ObjectiveNonalcoholic fatty liver disease （NAFLD） is a metabolic stress liver injury. Ferroptosis is involved in the occurrence and development of NAFLD. Exploring the efficacy and mechanism of schisandrin B in treating NAFLD facilitates the development of strategies for the prevention and treatment of NAFLD. MethodsThe molecular structure of schisandrin B was obtained by searching against PubChem， and the related targets were predicted by SwissTargetPrediction. The active ingredients and their targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the high-throughput experiment- and reference-guide database of traditional Chinese medicine （HERB）. GeneCards and FerrDb were searched for the targets of NAFLD and ferroptosis. The common targets were taken as the core targets， and the protein-protein interaction network of the core targets was established. DAVID was used for gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses. Finally， molecular docking was performed between schisandrin B and core targets， and the binding energy was calculated. C57BL/6 mice were fed with a methionine and choline-deficiency （MCD） diet for the modeling of NAFLD. Mice were randomized into normal， model， positive drug （essentiale）， and low- and high-dose schisandrin B groups. The body mass and liver index of mice were measured after drug administration. The levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in the serum and those of total cholesterol （TC）， triglyceride （TG）， malondialdehyde （MDA）， glutathione （GSH）， and Fe²⁺ in the liver homogenate were measured by biochemical assay kits. The pathological changes of the liver tissue were observed by hematoxylin-eosin （HE） and red oil O staining. Enzyme-linked immunosorbent assay was employed to determine the levels of interleukin （IL）-6， IL-1β， tumor necrosis factor （TNF）-α， and 4-hydroxynonenal （4-HNE） in the serum. Western blotting and real-time PCR were employed to determine the protein and mRNA levels， respectively， of solute carrier family 7 member 11 （SLC7A11）， solute carrier family 3 member 2 （SLC3A2）， glutathione peroxidase 4 （GPX4）， transferrin， and ferritin heavy chain （FTH） in the liver tissue. ResultsA total of 2 370， 2 547， and 1 451 targets of schisandrin B， NAFLD， and ferroptosis were obtained， in which 90 common targets were shared by the three. Enrichment analyses predicted 505 GO terms and 92 KEGG pathways. Molecular docking suggested that schizandrin B had strong binding affinity with the key targets of ferropstosis （SLC7A11 and SLC3A2）. Animal experiments showed that schizandrin B significantly decreased the liver index， lowered the levels of ALT， AST， TC， TG， IL-6， IL-1β， and TNF-α， alleviated hepatocyte ballooning and inflammatory cell infiltration， and reduced lipid accumulation in the liver of NAFLD mice. In addition， schisandrin B significantly lowered the levels of MDA， 4-HNE， and Fe²⁺， elevated the level of GSH， up-regulated the protein and mRNA levels of SLC7A11， SLC3A2， and GPX4， and down-regulated the protein and mRNA levels of transferrin in the liver tissue. ConclusionSchisandrin B can alleviate NAFLD by inhibiting ferroptosis in hepatocytes.

Room temperature stored platelets are associated with a higher risk of sepsis and related fatality. The risk of bacterial contamination of platelets is a leading risk of infection from blood transfusion. U.S. Food and Drug Administration recently issued a guidance on bacterial risk control strategies for blood collection establishments and transfusion services to enhance the safety and availability of platelets for transfusion. The prevention and control strategies in the guidance would be informative and instructive for further development of risk control strategies of platelet bacterial contamination in China.

Objective: To assess the association between the metabolic score for insulin resistance index (METS-IR) and overactive bladder (OAB) in the US population，so as to explore the potential of METS-IR as a predictive tool for OAB risk and to provide insights for early screening and intervention strategies. Methods: Based on the data from the National Health and Nutrition Examination Survey (NHANES) 2005-2018，a cross-sectional design was employed，and multivariate logistic regression models were used to analyze the association between METS-IR and OAB. METS-IR was analyzed both as a continuous variable and categorized into quartiles. To further validate the association between METS-IR and OAB across diverse populations，subgroup analyses were conducted in participants stratified by clinical characteristics. Smooth curve fitting was employed to test the linearity of the METS-IR-OAB relationship. Results: Elevated METS-IR was associated with an increased risk of OAB (P<0.001)，and this positive correlation remained stable when METS-IR was categorized into quartiles (P<0.001). Subgroup analyses revealed that the association between METS-IR and OAB was more pronounced in females，participants younger than 55 years，and non-diabetic individuals (P<0.05). Furthermore，smooth curve fitting confirmed a linear positive correlation between METS-IR and OAB，with this linear relationship observed in both diabetic and non-diabetic groups. Conclusion: This study，based on the NHANES 2005-2018 database，found a linear positive correlation between METS-IR and OAB.

