and provide access to a limited range of structures with varying levels of enantioselectivity. Here, we report the α-alkylation of unprotected alanine and glycine by pyridinium salts using pyridoxal (PLP)-dependent threonine aldolases with a Rose Bengal photoredox catalyst. The strategy efficiently prepares various a-tertiary amino acids in a single chemical step as a single enantiomer. UV-vis spectroscopy studies reveal a ternary interaction between the pyridinium salt, protein, and photocatalyst, which we hypothesize is responsible for localizing radical formation to the active site. This method highlights the opportunity for combining photoredox catalysts with enzymes to reveal new catalytic functions for known enzymes.

Photoredox Catalyzed Radical Fluoroalkylation with Non-Classical Fluorinated Reagents.

The emergence of photocatalysis has greatly advanced radical fluoroalkylation reactions. Central to this advancement is the introduction and refinement of radical reagents, which play a pivotal role in driving these reactions forward. Intriguingly, some of these reagents, previously not recognized for their radical properties, have emerged as key players in this area. In this Perspective, we provide an overview of four representative reagents pioneered by our laboratory, which have subsequently garnered extensive application in broader research contexts, including difluorocarbene precursors bromodifluoromethylphosphonium bromide, electrophilic sulfonylation reagent triflic anhydride, and nucleophilic trifluoromethylation reagent methyl fluorosulfonyldifluoroacetate (Chen's reagent). The integration of phosphonium reagents, triflic anhydride, and methyl fluorosulfonyldifluoroacetate into photocatalysis has enabled some unexpected reactivities and now notably expanded the capabilities in radical difluoromethylation, trifluoromethylation, and difluoroalkylation. Our discussion highlights how these atypical reagents have enriched the toolkit available for radical fluoroalkylations, offering insights that could inspire future research and application in this area.

Inflammation and comorbidities of chronic obstructive pulmonary disease: The cytokines put on a mask!

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a well-known complex multicomponent disease characterized by systemic inflammation that frequently coexists with other conditions. We investigated the relationship between some inflammatory markers and complications in COPD patients to explore the possible roles of inflammation in these comorbidities. METHODS: This study used cross-sectional and case-control methods. We included 336 hospitalized COPD patients, 64 healthy controls, and 42 major depression patients and evaluated all participants using the Hamilton Rating Scale. C-reactive protein (CRP), red blood cell distribution width (RDW), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), monocyte/lymphocyte ratio (MLR), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) were collected and measured in the study population. Statistical methods were used to analyze the association of inflammatory markers with COPD comorbidities. RESULTS: Cor pulmonale and psychological comorbidities (depression and anxiety) were more common in this study on COPD patients. We found that MLR (OR = 2.054, 95 % CI 1.129-3.735, p = 0.018) and RDW (OR = 1.367, 95 % CI 1.178-1.586, p = 0.000) were related to COPD patients complicated with cor pulmonale, while IL-6 (OR = 1.026, 95 % CI 1.001-1.053, p = 0.045) and RDW (OR = 1.280, 95 % CI 1.055-1.552, p = 0.012) were related to depression symptoms. CONCLUSION: MLR, RDW and IL-6 were closely related to cor pulmonale and depression in COPD patients. IL-1 ß and IL-6 are closely related to depression in humans.

Asymmetric Carbohydroxylation of Alkenes Using Photoenzymatic Catalysis.

Alkene difunctionalizations enable the synthesis of structurally elaborated products from simple and ubiquitous starting materials in a single chemical step. Carbohydroxylations of olefins represent a family of reactivity that furnish structurally complex alcohols. While examples of this type of three-component coupling have been reported, catalytic asymmetric examples remain elusive. Here, we report an enzyme-catalyzed asymmetric carbohydroxylation of alkenes catalyzed by flavin-dependent "ene"-reductases to produce enantioenriched tertiary alcohols. Seven rounds of protein engineering reshape the enzyme's active site to increase activity and enantioselectivity. Mechanistic studies suggest that C-O bond formation occurs via a 5-endo-trig cyclization with the pendant ketone to afford an α-oxy radical which is oxidized and hydrolyzed to form the product. This work demonstrates photoenzymatic reactions involving "ene"-reductases can terminate radicals via mechanisms other than hydrogen atom transfer, expanding their utility in chemical synthesis.

Research trends on vonoprazan-based therapy for Helicobacter pylori eradication: A bibliometric analysis from 2015 to 2023.

