Idiopathic pulmonary fibrosis (IPF), a chronic interstitial lung disease, is characterized by aberrant wound healing, excessive scarring and the formation of myofibroblastic foci. Although the role of alternative splicing (AS) in the pathogenesis of organ fibrosis has garnered increasing attention, its specific contribution to pulmonary fibrosis remains incompletely understood. In this study, we identified an up-regulation of serine/arginine-rich splicing factor 7 (SRSF7) in lung fibroblasts derived from IPF patients and a bleomycin (BLM)-induced mouse model, and further characterized its functional role in both human fetal lung fibroblasts and mice. We demonstrated that enhanced expression of Srsf7 in mice spontaneously induced alveolar collagen accumulation. Mechanistically, we investigated alternative splicing events and revealed that SRSF7 modulates the alternative splicing of pyruvate kinase (PKM), leading to metabolic dysregulation and fibroblast activation. In vivo studies showed that fibroblast-specific knockout of Srsf7 in conditional knockout mice conferred resistance to bleomycin-induced pulmonary fibrosis. Importantly, through drug screening, we identified lomitapide as a novel modulator of SRSF7, which effectively mitigated experimental pulmonary fibrosis. Collectively, our findings elucidate a molecular pathway by which SRSF7 drives fibroblast metabolic dysregulation and propose a potential therapeutic strategy for pulmonary fibrosis.

Humans ; Nephrotic Syndrome ; Hematopoietic Stem Cell Transplantation ; Tissue Donors ; Transplantation Conditioning ; Graft vs Host Disease

Background and purpose:For patients with human epidermal growth factor receptor 2(HER2)-positive metastatic breast cancer,trastuzumab treatment can prolong the overall survival and significantly improve the prognosis of patients.However,the reference original research trastuzumab(Herceptin?)is more expensive.Biosimilars have comparable efficacy and safety profiles while increasing patient access to treatment.This clinical trial aimed to evaluate the efficacy,pharmacokinetics,safety and immunogenicity of the trastuzumab biosimilar AK-HER2 compared to trastuzumab(Herceptin?)in patients with HER2-positive metastatic breast cancer.Methods:This multi-center,randomised,double-blind phase Ⅲ clinical trial was conducted in 43 subcenters in China.This study complied with the research protocol,the ethical principles stated in the Declaration of Helsinki and the quality management standards for drug clinical trials.It was approved by the hospital's medical ethics committee.The clinical trial registration agency is the State Food and Drug Administration(clinical trial approval number:2015L04224;clinical trial registration number:CTR20170516).Written informed consent was obtained from subjects before enrollment.Enrolled patients were randomly assigned to the AK-HER2 group and the control group,respectively receiving AK-HER2 or trastuzumab(initial loading dose 8 mg/kg,maintenance dose 6 mg/kg,every 3 weeks as a treatment cycle,total treatment time is 16 cycles)in combination with docetaxel(75 mg/m2,treatment duration is at least 9 cycles).The primary endpoint of this clinical trial was the objective response rate(ORR9)between the AK-HER2 group and the control group in the 9th cycle.Secondary efficacy endpoints included ORR16,disease control rate(DCR),clinical benefit rate(CBR),progression-free survival(PFS)and 1-year survival rate.In this study,100 subjects(AK-HER2 group to control group=1:1)were randomly selected for blood sample collection after the 6th cycle of medication,The collection time points were 45 minutes after infusion(the end of administration),4,8,24,72,120,168,336,and 504 hours after the end of administration.After collection,blood samples were analyzed by PK parameter set(PKPS).Other evaluation parameters included safety and immunogenicity assessment.Results:A total of 550 patients with HER2-positive metastatic breast cancer were enrolled in this clinical trial between Sep.2017 and Mar.2021.In the AK-HER2 group(n=237),129 subjects in the experimental group achieved complete response(CR)or partial response(PR),and the ORR9 was 54.4%.There were 134 subjects in the control group(n=241)who achieved CR or PR,and the ORR9 was 55.6%.The ORR9 ratio between the AK-HER2 group and the control group was 97.9%[90%confidence interval(CI):85.4%-112.2%,P=0.784],which was not statistically significant.In all secondary efficacy endpoints,no statistically significant differences were observed between the two groups.We conducted a mean ratio analysis of pharmacokinetics(PK)parameters between the AK-HER2 group and the control group,and the results suggested that the pharmacokinetic characteristics of the two drugs are similar.The incidence of treatment emergent adverse event(TEAE)leading to drug reduction or suspension during trastuzumab treatment was 3.6%(10 cases)in the AK-HER2 group and 8.1%(22 cases)in the control group.There was statistically significant difference between the two groups(P=0.027).The incidence rate was significantly lower in the AK-HER2 group than in the control group,and there was no statistically significant difference among the other groups.The differences in the positive rates of anti-drug antibodies(ADA)and neutralizing antibodies(NAB)between groups were of no statistical significance(P=0.385 and P=0.752).Conclusion:In patients with HER2-positive metastatic breast cancer,AK-HER2 was comparable to the trastuzumab(Herceptin?)in terms of drug efficacy,pharmacokinetics,safety and immunogenicity.

