Objective:To systematically elucidate the molecular mechanism of hesperetin in the treatment of heart failure by network pharmacology, molecular docking, and molecular dynamics, and to clarify its key targets and pathway regulatory networks.Methods:Potential targets of hesperetin were retrieved from the PubChem, Pharmmapper, SwissTargetPrediction, and Similarity ensemble approach databases. Heart failure-related targets were obtained from the OMIM, GeneCards, and TTD databases. Intersection targets were identified using Venny 2.1. A protein-protein interaction (PPI) network of potential targets was constructed using the STRING database and Cytoscape 3.9.0 software. Gene ontology (GO) functional and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analyses of key targets were performed using the Metascape database. Molecular docking was carried out using Autodock vina1.1.2. GROMACS (2024.03) was employed to conduct a 100 ns molecular dynamics simulation on the optimal affinity complex. The thermodynamic stability of the candidate complex during simulation was evaluated by analyzing the root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), and binding free energy. Data were analyzed by an independent sample t test or one-way analysis of variance. Results:A total of 356 related targets of hesperetin and 2 923 related targets of heart failure were screened, with 152 intersection targets identified as potential targets for hesperetin intervention in heart failure. PPI network topological analysis revealed key targets for hesperetin intervention in heart failure, including insulin-like growth factor 1, estrogen receptor 1 (ER1), cysteine aspartic acid specific protease-3, sarcoma proto-oncogene, matrix metalloproteinase 9 (MMP9), MMP2, Janus kinase 2 (JAK2), albumin, heat shock protein 90 alpha family class A member 1, epidermal growth factor receptor, and B-cell lymphoma-2 (Bcl-2). GO functional enrichment analysis indicated that biological processes were mainly enriched in response to hormone stimulation, positive regulation of cell migration, gland development, response to nutritional levels, regulation of system processes, and response to trauma. Molecular functions were primarily enriched in phosphotransferase activity, nuclear receptor activity, endopeptidase activity, kinase binding, heme binding, hormone binding and protease binding. Cellular components were mainly enriched in membrane-related structures such as vesicle cavity, membrane raft, vacuole cavity, receptor complex and extracellular matrix containing collagen. KEGG pathway enrichment analysis showed that these key targets were significantly enriched in lipid and atherosclerosis, diabetic cardiomyopathy, and the hypoxia-inducible factor-1 signaling pathway. Molecular docking results indicated that the binding energy of hesperetin to MMP9 (?46.442 kJ/mol) was significantly lower than that to other key targets. Molecular dynamics simulations revealed that the hesperetin-MMP9 complex maintained structural stability, with an average RMSD of 1.60 ?. The average RMSF values of MMP9 residues (0.83 ?) and ligand atoms (0.68 ?) indicated stable protein conformation and ligand-binding states. The Rg values of MMP9 [(15.04±0.60) ?] and hesperetin [(4.19±0.35) ?] showed minimal fluctuations, further supporting structural compactness. The total binding free energy of the hesperetin-MMP9 complex during the 100 ns simulation was (?142.3±6.3) kJ/mol, with minimal energy fluctuations, confirming that the complex remained structurally stable without significant energy transition throughout the simulation.Conclusions:Hesperetin may bind effectively to targets such as MMP9, JAK2, Bcl-2, and ER1, and form a stable complex with MMP9. It is suggested to influence biological processes related to lipids and signaling pathways such as atherosclerosis, diabetic cardiomyopathy, and hypoxia-inducible factor-1, thereby playing a role in heart failure intervention.

Objective: To find a viable alternative to reduce the number of doses required for the patients with post-traumatic stress disorder (PTSD), and to improve efficacy and patient compliance. Methods: In this study, we used ginger oil, a phytochemical with potential therapeutic properties, to prepare ginger oil patches. High-performance liquid chromatography (HPLC) was used to quantify the main active component of ginger oil, 6-gingerol. Transdermal absorption experiments were conducted to optimize the various pressure-sensitive adhesives and permeation enhancers, including their type and concentration. Subsequently, the ginger oil patches were optimized and subjected to content determination and property evaluations. A PTSD mouse model was established using the foot-shock method. The therapeutic effect of ginger oil patches on PTSD was assessed through pathological sections, behavioral tests, and the evaluation of biomarkers such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), and melatonin (MT). Results: The results demonstrated that ginger oil patches exerted therapeutic effects against PTSD by inhibiting inflammatory responses and modulating MT and BDNF levels. Pharmacokinetic experiments revealed that ginger oil patches maintained a stable blood drug concentration for at least one day, addressing the rapid metabolism drawback of 6-gingerol and enhancing its therapeutic efficacy. Conclusions Ginger oil can be prepared as a transdermal drug patch that meets these requirements, and the bioavailability of the prepared patch is better than that of oral administration. It can improve PTSD with good patient compliance and ease of administration. Therefore, it is a promising therapeutic formulation for the treatment of PTSD.

