Objective To explore the safety and effects of alpha-lipoic acid (ALA) in patients with ischemic heart failure (IHF). Methods A randomized, double-blind, placebo-controlled trial was designed (ClinicalTrial.gov registration number NCT03491969). From January 2019 to January 2023, 300 patients with IHF were enrolled in four medical centers in China, and were randomly assigned at a 1∶1 ratio to receive ALA (600 mg daily) or placebo on top of standard care for 24 months. The primary outcome was the composite outcome of hospitalization for heart failure (HF) or all-cause mortality events. The second outcome included non-fatal myocardial infarction (MI), non-fatal stroke, changes of left ventricular ejection fraction (LVEF) and 6-minute walking distance (6MWD) from baseline to 24 months after randomization. Results Finally, 138 patients of the ALA group and 139 patients of the placebo group attained the primary outcome. Hospitalization for HF or all-cause mortality events occurred in 32 patients (23.2%) of the ALA group and in 40 patients (28.8%) of the placebo group (HR＝0.753, 95%CI 0.473-1.198, P＝0.231; Figure 1A-1C). The absolute risk reduction (ARR) was 5.6%, the relative risk reduction (RRR) associated with ALA therapy was approximately 19.4% compared to placebo, corresponding to a number needed to treat (NNT) of 18 patients to prevent one event. In the secondary outcome analysis, the composite outcome of the major adverse cardiovascular events (MACE) including the hospitalization for HF, all-cause mortality events, non-fatal MI or non-fatal stroke occurred in 35 patients (25.4%) in the ALA group and 47 patients (33.8%) in the placebo group (HR＝0.685, 95%CI 0.442-1.062, P＝0.091; Figure 1D). Moreover, greater improvement in LVEF (β＝3.20, 95%CI 1.14-5.23, P＝0.002) and 6MWD (β＝31.7, 95%CI 8.3-54.7, P＝0.008) from baseline to 24 months after randomization were observed in the ALA group as compared to the placebo group. There were no differences in adverse events between the study groups. Conclusions These results show potential long-term beneficial effects of adding ALA to IHF patients. ALA could significantly improve LVEF and 6MWD compared to the placebo group in IHF patients.

This study aims to explore the effects and action mechanisms of the active ingredients in Buyang Huanwu Decoction(BYHWD), namely tetramethylpyrazine(TMP) and hydroxy-safflor yellow A(HSYA), on oxygen-glucose deprivation/reglucose-reoxygenation(OGD/R)-induced inflammation and oxidative stress of microglia(MG). Network pharmacology was used to screen the effective monomer ingredients of BYHWD and determine the safe concentration range for each component. Inflammation and oxidative stress models were established to further screen the best ingredient combination and optimal concentration ratio with the most effective anti-inflammatory and antioxidant effects. OGD/R BV2 cell models were constructed, and BV2 cells in the logarithmic growth phase were divided into a normal group, a model group, an HSYA group, a TMP group, and an HSYA + TMP group. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory cytokines such as interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6). Oxidative stress markers, including superoxide dismutase(SOD), nitric oxide(NO), and malondialdehyde(MDA), were also measured. Western blot was used to analyze the protein expression of both inflammation-related pathway [Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)] and oxidative stress-related pathway [nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)]. Immunofluorescence was used to assess the expression of proteins such as inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1). The most effective ingredients for anti-inflammatory and antioxidant effects in BYHWD were TMP and HSYA. Compared to the normal group, the model group showed significantly increased levels of IL-1β, TNF-α, IL-6, NO, and MDA, along with significantly higher protein expression of NF-κB, TLR4, Nrf2, and HO-1 and significantly lower SOD levels. The differences between the two groups were statistically significant. Compared to the model group, both the HSYA group and the TMP group showed significantly reduced levels of IL-1β, TNF-α, IL-6, NO, and MDA, lower expression of NF-κB and TLR4 proteins, higher levels of SOD, and significantly increased protein expression of Nrf2 and HO-1. Additionally, the expression of the M1-type MG marker iNOS was significantly reduced, while the expression of the M2-type MG marker Arg-1 was significantly increased. The results of the HSYA group and the TMP group had statistically significant differences from those of the model group. Compared to the HSYA group and the TMP group, the HSYA + TMP group showed further significant reductions in IL-1β, TNF-α, IL-6, NO, and MDA levels, along with significant reductions in NF-κB and TLR4 protein expression, an increase in SOD levels, and elevated Nrf2 and HO-1 protein expression. Additionally, the expression of the M1-type MG marker iNOS was reduced, while the M2-type MG marker Arg-1 expression increased significantly in the HSYA + TMP group compared to the TMP or HSYA group. The differences in the results were statistically significant between the HSYA + TMP group and the TMP or HSYA group. The findings indicated that the combined use of HSYA and TMP, the active ingredients of BYHWD, can effectively inhibit OGD/R-induced inflammation and oxidative stress of MG, showing superior effects compared to the individual use of either component.
Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Mice ; Glucose/metabolism* ; Cell Line ; Inflammation/genetics* ; Oxygen/metabolism* ; Pyrazines/pharmacology* ; Microglia/metabolism* ; NF-E2-Related Factor 2/immunology* ; NF-kappa B/immunology* ; Toll-Like Receptor 4/immunology* ; Anti-Inflammatory Agents/pharmacology* ; Humans

