Causal effects of circulating vitamin levels on the risk of heart failure:a Mendelian randomization study

BACKGROUND Observational studies suggest inverse associations between serum vitamin levels and the risk of heart failure(HF). However, the causal effects of vitamins on HF have not been fully elucidated. Here, we conducted a Mendelian randomization(MR) study to investigate the causal associations between genetically determined vitamin levels and HF.METHODS Genetic instrumental variables for circulating vitamin levels, including vitamins A, B, C, D, and E, which were assessed as either absolute or metabolite levels were obtained from public genome-wide association studies. Summary statistics for single-nucleotide-polymorphisms and HF associations were retrieved from the HERMES Consortium(47,309 cases and 930,014controls) and FinnGen Study(30,098 cases and 229,612 controls). Two-sample MR analyses were implemented to assess the causality between vitamin levels and HF per outcome database, and the results were subsequently combined by meta-analysis.RESULTS Our MR study did not find significant associations between genetically determined circulating vitamin levels and HF risk. For absolute vitamin levels, the odds ratio for HF ranged from 0.97(95% confidence interval [CI]: 0.85–1.09, P = 0.41) for vitamin C to 1.05(95% CI: 0.61–1.82, P = 0.85) for vitamin A. For vitamin metabolites, the odds ratio ranged between 0.94(95% CI:0.75–1.19, P = 0.62) for α-tocopherol and 1.11(95% CI: 0.98–1.26, P = 0.09) for γ-tocopherol.CONCLUSION Evidence from our study does not support the causal effects of circulating vitamin levels on HF. Therefore,there may be no direct beneficial effects of vitamin intake on the prevention of primary HF.

Application of Quality Control Circle Activity in Improving Effectiveness of Drug Intervention in Lung Cancer Patients with Moderate to Severe Pain

Objective:Lung cancer has the highest incidence and mortality of all malignant tumors in China.Cancer pain dramatically affects patients’comfort level,causing insomnia,anorexia,anxiety,fear,depression,and a decline in the quality of life(QOL).The literature suggests a shortage of adequate cancer pain management for 59.1% of patients in China.The quality control circle(QCC)activity reflects the people-oriented core idea of management.This study aimed to assess the efficacy of QCC in enhancing the effectiveness of drug interventions in lung cancer patients with moderate to severe pain.Methods:From January 2019 to July 2019,lung cancer patients with moderate to severe pain were treated with drugs.The total number of drug interventions was 3072.A QCC activity was performed following the ten steps of the plan-do-check-act(PDCA)model.The reasons for the poor effectiveness of drug intervention in lung cancer patients with moderate to severe pain were analyzed.Countermeasures were designed to improve the effectiveness of drug intervention,including setting up a pain college,writing a medication education manual,and formulating operational rules for the administration of narcotic drugs.The effectiveness of drug intervention in lung cancer patients with moderate to severe pain and activity ability scores of QCC members were analyzed statistically before and after QCC activity.The effectiveness of drug intervention was investigated and compared before and after establishing the QCC.Results:After establishing the PDCA model,the effectiveness of drug intervention for moderate to severe pain in lung cancer patients increased from 56.28% to 85.29%.Members had significant improvement in problem-solving ability,responsibility,communication,coordination,self-confidence,team cohesion,enthusiasm,QCC skills,and harmony.Conclusion:QCC activity can significantly improve the efficiency of drug intervention in lung cancer patients with moderate to severe pain and their quality of life.

Recent advances in network pharmacology applications in Chinese herbal medicine

Network pharmacology is a new discipline based on the theory of systems biology and network analysis of biological systems to design the drugs.It comprehensively observes the intervention and influence of drugs on the disease network,and reveals the mystery of multi-molecular drugs synergistically acting on disease.These concepts reflect the ideas of multi-component,multi-target and system regulation,and have many similarities with the research ideas of traditional Chinese medicine,which focuses on syndrome differentiation and treatment,emphasizes the overall understanding of the etiology and pathogenesis.Network pharmacology can be used to predict and identify the target and active component of traditional herbal medicine,to clarify the mechanism of action,to scientifically explain the rules of the prescription,to explore the rules of real-world prescription,to discover new indications and new active compounds,and to study drug relocation,etc.The applications of network pharmacology in traditional herbal medicine were systematically summarized to demonstrate the significant value in these areas.