Objective To assess the effect of ultrasonic thyroid artificial intelligence(AI)-assisted diagnostic system(AI-assisted diagnostic system)for diagnosing medullary thyroid carcinoma(MTC)compared with different physicians and taken papillary thyroid carcinoma(PTC)as the controls.Methods Totally 63 MTC,70 PTC and 62 benign thyroid nodules confirmed by pathology were enrolled.AI-assisted diagnostic system was utilized to analyze thyroid nodules and identify the likelihood of malignancy,and the probability value threshold was set at ≥0.40.All thyroid nodules were retrospectively reviewed and categorized by 3 physicians(1 senior physician,1 attending physician and 1 junior physician)according to Chinese thyroid imaging reporting and data system(C-TIRADS).The efficacy of AI-assisted diagnostic system and physicians for diagnosing MTC and PTC were evaluated.Results AI-assisted diagnostic system showed lower sensitivity,specificity,positive predictive value,negative predictive value,accuracy,and area under the curve(AUC)for diagnosing MTC and PTC compared with physicians.Significant differences of AUC were found between senior physician and AI-assisted diagnostic system,as well as between attending physician and AI-assisted diagnostic system for diagnosing MTC and PTC(all P＜0.01),while no significant difference of AUC was between junior physicians and AI-assisted diagnostic system(both P＞0.05).The sensitivity,specificity,positive predictive value,negative predictive value,accuracy and AUC for AI-assisted diagnostic system for diagnosing MTC were all lower than those for diagnosing PTC,but the AUC was not significantly different(P＞0.05).Conclusion Ultrasonic thyroid AI-assisted diagnostic system had relatively high value for diagnosing MTC.

Objective:To analyze the correlation between serum glycated hemoglobin (HbA 1c), γ-glutamyltranspeptidase(γ-GT) and intercellular adhesion factor-1 (ICAM-1) levels and cognitive impairment in elderly patients with hyperlipidemia complicated with cardiovascular disease. Methods:In this retrospective cohort study, 158 elderly patients who underwent examination and were diagnosed with hyperlipidemia complicated with cardiovascular disease at Beijing Anzhen Hospital Affiliated with Capital Medical University from January to December 2022 were selected as study subjects. The simple mental state scale (MMSE) was assessed in the subjects in combination with the subject′s level of education. Illiteracy≤17 points, primary school≤20 points, middle school and above≤24 points were classified as cognitive impairment group (67 cases), the rest were were classified into the non-cognitive impairment group (91 cases); and another 50 healthy elderly people who received physical examination in the same period were selected as the control group. The blood samples in the three groups were extracted to measure serum HbA 1c, γ-GT and ICAM-1. The correlation between HbA 1c, γ-GT and ICAM-1 levels with cognitive impairment were analyzed. Results:The serum levels of HbA 1c, γ-GT and ICAM-1 in the cognitive impairment group were all significantly higher than those in the non-cognitive impairment group and the control group [5.41%±1.04% vs 4.82%±0.95%, 4.39%±0.86%; (52.01±10.96) vs (41.28±9.23), (25.03±7.17) U/L; (336.61±85.36) vs (286.93±72.53), (143.52±64.20) g/ml], and the MMSE score was significantly lower [(20.19±2.85) vs (25.30±1.24), (27.14±1.56) points] (all P<0.05). Serum levels of HbA 1c, γ-GT and ICAM-1 were all significantly negatively correlated with MMSE score ( r=-0.512, -0.498, -0.563) (all P<0.05). The areas under the receiver operating characteristic curves (AUCs) for serum HbA 1c, γ-GT, and ICAM-1 levels in the assessment of cognitive dysfunction were 0.657, 0.816, and 0.691, respectively (all P<0.05). The optimal cut-off values were 5.115%, 47.65 U/L, and 304.58 g/ml, respectively. Conclusion:Serum HbA 1c, γ-GT and ICAM-1 levels in elderly patients with hyperlipidemia complicated with cardiovascular disease are negatively correlated with cognitive impairment, and have certain value for the evaluation and early diagnosis of cognitive impairment.

