Hepatic fibrosis refers to excessive accumulation and abnormal proliferation of fibrous connective tissue in the liver triggered by multiple pathogenic factors， and it may progress to liver cirrhosis， portal hypertension， and liver cancer. The pathological mechanisms of hepatic fibrosis involve hepatocyte injury， inflammatory cell infiltration with the release of inflammatory mediators， hepatic stellate cell activation， and extracellular matrix deposition. Recent studies have focused on mitochondrial dysfunction in disease progression， including the molecular pathways for hepatic fibrosis driven by metabolic disorders， energy deficiency， oxidative stress， mitochondrial dynamic imbalance， and autophagic dysfunction， all of which can induce liver injury. This article reviews the latest advances in hepatic fibrosis， in order to provide new therapeutic strategies for clinical management.

Objective: To elucidate the molecular mechanism by which prohibitin 2(PHB2) mediates periodontitis-induced bone tissue inflammation through regulating the nuclear factor kappa B(NF-κB) signaling pathway and its role in irreversible alveolar bone resorption. Methods: Quantitative real-time reverse transcription polymerase chain reaction(qRT-PCR) and immunohistochemistry(IHC) were used to detect the expression differences of inflammatory factors and PHB2 in healthy and inflamed alveolar bone tissues of mice in vivo. In vitro, an inflammatory model was established using lipopolysaccharide(LPS)-induced a mouse calvaria-derived preosteoblastic cell line, subclone E1(MC3T3-E1) cells. Western blot and qRT-PCR were used to clarify the regulatory relationship between PHB2 and inflammatory factors, and immunofluorescence staining was performed to observe changes in PHB2 subcellular localization. PHB2 overexpression plasmids were constructed using molecular cloning, and RNA interference was employed to knock down PHB2 expression to assess its regulatory role in inflammation. Based on RNA-seq data, differential expression analysis based on the negative binomial distribution, version 2(DESeq2) was used for differential expression analysis, and kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment along with gene ontology(GO) functional annotation were performed to identify key signaling pathways and differentially expressed genes. Results: In the mouse periodontitis model, PHB2 expression was significantly upregulated in alveolar bone tissues. In the in vitro inflammatory cell model, PHB2 levels positively correlated with interleukin(IL)-6, IL-1β, and tumor necrosis factor-alpha(TNF-α) levels, and its subcellular localization shifted during inflammation. RNA-seq data and the detection of the level of phosphorylation of p65 protein(p-p65) demonstrated that PHB2 exacerbated inflammatory responses through the NF-κB signaling pathway and was mechanistically linked to upregulation of the upstream chemokine C-X-C motif chemokine ligand 10(CXCL10). Conclusion PHB2 aggravates LPS-induced periodontitis inflammation via the NF-κB signaling pathway, providing new insights into the molecular mechanisms underlying the development of periodontitis.

Objective:To gain an in-depth understanding of the career development of male nurses in China, analyze trends, challenges, and opportunities, and provide a basis for policy-making, talent cultivation, and professional development in the nursing field.Methods:A descriptive qualitative research method was adopted. From March 29th to July 30th, 2023, the heads of the male nurses working groups of nursing associations in 26 regions of China were selected by purposive sampling method for semi-structured interviews. Content analysis was used to analyze the data.Results:The current situation of the career development of male nurses in China could be summarized into the following three themes. (1) Current situation: the organizational structure of provincial-level male nurses work was basically complete, but there were obvious differences at the grassroots level; the work was carried out in various forms, and diverse models developed in coordination; (2) Trends: there were obvious stratifications in professional ideology and professional abilities of male nurses among different regions and different-level medical institutions; the gender dividend was gradually decreasing, and male nurses should give play to their advantages in logical thinking ability; (3) Prospects: early intervention was needed to enhance professional identity and organizational support; male nurses should be trained in various aspects through multiple forms such as counterpart assistance, expert databases or online academic forums; interdisciplinary development might be the key to stimulating internal driving force.Conclusions:Significant progress has been made in the career development of male nurses in China, but there are still challenges and issues to address. Further improvements in related policies, enhancement of social recognition and professional status, and increased investment and support in research and education are needed to promote the sustained development of male nursing careers.