Phase I clinical trial of intracerebral injection of lentiviral-ABCD1 for the treatment of cerebral adrenoleukodystrophy

This was a single-arm,multicenter,open-label phase I trial.Lentiviral vectors(LV)carrying the ABCD1 gene(LV-ABCD1)was directly injected into the brain of patients with childhood cerebral adrenoleukodystrophy(CCALD),and multi-site injection was performed.The injection dose increased from 200 to 1600 lL(vector titer:1×10^(9) transduction units per mL(TU/mL)),and the average dose per kilogram body weight ranges from 8 to 63.6 lL/kg.The primary endpoint was safety,dose-exploration and immunogenicity and the secondary endpoint was initial evaluation of efficacy and the expression of ABCD1 protein.A total of 7 patients participated in this phase I study and were followed for 1 year.No injectionrelated serious adverse event or death occurred.Common adverse events associated with the injection were irritability(71%,5/7)and fever(37.2-38.5℃,57%,4/7).Adverse events were mild and selflimited,or resolved within 3 d of symptomatic treatment.The maximal tolerable dose is 1600 lL.In 5 cases(83.3%,5/6),no lentivirus associated antibodies were detected.The overall survival at 1-year was 100%.The ABCD1 protein expression was detected in neutrophils,monocytes and lymphocytes.This study suggests that the intracerebral injection of LV-ABCD1 for CCALD is safe and can achieve successful LV transduction in vivo;even the maximal dose did not increase the risk of adverse events.Furthermore,the direct LV-ABCD1 injection displayed low immunogenicity.In addition,the effectiveness of intracerebral LV-ABCD1 injection has been preliminarily demonstrated while further investigation is needed.This study has been registered in the Chinese Clinical Trial Registry(https://www.chictr.org.cn/,registration number:ChiCTR1900026649).

N-terminal pro-brain natriuretic peptide but not high-sensitivity C-reactive protein is related to severity of coronary artery stenosis in patients with acute coronary syndrome

Objective Biochemical indicators such as N-terminal pro-brain type natriuretic peptide（NT pro-BNP）and high-sensitivity Creactive protein（hsCRP）predict mortality in acute coronary syndrome（ACS）.However,little is known about the relationship of these factors with severity of coronary artery stenosis in patients with.Methods Three hundred and thirty-one subjects including 246 unstable angina pectoris patients and 85 myocardial infarction patients were recruited and classified into two groups：single-vessel disease group（1-vessel disease,n=93）and multiple-vessel disease group（≥2-vessels disease,n=238）according to selective coronary angiography.Plasma levels of NT pro-BNP and hsCRP were measured and severity of coronary stenosis was determined by Gensini score.Results NT pro-BNP but not hsCRP level was higher in patients with myocardial infarction than in patients with unstable angina pectoris.The patients with multiple-vessel disease had significantly higher NT pro-BNP level but not hsCRP compared with those with single-vessel disease.NT pro-BNP levels increased significantly as left ventricle（LV）function decreased,and only NT proBNP but not hsCRP level was related to Gensini score of severity of coronary stenosis in ACS.Conclusion NT proBNP but not hsCRP level is related to severity of coronary artery stenosis in patients in ACS.

Systematic evaluation and Meta-analysis of the efficacy of Xiaochaihu Decoction in the treatment of chronic superficial gastritis

Objective:To compare the effectiveness of Xiaochaihu Decoction(XCHD)or the modified XCHD combined with western medicine in the treatment of superficial gastritis.Methods:We collected the studies about XCHD or the modified XCHD combined with western medicine for superficial gastritis in China Biology Medicine(CBM)Database(2010-2018),China National Knowledge Infrastructure(CNKI)Database(2010-2018),VIP Database(2010-2018),Wanfang Database(2010-2018)and the Back Issues Database of Hebei University.The randomized controlled trials(RCTs)were included in this study.The literatures were independently extracted by two researchers and the Cochrane Review Handbook(version 5.1.0)was applied to assess the quality of included trials.Statistical analysis was performed with RevMan(version 5.3).Results:A total of 8 RCTs,including 732 cases,were included finally.Meta-analysis results showed that compared with the western medicine treatment group,XCHD or the modified XCHD combined with western medicine could improve the total effective rate[OR=4.67,95%CI(2.90,7.55),P<0.00001],physiological function[MD=10,95%CI(8.78,11.23),P<0.00001],role physical[MD=13.85,95%CI(11.19,16.51),P<0.00001],physical pain[MD=11.64,95%CI(9.05,14.23),P<0.00001],general health[MD=11.20,95%CI(9.52,12.88),P<0.00001],vitality[MD=13.46,95%CI(12.30,14.62),P<0.00001],social function[MD=19.20,95%CI(17.32,21.09),P<0.00001],affection function[MD=30.3,95%CI(28.99,31.62),P<0.00001],mental health[MD=9.80,95%CI(8.44,11.16),P<0.00001].Conclusion:XCHD or the modified XCHD combined with western medicine in the treatment of superficial gastritis has good performance in clinical efficacy and the improvement of quality of life.However,with several methodology problems existing in the included RCTs,the effectiveness of XCHD or the modified XCHD is still need more high-quality randomized,double-blind,placebo-controlled trials to further confirmed.

