BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

AIM:This study aimed to investigate the expression and localization of ALOX12P2 in oral squa-mous cell carcinoma(OSCC),as well as its effects on cell viability,migration,and invasion.METHODS:The expres-sion of ALOX12P2 in head and neck squamous cell carcinoma(HNSCC)tissues and its correlation with clinicopathologi-cal features were analyzed using the UALCAN database(University of Alabama at Birmingham Cancer Data Analysis Por-tal).Additionally,the expression of ALOX12P2 in OSCC and its impact on survival prognosis were evaluated through the GDC and UCSC Xena databases.The expression levels of ALOX12P2 in OSCC cell lines were assessed via quantitative re-al-time PCR(RT-qPCR).The subcellular localization of ALOX12P2 was determined using nucleoplasmic RNA isola-tion.CAL-27 cells were used to establish an ALOX12P2 knockdown group(SS-ALOX12P2)and a control group(SS-NC).HN30 cells were employed to form an ALOX12P2 overexpression group(ALOX12P2)and a control group(vector).The effects of altered ALOX12P2 expression on the epithelial-mesenchymal transition(EMT)-related gene E-cadherin and the PI3K/AKT signaling pathway were assessed through Western blot analysis.RESULTS:ALOX12P2 expression was significantly higher in HNSCC and OSCC tissues compared to normal tissues,with its expression correlating with poor prog-nosis.RT-qPCR analysis indicated that the relative expression of ALOX12P2 in OSCC cells was comparable to that in nor-mal cells(P<0.05).RNA nucleoplasmic isolation confirmed that ALOX12P2 localized in the nucleus.In comparison to the SS-NC group,the SS-ALOX12P2 group exhibited a marked reduction in ALOX12P2 expression(P<0.01),alongside significant decreases in cell viability,migration,and invasion(P<0.01).Conversely,the ALOX12P2 group showed sub-stantially higher relative expression compared to the vector group(P<0.01),with enhanced cell viability,migration,and invasion abilities(P<0.01).Western blot analysis demonstrated that ALOX12P2 knockdown resulted in upregulation of E-cadherin and downregulation of N-cadherin and Vimentin(P<0.01),while overexpression of ALOX12P2 yielded the opposite effects(P<0.01).Knockdown of ALOX12P2 led to decreased protein expression of p-PI3K and p-AKT(P<0.01),whereas overexpression increased these protein levels(P<0.01).CONCLUSION:ALOX12P2 is highly ex-pressed in OSCC and promotes cell viability,migration,and invasion.This effect may be linked to the activation of the PI3K/AKT signaling pathway,which facilitates the epithelial-mesenchymal transition(EMT)process.

Background Due to the limited availability of established research models, very few studies addressed the health effects and underlying mechanisms following exposure to diesel exhaust during the initiation of pulmonary respiration. It is highly demanded to elucidate such health effects and underlying mechanisms, so as to exert protective measures during the early stages of life. Objective To evaluate the health effects of diesel exhaust very-early-in-life inhalation in hatchling chicken with a novel chicken embryo air cell inhalation exposure model, and to explore the potential roles of aryl hydrocarbon receptor signaling pathways in the observed effects with a specific aryl hydrocarbon receptor inhibitor. Methods Fertilized chicken eggs were assigned into five groups randomly (15 eggs per group): control group, air control group, aryl hydrocarbon receptor inhibitor (PDM2) group, diesel exhaust group, and diesel exhaust + aryl hydrocarbon receptor inhibitor (PDM2) group. Fertilized eggs were incubated with standard procedure. At embryonic day 17 (ED17), aryl hydrocarbon receptor inhibitor was administered to the corresponding animals. During embryonic day 18-19 (ED18-19), chicken embryos were exposed to diesel exhaust via air cell inhalation, then placed back to incubator until hatch. The air control group received clean air infusion during ED18-19, while the control group did not receive any treatment. Within 24 h post-hatch, 26 hatchling chickens were anesthetized with sodium pentobarbital, subjected to electrocardiography, and sacrificed to harvest tissue samples of heart and lung. Cardiopulmonary toxicities were evaluated by histopathology, and potential changes in the protein expression levels of aryl hydrocarbon receptor pathway molecule cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) and fibrosis-related pathway molecule phosphorylated SMAD family member 2 (pSMAD2) were assessed by Western blotting. The remaining 29 hatchling chickens were reared until two weeks old, and then subjected to identical treatments. Results The inhalation exposure to diesel exhaust at initiation of pulmonary respiration resulted in thickened right ventricular wall (by 220.3% relative to the control group, same hereafter) and elevated heart rate (17.4%) in one-day-old hatchling chickens. Although no remarkable fibrotic lesions were observed at this point, the expression levels of CYP1A1 and phosphorylation levels of SMAD2 in the lung tissues significantly increased (by 81.3% and 71.6%, respectively). Such changes were effectively abolished by the aryl hydrocarbon receptor inhibitor PDM2 pretreatment. In the two-week-old animals, the thickened right ventricular wall (by 339.3%) and elevated heart rate (by 18.9%) persisted, and significant fibrotic lesions were observed in the lung tissue samples under Masson staining. Again, the aryl hydrocarbon receptor inhibitor PDM2 pretreatment effectively abolished such changes. In addition, no statistically significant changes in CYP1A1 expression levels were observed in the two-week-old chicken lung samples, and a remarkable down-regulation of SMAD2 phosphorylation was observed. The aryl hydrocarbon receptor inhibitor PDM2 pretreatment independently decreased the phosphorylation levels of SMAD2 in the two-week-old chicken lung samples. Conclusion Inhalation exposure to diesel exhaust at initiation of pulmonary respiration could result in persistent cardiopulmonary injury in hatchling chickens, and the underlying mechanism might be associated with the regulation of pSMAD2 by the aryl hydrocarbon receptor signaling pathway.

