The neutrophil-to-lymphocyte ratio is associated with all-cause and cardiovascular mortality among individuals with hypertension.

BACKGROUND: Identifying reliable prognostic markers is crucial for the effective management of hypertension. The neutrophil-to-lymphocyte ratio (NLR) has emerged as a potential inflammatory marker linked to cardiovascular outcomes. This study aims to investigate the association of NLR with all-cause and cardiovascular mortality among patients with hypertension. METHODS: This study analyzed data from 3067 hypertensive adults in the National Health and Nutritional Examination Surveys (NHANES) from 2009 to 2014. Mortality details were obtained from the National Death Index (NDI). Restricted cubic spline (RCS) was deployed to visualize the association of the NLR with mortality risk. Weighted Cox proportional hazards models were employed to assess the independent association of NLR with mortality risk. Time-dependent receiver operating characteristic curve (ROC) analysis was conducted to access the predictive ability of NLR for survival. Mediation analysis was used to explore the indirect impact of NLR on mortality mediated through eGFR. RESULTS: Over a median 92.0-months follow-up, 538 deaths occurred, including 114 cardiovascular deaths. RCS analysis revealed a positive association between NLR and both all-cause and cardiovascular mortality. Participants were stratified into higher (> 3.5) and lower (≤ 3.5) NLR groups. Weighted Cox proportional hazards models demonstrated that individuals with higher NLR had a significantly increased risk of all-cause (HR 1.96, 95% confidence interval (CI) 1.52-2.52, p < 0.0001) and cardiovascular mortality (HR 2.33, 95% CI 1.54-3.51, p < 0.0001). Stratified and interaction analysis confirmed the stability of the core results. Notably, eGFR partially mediated the association between NLR and both all-cause and cardiovascular mortality by a 5.4% and 4.7% proportion, respectively. Additionally, the areas under the curve (AUC) of the 3-, 5- and 10- year survival was 0.68, 0.65 and 0.64 for all-cause mortality and 0.68, 0.70 and 0.69 for cardiovascular mortality, respectively. CONCLUSION: Elevated NLR independently confers an increased risk for both all-cause and cardiovascular mortality in individuals with hypertension.

Modeling denitrification nitrogen losses in China's rice fields based on multiscale field-experiment constraints.

Denitrification plays a critical role in soil nitrogen (N) cycling, affecting N availability in agroecosystems. However, the challenges in direct measurement of denitrification products (NO, N2 O, and N2 ) hinder our understanding of denitrification N losses patterns across the spatial scale. To address this gap, we constructed a data-model fusion method to map the county-scale denitrification N losses from China's rice fields over the past decade. The estimated denitrification N losses as a percentage of N application from 2009 to 2018 were 11.8 ± 4.0% for single rice, 12.4 ± 3.7% for early rice, and 11.6 ± 3.1% for late rice. The model results showed that the spatial heterogeneity of denitrification N losses is primarily driven by edaphic and climatic factors rather than by management practices. In particular, diffusion and production rates emerged as key contributors to the variation of denitrification N losses. These findings humanize a 38.9 ± 4.8 kg N ha-1 N loss by denitrification and challenge the common hypothesis that substrate availability drives the pattern of N losses by denitrification in rice fields.

Comparison of New Glucose-Lowering Drugs on the Risk of Pancreatitis in Type 2 Diabetes: A Network Meta-Analysis.