The efficacy mechanism of the alcoholic extract of Gnaphalium affine was investigated by observing its influence on oxidative stress and intestinal flora in rats modeled for chronic obstructive pulmonary disease(COPD). UPLC-MS was used to evaluate the quality of the alcoholic extract of G. affine, and 72 rats were randomly divided into six groups, with COPD models established in five groups by cigarette smoke combined with airway drip lipopolysaccharide, and the rats were given the positive drug of Danlong Oral Solution, as well as low-, medium-, and high-doses alcoholic extract of G. affine, respectively. After two weeks of continuous gastric gavage, the body weights and general morphology observations were performed; HE staining and Masson staining were used to verify the effects of the alcoholic extract of G. affine on alveolar inflammation and collagen deposition area in COPD rats; the oxidative stress indexes CAT and GSH in serum and SOD and MDA in lung tissue of the rats were measured, and the mRNA expression of HO-1, Nrf2, and NQO1 were determined by qRT-PCR. The protein expressions of HO-1, Nrf2, and NQO1 were determined by the Western blot method, and the mechanism by which the alcoholic extract of G. affine affected oxidative stress in COPD rats was explored. Finally, the influence of G. affine on the changes in intestinal flora caused by COPD was studied by 16S rRNA sequencing. The results showed that a total of 121 chemical components were identified by UPLC-MS, including 70 positive and 51 negative ion modes. In animal experiments, it was found that the alcoholic extracts of G. affine were able to reduce the percentage of collagen deposition, affect the oxidative stress indexes such as CAT, GSH, SOD, MDA, as well as the mRNA and protein expression of Nrf2, HO-1, and NQO1. The 16S rRNA sequencing results showed an increase in the level of Lactobacillales and a decrease in the level of Desulfovibrio and Desulfovibrionales, suggesting that the alcoholic extracts of G. affine could reverse the changes in intestinal flora caused by COPD. In conclusion, the alcoholic extracts of G. affine may exert anti-COPD effects by affecting the oxidative stress pathway and modulating the changes in intestinal flora.
Animals ; Oxidative Stress/drug effects* ; Pulmonary Disease, Chronic Obstructive/genetics* ; Rats ; Male ; Gastrointestinal Microbiome/drug effects* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; NF-E2-Related Factor 2/metabolism* ; Humans ; Lung/metabolism*

OBJECTIVES: To report the development, validation, and findings of the Multi-dimensional Attention Rating Scale (MARS), a self-report tool crafted to evaluate six-dimension attention levels. METHODS: The MARS was developed based on Classical Test Theory (CTT). Totally 202 highly educated healthy adult participants were recruited for reliability and validity tests. Reliability was measured using Cronbach's alpha and test-retest reliability. Structural validity was explored using principal component analysis. Criterion validity was analyzed by correlating MARS scores with the Toronto Hospital Alertness Test (THAT), the Attentional Control Scale (ACS), and the Attention Network Test (ANT). RESULTS: The MARS comprises 12 items spanning six distinct dimensions of attention: focused attention, sustained attention, shifting attention, selective attention, divided attention, and response inhibition.As assessed by six experts, the content validation index (CVI) was 0.95, the Cronbach's alpha for the MARS was 0.78, and the test-retest reliability was 0.81. Four factors were identified (cumulative variance contribution rate 68.79%). The total score of MARS was correlated positively with THAT (r = 0.60, P < 0.01) and ACS (r = 0.78, P < 0.01) and negatively with ANT's reaction time for alerting (r = -0.31, P = 0.049). CONCLUSIONS The MARS can reliably and validly assess six-dimension attention levels in real-world settings and is expected to be a new tool for assessing multi-dimensional attention impairments in different mental disorders.
Humans ; Adult ; Male ; Attention/physiology* ; Female ; Middle Aged ; Reproducibility of Results ; Young Adult ; Psychometrics

Protein as the allergens could lead to allergy. In addition, a widespread class of allergens were known as glycans of N-glycoprotein. N-glycoprotein contained oligosaccharide linked by covalent bonds with protein. Recently,studies implicated that allergy was associated with glycans of heterologous N-glycoprotein found in food, inhalants, insect toxins, etc. The N-glycan structure of N-glycoprotein allergen has exerted an influence on the binding between allergens and IgE, while the recognition and presentation of allergens by antigen-presenting cells (APCs) were also affected. Some researches showed thatN-glycan structure of allergen was remodeled by N-glycosidase, such as cFase I, gpcXylase, as binding of allergen and IgE partly decreased. Thus, allergic problems caused by N-glycoproteins could potentially be solved by modifying or altering the structure ofN-glycoprotein allergens, addressing the root of the issue. Mechanism of N-glycans associated allergy could also be elaborated through glycosylation enzymes, alterations of host glycosylation. This article hopes to provide a separate insight for glycoimmunology perspective, and an alternative strategy for clinical prevention or therapy of allergic diseases.