Objective:To identify the change trajectory of intrinsic capacity in people aged ≥50 years in Shanghai and explore the impact of intrinsic capacity trajectory change on overall function and dalily life activities in this population.Methods:The longitudinal data from round 1 to 3 Study of Global Ageing and Adult Health in Shanghai were used. The total intrinsic ability scores from five dimensions of cognition, psychology, sensory, vitality and locomotion were calculated. The censored normal model of group-based trajectory was used to identify the trajectory of intrinsic capacity change over time. Linear regression model and multivariate logistic regression model were used to analyse the effects of different levels intrinsic capacity trajectory on the scores of the WHO Disability Assessment Schedule (WHODAS), the activity of daily living (ADL) and the instrumental activities of daily living (IADL).Results:A total of 2 302 study participants aged ≥50 years with 3 round complete data were included in this study, and 3 levels of intrinsic capacity trajectory were identified, low-level trajectory (9.3%), medium-level trajectory (41.7%), and high-level trajectory (49.0%). Compared with the high-level group, the medium-level and low-level groups had higher WHODAS scores, which increased by 3.578 (95% CI: 2.028-5.129) and 12.620 (95% CI: 9.951-15.289), respectively, and those with more severe disability and those in the low-level group were at higher risk for severe difficulty in ADLs ( OR=12.450, 95% CI: 4.310-35.966) and IADLs ( OR=5.479, 95% CI: 1.311-22.904). Conclusions:Heterogeneity in trajectory of intrinsic capacity exists in people aged ≥50 years in Shanghai. Middle-aged and elderly people with low initial level and rapid decline trajectory of intrinsic capacity are at greater risk for the decline of daily life ability and the increase of disability. It is necessary to strengthen the long-term dynamic monitoring and evaluation of the change trajectory of intrinsic capacity in this population.

AIM:This study aims to investigate the mechanism by which Zhilianwan(ZLW)decoction affects dextran sodium sulfate(DSS)-induced ulcerative colitis(UC)in mice,focusing on the Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-κB(NF-κB)signaling pathway.METHODS:Fifty male C57BL/6J mice were allowed ad libitum access to food for 1 week before the experiment.They were randomly divided into 5 groups:control group,model group,mesalazine(ME)group,high-dose ZLW(ZLW-H)group,and low-dose ZLW(ZLW-L)group,with ten mice in each group.All mice,except those in control group that received distilled water,were given a 3%DSS solution for seven consecutive days,starting the intervention on the first day of modeling.Each group re-ceived their respective treatments via gavage at volume of 20 μL/g for ten consecutive days.The mice in control and model groups received an equivalent volume of distilled water,while those in ME,ZLW-H,and ZLW-L groups were adminis-tered 0.2 g·kg-1·d-1 of ME,10.92 g·kg-1·d-1 of ZLW,and 2.73 g·kg-1·d-1 of ZLW,respectively.Body weight and dis-ease activity index(DAI)scores were recorded daily.At the end of the intervention,colon length was measured,and he-matoxylin-eosin staining was performed to assess pathological changes in colon tissues.ELISA and qPCR were employed to measure serum levels of interleukin-1β(IL-1β),IL-6,tumor necrosis factor-α(TNF-α)and IL-10,as well as the mRNA expression levels in colon tissues.Western blot analysis was conducted to evaluate the protein levels of TLR4,MyD88,cytosolic NF-κB and nuclear NF-κB in colon tissues.RESULTS:Compared with model group,the mice treated with ZLW exhibited an increase in body weight and colon length(P＜0.05),along with a decrease in DAI and colon histo-pathological scores(P＜0.05).Serum levels of IL-1β,IL-6,and TNF-α were significantly lower(P＜0.05),while IL-10 levels increased(P＜0.05).The mRNA expression levels of these inflammatory factors in colonic tissues reflected similar trends.Additionally,levels of TLR4,MyD88,and nuclear NF-κB proteins were reduced(P＜0.05),whereas cytosolic NF-κB protein expression was elevated(P＜0.05)in the colon tissues of treated mice.CONCLUSION:ZLW exerts at-tenuating effects on DSS-induced intestinal injury in UC mice,though modulation of the TLR4/MyD88/NF-κB signaling pathway.