Objective:To provide scientific basis for the prevention and control of pneumoconiosis and the formulation of relevant policies, this paper discusses the loss of health life and economic loss caused by coal worker's pneumoconiosis in a mining group.Methods:From March to October 2017, 1262 cases of coal worker's pneumoconiosis were diagnosed in a mining group from 1972 to 2013. The direct and indirect economic losses are calculated by the step-by-step model method. Direct economic losses include medical expenses, one-time disability allowance, disability allowance, funeral allowance, one-time work death allowance, living and nursing expenses, food allowance, pension for supporting relatives and transportation expenses, etc. Indirect economic losses includes loss of social productivity, additional training fee for new employees, transportation fee for accompanying family members, loss of social productivity of accompanying family members, loss of production suspension and production reduction, etc. Life table method was used to calculate the loss of social productivity caused by coal worker's pneumoconiosis.Results:All 1262 coal worker's pneumoconiosis patients were male. In the stage of pneumoconiosis, 95.40% (1204/1262) of the first stage of pneumoconiosis and 42.62% (538/1262) of the seventh stage of disability. The age of diagnosis (22.02-71.33) was 47.38 years on average. 1262 coal worker's pneumoconiosis patients caused a total of 9068.54 years of health life loss, of which YLD accounted for 93.56% (8484.69/9068.54) . The loss of YLD (0.06-33.30) years in 1262 coal worker's pneumoconiosis patients was 6.70 years per capita. The total economic loss of 1262 coal workers with pneumoconiosis was 2842185447.70 yuan, with a per capita of 2252127.93 yuan. The direct economic loss accounted for 81.59% (2318990168.46/2842185447.70) , which was 4.42 times of the indirect economic loss. Among the direct economic loss per capita, medical expenses accounted for a large proportion of 50.04% (919510.84/1837551.64) . The per capita indirect economic loss is 414576.29 yuan. The loss of social productivity accounted for 56.18% (232908.95/414576.29) .Conclusion:Coal worker's pneumoconiosis causes heavy economic burden and serious loss of social productivity.

Objective:To provide scientific basis for the prevention and control of pneumoconiosis and the formulation of relevant policies, this paper discusses the loss of health life and economic loss caused by coal worker's pneumoconiosis in a mining group.Methods:From March to October 2017, 1262 cases of coal worker's pneumoconiosis were diagnosed in a mining group from 1972 to 2013. The direct and indirect economic losses are calculated by the step-by-step model method. Direct economic losses include medical expenses, one-time disability allowance, disability allowance, funeral allowance, one-time work death allowance, living and nursing expenses, food allowance, pension for supporting relatives and transportation expenses, etc. Indirect economic losses includes loss of social productivity, additional training fee for new employees, transportation fee for accompanying family members, loss of social productivity of accompanying family members, loss of production suspension and production reduction, etc. Life table method was used to calculate the loss of social productivity caused by coal worker's pneumoconiosis.Results:All 1262 coal worker's pneumoconiosis patients were male. In the stage of pneumoconiosis, 95.40% (1204/1262) of the first stage of pneumoconiosis and 42.62% (538/1262) of the seventh stage of disability. The age of diagnosis (22.02-71.33) was 47.38 years on average. 1262 coal worker's pneumoconiosis patients caused a total of 9068.54 years of health life loss, of which YLD accounted for 93.56% (8484.69/9068.54) . The loss of YLD (0.06-33.30) years in 1262 coal worker's pneumoconiosis patients was 6.70 years per capita. The total economic loss of 1262 coal workers with pneumoconiosis was 2842185447.70 yuan, with a per capita of 2252127.93 yuan. The direct economic loss accounted for 81.59% (2318990168.46/2842185447.70) , which was 4.42 times of the indirect economic loss. Among the direct economic loss per capita, medical expenses accounted for a large proportion of 50.04% (919510.84/1837551.64) . The per capita indirect economic loss is 414576.29 yuan. The loss of social productivity accounted for 56.18% (232908.95/414576.29) .Conclusion:Coal worker's pneumoconiosis causes heavy economic burden and serious loss of social productivity.