OBJECTIVE: To explore whether new glucose-lowering drugs increase the risk of pancreatitis in individuals with type 2 diabetes. This present network meta-analysis aimed to investigate the risk of pancreatitis associated with the use of glucagon-like peptide-1 (GLP-1) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors in the treatment of type 2 diabetes mellitus. METHODS: PubMed, Web of Science, Embase, and the Cochrane Library were searched. The literature was published from the date of their inception to July 21, 2021, including placebo-controlled or head-to-head trials of 2 new glucose-lowering drugs. The relative ratio (RR) and 95% confidence interval (CI) were used to assess the risk of GLP-1 agonists and DPP-4 inhibitors for pancreatitis or pancreatic cancer among patients with type 2 diabetes. RESULTS: Seventeen studies were identified, covered 102 257 participants. The pooled results showed a neutral relationship between GLP-1 agonists and pancreatitis (overall RR, 0.96; 95% CI, 0.31-3.00) or pancreatic cancer (overall RR, 1.10; 95% CI, 0.31-4.10) compared with placebo. Meanwhile, DPP-4 inhibitors were not associated with the increased risk of pancreatitis (overall RR, 1.60; 95% CI, 0.25-11.00) or pancreatic cancer (overall RR, 0.79; 95% CI, 0.26-2.40). Among them, lixisenatide and saxagliptin may be the safest drugs compared with other drugs according to the ranking of probability. Sensitivity and subgroup analysis confirmed the stability of the core results. CONCLUSION: The most obvious finding of this study is that GLP-1 agonists and DPP-4 inhibitors are safe with respect to the risk of pancreatitis and pancreatic cancer compared with placebo. This conclusion may provide useful evidence for correlated clinical researches.

[Evidence mapping of clinical research on traditional Chinese medicine in treatment of diabetic foot].

The present study comprehensively summarized the clinical randomized controlled trials(RCTs) and systematic reviews/Meta-analyses of traditional Chinese medicine(TCM) in the treatment of diabetic foot by evidence mapping and clarified the distribution of evidence in this field.CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Web of Science were searched for clinical RCTs and systematic reviews on TCM in the treatment of diabetic foot published in the past ten years.The evidence was analyzed and displayed in the form of text combined with figures and tables.AMSTAR was used for the quality evaluation of systematic reviews.A total of 1 037 clinical RCTs and 20 systematic reviews/Meta-analyses were included.The overall publishing trend was stable, and the scale of RCTs was small.TCM interventions for diabetic foot mainly included external application and foot bath.Much attention was paid to the outcome indicators including total effective rate, ankle brachial index(ABI), and TCM syndromes, while less attention to neuropathy scores, emotional psychology, and long-term prognosis.The overall quality of systematic reviews was low, and the majority of studies indicated that TCM had potential efficacy in treating diabetic foot, and there was still a lack of clear clinical evidence of efficacy.TCM has both advantages and problems in the treatment of diabetic foot.At present, there is still a lack of high-quality research, suggesting that more large-sample, multi-center RCTs should be launched in the future, and the quality of related systematic reviews/Meta-analyses should be improved to fully explore and give full play to the advantages of TCM in the treatment of diabetic foot, and promote the development of the clinical and evidence-based medicine of TCM in the treatment of diabetic foot.

Health risks to local residents from the exposure of heavy metals around the largest copper smelter in China.

Non-ferrous smelting releases lots of heavy metals to the environment. Although numerous studies have focused on pollution in the environment, fewer have studied the adverse health effects. In the current study, samples of food, hair and urine were collected and analyzed for zinc (Zn), iron (Fe), chromium (Cr), nickel (Ni), lead (Pb) and copper (Cu) from residents of 3 villages near the largest copper smelter in China. The estimated daily intake (EDI), target hazard quotient (THQ), and Hazard Index (HI) were used to estimate and analyze the health risks to local residents (children, adults, and seniors). The Zn, Cr, Ni, Fe, Pb and Cu concentrations in food ranged from 16.02 to 61.48 mg kg-1, 0.23-13.64 mg kg-1, 0.10-5.90 mg kg-1, 19.16-170.05 mg kg-1, 0.15-3.62 mg kg-1, and 0.53-2.74 mg kg-1, respectively. Zn, Cr, Ni and Pb concentrations in all vegetables were above the national tolerance limits. Children had higher EDIs of heavy metals than that of adults and seniors. The THQ of single elements and the HI of combined elements indicated that the EDI of Pb and Cu showed the highest potential health risks, followed by the EDI of Zn and Fe, and Ni, Cr. High EDI of heavy metals resulted in much higher concentrations of heavy metals in hair and urine samples than those of normal Chinese residents, showing that residents around the smelter have potential health risks through daily food intake. The main sources of these heavy metals were from the consumption of rice and vegetables and it is imperative that measures should be taken to control this urgent problem.

A non-targeting magnetic metal-organic framework probe for highly specific peptide-mediated precise disease monitoring.