Objective:To investigate the safety and efficacy of a modified radiofrequency ablation（RFA）treatment method for primary great saphenous vein varicose.Methods:Clinical data of 90 patients with primary great saphenous vein varicose treated with ultrasound-guided RFA from January 2021 to April 2024 in the Ultrasound Department of the First Affiliated Hospital of Zhengzhou University were retrospectively analyzed. Among them，45 patients were treated with traditional RFA treatment method（traditional group）and 45 patients were treated with improved RFA treatment method（improved group）. Number of punctures，operation time，foam hardener dosage，intraoperative and postoperative complications were recorded in the two groups. The preoperative and postoperative venous clinical severity score（VCSS）and chronic venous insufficiency questionnaire（CIVIQ-14）were compared. The closure rate and recurrence rate of great saphenous vein varicose were followed up and the efficacy of the two methods were analyzed.Results:The success rate of the improved group and the traditional group was 100%.The number of punctures in the improved group was less than those of the traditional group［1（1，1） vs. 2（2，3）， Z = -7.431， P<0.001］，and the operation time of the modified group was shorter than that of the traditional group［（15.89 ± 3.63）min vs.（30.91 ± 5.58）min， t=-15.145， P<0.001］，the average volume of lauryl foam was lower than that of the traditional RFA group［（7.96 ± 2.36）ml vs.（15.69 ± 2.89）ml， t=-13.892， P<0.001］. The incidence of complications was similar between the two groups，with no statistical significance（all P>0.05）. Postoperative VCSS and CIVIQ-14 scores were significantly improved compared with before（all P<0.001），with no statistical significance between the two groups（all P>0.05）. At 12 months after the operation，there was no significant difference in the closure rate of the saphenous vein between the improved group and the traditional group（ P>0.05），and the recurrence rate of varicose veins in both groups was 0. Conclusions:This modified RFA treatment method for the treatment of lower extremity varicose veins is minimally invasive，safe，and has the same efficacy as the traditional RFA treatment method. Compared with the traditional RFA treatment method，the modified RFA treatment method has the advantages of convenient operation，less puncture times and shorter operation time，and is worthy of clinical promotion.

Objective:To identify the change trajectory of intrinsic capacity in people aged ≥50 years in Shanghai and explore the impact of intrinsic capacity trajectory change on overall function and dalily life activities in this population.Methods:The longitudinal data from round 1 to 3 Study of Global Ageing and Adult Health in Shanghai were used. The total intrinsic ability scores from five dimensions of cognition, psychology, sensory, vitality and locomotion were calculated. The censored normal model of group-based trajectory was used to identify the trajectory of intrinsic capacity change over time. Linear regression model and multivariate logistic regression model were used to analyse the effects of different levels intrinsic capacity trajectory on the scores of the WHO Disability Assessment Schedule (WHODAS), the activity of daily living (ADL) and the instrumental activities of daily living (IADL).Results:A total of 2 302 study participants aged ≥50 years with 3 round complete data were included in this study, and 3 levels of intrinsic capacity trajectory were identified, low-level trajectory (9.3%), medium-level trajectory (41.7%), and high-level trajectory (49.0%). Compared with the high-level group, the medium-level and low-level groups had higher WHODAS scores, which increased by 3.578 (95% CI: 2.028-5.129) and 12.620 (95% CI: 9.951-15.289), respectively, and those with more severe disability and those in the low-level group were at higher risk for severe difficulty in ADLs ( OR=12.450, 95% CI: 4.310-35.966) and IADLs ( OR=5.479, 95% CI: 1.311-22.904). Conclusions:Heterogeneity in trajectory of intrinsic capacity exists in people aged ≥50 years in Shanghai. Middle-aged and elderly people with low initial level and rapid decline trajectory of intrinsic capacity are at greater risk for the decline of daily life ability and the increase of disability. It is necessary to strengthen the long-term dynamic monitoring and evaluation of the change trajectory of intrinsic capacity in this population.

