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.

Background Job burnout has become an important factor affecting the mental and physical health and work efficiency of college counselors, and indirectly affects the quality and development of talent cultivation for college students. Objective To explore the relationship between job stress, job crafting, and job burnout among college counselors, and to test the mediating role of job crafting between job stress and job burnout, in order to take targeted measures to alleviate job stress and job burnout of college counselors, reduce associated health risks, and improve the effectiveness of higher education. Methods An anonymous questionnaire survey was conducted among 400 counselors from social network communication groups by convenience sampling. The Counselor Work Stress Scale, Job Crafting Scale, and Maslach Burnout Inventory-General Survey were used. Harman's single-factor method was used to evaluate common method bias in the survey data. One-way ANOVA was applied to test the difference in job stress, job crafting, and job burnout among college counselors by demographic characteristics, and chi-square test was used to analyze the difference in reporting job burnout. Partial correlation analysis was used to evaluate the correlation between selected variables. Structural equation modeling was used to analyze the relationship of job stress, job crafting, and job burnout among college counselors, and Bootstrap analysis was used to test if there was a mediating effect of job crafting on the relationship between job stress and job burnout. Results Of the 390 questionnaires recovered, there were 338 valid questionnaires (86.67%). Among the included subjects, the mean scores of job stress, job crafting, and job burnout were (2.70±0.62), (3.77±0.62), and (2.09±1.09), respectively. The positive rate of job burnout was 76.9% (260/338), with a positive rate of 72.8% in exhaustion dimension and 59.8% in cynicism dimension. There were significant differences in job crafting scores among the college counselors by different genders and professional titles (P<0.05). Female counselors had significantly higher job burnout scores and positive rates than male counselors (P<0.05). The partial correlation analysis showed that job stress, work load, school evaluation and expectation, and interpersonal relationship were positively correlated with job burnout (r=0.562, 0.442, 0.473, and 0.455, respectively, P<0.01), and negatively correlated with job crafting (r=−0.271, −0.169, −0.246, and −0.247, respectively, P<0.01); job crafting, cognitive crafting, relationship crafting, and task crafting were negatively correlated with job burnout (r=−0.447, −0.452, −0.366, and −0.340, respectively, P<0.01). The modified structural equation modeling indicated that job stress negatively affected job crafting (b=−0.348, P<0.001) and positively affected job burnout (b=0.454, P<0.001); job crafting negatively affected job burnout (b=−0.459, P<0.001), and played a partial mediating role in the relationship between job stress and job burnout, and the effect value was 0.160 (95%CI: 0.102, 0.230) that accounted for 26.10% of the total effect. Conclusion Job burnout among the college counselors is prominent. Job crafting presents an inhibitory effect on job burnout. Job stress indirectly affects the occurrence of job burnout by inhibiting the generation of job crafting.

Objectives:Present study analyzed the efficacy and safety of percutaneous coronary intervention(PCI)using the distal transradial access(dTRA)for patients with complex coronary lesions. Methods:A total of 10 033 patients with complex coronary artery lesions(type B2 and type C lesions)who underwent percutaneous coronary intervention(PCI)via dTRA or conventional transradial access(TRA)at Fuwai Hospital between June 2021 and May 2022 were included(9 625 patients in the TRA group and 408 patients in the dTRA group).After propensity score matching,391 patients were included in each group.Baseline data,PCI intraoperative data(including lesion characteristics,intervention success rate,etc.),and incidence of major bleeding related to the access were compared between the two groups before and after propensity score matching. Results:Before propensity score matching,the proportions of patients with hypertension,hyperlipidemia,family history of coronary heart disease,history of myocardial infarction,and history of coronary artery bypass grafting were significantly higher in the dTRA group than in the TRA group(all P<0.05).After propensity score matching,the baseline data of the two groups were similar(all P>0.05).Before propensity score matching,compared with the TRA group,patients in the dTRA group had a higher proportion of patients with type B2 lesions,while the proportions of patients with type C lesions and those using intravascular ultrasound(IVUS)were lower(all P<0.05).The proportion of patients with chronic complete occlusion was similar between the two groups(P>0.05).After propensity score matching,compared with the TRA group,patients in the dTRA group had a lower proportion using IVUS and had a higher percent of stent implantation(both P<0.05).There was no statistically significant difference between the two groups in terms of SYNTAX score,guide catheter size,target lesion distribution,proportion of patients using intra-aortic balloon counterpulsation,success rate of intervention procedures,and incidence of major bleeding events related to the access(all P>0.05). Conclusions:Compared with the conventional TRA,interventional treatment of complex lesions through dTRA is equally safe and effective for patients with complex coronary lesions.

Objective:To explore the genetic etiology of a child with Cowden syndrome 1 (CS1).Methods:A child who had visited the Ningbo Women and Children's Hospital on August 26, 2022 was selected as the study subject. Clinical information of the child was collected. Genomic DNA was extracted from peripheral blood samples of the child and his family members and subjected to whole exome sequencing (WES). Candidate variant was verified by Sanger sequencing.Results:The child, a 13-year-old boy, had manifested with severe mental retardation, hyperactivity, autistic behavior, sparse and prominent teeth, macrocephaly, and skin freckles on the penis. His mother had presented with multiple papules, hamartomatous polyps, thyroid adenoma and macrocephaly. WES results revealed that the child has harbored a nonsense c. 781C>T (p.Q261*) variant of the PTEN gene, which was inherited from his mother. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.781C>T variant was classified as likely pathogenic (PVS1+ PM2_Supporting). Conclusion:The c. 781C>T variant of the PTEN gene probably underlay the pathogenesis in the child and his mother. Above finding has facilitated genetic counseling for this family.

Objective To evaluate the stability,safety and immune enhancement and anti-tumor effects of Wilms'tumor gene 1(WT1)peptide combined with AddaVaxTM emulsion vaccine for acute myeloid leukemia.Methods The stability of WT1 peptide in the adjuvant vaccine was evaluated using MALDI-TOF-MS time-of-flight mass spectrometry.Female C57BL/6 mice were randomly divided into PBS group,WT1 peptide group,and WT1 peptide+AddaVaxTMemulsion adjuvant vaccine group.The immunization was performed at a dose of 50 μg/mouse for antigen and 50 μg/mouse for adjuvant,with intramuscular injection on days 0,14,and 28.HE staining was used to assess the toxicity of intramuscular vaccination on mouse organ tissues.Cytokine levels were detected by ELISA,and the number of IFN-γ-secreting splenocytes was measured by ELISpot.Flow cytometry was employed to detect the maturation of bone marrow-derived dendritic cells(BMDCs)promoted by the vaccine in vitro and the promotion for lymphocyte activation,and H-2Db WT1 tetramer was utilized to detect the proportion of specific CD8+T cells.After establishing a mouse leukemia tumor model using the C1498-mWT1 stable cell line,the anti-tumor effects of the vaccine for prevention and treatment were evaluated.Results The WT1 peptide stably existed in the vaccine without causing significant organ tissue changes in mice after intramuscular injection.Compared to the mice immunized with WT1 aqueous solution,the mice after intramuscular injection of the WT1 peptide emulsion adjuvant vaccine showed stronger immune responses of Th1 cells,including IFN-γ and TNF-α,as well as Th17 cells of IL-17A(P＜0.05),and the mice had not only promoted number of IFN-γ secreting splenocytes(P＜0.01)but also enhanced maturation of BMDCs,as indicated by an increase in the proportions of CD40+/CD11c+and CD86+CD80+/CD11c+ cells(P＜0.05).Additionally,there were increases in both the proportion of CD4+/CD3+T and CD69+/CD8+T cells(P＜0.05)and the proportion of specific CD8+T cells(P＜0.05).In the anti-tumor effect study using the C1498-mWT1 mouse model,the median survival time of the WT1+AddaVaxTM group was extended by 6 d compared to the WT1 aqueous solution group.At day 50,the survival rate of mice in the WT1+AddaVaxTM group was still 28.5％,while all mice in the other groups had died(P＜0.05).Conclusion The vaccine with the WT1 peptide and AddaVaxTM emulsion adjuvant exhibits good immunological and anti-tumor effects.

Objective:To investigate the distribution and research status of domestic journals on corticobasal degeneration(CBD)in China.Methods:Articles on CBD from the Wanfang, CNKI, and Vip databases, published in domestic journals before December 31st, 2022, were systematically categorized and analyzed.Utilizing bibliometric methods, the distribution, types, citations, and overall research status of CBD literature were assessed.Results:A total of 61 documents related to CBD were published in domestic journals.The highest number of publications were in 2022 and 2019(7 articles each, 11.48%), followed by 2021 with 6 articles(9.84%).Additionally, 2013, 2012, and 2004 each had 4 articles(6.56%).These articles came from 39 institutions, with the First Medical Center of the People's Liberation Army General Hospital leading with 9 articles(14.75%), followed by Zhejiang Litongde Hospital with 4 articles(6.56%).Across 18 provinces, Beijing had the highest number of publications with 16 articles(26.23%), followed by Tianjin with 7 articles(11.48%).The majority of the publications were clinical studies(59 articles, 96.72%), with clinical feature analysis, clinical scale evaluation, clinical pathological evaluation, and neuroimaging evaluation being the most common topics.Most articles were in the form of full-length papers(40 articles, 65.57%), delving into the clinical characteristics, pathology, neuroimaging, diagnosis, and differential diagnosis of CBD.Of the 61 documents, 26(42.62%)received funding support, with 18 articles(29.51%)supported by national fund projects, 13 articles(21.31%)supported by provincial and ministerial fund projects, and 12 articles(19.67%)supported by multiple fund projects, including 3 supported by two national fund projects(4.92%).Conclusions:The volume of domestic CBD literature remains low, but the number of published articles has shown a significant increase from 2011 to 2022, with Beijing emerging as the primary publishing hub.There is a limited number of funded projects, highlighting the need for stronger discipline construction.Research on the diagnosis, clinical characteristics, and neuroimaging features of CBD is highly prioritized.

Background: The objective of this study was to investigate the impact of robot-assisted surgery (RA) on the risk of new vertebral compression fracture (NVCF) and bone cement leakage in patients with osteoporotic vertebral compression fractures (OVCF) after percutaneous vertebral augmentation (PVA), including percutaneous kyphoplasty (PKP) and percutaneous vertebroplasty (PVP). Methods: A meta-analysis was performed to evaluate the clinical outcomes and adverse effects of RA-PVA versus fluoroscopy-assisted (FA)-PVA in patients with OVCF. A validation cohort of 385 patients who underwent PVP or PKP was retrospectively analyzed.In addition, we attempted to create well-calibrated nomograms to estimate the risk of NVCF and bone cement leakage. Results: The meta-analysis revealed that the incidence of NVCF and bone cement leakage was significantly lower in RA-PVA than in FA-PVA. The validation cohort confirmed that RA-PVA provided better results than FA-PVA in terms of NVCF and bone cement leakage. Conclusions The meta-analysis and the validation cohort suggest that RA reduced the risk of NVCF and bone cement leakage in patients with OVCF after PVA. The nomograms are accurate and easy-to-implement methods for clinicians to estimate the risk of NVCF and bone cement leakage after PVA.

Background: The objective of this study was to investigate the impact of robot-assisted surgery (RA) on the risk of new vertebral compression fracture (NVCF) and bone cement leakage in patients with osteoporotic vertebral compression fractures (OVCF) after percutaneous vertebral augmentation (PVA), including percutaneous kyphoplasty (PKP) and percutaneous vertebroplasty (PVP). Methods: A meta-analysis was performed to evaluate the clinical outcomes and adverse effects of RA-PVA versus fluoroscopy-assisted (FA)-PVA in patients with OVCF. A validation cohort of 385 patients who underwent PVP or PKP was retrospectively analyzed.In addition, we attempted to create well-calibrated nomograms to estimate the risk of NVCF and bone cement leakage. Results: The meta-analysis revealed that the incidence of NVCF and bone cement leakage was significantly lower in RA-PVA than in FA-PVA. The validation cohort confirmed that RA-PVA provided better results than FA-PVA in terms of NVCF and bone cement leakage. Conclusions The meta-analysis and the validation cohort suggest that RA reduced the risk of NVCF and bone cement leakage in patients with OVCF after PVA. The nomograms are accurate and easy-to-implement methods for clinicians to estimate the risk of NVCF and bone cement leakage after PVA.

Background: The objective of this study was to investigate the impact of robot-assisted surgery (RA) on the risk of new vertebral compression fracture (NVCF) and bone cement leakage in patients with osteoporotic vertebral compression fractures (OVCF) after percutaneous vertebral augmentation (PVA), including percutaneous kyphoplasty (PKP) and percutaneous vertebroplasty (PVP). Methods: A meta-analysis was performed to evaluate the clinical outcomes and adverse effects of RA-PVA versus fluoroscopy-assisted (FA)-PVA in patients with OVCF. A validation cohort of 385 patients who underwent PVP or PKP was retrospectively analyzed.In addition, we attempted to create well-calibrated nomograms to estimate the risk of NVCF and bone cement leakage. Results: The meta-analysis revealed that the incidence of NVCF and bone cement leakage was significantly lower in RA-PVA than in FA-PVA. The validation cohort confirmed that RA-PVA provided better results than FA-PVA in terms of NVCF and bone cement leakage. Conclusions The meta-analysis and the validation cohort suggest that RA reduced the risk of NVCF and bone cement leakage in patients with OVCF after PVA. The nomograms are accurate and easy-to-implement methods for clinicians to estimate the risk of NVCF and bone cement leakage after PVA.

Background: The objective of this study was to investigate the impact of robot-assisted surgery (RA) on the risk of new vertebral compression fracture (NVCF) and bone cement leakage in patients with osteoporotic vertebral compression fractures (OVCF) after percutaneous vertebral augmentation (PVA), including percutaneous kyphoplasty (PKP) and percutaneous vertebroplasty (PVP). Methods: A meta-analysis was performed to evaluate the clinical outcomes and adverse effects of RA-PVA versus fluoroscopy-assisted (FA)-PVA in patients with OVCF. A validation cohort of 385 patients who underwent PVP or PKP was retrospectively analyzed.In addition, we attempted to create well-calibrated nomograms to estimate the risk of NVCF and bone cement leakage. Results: The meta-analysis revealed that the incidence of NVCF and bone cement leakage was significantly lower in RA-PVA than in FA-PVA. The validation cohort confirmed that RA-PVA provided better results than FA-PVA in terms of NVCF and bone cement leakage. Conclusions The meta-analysis and the validation cohort suggest that RA reduced the risk of NVCF and bone cement leakage in patients with OVCF after PVA. The nomograms are accurate and easy-to-implement methods for clinicians to estimate the risk of NVCF and bone cement leakage after PVA.