ObjectiveTo investigate the effect of Huangqi jiuni decoction （HQJND） on acute liver injury in severely scalded rats and its possible molecular mechanism by animal experiments and modern pharmacological tools. MethodsFirstly， the rat model of sepsis was established and randomly divided into 4 groups. The normal saline group was given 1 mL of normal saline twice a day， and the traditional Chinese medicine group was given 1 mL of concentrated huangqi jiuni decoction twice a day. After 72 hours of shock， the samples were sacrificed， and then the serum liver function and （+）-haematoxylin eosin staining were performed to verify the efficacy of the drug. Sham Operation Group and sepsis group were fed normally without any special treatment. Then， network pharmacology was used to screen the targets of drugs and drug responses and predict the signaling pathways that might play a role in the treatment of diseases. Finally， fluorescence quantitative PCR （RT-qPCR） was performed to detect gene expression， Western blot （WB） was performed to detect tumor necrosis factor （TNF-α）， P65， phosphorylated P65 （P-P65）， and immunohistochemical （IHC） were performed assays to verify drug efficacy and explore the mechanism of drug treatment. ResultsSerum liver function and histopathology in rats showed that HQJND significantly improved liver function in severely burned rats. Network pharmacology screening was used to identify 353 disease-related marker genes and 286 drug targets. It was predicted that tumor necrosis/NF-NF-κB pathway （TNF/NF-NF-κB pathway） might be a key pathway for HQJND to treat acute liver injury after severe burns. The results of immunohistochemistry （IHC） showed that the staining of TNF-α in the liver of the sepsis group was more than that of the sham operation group and the traditional Chinese medicine group. The results of RT-qPCR and WB showed that the expression of TNF-α， TNFR1 and P65 proteins in the liver of rats in the sepsis group was significantly higher than that in the sham operation group and the traditional Chinese medicine group； on the contrary， the expression of TNF-α， TNFR1 and P65 proteins in the liver of rats in the sepsis group was significantly higher than that in the sham operation group and the traditional Chinese medicine group. The expression level of nuclear factor-kappa B（IκBα） was higher in the sham operation group and the traditional Chinese medicine group， indicating that drug treatment effectively inhibited the activation of the TNF/NF-κb signaling pathway. ConclusionAnimal experiments and network pharmacology results confirm that HQJND has a protective effect on acute liver injury in severely burned rats， which may be related to the inhibition of TNF/NF-κB signaling pathway.

Objective To explore the potential role and underlying mechanism of the functionally uncharacterized gene Gm49394 on regulating β-cell apoptosis under diabetic conditions.Methods The expression and translational activity of Gm49394 in pancreatic β-cell lines and non-β-cell lines were validated using RNA fluorescence in situ hybridization(RNA-FISH),quantitative real-time PCR(qPCR),Western blotting,and immunofluorescence(IF)assay.The β-cell lines(NIT-1/Min6)with Gm49394 overexpression or knockdown were constructed.The proliferation,apoptosis,mitochondrial function,as well as oxidative stress and endoplasmic reticulum stress markers in these β-cell lines under physiological homeostasis or pathological stress conditions,such as high glucose(30 mmol/L),inflammation(10 ng/mL IFN-γ alone or combined with 10 ng/mL IL-6),and hydrogen peroxide(100 μmol/L H2O2)were detected by flow cytometry and Western blotting.Results RNA-FISH and qPCR indicated that Gm49394 was specifically expressed in pancreatic β-cell lines and up-regulated under high glucose or inflammatory stimulation.IF assay and Western blotting showed that Gm49394 had protein-coding activity.Flow cytometry and Western blotting identified that Gm49394 overexpression did not affect β-cell proliferation,but promoted β-cell apoptosis and increased reactive oxygen species(ROS)and mitochondrial superoxide(MitoSOX)levels in β cells under physiological homeostasis or pathological stress conditions(P<0.05).Under physiological conditions,Gm49394 knockdown failed to induce significant alterations on β-cell apoptosis,ROS,or MitoSOX levels.Under pathological stress conditions,Gm49394 knockdown significantly suppressed β-cell proliferation,apoptosis,as well as oxidative and endoplasmic reticulum stress(P<0.05).Conclusion Gm49394 may promote β-cell apoptosis via oxidative stress and endoplasmic reticulum stress.