Modulating Tankyrases (TNKS), interactions with USP25 to promote TNKS degradation, rather than inhibiting their enzymatic activities, is emerging as an alternative/specific approach to inhibit the Wnt/β-catenin pathway. Here, we identified UAT-B, a novel neoantimycin analog isolated from Streptomyces conglobatus, as a small-molecule inhibitor of TNKS-USP25 protein-protein interaction (PPI) to overcome multi-drug resistance in colorectal cancer (CRC). The disruption of TNKS-USP25 complex formation by UAT-B led to a significant decrease in TNKS levels, triggering cell apoptosis through modulation of the Wnt/β-catenin pathway. Importantly, UAT-B successfully inhibited the CRC cells growth that harbored high TNKS levels, as demonstrated in various in vitro and in vivo studies utilizing cell line-based and patient-derived xenografts, as well as APC^min/+ spontaneous CRC models. Collectively, these findings suggest that targeting the TNKS-USP25 PPI using a small-molecule inhibitor represents a compelling therapeutic strategy for CRC treatment, and UAT-B emerges as a promising candidate for further preclinical and clinical investigations.

Objective: The characteristics and differences of the general notice between the Chinese Pharmacopoeia and the Japanese Pharmacopoeia were investigated to provide references and suggestions for the compilation of the Chinese Pharmacopoeia.
Methods: From the perspective of frame structure and main contents, the general notice between the Chinese Pharmacopoeia and the Japanese Pharmacopoeia was compared.
Results: Each volume of the Chinese Pharmacopoeia had its general notice, including 34 to 48 items and 10 to 12 chapters based on different varieties collected in each volume. The Japanese Pharmacopoeia had 49 items not arranged by chapters. There are many differences on the general notice between the Chinese Pharmacopoeia and the Japanese Pharmacopoeia, such as the definitions and expressions of names, determination of appearance, revision rules, risk assessment and quality control conception. The framework of the general notice in the Chinese Pharmacopoeia was clear, the content was specific and the operation was friendly. The term description of the general notice in the Japanese Pharmacopoeia was concise, and some terms need to be implemented under the guidance of professional knowledge.
Conclusion: In light of comparative study, every volume’s general notice of the Chinese Pharmacopoeia has its own characteristics. By integrating advanced analytical technique, combining the requirements with laws and regulations, and optimizing content and terms, all volume’s general notice could be explored to be coordinated and unified.

This article provides an interpretive review of the "2023 ACC/AHA/ACCP/HRS guideline for the diagnosis and management of atrial fibrillation", which was updated and published by the American College of Cardiology (ACC), the American Heart Association (AHA), the American College of Chest Physicians (ACCP), and the Heart Rhythm Society (HRS) based on the latest clinical evidence. It delves into the classification and management strategies for atrial fibrillation (AF), grounded in the most current evidence-based medical research. The guideline offers significant updates in various aspects such as the definition and staging of AF, clinical evaluation and treatment, modification of risk factors, prevention of thromboembolism, and management of specific populations. Notably, the introduction of a new staging model for AF and corresponding management strategies stands out, underscoring the importance of prevention and early intervention. This article focuses on the three pillars of integrated AF management—stroke risk assessment, modification of risk factors, and management of specific patient groups, in addition to rate and rhythm control, analyzes their substantial significance in clinical practice and guides clinicians in providing more precise treatment.