Circulating platelet miRNAs for coronary artery disease and acute myocardial infarction elderly patients

Background:Platelet activation is considered as the early stage of thrombus,which is important to thrombogenesis in acute myocardial infarction.Platelet miRNAs could be regarded as biomarkers of platelet activation.Here,the expression of platelet miRNA-200b and miRNA-223 were detected to predict platelet activation in acute myocardial infarction.Methods:Twenty elderly acute myocardial infarction patients(group A),20 elderly coronary artery disease patients(group B),and 20 healthy elder people(group C)were included in our research.The platelet miR-200b and miR223 were determined using fluorogenic quantitative polymerase chain reaction.Results:Platelet miR-200b and miR-223 were differentially expressed among the acute myocardial infarction patients,coronary artery disease patients and control groups.Acute myocardial infarction patients had the highest expression of platelet miR-200b and miR-223,while coronary artery disease patients had the lowest level(P<0.05).Conclusions:For the elderly,platelet miRNA regarded as the biomarker of platelet activation was an easy method to discover acute cardiovascular events.

Corrigendum to“Generation of Leydig-like cells:approaches,characterization,and challenges”

In the published article by Li et al.,1 an error occurred in the Acknowledgments.The funding agency should be“the Guangdong Basic and Applied Basic Research Foundation(No.2021A1515010947)”,not“the Natural Science Foundation of Guangdong Province(No.2021A1515010947)”.The authors sincerely apologize for the error.

Generation of Leydig-like cells:approaches,characterization,and challenges

Testosterone production by Leydig cells(LCs)plays a crucial role in male reproduction.The functional degeneration of LCs can cause testosterone deficiency,ultimately resulting in primary male hypogonadism.Transplantation of exogenous LCs with the ability to produce testosterone in response to the regulation of the hypothalamus-pituitary-gonad axis could be a promising alternative option to treat male primary hypogonadism.Recent studies have shown that it is possible to generate Leydig-like cells from stem cells by various approaches.In addition,somatic cells,such as embryonic or adult fibroblasts,have also been successfully reprogrammed into Leydig-like cells.In this review,we summarized the recent advances in the generation of Leydig-like cells,with an emphasis on comparing the effectiveness and safety of different protocols used and the cells generated.By further analyzing the characteristics of Leydig-like cells generated from fibroblasts based on small signaling molecules and regulatory factors,we found that although the cells may produce testosterone,they are significantly different from real LCs.For future in vivo applications,it is important that the steroidogenic cells generated be evaluated not only for their steroidogenic functions but also for their overall cell metabolic state by proteomics or transcriptomic tools.

自由基交替共聚法制备酰亚胺基微孔有机聚合物

通过Friedel-Crafts烷基化反应发生的超交联聚合会产生大量腐蚀性气体以及废弃的Lewis酸催化剂.为了实现微孔有机聚合物的绿色制备工艺,选用3类双马来酰亚胺单体与4种乙烯基醚单体进行自由基共聚,制备了12种新型酰亚胺基超交联微孔有机聚合物材料.通过反应单体之间形成电荷转移配合物,可以实现自由基交替共聚.得到的多孔聚合物具有可预测的分子结构和高比表面积(591 m^(2)/g),表现出优异的CO_(2)/N_(2)吸附选择性(74.38),在CO_(2)捕获和气体分离方面具有良好的应用前景.本研究拓展了自由基共聚超交联微孔聚合物构筑单元的选择范围,对微孔有机聚合物绿色制备具有参考价值.