Objective To evaluate the application effect of perioperative cluster nursing interventions in patients under-going robot-assisted radical prostatectomy.Methods A total of 122 prostate cancer patients who underwent robot-assisted sur-gery from January 2023 to December 2024 were divided into the control group(routine care,55 cases)and the observation group(cluster nursing,67 cases)according to the nursing methods.The psychological status,surgery-related indicators,postoperative recovery,incidence of perioperative complications,and patient satisfaction were compared between the two groups.Results The observation group demonstrated a statistically significant decrease in postoperative anxiety and depression scores compared to the control group(P=0.034,P=0.005).The observation group exhibited shorter operative time and less intraoperative blood loss,with both differences being statistically significant(P=0.016,P＜0.001).In terms of postoperative recovery,the obser-vation group showed faster recovery of bowel function,shorter time for catheter insertion and postoperative hospital stay compared to the control group(P=0.010,P＜0.001,P＜0.001).In the observation group,the incidence of systemic postoperative in-fection was lower than that of the control group(4.5％vs 18.2％,P=0.015).The perioperative hypothermia rate in the obser-vation group was lower than that of the control group(38.8％vs 60.0％,P=0.020).There was no statistically significant difference in postoperative urinary fistula rate between the two groups(P=0.477).The observation group achieved an overall patient satisfaction rate of 98.51％,with higher satisfaction scores compared to the control group(P=0.008).Conclusion Perioperative cluster nursing measures yield favorable outcomes in patients undergoing robot-assisted radical prostatectomy.It can not only shorten the operation time,promote the postoperative recovery of patients,but also reduce the anxiety and depression of patients and complica-tions,and improve patient satisfaction.

Under the background of increasingly severe drug-resistant bacteria infections,protracted course of chronic wounds has become clinical difficulties disturbing both patients and doctors.With the unique advantages of broad antibacterial spectrum,low drug resistance rate and high safety,polyhexanide antibacterial agent has gradu-ally become a major approach for treatment and nursing of chronic wounds.The application of polyhexamethylene biguanide(PHMB)antimicrobial agents in treatment and nursing of chronic wounds was reviewed in the article,including the antibacterial properties,comparisons with other antimicrobial agents,actual clinical practice and potential side effects,aiming to guide the further application of PHMB antimicrobial agents in treatment of chronic wounds.

Objective:To investigate the effects and underlying mechanisms of silent information regulator 1(SIRT1)on the dysfunction of umbilical vein endothelial cells(HUVECs)induced by oxidized low-density lipoprotein(ox-LDL).Methods:The impact of ox-LDL on the viability of HUVEC was assessed using the Cell Counting Kit-8(CCK-8)assay, which also facilitated the determination of the optimal ox-LDL concentration.Subsequent to ox-LDL treatment, several parameters were evaluated, including reactive oxygen species(ROS)production, apoptosis, migration, and angiogenesis, utilizing a ROS detection kit, flow cytometry, a Transwell migration assay, and an angiogenesis assay, respectively.The expression levels of apoptosis-related proteins, namely cleaved caspase-3(c-caspase-3), Bcl-2-associated X protein(Bax), B-cell lymphoma-2(Bcl-2), SIRT1, and peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α), were quantified using Western blot analysis.Adenoviral vectors were employed to either overexpress or silence SIRT1, while the ROS inhibitor N-acetylcysteine(NAC)was applied to assess its effects on cell function.Additionally, PGC-1α acetylation(Ac-Lys)was investigated through co-immunoprecipitation.Results:In the oxidative model of ox-LDL-stimulated HUVECs, compared to controls, we observed a significant increase in ROS-positive cells(35.9±3.1 vs.5.4±0.9), heightened apoptosis(16.3±0.9 vs.7.6±0.7), diminished endothelial cell migration capacity, and reduced angiogenic capacity.Additionally, there was an elevation in the pro-apoptotic protein c-caspase3 and Bax, alongside a decrease in the anti-apoptotic protein bcl-2.Furthermore, SIRT1 expression was increased, as was the expression of PGC-1α.In comparison to the GFP group(28.5±1.9), the reduction in SIRT1 expression resulted in an increase in apoptosis(37.0±1.9).Conversely, overexpression of SIRT1 mitigated ox-LDL-induced apoptosis(25.2±1.6)(all P<0.05).Notably, the expression levels of PGC-1α and SIRT1 exhibited consistent changes: PGC-1α expression increased with SIRT1 overexpression and decreased when SIRT1 expression was reduced(both P<0.05).The administration of NAC to the ox-LDL-treated group led to a reduction in ROS production( t=11.18, P<0.01)and a significant enhancement in cell function.Immunoprecipitation results indicated that SIRT1 overexpression decreased ox-LDL-induced PGC-1α acetylation( t=18.18, P<0.01), whereas silencing of SIRT1 further increased PGC-1α acetylation levels( t=-19.09, P<0.01). Conclusions:SIRT1 is shown to protect against ox-LDL-induced apoptosis and dysfunction in HUVECs by deacetylating and activating PGC-1α, thereby highlighting its therapeutic potential in the context of endothelial cell injury.