Objective:To construct the "3+2" counterpart cut-through sectional training nursing major un-dergraduate curriculum system, which is oriented by vocational competence. Methods: The preliminary draft of"3+2" nursing undergraduate curriculum setting was established base on the literature review and expert group in-terview, and the 25 experts was conducted two rounds of expert questionnaire consultation using Delphi method. Results:Experts' opinions tended to be consistent after two rounds of consultation, the expert authority coefficient was 0 . 92 , the coordination coefficient of Kendall was 0 . 44 in the second round of expert consultation and finally established 5 curriculum groups, including total 28 courses of public elementary courses, professional basic cour-ses, professional core courses, professional oriented courses and centralized practice courses. Conclusion: It should construct the"3+2" counterpart cut-through nursing major undergraduate curriculum system, which is o-riented by vocational competence, and achieve effective connection between the knowledge structure and the quality of the nursing students, in order to provide the reference for perfecting the curriculum system of vocational educa-tion in our country.

With the improvement of living standard and the change of diet structure,the incidence of multiple primary carcinoma has increased significantly,which is related to the improvement of diagnosis level.In clinical work,multiple primary carcinoma was easily misdiagnosed with metastatic cancer.Many patients lost their best time to treat,because principles and prognosis of them were distinctly different.Strengthen the understanding of multiple primary carcinoma,in order to detect,diagnose and treat earlier,is beneficial to improve the survival of patients.Based on this background,this article reviewed the epidemiology,etiology,pathogenesis,diagnosis and treatment strategies of multiple primary carcinoma,aiming at improving the prognosis of patients.

Objective To analyze the clinical distribution ,antimicbial resistance and Staphylococcal cassette chromosome mec (SCCmec) genotype characteristics of 346 methicillirrresistant Staphylococcus aureus (MRSA) clinical isolates in the hospital . Methods A total of 784 strains of Staphylococcus aureus isolated from January 2014 to January 2015 in the hospital ,MRSA identi-fication and the SCCmec genotype was conducted by PCR assay .Results 346 strains of MRSA (44 .13% ) were isolated from 784 strains of Staphylococcus aureus ,the detection rate of MRSA from sputum accounted for 43 .06% ,the secretion accounted for 48 .55% .MRSA was resistant to penicillin ,levofloxacin and erythromycin ,sensitive to vancomycin ,linezolid and teicoplanin .SCC-mec genotyping result showed that SCCmecⅡ was identified in 130 ,SCCmecⅢ in 196 ,SCCmecⅣ in 11 ,SCCmecⅤ in 9 .Conclusion SCCmecⅢ is the main genotypes of MRSA from our Hospital ,all of the MRSA strains are multi-resistant to tested antibiotics , but sensitive to vancomycin and teicoplanin .

Objective To assess the feasibility and short-term effect of transanal everted extraction of laparoscopic rectal excision without abdominal incision.Methods Eleven patients were operated by transanal everted extraction of laparoscopic rectal excision without abdominal incision.Results All the operations were accomplished successfully,the average operative duration was (189.5±25.2) min,the intra-operative blood loss volume was (25.4±9.4) ml,the average time to flatus was (38.9±8.6) h,the average postoperative hospital stay was (12.7±2.5) d,and the number of lymph nodes harvested was 13.5±4.1.There were no post-operative complications.Conclusion The technique of transanal everted extraction of laparoscopic rectal excision without abdominal incision is safe and feasible,but the long-term effects need more observation.

Objective To compare the predicting values for Prognosis among Global Risk Classification (GRS),Synergy Between Percutaneous Coronary Intervention With TAXUS and Cardiac Surgery (SYNTAX) score,the European System for Cardiac Operative Risk Evaluation (EuroSCORE) in patients who received stenting because of unprotected left main coronary artery (ULMCA) lesion.Methods Totally 105 successive elderly patients with ULMCA lesion who received stenting were divided into 2 groups:with and without main adverse cardiac events (MACE).The clinical and angiographic characteristics were analyzed and then compared among GRC,SYNTAX score and EuroSCORE.Results As compared with none MACE group,MACE group had higher EuroSCORE score (2.0±2.3 vs.6.5±2.9,t=8.18,P=0.002),and more trivessel disease and left main bifurcation lesion (x2 =8.96,6.96,P =0.011,P =0.008).High risk GRC showed more MACE than medium or low risk GRC [55.9％ (19/34) vs.20.5％(9/44),7.4％ (2/27),x2 =19.77,P=0.001].AUC(95％CI )of GRC,SYNTAX score and EuroSCORE were [0.821 (0.730-0.912),0.586(0.462-0.709) and 0.631 (0506-0.757)],respectively.Compared with SYNTAX score and EuroSCORE,GRC was superior in the MACE predicting value (Z=3.29,2.63,P＜0.01 or P＜0.05).