BACKGROUND: Vonoprazan is an emerging option for the treatment of Helicobacter pylori infection. We aimed to assess the research trends and hotspots of vonoprazan-based therapy for H. pylori eradication through bibliometric analysis. MATERIALS AND METHODS: Vonoprazan-based studies for eradicating H. pylori published from 2015 to 2023 were extracted from the Web of Science using a combination of the search terms "H. pylori" and "vonoprazan." Each study was weighted according to the number of included patients. RESULTS: A total of 65 studies were included. Japan was the most productive and cooperative country, accounting for 69.2% of publications. Vonoprazan in combination with amoxicillin and clarithromycin (41.8%) was most used for eradicating H. pylori, followed by vonoprazan in combination with amoxicillin (20.4%) and vonoprazan in combination with amoxicillin and metronidazole (19.4%). The eradication rates for first-line vonoprazan-based therapies by intention to treat were: dual therapy (82.9%, 95% CI: 77.7%-88.0%), triple (83.3%, 95% CI: 79.7%-86.8%) and quadruple therapy (91.5%, 95% CI: 85.5%-97.4%), and per protocol: dual therapy (86.1%, 95% CI: 81.5%-90.7%), triple (89.3%, 95% CI: 87.9%-90.6%) and quadruple therapy (94.0%, 95% CI: 88.6%-99.4%). Vonoprazan was superior to proton pump inhibitors in triple therapy regarding empirical therapy (RR = 1.18, 95% CI, 1.14-1.22, p < 0.01) and clarithromycin-resistant group (RR = 1.71, 95% CI, 1.33-2.20, p < 0.01), but there is no significant difference between triple therapy and dual therapy (RR = 1.02, 95% CI, 0.98-1.07, p = 0.33). CONCLUSIONS: Vonoprazan has been widely used for H. pylori eradication. Further studies are needed to optimize the best duration and dosage of vonoprazan-based regimens in different regions.

Research trends on artificial intelligence and endoscopy in digestive diseases: A bibliometric analysis from 1990 to 2022.

BACKGROUND: Recently, artificial intelligence (AI) has been widely used in gastrointestinal endoscopy examinations. AIM: To comprehensively evaluate the application of AI-assisted endoscopy in detecting different digestive diseases using bibliometric analysis. METHODS: Relevant publications from the Web of Science published from 1990 to 2022 were extracted using a combination of the search terms "AI" and "endoscopy". The following information was recorded from the included publications: Title, author, institution, country, endoscopy type, disease type, performance of AI, publication, citation, journal and H-index. RESULTS: A total of 446 studies were included. The number of articles reached its peak in 2021, and the annual citation numbers increased after 2006. China, the United States and Japan were dominant countries in this field, accounting for 28.7%, 16.8%, and 15.7% of publications, respectively. The Tada Tomohiro Institute of Gastroenterology and Proctology was the most influential institution. "Cancer" and "polyps" were the hotspots in this field. Colorectal polyps were the most concerning and researched disease, followed by gastric cancer and gastrointestinal bleeding. Conventional endoscopy was the most common type of examination. The accuracy of AI in detecting Barrett's esophagus, colorectal polyps and gastric cancer from 2018 to 2022 is 87.6%, 93.7% and 88.3%, respectively. The detection rates of adenoma and gastrointestinal bleeding from 2018 to 2022 are 31.3% and 96.2%, respectively. CONCLUSION: AI could improve the detection rate of digestive tract diseases and a convolutional neural network-based diagnosis program for endoscopic images shows promising results.

Photobiocatalytic Strategies for Organic Synthesis.

Biocatalysis has revolutionized chemical synthesis, providing sustainable methods for preparing various organic molecules. In enzyme-mediated organic synthesis, most reactions involve molecules operating from their ground states. Over the past 25 years, there has been an increased interest in enzymatic processes that utilize electronically excited states accessed through photoexcitation. These photobiocatalytic processes involve a diverse array of reaction mechanisms that are complementary to one another. This comprehensive review will describe the state-of-the-art strategies in photobiocatalysis for organic synthesis until December 2022. Apart from reviewing the relevant literature, a central goal of this review is to delineate the mechanistic differences between the general strategies employed in the field. We will organize this review based on the relationship between the photochemical step and the enzymatic transformations. The review will include mechanistic studies, substrate scopes, and protein optimization strategies. By clearly defining mechanistically-distinct strategies in photobiocatalytic chemistry, we hope to illuminate future synthetic opportunities in the area.

The Role of CD40, CD86, and Glutathione S-Transferase Omega 1 in the Pathogenesis of Chronic Obstructive Pulmonary Disease.

Objective: The aim of the study was to explore the relevance of CD40, CD86, and GSTO1 with the pathogenesis of COPD. Methods: Patients with acute exacerbation of COPD were contrasted with the healthy and nonsmoking ones and smoking but without COPD ones. The changes of CD40, CD86, and GSTO1 in the peripheral blood, collected from different groups, were detected by flow cytometry and western blotting, respectively. Results: Compared with the nonsmoking group and smoking but without the COPD group, the expression of CD40 and CD86 of the patients with COPD increased significantly, but the expression of GSTO1 decreased. CD40 and CD86 were negatively correlated with FEV1%, while GSTO1 was positively correlated with FEV1% and negatively correlated with CD40 and CD86. Conclusion: CD40, CD86, and GSTO1 may play a role in the pathogenesis of COPD, and they are related to the severity of COPD and the degree of changes in the lung function.

Analysis of oral microbiota alterations induced by Helicobacter pylori infection and vonoprazan-amoxicillin dual therapy for Helicobacter pylori eradication.

BACKGROUND: The oral cavity is considered a potential reservoir of Helicobacter pylori (H. pylori), and the imbalance of oral microbiota directly reflects the health of the host. We aimed to explore the relationship among oral microbiota, H. pylori infection, and vonoprazan-amoxicillin (VA) dual therapy for H. pylori eradication. METHODS: Helicobacter pylori-positive patients were randomized into low- or high-dose VA dual therapy (i.e., amoxicillin 1 g b.i.d. or t.i.d. and vonoprazan 20 mg b.i.d) for 7 or 10 days. H. pylori-negative patients served as normal controls. Saliva samples were collected from 41 H. pylori-positive patients and 13 H. pylori-negative patients. The oral microbiota was analyzed by 16S rRNA gene sequencing, followed by bioinformatics analysis. RESULTS: Helicobacter pylori-positive patients had higher richness and diversity and better evenness of oral microbiota than normal controls. Beta diversity analysis estimated by Bray-Curtis or weighted UniFrac showed distinct clustering between H. pylori-positive patients and normal controls. The number of bacterial interactions was reduced in H. pylori-positive patients compared with that in negative patients. Forty-one patients evaluated before and after successful H. pylori eradication were divided into low (L-VA) and high dose (H-VA) amoxicillin dose groups. The alpha and beta diversity of the oral microbiota between L-VA and H-VA patients exhibited no differences at the three time points (before eradication, after eradication, and at confirmation of H. pylori infection cure). CONCLUSION: Helicobacter pylori infection could alter the diversity, composition, and bacterial interactions of the oral microbiota. Both L-VA and H-VA dual therapy showed minimal influence on the oral microbiota.

Altered Gut Microbiota and Short-Chain Fatty Acids After Vonoprazan-Amoxicillin Dual Therapy for Helicobacter pylori Eradication.

The combination of vonoprazan (VPZ) and amoxicillin (VA therapy) has been shown to achieve acceptable eradication rates for Helicobacter pylori (H. pylori). Herein, our aim was to explore the short-term effect of VA therapy on the gut microbiota and short-chain fatty acids (SCFAs) using human fecal samples. A total of 119 H. pylori-positive patients were randomized into low- or high-dose VA therapy (i.e., amoxicillin 1 g b.i.d. or t.i.d. and VPZ 20 mg b.i.d.) for 7 or 10 days. Thirteen H. pylori-negative patients served as controls. Fecal samples were collected from H. pylori-positive and H. pylori-negative patients. The gut microbiota and SCFAs were analyzed using 16S rRNA gene sequencing and gas chromatography-mass spectrometry, respectively. The gut microbiota in H. pylori-positive patients exhibited increased richness, diversity, and better evenness than matched patients. Fifty-three patients studied before and after H. pylori eradication were divided into low (L-VA) and high (H-VA) amoxicillin dose groups. The diversity and composition of the gut microbiota among L-VA patients exhibited no differences at the three time points. However, among H-VA patients, diversity was decreased, and the microbial composition was altered immediately after H-VA eradication but was restored by the confirmation time point. The decreased abundance of Anaerostipes, Dialister, and Lachnospira induced by H-VA was associated with altered SCFA levels. VA dual therapy for H. pylori eradication has minimal negative effects on gut microbiota and SCFAs.

Study on Tourism Consumer Behavior Characteristics Based on Big Data Analysis.

In terms of scenic marketing, big data research also plays an important role in the precise marketing of scenic spots. This paper has focused on the big data related to scenic spots as the research object, explores the relationship between various subdivision big data and the number of tourists in scenic spots, and investigates the difference and influence of the consumption behavior of the secondary consumption items in the scenic area, to find the potential of the scenic area's business growth and to promote the continuous and stable growth of the scenic area's sales and tourism economy. Using the relevant theories and analysis methods, such as consumer behavior, big data, and tourism consumer behavior, the content mainly focuses on the establishment of the analysis model of the number of tourists in the scenic spot, the data collection, the estimation of the model parameters, the various types of big data, the calculation of the contribution rate of the data to the number of tourists in the scenic spot, and the difference analysis of the secondary consumption items of different types of tourists in the scenic spot. Results show that a multi-objective analysis model is established based on the relevant econometric theories, and an optimization plan is proposed after the multicollinearity diagnosis of the model; to establish a data envelopment analysis (DEA) model of the difference and influence of different types of tourists' consumption behavior in scenic spots and study the consumption behavior characteristics of different types of tourists when they purchase secondary consumption items in scenic spots; the econometric model is used to analyze the big data, adjust the linear relationship of some variables, then adopt the method of gradually adding variables combined with the consumer theory, and finally determine the number of daily tourists as the explained variable, the number of internet protocol (IP), Baidu index, and the virtual value of the weekend, dummy variables for variables, bounce rate, and air pollution as explanatory variables.

Optimization of vonoprazan-amoxicillin dual therapy for eradicating Helicobacter pyloriinfection in China: A prospective, randomized clinical pilot study.

BACKGROUND: Vonoprazan-amoxicillin (VA) dual therapy has been shown to achieve acceptable cure rates for treatment of Helicobacter pylori(H. pylori) in Japan. Its effectiveness in other regions is unknown. We aimed to explore the efficacy of VA dual therapy as first-line treatment for H. pyloriinfection in China. METHODS: This was a single center, prospective, randomized clinical pilot study conducted in China. Treatment naive H. pyloriinfected patients were randomized to receive either low- or high-dose amoxicillin-vonoprazan consisting of amoxicillin 1 g either b.i.d. or t.i.d plus VPZ 20 mg b.i.d for 7 or 10 days. 13 C-urea breath tests were used to access the cure rate at least 4 weeks after treatment. RESULTS: Three hundred and twenty-three patients were assessed, and 119 subjects were randomized. The eradication rates of b.i.d. amoxicillin for 7 and 10 days, t.i.d. amoxicillin for 7 and 10 days were 66.7% (16/24), 89.2% (33/37), 81.0% (17/21), and 81.1% (30/37) (p = .191) by intention-to-treat analysis, respectively, and 72.7% (16/22), 89.2% (33/37), 81.0% (17/21), and 81.1% (30/37) (p = .454) by per-protocol analysis, respectively. CONCLUSION: Neither 7- or 10-day VA dual therapy with b.i.d. or t.i.d. amoxicillin provides satisfied efficacy as the first-line treatment for H. pyloriinfection in China. Further optimization is needed.

Fourteen-day vonoprazan and low- or high-dose amoxicillin dual therapy for eradicating Helicobacter pylori infection: A prospective, open-labeled, randomized non-inferiority clinical study.

Background and aim: We previously reported that vonoprazan-amoxicillin (VA) dual therapy for 7 or 10 days is not satisfactorily efficacious for Helicobacter pylori (H. pylori) eradication. We aimed to explore the efficacy of VA dual therapy for 14 days as a first-line treatment for H. pylori infection. Methods: This was a single center, prospective, open-labeled, randomized non-inferiority clinical study conducted in China. Treatment naïve H. pylori infected patients were randomized into two groups: 20 mg vonoprazan (VPZ) b.i.d. in combination with low-dose (1000 mg b.i.d.) or high-dose (1000 mg t.i.d) amoxicillin for 14 days. 13C-urea breath tests were used to access the cure rate at least 4 weeks after treatment. Results: A total of 154 patients were assessed and 110 subjects were randomized. The eradication rate of VPZ with b.i.d. amoxicillin or t.i.d. amoxicillin for 14 days was 89.1% and 87.3% by intention-to-treat analysis, respectively, and 94.1% and 95.9% by per-protocol analysis, respectively. The eradication rate and incidence of adverse events were not different between the two groups. Conclusion: VPZ with b.i.d. or t.i.d. amoxicillin for 14 days provides satisfactory efficacy as a first-line treatment for H. pylori infection in China.

Electrochemical Trifluoromethoxylation of (Hetero)aromatics with a Trifluoromethyl Source and Oxygen.

Trifluoromethoxylated aromatics (ArOCF3 ) are valuable structural motifs in the area of drug discovery due to the enhancement of their desired physicochemical properties upon the introduction of the trifluoromethoxy group (CF3 O). Although significant progress has been made recently in the introduction of CF3 O group into aromatics, current methods either require the use of expensive trifluoromethoxylation reagents or require harsh reaction conditions. We present a conceptually new and operationally simple protocol for the direct C-H trifluoromethoxylation of (hetero)aromatics by the combination of the readily available trifluoromethylating reagent and oxygen under electrochemical reaction conditions. This reaction proceeds through the initial generation of CF3 radical followed by conversion to CF3 O radical, addition to (hetero)aromatics and rearomatization. The utility of this electrochemical trifluoromethoxylation is illustrated by the direct incorporation of CF3 O group into a variety of (hetero)aromatics as well as bio-relevant molecules.

Performance of COPD population screener questionnaire in COPD screening: a validation study and meta-analysis.

This study aimed to validate the chronic obstructive pulmonary disease (COPD) Population Screener (COPD-PS) questionnaire as a screening tool in a cohort of Chinese subjects who underwent a health examination, and to summarise its overall performance through a meta-analysis. We enrolled 997 subjects aged ≥40 years who underwent a health examination, both lung function and COPD-PS data were collected. The screening performance of COPD-PS was evaluated with a receiver operating characteristic (ROC) curve analysis, using the area under the curve (AUC) to assess the screening accuracy. A standard diagnostic meta-analysis was used to summarise the screening performance of COPD-PS for COPD. Of the 997 subjects, 157 were identified as having COPD. The COPD-PS score was significantly higher in COPD patients than controls (5.03 ± 5.11 vs. 2.72 ± 1.80, p < .001). At a cut-off of 4, the sensitivity and specificity of COPD-PS for identifying COPD were 74.52 and 70.24%, respectively, with an AUC of 0.79. Eight studies (including this study) were included in this meta-analysis. The pooled estimates for COPD-PS were as follows: sensitivity of 0.66 (95% CI: 0.47-0.63), specificity of 0.86 (95% CI: 0.84-0.89), positive likelihood ratio of 3.00 (95% CI: 1.65-5.47), negative likelihood ratio of 0.43 (95% CI: 0.35-0.52) and diagnostic odds ratio of 7.24 (95% CI: 3.91-13.40). The AUC of the summary ROC curve was 0.78. COPD-PS appears to be a useful tool for screening individuals with a high risk of COPD and guiding the selection of individuals for subsequent spirometry examination.KEY MESSAGESCOPD-PS is a simple and useful method to screen COPD.The combination of COPD-PS with other tools may improve the screen performance.

Copper and Zinc Copromoted Bromo(chloro)trifluoromethylation of Alkenes and Alkynes with Trifluoromethanesulfonic Anhydride.

The first copper and zinc copromoted trifluoromethylation using trifluoromethanesulfonic anhydride (Tf2O) as a trifluoromethylating reagent has been developed. The reaction of alkenes or alkynes with Tf2O in the presence of CuX2 (X = Br, Cl), Zn powder, and 2,2'-bipyridine affords bromo(chloro)trifluoromethylated products in good yields. CuX2 plays a dual role as the catalyst and halide source, whereas 2,2'-bipyridine acts as both the activation reagent and ligand.

Serum Levels of Gamma-Glutamyltransferase During Stable and Acute Exacerbations of Chronic Obstructive Pulmonary Disease.

BACKGROUND One of the most important factors in the pathogenesis of COPD (chronic obstructive pulmonary disease) is oxidative stress. GGT (gamma-glutamyltransferase) has been regarded as a novel marker of oxidative stress over the last few years. This study aimed to compare the serum levels of GGT during stable and acute exacerbations of COPD at a single center. MATERIAL AND METHODS The research included 117 patients with AECOPD (acute exacerbation of chronic obstructive pulmonary disease), 107 patients with stable COPD, and 112 control subjects. Serum GGT, spirometry function, and other clinical parameters (anthropometric and biochemical measurements) were evaluated and compared among the subjects. RESULTS Serum GGT was elevated in patients with stable COPD in comparison to the control subjects. Its level was inversely related to lung function. It was also significantly higher in AECOPD patients compared to stable COPD patients. We also found that a GGT level of 21.2 IU/L displays a reliable diagnostic prediction of COPD and that a GGT level of 26.5 IU/L can be applied to predict the exacerbation of COPD. CONCLUSIONS Our research demonstrates that serum GGT level is inversely associated with pulmonary function and may serve as a biomarker during the progression of COPD. The monitoring of GGT values can be applied to evaluating COPD and its exacerbation risk.