Alzheimer's disease (AD) is a universal neurodegenerative disease in older adults with incurable and progressive properties, urging for precise monitoring to perform timely treatment to delay its progression. Herein, we introduced a non-targeting magnetic metal-organic framework probe coupled with high-throughput mass spectrometry, creating a rapid screening strategy for highly specific peptides associated with AD. Notably, an elution-free extraction process was proposed, significantly reducing sample preprocessing time while simultaneously ensuring the efficient detection of captured peptides. Using this elution-free extraction process, high-quality peptide profiles were rapidly extracted from the hundreds of samples from both diseased and healthy individuals. By integrating machine learning algorithms, LC-MS/MS, and Uniprot database searching, we identified three specific serum endogenous peptides (m/z = 4215.41, 2884.77 and 2704.61) closely associated with AD. Remarkably, with the use of any single specific peptide, the AUC (Area Under the Curve) values can reach approximately 0.9 during monitoring AD. Moreover, integrating three specific biomarkers provides a robust basis for machine learning algorithms to build monitoring models, with AUC value up to 1.000. This work represents a substantial advancement in the development of peptide-specific precise monitoring approaches for complex diseases, serving as a catalyst for increased dedication to the molecular detection field.

Different microbial functional traits drive bulk and rhizosphere soil phosphorus mobilization in an alpine meadow after nitrogen input.

Enhanced nitrogen (N) input is expected to influence the soil phosphorus (P) cycling through biotic and abiotic factors. Among these factors, soil microorganisms play a vital role in regulating soil P availability. However, the divergent contribution of functional microorganisms to soil P availability in the rhizosphere and bulk soil under N addition remains unclear. We conducted an N addition experiment with four N input rates (0, 5, 10, and 15 g N m-2 year-1) in an alpine meadow over three years. Metagenomics was employed to investigate the functional microbial traits in the rhizosphere and bulk soil. We showed that N addition had positive effects on microbial functional traits related to P-cycling in the bulk and rhizosphere soil. Specifically, high N addition significantly increased the abundance of most microbial genes in the bulk soil but only enhanced the abundance of five genes in the rhizosphere soil. The soil compartment, rather than the N addition treatment, was the dominant factor explaining the changes in the diversity and network of functional microorganisms. Furthermore, the abundance of functional microbial genes had a profound effect on soil available P, particularly in bulk soil P availability driven by the ppa and ppx genes, as well as rhizosphere soil P availability driven by the ugpE gene. Our results highlight that N addition stimulates the microbial potential for soil P mobilization in alpine meadows. Distinct microbial genes play vital roles in soil P availability in bulk and rhizosphere soil respectively. This indicates the necessity for models to further our knowledge of P mobilization processes from the bulk soil to the rhizosphere soil, allowing for more precise predictions of the effects of N enrichment on soil P cycling.

Efficacy of Electronic Cigarettes vs Varenicline and Nicotine Chewing Gum as an Aid to Stop Smoking: A Randomized Clinical Trial.