OBJECTIVE To explore the effect and safety of dapagliflozin on cardiac function and renal function， blood glucose， and quality of life in patients with heart failure （HF） combined with chronic kidney disease （CKD）. METHODS A total of 156 patients with HF combined with CKD admitted to Shangqiu First People’s Hospital from January 1， 2021 to January 1， 2023 were included. According to the random number table， the patients were randomly divided into conventional treatment group （n＝80） and dapagliflozin group （n＝76）. Conventional treatment group was given conventional treatment； dapagliflozin group was additionally given Dapagliflozin tablets 10 mg orally， once a day， based on conventional treatment group. Both groups were treated for 6 months. Cardiac function [left ventricular ejection fraction （LVEF）， left ventricular end-systolic diameter （LVESD）， left ventricular end-diastolic diameter （LVEDD）， N-terminal pro-brain natriuretic peptide （NT-proBNP）]， renal function [blood creatinine， urea nitrogen， urinary albumin excretion rate （UAER）， glomerular filtration rate （GFR）， creatinine 806731979@qq.com clearance rate （CCR）]， glycosylated hemoglobin， and the quality of life were observed in 2 groups before and after treatment. The occurrence of ADR was recorded. RESULTS After treatment， LVESD， LVEDD， NT-proBNP， blood creatinine， urea nitrogen， UAER in 2 groups as well as the level of glycosylated hemoglobin in dapagliflozin group were significantly lower than before treatment； the dapagliflozin group was significantly lower than the conventional treatment group. LVEF， GFR， CCR and Kansas City Cardiomyopathy Questionnaire score were significantly higher than before treatment， and the dapagliflozin group was significantly higher than the conventional treatment group （P＜0.05）. There was no statistical significance in glycosylated hemoglobin of conventional treatment group before and after treatment （P＞ 0.05）. There was no statistically significant difference in the incidence of dizziness， rash， liver dysfunction， urinary system infection， new dialysis and hypotension between the two groups （P＞0.05）. CONCLUSIONS Dapagliflozin can improve the cardiac function and renal function of patients with HF complicated with CKD， improve patients’ quality of life and lower blood sugar levels without increasing the risk of adverse events.

Objective To explore the relationship between the expression levels of serum cingulate protein(CGN)and polyligand glycan 1(SDC-1)and the disease condition and outcome of hypertensive basal ganglia hemorrhage(HBGH).Methods A total of 123 patients with HBGH admitted to the Second People's Hospi-tal of Lianyungang from February 2019 to February 2022 were selected as the study objects,and 120 healthy volunteers who underwent physical examination in the hospital during the same period were selected as the health group.Serum CGN and SDC-1 expression levels were detected in the two groups.According to the dis-ease outcome,the patients were divided into the improved group(92 cases)and the deteriorated group(31 ca-ses).Receiver operating characteristic(ROC)curve and the area under the curve(AUC)were used to analyze the predictive value of serum CGN and SDC-1 expression levels on the disease outcome of patients with HB-GH.Results Serum CGN and SDC-1 expression levels in the severe group were higher than those in the mod-erate group and the mild group,and serum CGN and SDC-1 levels in the moderate group were higher than those in the mild group,and the differences were statistically significant(P＜0.05).Serum CGN and SDC-1 expression levels in HBGH patients in three groups were higher than those in health group,and the differences were statistically significant(P＜0.05).Serum CGN and SDC-1 expression levels in the deteriorated group were higher than those in the improved group,and the differences were statistically significant(P＜0.05).The AUC of serum CGN and SDC-1 for predicting the disease outcome of HBGH patients was 0.742(95％CI:0.792-0.697)and 0.861(95％CI:0.906-0.910),respectively,and the AUC of the combination of the two was 0.917(95％CI:0.962-0.870).The amount of blood loss and ventricular rupture in the deteriorated group were higher than those in the improved group,and the Glasgow Coma Scale(GCS)score on admission was lower than that in the improved group,and the differences were statistically significant(P＜0.05).Multi-variate Logistic regression analysis showed that serum CGN≥51.63 pg/mL(OR=3.815),serum SDC-1≥450.67 μg/L(OR=4.230)and GCS score ≤8(OR=5.333)were the influencing factors for disease outcome of HBGH patients(P＜0.05).Conclusion The increased expression levels of serum CGN and SDC-1 are closely related to the disease aggravation and the deterioration of the disease outcome in patients with HBGH,and they have certain predictive value for the disease outcome in patients with HBGH.