As the predominant toxic constituent within the Aconitum genus, Aconitum alkaloids (ATs) exhibit both significant pharmaceutical value and substantial toxicity, have been widely used in traditional Chinese medicine and the realm of contemporary clinical medicine. However, owing to their high toxicity, inappropriate employment of ATs in pharmaceuticals, edibles, and the environment will pose serious threats to human health, inciting a series of toxic incidents. Consequently, it is very important to develop effective analytical methods. This paper presents a comprehensive review of the advancements in research pertaining to the pretreatment and detection methods in common substrates, including high performance liquid chromatography, liquid chromatography-mass spectrometry and rapid detection methods. To explore the specific sources of ATs in actual poisoning cases, the comprehensive traceability strategy based on plant morphology, chemical fingerprint analysis and DNA barcoding technology was discussed, proposing a comprehensive prospect for the development of ATs analysis and traceability, in order to provide guidance for related research within the forensic science domain.

Objective To describe the current state of research and future research hotspots through a metrological analysis of the literature in the field of forensic anthropological remains identification re-search.Methods The data retrieved and extracted from the Web of Science Core Collection (WoSCC),the core database of the Web of Science information service platform (hereinafter referred to as "WoS"),was used to analyze the trends and topic changes in research on forensic identification of human re-mains from 1991 to 2022.Network visualisation of publication trends,countries (regions),institutions,authors and topics related to the identification of remains in forensic anthropology was analysed using python 3.9.2 and Gephi 0.10.Results A total of 873 papers written in English in the field of forensic anthropological remains identification research were obtained.The journal with the largest number of publications was Forensic Science International (164 articles).The country (region) with the largest number of published papers was China (90 articles).Katholieke Univ Leuven (Netherlands,21 articles) was the institution with the largest number of publications.Topic analysis revealed that the focus of forensic anthropological remains identification research was sex estimation and age estimation,and the most commonly studied remains were teeth.Conclusion The volume of publications in the field of forensic anthropological remains identification research has a distinct phasing.However,the scope of both international and domestic collaborations remains limited.Traditionally,human remains identifica-tion has primarily relied on key areas such as the pelvis,skull,and teeth.Looking ahead,future re-search will likely focus on the more accurate and efficient identification of multiple skeletal remains through the use of machine learning and deep learning techniques.

AIM To study the chemical constituents from the branches and leaves of Toona ciliata Roem.var.pubescens(Franch.)Hand-Mazz.and their antitumor activities.METHODS The compounds were isolated and purified by silica gel,RP-18 reverse phase silica gel and semi-preparative HPLC,the structures of compounds were identified by physicochemical properties and spectral data.The antitumor activities were determined by MTT method.RESULTS Fifteen compounds were isolated and identified as toonaolide D(1),toonaciliatin E(2),bourjotinolone A(3),(21R,23R)-epoxy-21α-ethoxy-24S,25-dihydroxyapotirucalla-7-en-3-one(4),(Z)-toonasterone C(5),(E)-toonasterone(6),3-epi-dyscusin C(7),(Z)-aglawone(8),(E)-volkendousin(9),8(14),15-isopimaradiene-2α,3α,19-triol(10),(-)-loliolide(11),cyclohexenone(12),pubinernoid A(13),quercetin-3-O-(4″-methoxy)-α-L-rahmnopyranosyl(14),5-hydroxymethyl-2-furancarboxaldehyde(15).The IC50 values of compounds 3 and 4 on K562 cells were 54.2 and 47.3 μmol/L,respectively,and the IC50 values on HEL cells were 47.3 and 61.1 μmol/L,respectively.CONCLUTION Compounds 4,7,10 and 11 are isolated from Toona genus for the first time,and compounds 2,15 are first isolated from this plant.Compounds 3 and 4 show weak antitumor activities.

In order to improve the level of refined management of medical consumables, a hospital used radio frequency identification (RFID) technology to map the unique device identification barcode of medical devices to the supply-processing-distribution (SPD) code, generating a medical consumables RFID tag code with dual code carrier function and a unique serial number. The " three streams in one" mutual integration management mode of hospital information flow, material flow and financial flow was constructed, which realized the whole lifecycle traceability of medical consumables, effectively improved the intelligence and accuracy of inventory control, further optimized the integration function of medical consumables industry and finance, and provided strong data support for the decision-making analysis of hospital operation and management.

The gut microbiota plays a crucial role in the development of colorectal cancer (CRC). The imbalanced gut microbiota causes damage to the body and disrupts bile acids metabolism, increases susceptibility to CRC, and affects the signaling of farnesol X receptor (FXR), thereby promoting CRC progression. Traditional Chinese medicine has unique advantages in the treatment of CRC due to its synergistic regulatory effects of multiple components, targets, and pathways. It can regulate gut microbiota, intervene in bile acids metabolism, and activate its receptor FXR to inhibit the occurrence and development of CRC. Based on this, this article discusses the main role of the gut microbiota-bile acids-FXR axis in the development of CRC, and reviews the anti CRC effects and mechanisms of traditional Chinese medicine intervention on gut microbiota-bile acids-FXR axis, in order to provide new ideas and methods for the prevention and treatment of CRC.