In recent years, organ donation and transplantation have entered a stage of steady development in China. Nevertheless, the shortage of transplant organs and the contradiction between supply and demand of organs are still the bottlenecks to achieve the strategy of "self-sufficiency in organ transplantation" advocated by the World Health Organization (WHO). The key reasons for donor loss described in the "critical pathway of organ donation" defined by the WHO include the identification and referral of potential donors and the maintenance and repair of organs. Smooth development, high efficiency and high-quality development of organ donation cannot be achieved without the support of intensive care medicine, which are highly associated with the cognition, recognition and participation of intensive care unit(ICU) staff. In this article, research progress in ICU staff’s cognition, attitude and willingness for organ donation were reviewed and relevant influencing factors were discussed, aiming to offer targeted suggestions on how to resolve these difficulties.

Objective:To explore the mediating effect of social support and exercise self-efficacy on the intrinsic capacity of community-dwelling older adults and healthy aging, so to provide a basis for improving the healthy aging of community-dwelling older adults.Methods:From January to July 2022, cluster random sampling was used to select 1 303 community-dwelling older adults from Urumqi City as the research subject. The survey was conducted using the General Information Questionnaire, Healthy Aging Instrument, Intrinsic Capacity Questionnaire, Social Support Rating Scale, and Exercise Self Efficacy Scale for Aged People in Community. The conceptual model was used to explore the relationship among social support, exercise self-efficacy, intrinsic capacity, and healthy aging in community-dwelling older adults. A total of 1 303 questionnaires were distributed, and 1 042 valid questionnaires were collected, with an effective response rate of 80%.Results:Among 1 042 community-dwelling older adults, the scores of the Intrinsic Capacity Questionnaire, Healthy Aging Instrument, Social Support Rating Scale, and Exercise Self Efficacy Scale for Aged People in Community were [1.00 (0, 2.00) ] , [146.00 (133.75, 155.00) ] , [41.00 (36.00, 46.00) ] and [51.00 (39.00, 61.00) ] , respectively. The intrinsic capacity of community-dwelling older adults was negatively correlated with social support, exercise self-efficacy, and healthy aging ( r=-0.112, -0.121, -0.120, P<0.01) , and social support and exercise self-efficacy were positively correlated with healthy aging (r=0.129, 0.113, P<0.01) . Bootstrap mediating effect test showed that the mediating effect of social support and exercise self-efficacy between the intrinsic capacity of community-dwelling older adults and healthy aging was established, with a mediating effect value of -0.477, accounting for 24.75% of the total effect. The path effect value of intrinsic capacity→ social support→ healthy aging was -0.262, accounting for 54.93% of the mediating effect value. The path effect value of intrinsic capacity → exercise self-efficacy→ healthy aging was -0.214, accounting for 44.86% of the mediating effect value. Conclusions:In the community elderly population, social support and exercise self-efficacy can play a mediating role between intrinsic capacity and healthy aging. Community health care providers should pay attention to the internal capacity of the older adults, improve social support and exercise self-efficacy, and thus promote the realization of healthy aging of the older adults.