Importance: Electronic cigarettes (ECs) are often used by smokers as an aid to stopping smoking, but evidence is limited regarding their efficacy compared with nicotine replacement therapy (NRT), and no evidence is available on how their efficacy compares with that of varenicline. Objective: To evaluate whether ECs are superior to NRT and noninferior to varenicline in helping smokers quit. Design, Setting, and Participants: This was a randomized clinical trial conducted at 7 sites in China and including participants who were smoking at least 10 cigarettes per day and motivated to quit, not using stop-smoking medications or EC, and willing to use any of the study products. Participants were first recruited in May 2021, and data analysis was conducted in December 2022. Interventions: A cartridge-based EC (30 mg/mL nicotine salt for 2 weeks and 50 mg/mL after that), varenicline (0.5 mg, once a day for 3 days; 0.5 mg, twice a day for 4 days; and 1 mg, twice a day, after that), and 2 mg (for smokers of ≤20 cigarettes per day) or 4 mg (>20 cigarettes per day) nicotine chewing gum, all provided for 12 weeks and accompanied by minimal behavioral support (an invitation to join a self-help internet forum). Main Outcomes and Measures: The primary outcome was sustained abstinence from smoking at 6 months as validated by an expired-air carbon monoxide reading (<8 parts per million). Participants lost to follow-up were included as nonabstainers. Results: Of 1068 participants, 357 (33.5%) were female, and the mean (SD) age was 33.9 (3.1) years. A total of 409 (38.3%), 409 (38.3%), and 250 (23.4%) participants were randomized to the EC, varenicline, and NRT arms, respectively. The 6-month biochemically validated abstinence rates were 15.7% (n = 64), 14.2% (n = 58), and 8.8% (n = 22) in the EC, varenicline, and NRT study arms, respectively. The quit rate in the EC arm was noninferior to the varenicline arm (absolute risk reduction, 1.47%; 95% CI, -1.41% to 4.34%) and higher than in the NRT arm (odds ratio, 1.92; 95% CI, 1.15-3.21). Treatment adherence was similar in all study arms during the initial 3 months, but 257 participants (62.8%) in the EC arm were still using ECs at 6 months, with no further use in the 2 other study arms. The most common adverse reactions were throat irritation (32 [7.8%]) and mouth irritation (28 [6.9%]) in the EC arm, nausea (36 [8.8%]) in the varenicline arm, and throat irritation (20 [8.0%]) and mouth irritation (22 [8.8%]) in the NRT arm. No serious adverse events were recorded. Conclusions and Relevance: The results of this randomized clinical trial found that when all treatments were provided with minimal behavior support, the efficacy of EC was noninferior to varenicline and superior to nicotine chewing gum. Trial Registration: Chinese Clinical Trial Registry: ChiCTR2100048156.

Pharmacokinetics, safety, and efficacy of Fuqi Guben Gao in the treatment of kidney-yang deficiency syndrome: a randomized, double-blind phase I trial.

Introduction: Fuqi Guben Gao (FQGBG) is a botanical drug formulation composed of FuZi (FZ; Aconitum carmichaelii Debeaux [Ranunculaceae; Aconiti radix cocta]), Wolfberry (Lycium barbarum L. [Solanaceae; Lycii fructus]), and Cinnamon (Neolitsea cassia (L.) Kosterm. [Lauraceae; Cinnamomi cortex]). It has been used to clinically treat nocturia caused by kidney-yang deficiency syndrome (KYDS) for over 30 years and warms kidney yang. However, the pharmacological mechanism and the safety of FQGBG in humans require further exploration and evaluation. Methods: We investigated the efficacy of FQGBG in reducing urination and improving immune organ damage in two kinds of KYDS model rats (hydrocortisone-induced model and natural aging model), and evaluated the safety of different oral FQGBG doses through pharmacokinetic (PK) parameters, metabonomics, and occurrence of adverse reactions in healthy Chinese participants in a randomized, double-blind, placebo-controlled, single ascending dose clinical trial. Forty-two participants were allocated to six cohorts with FQGBG doses of 12.5, 25, 50, 75, 100, and 125 g. The PKs of FQGBG in plasma were determined using a fully validated LC-MS/MS method. Results: FQGBG significantly and rapidly improved the symptoms of increased urination in both two KYDS model rats and significantly resisted the adrenal atrophy in hydrocortisone-induced KYDS model rats. No apparent increase in adverse events was observed with dose escalation. Major adverse drug reactions included toothache, thirst, heat sensation, gum pain, diarrhea, abdominal distension, T-wave changes, and elevated creatinine levels. The PK results showed a higher exposure level of benzoylhypaconine (BHA) than benzoylmesaconine (BMA) and a shorter half-life of BMA than BHA. Toxic diester alkaloids, aconitine, mesaconitine, and hypaconitine were below the lower quantitative limit. Drug-induced metabolite markers primarily included lysophosphatidylcholines, fatty acids, phenylalanine, and arginine metabolites; no safety-related metabolite changes were observed. Conclusion: Under the investigated dosing regimen, FQGBG was safe. The efficacy mechanism of FQGBG in treating nocturia caused by KYDS may be related to the improvement of the hypothalamus-pituitary-adrenal axis function and increased energy metabolism. Clinical Trial Registration: https://www.chictr.org.cn/showproj.html?proj=26934, identifier ChiCTR1800015840.