Objective: To reveal the therapeutic effects of moxibustion in collagen-induced arthritis (CIA) rat models using the combined analysis of plasma and synovial membrane lipidomic profiling and to enhance the understanding of how moxibustion affects lipid metabolism in rheumatoid arthritis (RA). Methods: A total of 32 male Sprague-Dawley (SD) rats were randomly assigned to four groups: control, moxibustion control (MC), model, and moxibustion model (MM) groups, with 8 rats in each group. CIA was induced in SD rats by two immunizations. The paw volume was measured before the induction of CIA. Following induction, after assessing paw volume and arthritis index (AI) scores, the MC and MM groups received treatment at bilateral Shenshu (BL23) and Zusanli (ST36) acupoints for 10 min per acupoint. The intervention included three treatment courses, each spanning 6 d and followed by a 1-d interval. Paw volume and AI scores were assessed after each treatment course. After the completion of the three treatment courses, serum, plasma, synovial tissue, and ankle joint samples were collected. Enzyme-linked immunosorbent assay (ELISA) was employed to quantify the levels of interleukin (IL)-6 and tumor necrosis factor (TNF)-α in serum. Hematoxylin and eosin (HE) staining was performed for histopathological examination of the ankle joint tissues. Meanwhile, ultra-high-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap MS) was utilized to analyze the plasma and synovial tissue samples. In addition, multivariate statistical analysis was performed to identify differential lipid metabolites, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was applied to explore metabolic pathways modulated by moxibustion therapy. Results: No significant difference in hind paw volume and AI scores was observed among the groups (P > 0.05). After CIA induction, model group showed increased hind paw volume and AI scores compared with control group (P < 0.05), which were significantly reduced after moxibustion treatment in MM group compared with model group (P < 0.05). The levels of IL-6 and TNF-α were significantly higher in model and MM groups compared with control group (P < 0.05), but were lower in MM group than those in model group (P < 0.05). Histopathological analysis showed improved cartilage and reduced inflammation in MM group. A total of 33 differential lipid metabolites in the plasma and 24 in the synovial membranes of CIA rat models were identified when compared with control group. Among these lipid metabolites, 31 in the plasma and all 24 in the synovial membranes were regulated by moxibustion treatment. Pathological analysis revealed upregulation of diacylglycerol (DG) and fatty acid (FA) levels, alongside downregulation of lysophosphatidylcholine (LPC), phosphatidylcholine (PC), and phosphatidylethanolamine (PE). Under physiological conditions, the treatment specifically reduced LPC and PC levels. Pathway enrichment analysis revealed that moxibustion predominantly affected α-linolenic acid, glycerophospholipid, and sphingolipid metabolism under pathological conditions. Under physiological conditions, the regulation was centered around α-linolenic acid and glycerophospholipid metabolism. Conclusion The RA rat models exhibited significant lipid metabolic disturbances. Moxibustion alleviated paw swelling, reduced AI scores, modulated inflammatory cytokine levels, and partially corrected the altered levels of multiple lipid metabolites. The potential metabolic pathways implicated in the regulation of lipid metabolism under both physiological and pathological conditions include α-linolenic acid, glycerophospholipid, and sphingolipid metabolism.