Objective:To observe the effects of Huatan Quyu Decoction on the protein expressions of β-catenin and GSK-3 β and the expression of anticardiolipin antibody and β-amyloid protein related to cognitive function in rats with vascular dementia based on Wnt/β-catenin signal pathway.Methods:A total of 96 male SD rats were divided into blank group, model group, Donepezil hydrochloride group and Huatan Quyu Decoction low-, midium-, high-dosage group according to random number table method, with 16 rats in each group. Except for the blank group, the rat model of vascular dementia was prepared by modified 2-VO method. Huatan Quyu Decoction low-, medium- and high-dosage groups were administrated with Huatan Quyu Decoction 6.1, 12.1 and 24.2 g/kg, respectively; the Western medicine group was administrated with Donepezil hydrochloride 0.5 mg/kg; the blank group and the model group were administrated with the same amount of normal saline for 28 consecutive days. On the 1st, 7th, 14th and 28th day after administration, the learning and memory ability of rats was evaluated by Morris water maze test, the levels of ACA and Aβ in serum were measured by enzyme linked immunosorbent assay (ELISA), and the expressions of β-catenin and GSK-3β proteins related to Wnt/β-catenin signal pathway in hippocampus were measured by Western blot.Results:Compared with model group, the escape latency was shortened in the Huatan Quyu Decoction high-dosage group and Donepezil group on 7 and 14 days of administration ( P<0.05), and the times of crossing the platform increased in Huatan Quyu Decoction high-dosage group on 1 and 28 days of administration ( P<0.05). Compared with model group, the serum ACA level in Donepezil group, Huatan Quyu Decoction medium- and high-dosage groups decreased at day 1, 7, 14 and 28 after administration ( P<0.05). The serum Aβ level in Donepezil group, Huatan Quyu Decoction medium- and high-dosage groups decreased at 7, 14 and 28 days after administration ( P<0.05); On the 14th and 28th days after administration, the levels of ACA and Aβ in TCM low-dosage group decreased ( P<0.05). Compared with model group, the expression of β-catenin protein in hippocampus of Donepezil group and Huatan Quyu Decoction medium- and high-dosage groups increased ( P<0.05), while the expression of GSK-3β in hippocampus of Donepezil group and Huatan Quyu Decoction low-, medium- and high-dosage groups decreased ( P<0.01). Conclusion:Huatan Quyu Decoction can activate the Wnt/β-catenin signaling pathway, up-regulate the expression of β-catenin protein in hippocampal tissue of rats, inhibit the expression of GSK-3β, reduce the levels of ACA and Aβ in serum of rats, and improve the cognitive function of rats with vascular dementia.

Objective:The antimicrobial resistance of Staphylococcus aureus(S.aureus)has become a challenge in the treatment of infectious diseases.It is of great clinical value to discovery effective antimicrobial agents against multi-drug resistant S.aureus and its biofilms.This study aims to explore the antibacterial activity of the antiparasitic drug closantel against methicillin-resistant S.aureus and its biofilms through drug repurposing. Methods:The sensitivity of S.aureus to closantel was assessed using microbroth dilution and disk diffusion methods.The bacteriostatic and bactericidal activities of closantel were determined by time-kill curves and colony count.Scanning electron microscopy combined with SYTOX Green and DiSC3(5)fluorescence probes were used to study the bactericidal mechanism of closantel.The influence of resistance was assessed by continuous exposure to sub-inhibitory concentrations of closantel.The anti-biofilm activity was evaluated using 96-well plates and crystal violet staining,and cytotoxicity was measured using the CCK-8 assay. Results:The minimal inhibitory concentration(MIC)of closantel for both methicillin-sensitive and methicillin-resistant S.aureus ranged from 0.125 to 1.000 μg/mL.Disk diffusion tests showed that 80 pg of closantel created an inhibition zone,which increased in diameter with higher drug amounts.Sub-inhibitory concentrations(0.031 μg/mL)of closantel significantly inhibited S.aureus proliferation,reducing bacterial turbidity from 0.26±0.00 to 0.11±0.01(t=16.06,P＜0.001),with stronger inhibition at higher concentrations.Closantel at 0.25×MIC inhibited S.aureus proliferation for 12 hours,while lxMIC inhibited it for over 24 hours,with the number of viable bacteria decreasing as the drug concentration increased.Mechanistic studies indicated that closantel effectively disrupted the integrity of S.aureus cell membranes,significantly increasing SYTOX Green and DiSC3(5)fluorescence intensity.Even after 25 days of continuous exposure to sub-inhibitory concentrations of closantel,no resistance developed.Closantel at 0.0625 μg/mL significantly inhibited biofilm formation,reducing it from 1.29±0.16 to 0.62±0.04(t=11.62,P＜0.001),showing a clear dose-dependent effect.Closantel at 2 μg/mL also significantly eradicated established biofilms,reducing biofilm mass from 1.62±0.34 to 0.51±0.39(t=4.84,P＜0.01).Additionally,closantel exhibited extremely low cytotoxicity,with half-maximal lethal concentrations for HepG2 liver cancer cells and normal LO2 liver cells both exceeding 64 μg/mL. Conclusion:Closantel exhibits strong antibacterial activity against S.aureus and its biofilm with low cytotoxicity against human cells,making it a promising candidate for new therapeutic strategies against S.aureus-related infections.