Catalytic Atroposelective Catellani Reaction Enables Construction of Axially Chiral Biaryl Monophosphine Oxides

An unprecedented atroposelective Catellani reaction between phosphine oxide-containing aryl bromides,aryliodides,and nucleophiles for the construction of phosphine-containing biaryl atropisomers was established using an enantiopure norbornene derivative as the chiral mediator.A broad range of atropisomeric biaryl-based monophosphine oxides were obtained in good efficiency with excellent enantioselectivity.

Molecular Investigation of an Anthrax Epidemic in Guizhou Province, China

To the Editor： Anthrax is a zoonosis to which most mammals, especially herbivores, are considered susceptible. Humans almost invariably contract anthrax from handling infected animals, from carcasses of animals that have died from the disease, or from the meat, skin, hair, bones, etc., of such animals, Guizhou Province is a historical epicenter of anthrax in the southwest of China？ In June 2013, an epidemic suspected to be anthrax consisting of five human cases occurred in Wengan County. The clinical symptoms included erythema, papules, and vesicles on the skin of the hands and forearm, accompanied by tissue swelling, infiltration.

A fast mapping method to evaluate immersed boundary hydrodynamic forces

Immersed boundary method is a crucial method to deal with particle suspension flow.Particle shapes involved in such flow are usually simple geometry,such as sphere and ellipsoid,which can be conveniently represented by the triangular surface grid.When the number of particles and resolution of the surface grid increase,calculating the hydrodynamic force on the particle surface through integration can be time-consuming.Hence,the present paper establishes a fast mapping method to evaluate immersed boundary hydrodynamic force.Firstly,the particle surface grid is generated by an initial triangular element grid.Subsequently,the initial surface grid is refined by bisection refinement to the desired resolution.The final step is to find the triangular element index on the particle triangular surface grid,which contains the projective point.Test cases show that the present mapping algorithm has good accuracy and efficiency for calculating hydrodynamic forces of particles.

Regioselectivity of Pd-catalyzed o-carboranearylation: a theoretical view

The mechanism and the regioselectivity of Pd-catalyzed B(4)–H arylation and B(4,5)–H diarylation foro-carborane with bidentate directing groups were investigated. The complete catalytic cycle involves Pdmediated concerted metalation–deprotonation, oxidative addition, counterion exchange, and reductiveelimination, where counterion exchange is critical. The reductive elimination is the rate- and regioselectivity-determining step for the whole catalytic cycle. B(3)-Arylation is unfavorable because the stericrepulsion between the substituent group on C(2) and the metal moiety would lead to significant distortionof o-carborane and would result in a higher activation energy for reductive elimination. The distortion ofo-carborane can be clearly observed from the change of its aromaticity in the corresponding transitionstates by the calculation of nucleus-independent chemical shifts. Moreover, counterion exchange withcarboxylate before reductive elimination significantly increases the positive charge of palladium, whichleads to a lower activation free energy for the sequential step.

Carbene-enabled ether activation through the formation of oxonium: a theoretical view

Here,we report a theoretical investigation of the reactivity and chemoselectivity of carbene-enabled ether activation.The mechanism obtained from DFT calculations revealed that the final products were dependent on the stability of the oxonium intermediate,which was afforded by nucleophilic attack of the corresponding ether onto a carbene species.Interestingly,we found that the nucleophilicity of ethers was crucial but not their solvation.Energy decomposition analysis based on absolutely localized molecular orbitals showed that the nucleophilicity of ethers was critical for polarization and charge transfer,leading to the chemoselectivity.

Atom Recombination of Difluorocarbene Enables 3-Fluorinated Oxindoles from 2-Aminoarylketones

Contrary to the traditional implementation as a difluoromethyl group and recently disclosed role of C1 synthons in synthetic organic chemistry,difluorocarbene(:CF_(2))is reported herein to proceed in unprecedented atom recombination as both a C1 synthon and F1 reagent simultaneously to render valuable 3-fluorinated oxindoles from 2-aminoarylketones.The reaction does not require catalyst and features a broad range of substrates with good functional group compatibility and ease of execution.This transformation could be employed to the quick-constructions of certain bioactive molecule derivatives.The mechanistic experiments and density functional theory(DFT)calculations indicate that this atom recombination reaction of:CF_(2) for the synthesis of 3-fluorinated oxindoles may involve a rearrangement process of epoxide intermediates.