Objective:To investigate the use of non-vitamin K antagonist oral anticoagulants(NOACs)and their associated comorbidities in patients aged 80 years and older with non-valvular atrial fibrillation(NVAF), as well as to understand the challenges faced by elderly patients receiving NOAC therapy.Methods:We retrospectively enrolled elderly patients(≥80 years old)with NVAF who were treated with NOACs at a hospital in Beijing from January 2018 to August 2023.Patients were categorized into two age groups: 80-89 years and ≥90 years.We collected baseline data, including demographic characteristics, details of atrial fibrillation, comorbidities, laboratory test results, and medication combinations, for descriptive statistical analysis and intergroup comparisons.Results:A total of 695 elderly patients with NVAF receiving NOACs were included in the study, with a median age of 84 years.Among these patients, there were 328 males(47.19%, 328/695)and 422 cases of paroxysmal atrial fibrillation(60.72%, 422/695).The age group of 80-89 years comprised 640 cases(92.09%, 640/695), while the group aged 90 years and above included 55 cases(7.91%, 55/695).The use of NOACs in patients aged 90 and older exhibited an increasing trend over the years.Inter-group comparisons indicated that the ≥90 years group had lower body mass index, longer hospital stays, increased bedridden time, poorer renal function, lower levels of albumin and hemoglobin, and higher D-dimer levels.Inappropriate dosing of DOACs occurred in 49.64%(345/695)of cases, with 90.72%(313/345)receiving doses lower than recommended.Lower-than-recommended doses were more prevalent in the ≥90 years group, while higher-than-recommended doses were more common in the 80-89 years group.Polypharmacy was noted in 61.29%(426/695)of patients.The concurrent use of antiplatelet drugs, rhythm control medications, and ventricular rate control drugs was observed in 12.52%(87/695), 19.57%(136/695), and 54.53%(379/695)of patients, respectively, with no significant differences between groups.Conclusions:Inappropriate dosing and polypharmacy are prevalent issues among elderly NVAF patients.Therefore, it is essential to enhance multidisciplinary collaboration to optimize anticoagulation treatment strategies.

Objective:To analyze the pangenome, pan drug resistance genes, pan virulence genes, pan replicons, and others of the plasmids carried by hypervirulent Klebsiella pneumoniae (hvKP) in the world and their evolutionary trends over time, and provide evidence for more comprehensive understanding of the evolution of genetic diversity, drug resistance genes, and virulence genes of the plasmids. Methods:From the National Center for Biotechnology Information database, a total 1 738 plasmids were screened from 524 strains with completed genome sequences in 2 136 strains of hvKP carrying plasmids. Through pangenome, pan drug resistance gene, and pan-virulence gene composition and functional analyses, the curves of pangenome size and new gene size against plasmid isolation time were established, revealing the diversity of the plasmid pangenome and its evolutionary patterns.Results:The homologous genes, homologous drug resistance genes, homologous virulence genes, and replicons of the plasmids carried by hvKP comprised of 12 906, 149, 107 and 89 types, respectively. The fitting curves for the number of new genes, new drug resistance genes and new replicons increased with the increase of plasmids in an open state, while the curve for novel virulence genes was in a closed state. A obvious increase in new drug resistance genes was observed during 2018-2019. Among the newly added drug resistance genes during 2021-2023, beside those conferring aminoglycoside resistance, they were mainly new subtypes conferring carbapenem resistance.Conclusions:The pangenome of plasmids carried by hvKP exhibited high diversity, with the plasmid pan genes, pan drug resistance genes, and pan replicon types gradually expanding, while the pan virulence genes remains stable. The increase in novel drug resistance genes in specific years and the emergence of new carbapenem-resistant gene subtypes during 2021-2023 suggested the need for strengthened drug resistance surveillance and prevention efforts, with particular attention to carbapenem resistance.