Objective To explore the protective effects and mechanism of Zuogui Jiangtang Jieyu Formula (左归降糖解郁方, ZGJTJYF) on hippocampal neurons in rats of diabetes complicated with depression (DD) via the TRP/KYN metabolic pathway. Methods (i) In vivo experiments: 60 specified pathogen free (SPF) grade male Sprague-Dawley (SD) rats were randomly divided into six groups with 10 rats in each groups: control, DD model, positive (1.8 mg/kg fluoxetine + 0.18 g/kg metformin), high-dose ZGJTJYF (ZGJTJYF-H, 40.500 g/kg ZGJTJYF), middle-dose ZGJTJYF (ZGJTJYF-M, 20.250 g/kg ZGJTJYF), and low-dose ZGJTJYF (ZGJTJYF-L, 10.125 g/kg ZGJTJYF) groups. Except for the control group, other groups were established DD model by high-fat emulsion intake with single tail vein streptozotocin (STZ) and four weeks of chronic unpredictable mild stress (CUMS). All drug administration groups were treated by gavage during CUMS modeling, and the control and model groups were given equal amount of distilled water. After four weeks, the serum levels of blood glucose and glycosylated hemoglobin were measured to determine the hypoglycemic effect of ZGJTJYF. Moreover, the open field test and Morris water maze test were performed to evaluate the antidepressant effect of ZGJTJYF. Changes in 5-hydroxytryptamine (5-HT) level were detected via high-performance liquid chromatography with electrochemical detection (HPLC-ECD); the levels of tryptophan (TRP), kynurenine (KYN), and indoleamine 2,3-dioxygenase (IDO) in the hippocampus were detected using enzyme-linked immunosorbent assay (ELISA); the protein expression levels of synaptophysin (SYN) and postsynaptic density material-95 (PSD-95) were detected via immunohistochemistry (IHC); and the protein expression levels of N-methyl-D-aspartate receptor (NR) 2A and NR2B were detected using Western blot. (ii) In vitro experiments: five SPF grade SD pregnant rats (E16 – 18) were used to obtain primary hippocampal neurons (Ne), six SD new-born rats were used to collected primary astrocytes (As) and microglia (MG), and to establish a Ne-As-MG co-culture system. All co-culture systems were divided into six groups: control (PBS), model [150 mmol/L glucose + 200 μmol/L corticosterone (G&P) + PBS], blank (G&P + blank serum), positive (G&P + positive drug-containing serum), ZGJTJYF (G&P + ZGJTJYF serum), and 1-methyl-D-tryptophan (1-MT, IDO inhibitor) (G&P + 1-MT) groups. After 18 h of intervention by corresponding treatment, immunofluorescence was used to analyze the protein expression levels of SYN, PSD-95, NR2A, and NR2B; ELISA was performed to measure the levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α , and TRP/KYN metabolic pathway-related factors [TRP, KYN, kynurenine acid (KYNA), quinolinic acid (QUIN)]. Results (i) In vivo experimental results showed that ZGJTJYF-M and ZGJTJYF-L significantly improved the elevated blood glucose state of DD rats (P < 0.01 and P < 0.05, respectively); ZGJTJYF-H, ZGJTJYF-M, and ZGJTJYF-L increased their autonomous activity, learning, and memory ability (P < 0.01, P < 0.01, and P < 0.05, respectively). Moreover, the levels of 5-HT and TRP were significantly increased (P < 0.01), and the levels of KYN and IDO were significantly decreased in the hippocampus (P < 0.01) of rats after ZGJTJYF-M treatment. The protein expression levels of SYN and PSD-95 were significantly upregulated in hippocampal neurons (P < 0.01), while the abnormal activation of NR2A and NR2B was markedly inhibited in hippocampus (P < 0.05) of rats after ZGJTJYF-M treatment. (ii) In vitro experimental results showed that ZGJTJYF-containing serum significantly increased the protein expression levels of SYN and PSD-95 in hippocampal neurons (P < 0.01), decreased the levels of IL-1β (P < 0.01), IL-6 (P < 0.05), TNF-α (P < 0.01), IDO (P < 0.05), KYN (P < 0.05), and QUIN (P < 0.01), and increased the levels of TRP and KYNA (P < 0.01) in the simulated DD state. ZGJTJYF also had an significantly inhibitory effect on the abnormal activation of NR2A and NR2B in neurons (P < 0.05) in a stimulated DD state. Conclusion ZGJTJYF can effectively improve 5-HT deficiency in the hippocampus of rats by inhibiting IDO expression and regulating the TRP/KYN metabolic pathway, and it has a favorable protective effect on hippocampal neuron injury caused by DD. Therefore, ZGJTJYF is an effective potential therapeutic drug for the prevention and treatment of DD.