Zwitterionic mesoporous engineering aids peptide-dependent pattern profiling for identification of different liver diseases.

Liver disease remains a global health challenge, with its incidence steadily increasing worldwide. Herein, zwitterionic mesoporous engineering was developed for the identification of different liver diseases including liver cirrhosis and liver cancer. Based on this engineering, a total of 2633 m/z signals were observed to be enriched. Notably, three key peptides were identified and showed high accuracy and precision for distinguishing the healthy and disease states, propelling the field of nanomedicine toward genuine personalized medicine.

The driving effects of nitrogen deposition on nitrous oxide and associated gene abundances at two water table levels in an alpine peatland.

Alpine peatlands are recognized as a weak or negligible source of nitrous oxide (N2O). Anthropogenic activities and climate change resulted in the altered water table (WT) levels and increased nitrogen (N) deposition, which could potentially transition this habitat into a N2O emission hotspot. However, the underlying mechanism related with the effects is still uncertain. Hence, we conducted a mesocosm experiment to address the response of growing-season N2O emissions and the gene abundances of nitrification (bacterial amoA) and denitrification (narG, nirS, norB and nosZ) to the increased N deposition (20 kg N ha-1 yr-1) at two WT levels (WT-30, 30 cm below soil surface; WT10, 10 cm above soil surface) in the Zoige alpine peatland, Qinghai-Tibetan Plateau. The results showed that the WT did not affect N2O emissions, and this was attributed with the limitation of soil NO3-. The higher WT level increased denitrification (narG and nirS gene abundance) resulting in the depletion of soil NO3-, but the consequent NO3- deficiency further limited denitrification, while the WT did not affect nitrification (bacterial amoA gene abundance). Meanwhile, the N deposition increased N2O emissions, regardless of WT levels. This was associated with the N-deposition induced increase in denitrification-related gene abundances of narG, nirS, norB and nosZ at WT-30 and narG at WT10. Additionally, the N2O emission factor assigned to N deposition was 1.3 % at WT-30 and 0.9 % at WT10, respectively. Our study provided comprehensive understanding of the mechanisms referring N2O emissions in response to the interactions between climate change and human disturbance from this high-altitude peatland.

Network pharmacology and LC-MS approachs to explore the active compounds and mechanisms of Yuanjiang decoction for treating bradyarrhythmia.

BACKGROUND: Yuanjiang decoction (YJD), a traditional Chinese medicinal prescription, has been found to have a significant heart rate-increasing effect and is effective in the treatment of symptomatic bradyarrhythmia in previous studies. However, its specific components and potential mechanisms remain unclear. METHODS: In this study, we detected and identified the main compounds of YJD using liquid chromatography-mass spectrometry (LC-MS). Through the approach of network pharmacology, we predicted the core targets of the active components, bradyarrhythmia targets, and obtained potential anti-bradyarrhythmia targets of YJD. We further performed protein to protein interaction (PPI), gene ontology (GO) enrichment analyses and kyoto encyclopedia of genes and genomes (KEGG) signaling pathway analyses for core targets, and constructed network of key active ingredients-core targets of YJD. Finally, molecular docking and molecular dynamics simulation were performed for key active ingredients and core targets. RESULTS: The YJD contains a total of 35 main chemical components. The key active ingredients-core targets network contains 36 nodes and 90 edges, including 20 key active ingredients and 16 core targets. The core targets in the PPI network were TP53, TNF, HRAS, PPARG, IL1B, KCNH2, SCN5A, IDH1, LMNA, ACHE, F2, DRD2, CALM1, KCNQ1, TNNI3, IDH2 and TNNT2. KEGG pathway analysis showed that YJD treatment of bradyarrhythmia mainly involves neuroactive ligand-receptor interaction, adrenergic signaling in cardiomyocytes, cAMP signaling pathway, calcium signaling pathway, cholinergic synaptic and serotonergic synapse signaling pathway. The biological processes mainly include regulation of hormone levels, regulation of cardiac contraction, chemical synaptic transmission, circadian rhythm, positive regulation of heart rate, smooth muscle contraction, response to metal ion, oxidation-reduction process, neurotransmitter transport and import across plasma membrane. Molecular docking and molecular dynamics simulation results showed that hesperidin and tetrahydropalmatine had higher affinity with DRD2 and KCNQ1, respectively. CONCLUSION: This study reveals the pharmacodynamic material basis of YJD and its potential multicomponent-multitarget-multipathway pharmacological effects, predicted its potential anti-bradyarrhythmia mechanism may be related to the regulation of myocardial autonomic nervous function and related ion channels. Our work demonstrates that YJD has great potential for treating bradyarrhythmias as a complementary medicine, and the results can provide a theoretical basis for the development and clinical application of YJD.