Osteoarthritis is a chronic inflammatory disease characterized by damage to the articular cartilage, synovitis, and subchondral bone remodeling. Its pathological mechanisms involve extracellular matrix degradation, cell apoptosis, autophagy, and inflammatory responses. Among these, dysregulated apoptosis is a central driver of disease progression, making chondrocyte apoptosis a critical therapeutic target. This review summarizes current understanding of OA pathogenesis. Pro-inflammatory cytokines [e.g., interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and IL-6] exacerbate cartilage catabolism by activating signaling pathways like NF-κ B and MAPK. Chemokines, including the C-C motif chemokine ligand (CCL) family and the C-X-C motif chemokine ligand (CXC) family, amplify the inflammatory cascade by recruiting inflammatory cells, thereby contributing to the pathological process of osteoarthritis. In the study of programmed cell death, apoptosis is divided into extrinsic (death receptor pathway) and intrinsic (mitochondrial pathway) types. Both pathways induce chondrocyte apoptosis by activating the caspase cascade. Reactive oxygen species and inflammatory factors can promote excessive chondrocyte apoptosis through these pathways. Therapeutic strategies targeting apoptosis are diverse and include non-coding RNAs (miRNA, lncRNA, circRNA) that inhibit apoptosis by regulating related signaling pathways; phytochemicals that exert anti-inflammatory and anti-apoptotic effects; exosomes that suppress apoptosis by modulating immune responses and metabolism; and proteins/cytokines as well as melatonin, which protect chondrocytes by regulating specific signaling pathways. Clinical studies suggest these approaches hold promise for precision and personalized therapy, though challenges such as high cost, off-target effects, and drug resistance remain. In addition, drug delivery systems based on biomaterials (hydrogels) and nanotechnology can improve drug bioavailability and targeting. For example, drug-loaded hydrogels enable sustained release, and nanoparticles enhance drug stability and delivery efficiency, offering new perspectives for the treatment of osteoarthritis.

Objective The aim of this study is to discuss the causal relationship between periodontal disease(PD)and prostate cancer(PCa).Methods A two-sample bidirectional Mendelian randomization(MR)analysis based on publicly statistical data from genome-wide association studies(GWAS)was conducted.MR Egger,weighted medium,simple mode and weighted mode were supplemented,while inverse variance weighted analysis(IVW)was the main method of analysis.Heterogeneity testing,pleiotropy testing and leave-one-out testing were used to assess the sensitivity and stabili-ty.Results The results of MR analysis showed that PD had no significant impact on the occurrence of PCa:East Asian(IVW,PD:OR=1.07,P=0.48);European(IVW,PD:OR=1.00,P=0.37,periodontitis:OR=1.03,P=0.14,chronic gingivitis:OR=0.99,P=0.37,chronic periodontitis:OR=1.03,P=0.22).The reverse MR analysis also did not show a causal relationship between PCa and PD:East Asian(IVW,PD:OR=0.97,P=0.22);European(IVW,PD:OR=0.84,P=0.44,periodontitis:OR=1.01,P=0.75,chronic gingivitis:OR=0.93,P=0.23,chronic periodontitis:OR=0.99,P=0.80).The results of other analysis were consistent with those of IVW analysis.Conclusions The results of our two-sample bidirectional MR analysis do not support a causal relationship between PD and PCa.

Objective To investigate the impact of various health education intervention strategies on the proper use of personal respiratory protective equipment (RPE) among workers exposed to dust. Methods Dust-exposed workers were recruited from 60 selected enterprises in Guangdong Province using cluster random sampling method. They were randomly allocated to the control, low-intensity intervention, and high-intensity intervention groups, with 358, 346, and 371 workers in each group, respectively. Workers in the control group received no designed intervention. Workers in the low-intensity intervention group received traditional plus mobile health education on the proper use of RPE. Workers in the high-intensity intervention group received all components of the low-intensity intervention, supplemented with peer education. The intervention lasted for six months. RPE usage was compared among the three groups of workers before and after the intervention. Results Workers in the control, low-intensity intervention, and high-intensity intervention groups showed higher rates of both RPE wearing and correct RPE wearing after the intervention than before it within their respective groups (RPE wearing rate: 94.1% vs 99.2%, 95.7% vs 100.0%, 94.6% vs 100.0%, all P<0.01; correct RPE wearing rate: 66.8% vs 91.1%, 67.3% vs 95.7%, 66.6% vs 96.5%, all P<0.01). Post-intervention correct RPE wearing rates were highest in the high-intensity intervention group, followed by the low-intensity intervention group, and the control group, with the percentage of 96.50%, 95.66% and 91.06%, respectively (P<0.01). Binary logistic regression analysis result showed that different intervention strategies affected the correct use of personal RPE among dust-exposed workers after adjusting for gender, age, and other confounding factors (P<0.05). Compared with the control group, the rates of correct RPE use increased in the low-intensity intervention group and the high-intensity intervention group (odd ratio was 2.14 and 3.01; 95% confidence interval was 1.12 - 4.10 and 1.53 - 5.91, respectively). Conclusion The implementation of traditional plus mobile health education interventions on the proper use of RPE can promote correct RPE utilization among dust-exposed workers, and integrating peer education further enhances the intervention effectiveness.