Objective To identify long non-coding RNA (lncRNA) associated with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and investigate their mechanisms. Methods Peripheral blood samples were collected from RA-ILD patients (n＝3), RA patients without lung involvement (n＝3), and healthy controls (n＝3). Next-generation sequencing was performed to screen differentially expressed lncRNA. A human fibrotic lung cell model was established by inducing the MRC-5 cell line with transforming growth factor-β (TGF-β). Following siRNA-mediated knockdown of target genes, changes in inflammatory and oxidative stress-related genes were analyzed via real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR). Western blotting and dual-luciferase reporter (DLR) assays were used to validate protein expression, ubiquitination levels, and nuclear translocation of oxidative stress regulators, and antioxidant response element (ARE) transcriptional activity. Rescue experiments were conducted to confirm the role of target lncRNA in oxidative stress and inflammation in fibrotic lung cells. Results High-throughput sequencing revealed significant downregulation of LINC00638 in RA-ILD patients. Knockdown of LINC00638 markedly reduced transcriptional levels of interleukin (IL)-4, nuclear factor erythroid-2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and superoxide dismutase 2 (SOD2), while increasing IL-6, IL-1β, interferon-γ (IFN-γ), and reactive oxygen species (ROS) levels. Furthermore, LINC00638 knockdown decreased Nrf2 protein expression, increased its ubiquitination, reduced nuclear translocation, and suppressed ARE transcriptional activity. In MRC-5 cells, LINC00638 knockdown combined with N-acetylcysteine treatment restored Nrf2 and HO-1 levels while reducing IL-6 expression. Conclusions LINC00638 suppresses inflammatory responses in RA-ILD by activating the Nrf2/ARE antioxidant signaling pathway, suggesting its potential as a therapeutic target for diagnosis and treatment.

OBJECTIVES: To investigate the correlation of PRELID1 with gastric cancer (GC) progression, prognosis, and epithelial-mesenchymal transition (EMT) and the underlying mechanisms. METHODS: We analyzed the data of 115 patients undergoing radical gastrectomy for GC in our hospital between February, 2018 and March, 2023 to explore the correlation of PRELID1 expression level in GC tissues with tumor progression and patient prognosis. In cultured GC cells, the effects of lentivirus-mediated overexpression or interference of PRELID1 were observed on cell migration, invasion and EMT. RESULTS: Immunohistochemical staining revealed significantly higher PRELID1 expression in GC tissues (P<0.001), whose expression level was positively correlated with CEA ≥5 ng/mL (P=0.007), CA199 ≥37 U/mL (P=0.007), G_3-4 stages (P=0.001), T_3-4 stages (P=0.001), and N_2-3 stages (P=0.020). Univariate and Cox multifactorial analysis showed that high PRELID1 level was an independent risk factor affecting 5-year survival of GC patients (P=0.001). In cultured GC cells, PRELID1 overexpression obviously promoted cell proliferation, migration, invasion, and the expressions of MMP2 and MMP9, and interference of PRELID1 produced the opposite changes. PRELID1 overexpression also increased the expressions of N-cadherin and vimentin and reduced the expression of E-cadherin. Mechanistic analyses showed that up-regulation of PRELID1 increased the expression of p-PI3K, p-AKT, and p-mTOR in GC cells, whereas its interference caused the opposite changes; the application of 740 Y-P, a PI3K/AKT pathway activator, significantly enhanced the migration, invasion, and EMT of GC cells with PRELID1 knockdown. CONCLUSIONS PRELID1 is highly expressed in GC and affects prognosis of the patients, and its high expression promotes migration, invasion and epithelial mesenchymal transition of GC cells possibly by activating the PI3K/AKT/mTOR pathway.
Humans ; Stomach Neoplasms/metabolism* ; Epithelial-Mesenchymal Transition ; Prognosis ; Cell Movement ; Cell Line, Tumor ; Male ; Female ; Middle Aged ; Signal Transduction ; Neoplasm Invasiveness ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism*