Idiopathic pulmonary fibrosis (IPF) is a progressive disease lacking effective therapy. Metformin, an antidiabetic medication, has shown promising therapeutic properties in preclinical fibrosis models; however, its precise cellular targets and associated mechanisms in fibrosis resolution remain incompletely defined. Most research on metformin's effects has focused on mesenchymal and inflammatory responses with limited attention to epithelial cells. In this study, we utilized Sftpc lineage-traced and Fgfr2b conditional knockout mice, along with BMP2/PPARγ and AMPK inhibitors, to explore metformin's impact on alveolar epithelial cells in a bleomycin-induced pulmonary fibrosis model and cell culture. We found that metformin increased the proliferation and differentiation of alveolar type 2 (AT2) cells, particularly the recently identified injury-activated alveolar progenitors (IAAPs)-a subpopulation characterized by low SFTPC expression but enriched for PD-L1. Single-cell RNA sequencing revealed a reduction in apoptosis among mature AT2 cells. Interestingly, metformin's therapeutic effects were not significantly affected by BMP2 or PPARγ inhibition, which blocked the lipogenic differentiation of myofibroblasts. However, Fgfr2b deletion in Sftpc lineage cells significantly impaired metformin's ability to promote fibrosis resolution, a process linked to AMPK signaling. In conclusion, metformin alleviates fibrosis by directly activating AT2 cells, especially the IAAPs, through a mechanism that involves AMPK and FGFR2b signaling, but is largely independent of BMP2/PPARγ pathways.

Objective : To pathological changes and inducible nitric oxide synthase(iNOS), phosphorylated insulin receptor substrate 1 serine 307(p-IRS1ser 307), phosphorylated protein kinase B serine 473(p-AKTser 473), glycogen synthase kinase-3β(GSK-3β), and gluconeogenic synthase(GS) proteins were observed in the liver of rats under the condition of chronic intermittent hypoxia-replicated oxygen in control. And to explore the role of iNOS/IRS1/AKT/GSK-3β signaling pathway in chronic intermittent hypoxia-induced insulin resistance. Methods : Forty SD rats were randomly divided into a control group(NC group) and an experimental group(CIH group), with 20 rats in each group. The NC group was placed in a normoxic environment for 12 weeks, while the CIH group was first subjected to intermittent hypoxia for 8 weeks, and then resumed normoxic rearing until the 12th week. Fasting blood glucose(FBG) and fasting insulin(FINS) were measured at baseline, week 8 and week 12, and liver tissues were taken for pathology and measurement of iNOS, p-IRS1ser 307, p-AKTser 473, GSK3β and GS levels, to compare the differences between groups. Results: t baseline, there was no significant difference in liver pathology between the two groups, and the observed indexes were not statistically significant(P>0.05); at 8 weeks, compared with the NC group, liver pathology in the CIH group showed significant disorganization of hepatic blood sinusoids and hepatocyte cords, obvious hepatocyte edema, smaller nuclei, increased lymphocyte infiltration, and a small number of fat vacuoles, significantly higher levels of FBG, FINS, insulin resistance index(HOMA-IR), iNOS mRNA, p-IRS1ser 307 protein, GSK-3β protein levels, and decreased p-AKTser 473 protein and GS protein levels, all of which were statistically significant(allP<0.05). IRS1ser 307 protein, GSK-3β protein levels were increased, p-AKTser 473 protein and GS protein levels were decreased, and the differences were statistically significant(allP<0.05); at 12 weeks, no lymphocyte infiltration was seen in the CIH group compared with that of the NC group and fat vacuoles significantly increased, and there was no improvement in the other pathological damage that had already occurred, and the levels of p-AKTser 473 protein significantly increased. AKTser 473 protein level significantly increased, p-IRS1ser 307 protein and GS protein levels were significantly reduced, all of which were statistically significant(allP<0.05), and the rest of the observational indexes were not statistically significant. Pearson′s correlation analysis showed that HOMA-IR of CIH group was significantly positively correlated with the levels of iNOS mRNA, p-IRS1ser 307 protein, and GSK-3β protein at 8 weeks(r=0.874, 0.817,0.872;allP<0.05), and significantly negatively correlated with the levels of p-AKTser 473 protein and GS protein(r=-0.886,-0.879;allP<0.05). Conclusion Chronic intermittent hypoxia can lead to hepatic pathological damage that cannot be reversed even by reoxygenation interventions and may mediate the development of insulin resistance by upregulating the IRS1/AKT/GSK-3β signaling pathway through the upregulation of iNOS mRNA expression.

To summarize the nursing experience of a patient with acute injection botulism complicated with respiratory failure.The key nursing points include early standard use of botulinum antitoxin therapy to improve the signs of myasthenia;to strengthen respiratory support and airway management,to carry out respiratory training,and to promote the recovery of respiratory function;swallowing function training and dynamic evaluation were carried out to promote the recovery of swallowing function;narrative nursing was carried out to relieve patient's negative emotions.After 17 days of treatment and nursing care,the patient was removed from the tracheal tube on the 7th day,transferred to the general ward on the 14th day,and discharged successfully on the 17th day with a good prognosis.A telephone follow-up was conducted 4 months after discharge,and the patient recovered well.

Objective To investigate the effect of ankle pump exercises,based on hemodynamic mechanisms,on the prevention of venous thrombosis in stroke patients.Methods A total of 110 stroke patients,admitted to a tertiary A hospital in Jiangsu Province between June 2023 and June 2024,were selected using a convenience sampling method.The patients were divided into an experimental group and a control group,with 55 patients in each group.The experimental group received ankle pump exercise nursing interventions based on hemodynamic mechanisms,while the control group received routine nursing interventions.The incidence of lower extremity deep vein thrombosis,Pittsburgh Rehabilitation Participation Scale scores,subjective perceived fatigue,and exercise self-efficacy scores were compared between 2 groups on the 7th day of hospitalization.Results No dropouts occurred in either group.The incidence of deep vein thrombosis was significantly lower in the experimental group than it in the control group(P=0.004).The Pittsburgh Rehabilitation Participation scores on day 1,3,5,and 7 were higher in the experimental group compared to them in the control group(P＜0.001).A significant time-dependent trend was observed in Pittsburgh Rehabilitation Participation scores(P=0.034).Subjective fatigue was significantly lower in the experimental group at various time points(P＜0.001).Both groups showed an increase in exercise self-efficacy over time(P=0.016),with the experimental group demonstrating higher exercise self-efficacy than the control group on the day before discharge(P=0.003).Conclusion Ankle pump exercises,based on hemodynamic mechanisms,can effectively reduce the incidence of deep vein thrombosis in stroke patients,enhance rehabilitation participation and exercise self-efficacy,without increasing subjective fatigue.

BACKGROUND: Doxorubicin hydrochloride (DOX) is extensively used in the treatment of various tumors. However, its clinical application is limited due to dose-dependent cardiotoxicity. Currently, few effective strategies exist to mitigate or eliminate DOX-induced cardiomyopathy (DIC). Although ferroptosis is implicated in DIC and its inhibition partially alleviates the condition, the direct targets of DOX in the progression of cardiotoxicity remain unclear. This study aimed to discover the direct targets of DOX in ferroptosis-mediated DIC. METHODS: A DOX pulldown assay was performed to identify proteins specifically binding to DOX in murine hearts, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify candidate proteins. A cardiac injury mouse model was established by DOX treatment. Based on this, multiple ferroptosis biomarkers were detected by flow cytometry, quantitative real-time polymerase chain reaction, western blotting, immunochemistry, etc. Besides, specific activator and inhibitor of signaling pathways were applied to illuminate molecular mechanisms. RESULTS: Glutathione S-transferase P1 (GSTP1) was identified as a DOX target. GSTP1 activity was inhibited in DOX-treated cardiomyocytes, while its overexpression significantly alleviated DIC. Moreover, GSTP1 overexpression inhibited acyl-CoA synthetase long-chain family member 4 (ACSL4)-dependent ferroptosis. Mechanistically, GSTP1 overexpression suppressed c-Jun N-terminal kinase (JNK) phosphorylation, thereby reducing reactive oxygen species (ROS) production and inhibiting ferroptosis in DIC. CONCLUSIONS This study identifies the DOX/GSTP1/JNK axis as a critical pathway mediating ACSL4-dependent ferroptosis in DIC. GSTP1 is highlighted as a potential key mediator of ferroptosis and a promising therapeutic target for DIC.

Objective:To investigate the clinicopathological and molecular characteristics of neurocutaneous melanosis in children caused by NRAS gene variants.Methods:Three cases of neurocutaneous melanosis from Children's Hospital of Fudan University (case 1 and case 2) and Shanghai Children′s Hospital, School of Medicine Shanghai Jiaotong University (case 3) from July 2022 to February 2023 were collected. The clinical, histopathological, immunohistochemical and genetic results of three patients were retrospectively analyzed. The literatures were reviewed.Results:The patients were all female, aged 5, 4 and 3 years, respectively. The patients presented with severe headache with other symptoms of increased intracranial pressure. Physical examination showed multiple congenital melanocytic nevi throughout the body. Imaging examination showed intracranial masses, which were located in the right cerebellum, pineal gland and left temporal lobe, respectively. The maximum diameters were 39.1 mm, 72.8 mm and 52.2 mm, respectively. Histologically, the tumor showed diffuse sheets of round or oval-shaped cells arranged in nests, with marked nuclear atypia, eosinophilic cytoplasm, dark nuclei, and prominent nucleoli. Giant tumor cells were seen and mitotic figures were easily observed. There were hemorrhage and necrosis. Pigment granules were found in the cytoplasm and stroma in case 1 and case 2. Immunohistochemically, the tumor cells showed diffuse and strong staining of SOX10, S-100, HMB45 and Melan A, but did not express GFAP and CKpan. The Ki-67 proliferation index ranged from 30% to 80%. Genetic testing showed that case 1 and case 2 had NRAS Q61K matation, and case 3 had NRAS Q61R mutation. Case 1 and case 3 underwent complete resection of the tumor combined with chemotherapy. Case 2 was diagnosed by biopsy and underwent resection after chemotherapy and radiotherapy. All patients were followed up for 18, 21 and 25 months, respectively. All patients died due to complications such as increased intracranial pressure and hydrocephalus.Conclusions:Neurocutaneous melanosis is a congenital neurocutaneous syndrome caused by abnormal development of embryonic neuroectodermal melanoblasts. Most cases are associated with somatic mutations of NRAS gene. Clinicians should pay attention to the skin manifestations and neuroimaging examination in patients with unexplained intracranial hypertension or epilepsy. The diagnosis of neurocutaneous melanosis depends on histopathology and genetic testing.

Objective:To establish a risk prediction model by analyzing the influencing factors of delivery be-fore 34 weeks' gestatior with singleton pregnancies who underwent transcervical McDonald's cervical cerclage.Methods:Clinical data of 500 pregnant women with singleton pregnancies who underwent McDonald's cervical cerclage in the Department of Obstetrics and Gynecology,Heping Hospital,General Hospital of the People's Lib-eration Army Northern Theater of Operations from January 1,2019 to February 29,2024 were retrospectively ana-lyzed,and were randomly divided into a training set of 350 cases versus a validation set of 150 cases in accord-ance with a 7∶3 randomization.The data in the training set were screened for predictive variables affecting deliv-ery before 34 weeks' gestation after cervical cerclage using univariate combined multivariate Logistic regression,predictive modeling and assessment were established,and internal validation was performed in the validation set.Results:Preoperative cervical length(CL)＜20 mm,amniotic fluid deposits(AFS),absence of Lactobacillus vagi-nalis,and cervical dilatation＞3 cm were independent risk factors for adverse outcomes of labor and delivery be-fore 34 weeks' gestation after cervical cerclage(OR＞1,P＜0.05),and the Nomogram model constructed on the basis of this was found to have an AUC of 0.887,with a good agreement of the model(H-L test:P=0.905,Brier score of 0.095).The results of the clinical decision curve showed that the clinical decision value of the model was high when the threshold was between 0.10-0.92.The model was internally validated with an AUC of 0.812,and there was a high degree of agreement between the predictions and the actual situation(H-L test:P=0.859).Conclusions:The column-line diagram model constructed on this basis has a high clinical value,which can help us to screen out the high-risk pregnant women and give them individualized interventions in a timely manner.

Objective:To develop a journey map for health management of patients with disability caused by accidental trauma from the social ecosystem theory perspective, so as to gain deeper insights into their actual needs during medical treatment and rehabilitation.Methods:The descriptive qualitative research was adopted. Purposeful sampling was employed to select patients with disability caused by accidental trauma admitted to the Trauma Center of the Department of Emergency and Critical Care Medicine at the First Affiliated Hospital with Nanjing Medical University between April and May 2024 for semi-structured interviews. Traditional content analysis method was employed to analyze the interview data.Results:From three dimensions of microsystem, mesosystem, and macrosystem, the needs and potential issues of medical treatment at different stages of the health management process for patients with disability caused by accidental trauma were analyzed, forming a patient journey map.Conclusions:Patients with disability caused by accidental trauma face prolonged periods of medical treatment, rehabilitation, and lifestyle readjustment, imposing significant burdens on themselves, their caregivers, and their families. Healthcare providers may proactively engage with patients based on their current and potential issues and needs, offer specialized guidance at critical junctures and meet the need of patients for continuity of care, thereby improving patients' quality of life and overall health outcomes.

Objective To study the efficacy and safety of less invasive surfactant administration(LISA)combined with budesonide and supported by nasal intermittent positive pressure ventilation(NIPPV)in preterm infants with respiratory distress syndrome(RDS).Methods Premature infants with RDS at the gestational age of 26-32 weeks in the neonatal ward of Xuzhou Central Hospital from Feb-ruary 2022 to March 2024 were divided into the observation group and the control group in this prospective randomized controlled trial.The control group suspended nasal continuous positive airway pressure(NCPAP),they were intubated and infused with PS into the lung through endotracheal tube and extubated(INSURE),then continued to receive NCPAP.In the observation group,a LISA tube was insert-ed through the vocal cords under direct vision with direct laryngoscope,then infused pulmonary surfactant(PS)and budesonide into the lung when NIPPV ventilation was applied.The results of blood gas analysis at 1h and 6h after intratracheal instillation of PS,medication administration,clinical efficacy,related complications of budesonide,bronchopulmonary dysplasia(BPD)were compared between the two groups.Results A total of 126 preterm infants with RDS were enrolled in the study,including 65 in the observation group and 61 in the control group.The incidence of regurgitation in the observation group were lower than those in the control group[(10.8％(7/65)vs 24.6％(15/61)],and the differences were statistically significant(P＜0.05).The PaO2/FiO2(P/F)in the observation group at 1h and 6h were higher than those in the control group,while PaCO2were lower than those in the control group,and the differences were statis-tically significant(all P＜0.05).The duration of non-invasive respiratory support(11.4±4.6 days vs 15.9±5.6 days),total oxygen inhaling(14.9±6.9 days vs 21.2±8.5 days),failure rate of machine withdrawal[(10.8％(7/65)vs 24.6％(15/61)],the rate of tracheal intubation within 72h[9.2％(6/65)vs 23.0％(14/61)],and re-administration of PS[18.5％(12/65)vs 34.4％(21/61)],the times of apnea[9.0(3.0-25.0)times vs 17.0(5.0-29.0)times]in the observation group were lower than those in the control group,and the differences were statistically significant(P＜0.05).The occurrence of BPD in the observational group were lower than those in the control group[15.4％(10/65)vs 34.4％(21/61)](P＜0.05).There were no significant differences between two groups in the related complications of budesonide(all P＞0.05).Conclusion LISA combined with budesonide and supported by NIPPV can effectively improve oxygenation,shorten the duration of non-invasive respiratory support,reduce the mechanical ventilation rate,and reduce the incidence of BPD in the treatment of premature infants with RDS at the gestational age of 26-32 weeks.

Objective To compare six existing Chinese standards related to visual disability,including Disability Assessment and Code for Life Insurance(Insurance Standard),Specification for Ability Assessment of Older Adults(Elderly Stan-dard),Grading of Disability due to Human Body Injury(Judicial Standard),Standard for Identify Work Ability—Gradation of Disability Caused by Work-related Injuries and Occupational Diseases(Work Injury Standard),Standard for Assessment of Disability Grades of Military Personnel(Military Standard),and Classification and Grading Criteria of Disability(Disability Classification Standard).Methods Based on the theoretical framework of International Classification of Functioning,Disability and Health(ICF)and International Classification of Diseases,the 11th Revision(ICD-11),and with reference to World Report on Vision(WRV),this study analyzed and compared five key dimensions of visual disability across the six stan-dards:definition,classification,grading,assessment methods and coding systems.Results In terms of definition,the insurance,work injury,military,and disability classification standards emphasized vi-sual structure and function,focusing on visual acuity and visual field;the insurance and elderly standards incor-porated activities and participation,reflecting the concept of functional vision;the judicial standard lacked a dedi-cated definition of visual disability.In terms of grading,each standard graded visual disability into different lev-els acoording to different functional indicators.In terms of coding,only the insurance standard adopted the ICF framework,while others used non-ICF numeric codes or lacked standardized coding.In terms of assessment tools,the elderly standard employed a customized perceptual and participation scoring system,while others re-lied primarily on vision charts.Conclusion Most current Chinese standards focus on impairments in visual function,with limited attention to activity limitations and participation restrictions.It is needed for incorporating the concept of functional vision,aligned with ICF and WRV,to establish a unified conceptual framework,terminology,coding system for visual disability,and comprehensive assessments that reflect not only impairments but also the impact on daily functioning and en-vironmental interaction.