Public trust is the foundation for supporting the sustainable development of various social donation systems. However, the construction of trust system is continuous, long-term, and easily lost and difficult to defend. This study explored the multi-object and multi-dimensional trust demands of the public, donors and their families in interpersonal, system, social and supervision aspects. It was proposed that participating institutions and practitioners should take the multidimensional claims as an action-oriented, break the crisis of trust by building two major support systems centered on the public and donors’ families, and jointly safeguard the sustainable and high-quality development of organ donation.

At present, interdisciplinary integration has become a major feature of the development of science and technology, and multi-disciplinary integration will gradually become the norm. Professional and technological multi-disciplinary integration has unpredictable potential, which will produce new disciplinary frontiers, new fields of science and technology and new patterns of innovation. Organ donation is a new discipline in China's new era. Constructing and promoting an organ donation disciplinary system with the overall goal of safeguarding legal and reasonable rights and interests of donors and their families and the health rights and interests of the recipients are in line with the fundamental requirements of maintaining high-quality development of organ donation and transplantation in China. Meantime, organ donation is a complex medical and social behavior, and organs donated by citizens belong to national resources, which also endows organ donation with a social welfare attribute and relevance with all parties in society. In this article, the essence of current problems encountered during organ donation in China, the whole process of organ donation and theoretical knowledge, professional skills and personnel support required by donors in different clinical stages were analyzed to illustrate the necessity and feasibility of establishing an organ donation disciplinary system based on multi-disciplinary integration. Besides, how to integrate organ donation disciplinary construction into the national policy was also investigated. Taking safeguarding the rights and interests of donors, family members and recipients as the core and taking organ donation and transplantation as the main line, cooperative principles of co-creation, co-construction, mutual promotion, sharing and win-win should be upheld, aiming to promote multi-disciplinary integration and comprehensive talent cultivation of organ donation, jointly enhance the recognition rate and donation rate of organ donation, and make organ donation widely recognized by citizens from all walks of life.

Objective:To investigate the post competency of "Academic-Practical" of clinical nursing teachers, and analyze related influencing factors.Methods:A total of 312 "Academic-Practical" and "Non-Academic-Practial" clinical nursing teachers from The Affiliated Hospital of Southwest Medical University were surveyed by the Clinical Nursing Teacher Post Competency Evaluation Questionnaire. SPSS 20.0 software was used for t test, chi-square test and rank sum test. Results:The average self-evaluation scores of post competency of "Academic-Practical" clinical nursing teachers were (4.26±0.41) points, which were higher than those of the "Non-Academic-Practical" teachers [(3.19 ±0.50) points], showing good post competency. There were significant differences in the scores of professional quality (17.39±1.54), professional attitude (21.75±2.21), professional ability (21.14±2.31), teaching ability (50.39±5.93), interpersonal coordination ability (25.57±3.04), and personality characteristics (17.27±2.04) between the "Academic-Practical" and "Non-Academic-Practical" teachers (all P<0.01). And there were significant differences in self-evaluation post competency scores of "Academic-Practical" teachers in "with or without teacher qualification certificate" ( P=0.001), "whether she/he is the backbone of the department" ( P=0.002), degree ( P=0.001), age ( P<0.001), positional title ( P<0.001) and working year ( P<0.001) (all P<0.01). But there was no significant difference in gender ( P=0.735) and "whether she/he is a specialized nurse" ( P=0.335). Conclusion:"Academic-Practical" and "Non-Academic-Practical" medical teachers should take the post competency as the core orientation, adopt the "Ladder" mode of training and management, and constantly improve the training plan of post competencey.

Acetaminophen (APAP) overdose is the leading cause of drug-induced liver injury, and its prognosis depends on the balance between hepatocyte death and regeneration. Sirtuin 6 (SIRT6) has been reported to protect against oxidative stress-associated DNA damage. But whether SIRT6 regulates APAP-induced hepatotoxicity remains unclear. In this study, the protein expression of nuclear and total SIRT6 was up-regulated in mice liver at 6 and 48 h following APAP treatment, respectively.