Colorimetric detection of RNA fragments based on associated toehold-mediated reaction and gold nanoparticles.

Herein we report a reverse transcription-free, label-free and enzyme-free colorimetric method for RNA nucleic acid fragments detection. The method can conveniently determine the presence of dual gene targets and distinguish single nucleotide polymorphism by visual observation.

Mycorrhizal Inoculation Enhances Nutrient Absorption and Induces Insect-Resistant Defense of Elymus nutans.

The majority of terrestrial plants can form symbiotic associations on their roots with arbuscular mycorrhizal fungi (AMF) in the soil to stimulate the growth and nutrient uptake of the host plant and to improve plant resistance to insects and disease. However, the use of AMF for insect control on gramineous forages requires further study. Here, we evaluated the effects of AMF (Funneliformis mosseae) inoculation on the defense against Locusta migratoria attack in Elymus nutans. Inoculation assays showed that mycorrhizal plants had a higher resistance than non-inoculated plants, as evidenced by plants having more plant biomass, a higher nitrogen and phosphorus content, and greater lipoxygenase (LOX) activity. The results of insect damage showed that in addition to a decrease in the enzyme phenylalanine-ammonia-lyase, the activities of other plant defense-related enzymes (including polyphenol oxidase and ß-1,3-glucanase) were increased. A key enzyme, LOX, belonging to the jasmonic acid (JA) signaling pathway was notably increased in mycorrhizal treatment. Volatile organic compounds (VOCs) were identified using gas chromatography mass spectrometry and the results showed that several metabolites with insect-resistant properties, including D-Limonene, p-Xylene, 1,3-Diethylbenzene were detected in mycorrhizal plants. These findings suggest that mycorrhizal inoculation has potential applications in insect management on forage grasses and demonstrates that the JA signaling pathway is essential for insect resistance in Elymus nutans.

Cooperation between arbuscular mycorrhizal fungi and plant growth-promoting bacteria and their effects on plant growth and soil quality.

The roles of arbuscular mycorrhizal fungi (AMF) and plant growth-promoting rhizobacteria (PGPR) in improving nutrition uptake and soil quality have been well documented. However, few studies have explored their effects on root morphology and soil properties. In this study, we inoculated Elymus nutans Griseb with AMF and/or PGPR in order to explore their effects on plant growth, soil physicochemical properties, and soil enzyme activities. The results showed that AMF and/or PGPR inoculation significantly enhanced aboveground and belowground vegetation biomass. Both single and dual inoculations were beneficial for plant root length, surface area, root branches, stem diameter, height, and the ratio of shoot to root, but decreased root volume and root average diameter. Soil total nitrogen, alkaline phosphatase, and urease activities showed significant growth, and soil electrical conductivity and pH significantly declined under the inoculation treatments. Specific root length showed a negative correlation with belowground biomass, but a positive correlation with root length and root branches. These results indicated that AMF and PGPR had synergetic effects on root morphology, soil nutrient availability, and plant growth.

Analysis of prescription medication rules of traditional Chinese medicine for bradyarrhythmia treatment based on data mining.

BACKGROUND: Multiple studies have revealed that Traditional Chinese Medicine (TCM) prescriptions can provide protective effect on the cardiovascular system, increase the heart rate and relieve the symptoms of patients with bradyarrhythmia. In China, the TCM treatment of bradyarrhythmia is very common, which is also an effective complementary therapy. In order to further understand the application of Chinese medicines in bradyarrhythmia, we analyzed the medication rules of TCM prescriptions for bradyarrhythmia by data mining methods based on previous clinical studies. METHODS: We searched studies reporting the clinical effect of TCM on bradyarrhythmia in the PubMed and Chinese databases China National Knowledge Infrastructure database, and estimated publication bias by risk of bias tools ROB 2. Descriptive analysis, hierarchical clustering analysis and association rule analysis based on Apriori algorithm were carried out by Microsoft Excel, SPSS Modeler, SPSS Statistics and Rstidio, respectively. Association rules, co-occurrence and clustering among Chinese medicines were found. RESULTS: A total of 48 studies were included in our study. Among the total 99 kinds of Chinese medicines, 22 high-frequency herbs were included. Four new prescriptions were obtained by hierarchical cluster analysis. 81 association rules were found based on association rule analysis, and a core prescription was intuitively based on the grouping matrix of the top 15 association rules (based on confidence level), of which Guizhi, Zhigancao, Wuweizi, Chuanxiong, Danshen, Danggui, Huangqi, Maidong, Dangshen, Rougui were the most strongly correlated herbs and in the core position. CONCLUSION: In this study, data mining strategy was applied to explore the TCM prescription for the treatment of bradyarrhythmia, and high-frequency herbs and core prescription were found. The core prescription was in line with the treatment ideas of TCM for bradyarrhythmia, which could intervene the disease from different aspects and adjust the patient's Qi, blood, Yin and Yang, so as to achieve the purpose of treatment.

The characteristics and patterns of e-cigarette use and its association with cigarette cessation intention in a Chinese smoking population: A mediation analysis.

INTRODUCTION: The use of e-cigarettes has become more common in China, but the research on e-cigarettes in China, while growing, is still limited. This study examined the characteristics and patterns of e-cigarette use, and analyzed the possible mediators between cigarette cessation intention and e-cigarette use in a Chinese smoking population. METHODS: This was a cross-sectional study conducted in mainland China. By convenience sampling method, the participants were recruited from 85 major commercial streets of several large cities in China. The study interviewers completed face-to-face interviews and uploaded the completed questionnaires into the online survey platform. The participants were contacted for clarification if any problems were detected. Logistic regression yielded adjusted odds ratios (ORs) for ever use of e-cigarettes. We further conducted a mediation analysis to estimate the effect of possible mediators. RESULTS: From July to August 2020, a total of 738 smokers were invited to participate in this study; 613 smokers were identified as eligible and 609 smokers were included in this analysis. Of them, 24 (3.94%) participants were currently using e-cigarettes, and 165 (27.09%) participants have ever used e-cigarettes. The participants with younger age were more likely to have ever used e-cigarettes, ranging from 37.5% in the 18-29 years age group to 6.5% in the 60-69 years age group. After controlling for demographic characteristics and nicotine dependence, the ever use of e-cigarettes was significantly associated with younger age, higher education level, higher monthly income, previous smoking cessation attempts and quitting intention. With the mediation analysis, the education level is confirmed as a mediating factor, and approximately 42.86% of the effects were mediated through the channel of higher socioeconomic status. CONCLUSIONS: This is the first study to examine the possible mediators between cigarette cessation intention and e-cigarette use in a Chinese smoking population. The findings revealed that high socioeconomic status, particularly higher education level, was a major mediating factor.

Asynchronous responses of microbial CAZymes genes and the net CO2 exchange in alpine peatland following 5 years of continuous extreme drought events.

Peatlands act as an important sink of carbon dioxide (CO2). Yet, they are highly sensitive to climate change, especially to extreme drought. The changes in the net ecosystem CO2 exchange (NEE) under extreme drought events, and the driving function of microbial enzymatic genes involved in soil organic matter (SOM) decomposition, are still unclear. Herein we investigated the effects of extreme drought events in different periods of plant growth season at Zoige peatland on NEE and microbial enzymatic genes of SOM decomposition after 5 years. The results showed that the NEE of peatland decreased significantly by 48% and 26% on average (n = 12, P < 0.05) under the early and midterm extreme drought, respectively. The microbial enzymatic genes abundance of SOM decomposition showed the same decreasing trend under early and midterm extreme drought, but an increasing trend under late extreme drought. The microbial community that contributes to these degradation genes mainly derives from Proteobacteria and Actinobacteria. NEE was mainly affected by soil hydrothermal factors and gross primary productivity but weakly correlated with SOM enzymatic decomposition genes. Soil microbial respiration showed a positive correlation with microbial enzymatic genes involved in the decomposition of labile carbon (n = 18, P < 0.05). This study provided new insights into the responses of the microbial decomposition potential of SOM and ecosystem CO2 sink function to extreme drought events in the alpine peatland.

Effects of tobacco smoking on cardiovascular disease in patients with systemic lupus erythematosus: A systematic review and meta-analysis.

Background: Patients with systemic lupus erythematosus (SLE) are at increased risk of cardiovascular disease (CVD) compared to the general population. However, little is known about the effects of tobacco smoking on CVD in patients with SLE. Objective: To systematically review and summarize the available literature regarding the effects of tobacco smoking on developing CVD in patients with SLE. Methods: We retrieved relevant studies from the following databases: PubMed, EMBASE, Web of Science and China National Knowledge Internet (CNKI) database. Two reviewers independently reviewed the eligible studies, assessed their validity, and extracted relevant data. Sensitivity and subgroup analyses were performed to distinguish sources of heterogeneity. Results: A total of 10 studies, which comprised 6984 participants, were included in the analysis. The overall quality of evidence was rated as moderate to low. The smoking prevalence among CVD patients was 39.28% (271/690), which was higher than 31.36% (1974/6294) among non-CVD patients. Compared with never-smokers, the risk of developing CVD in current smokers was 1.42 (95% CI: 1.21-1.66). No significant publication bias was found in our meta-analysis. Conclusions: In spite of the several negative results, this study found that current smokers with SLE have an increased risk of developing CVD, although most of the included studies were in low-to-moderate quality. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42022338109.

The clinical population pharmacokinetics, metabolomics and therapeutic analysis of alkaloids from Alstonia scholaris leaves in acute bronchitis patients.

BACKGROUND: Capsule of alkaloids from leaf of Alstonia scholaris (CALAS) is a new investigational botanical drug (No. 2011L01436) for respiratory disease. Clinical population pharmacokinetics (PK), metabolomics and therapeutic data are essential to guide dosing in patients. Previous research has demonstrated the potential therapeutic effect of CALAS on acute bronchitis. Further clinical trial data are needed to verify its clinical efficacy, pharmacokinetics behavior, and influence of dosage and other factors. PURPOSE: To verify the clinical efficacy and explore the potential biomarkers related to CALAS treatment for acute bronchitis. MATERIALS AND METHODS: Oral CALAS was assessed in a randomized, double-blind, placebo-controlled trial. Fifty-five eligible patients were randomly assigned to four cohorts to receive 20, 40 or 80 mg, of CALAS three times daily for seven days, or placebo. Each CALAS cohort included 15 subjects, and the placebo group included 10 subjects. A population PK model of CALAS was developed using plasma with four major alkaloid components. Metabolomics analysis was performed to identify biomarkers correlated with the therapeutic effect of CALAS, and efficacy and safety were assessed based on clinical symptoms and adverse events. RESULTS: The symptoms of acute bronchitis were alleviated by CALAS treatment without serious adverse events or clinically significant changes in vital signs, electrocardiography or upper abdominal Doppler ultrasonography. Moreover, one compartment model with first-order absorption showed that an increase in aspartate transaminase will reduce the clearance (CL) of scholaricine, and picrinine CL was inversely proportional to body mass index, while 19-epischolaricine and vallesamine CL increased with aging. The serum samples from acute bronchitis patients at different time points were analyzed using UPLC-QTOF in combination with the orthogonal projection to latent structures-discriminant analysis, which indicated higher levels of lysophosphatidylcholines, lysophosphatidylethanolamines and amino acids with CALAS treatment than with placebo. CONCLUSION: This is the first study to evaluate the clinical efficacy and explored the potential biomarkers related to CALAS therapeutic mechanism of acute bronchitis by means of clinical trial combined the metabolomics study. This exploratory study provides a basis for further research on clinical efficacy and optimal dosing regimens based on pharmacokinetics behavior. Additional acute bronchitis patients and CALAS PK samples collected in future studies may be used to improve model performance and maximize its clinical value.