Objective:To translate the Dysfunctional Beliefs and Attitudes about Sleep Scale for Cancer Patients (C-DBAS-14) into Chinese and test its reliability and validity.Methods:The Korean version of C-DBAS-14 was translated, back-translated, and culturally adapted into Chinese based on Brislin's translation model, forming the Chinese version of C-DBAS-14. From October 2022 to May 2023, 361 hospitalized cancer patients at the First Affiliated Hospital of Anhui Medical University were selected as research objects by convenient sampling method. They were surveyed using a general information questionnaire, the Chinese version of C-DBAS-14, the Insomnia Severity Index (ISI), and the Hospital Anxiety and Depression Scale (HADS) to evaluate the reliability and validity of the scale. The scale's item analysis was based on correlation coefficients and critical ratio values; structural validity, content validity, and convergent validity were used to evaluate the scale's validity; Cronbach's α coefficient and intraclass correlation coefficient were used to assess its reliability.Results:A total of 361 questionnaires were distributed, 356 were effectively returned, with an effective response rate of 98.6% (356/361). The Chinese version of C-DBAS-14 contained 14 items across four dimensions. The scale-level content validity index was 0.976, and the item-level content validity index ranged from 0.833 to 1.000. Totally four common factors were extracted in exploratory factor analysis, explaining 78.8% of the total variance. Confirmatory factor analysis showed a Chi-square/degrees of freedom ratio of 1.286, comparative fit index of 0.991, goodness of fit index of 0.945, incremental fit index of 0.991, Tucker-Lewis index of 0.988, and root mean square error of approximation of 0.036. The total Cronbach's α coefficient of the scale was 0.874, and the intraclass correlation coefficient was 0.863. The C-DBAS-14 score was negatively correlated with the ISI and HADS scores ( r=-0.734, -0.639; P<0.01) . Conclusions:The Chinese version of C-DBAS-14 has good reliability and validity and can be used as an assessment tool for irrational sleep beliefs in Chinese cancer patients.

Objective:To systematically evaluate qualitative studies on disease experience in diabetic retinopathy patients.Methods:Qualitative studies on the disease experience of diabetic retinopathy patients were searched by computer from Web of Science, PubMed, Cochrane Library, Embase, CINAHL, EBSCO, China National Knowledge Infrastructure, WanFang Data, China Biology Medicine disc, VIP, and other databases. The search period was from the establishment of the databases to July 1, 2023. The qualitative research quality evaluation criteria of the Evidence-based Health Care Center of Briggs Institute in Australia were used to evaluate the literature quality, and the results were integrated by the pooled integration method.Results:A total of 12 articles were included, and 47 research results were extracted, which were summarized into 11 categories and integrated into three integrated results, that was, multiple aspects affected by diseases and low quality of life, utterly different coping styles of patients with different emotional experiences including post-traumatic growth and self-abandonment, and a lack of disease-related knowledge and is eager to receive comprehensive support.Conclusions:The physiology and psychology of patients with diabetes retinopathy are affected by the disease. Nurses should pay attention to early prevention education, strengthen disease knowledge publicity, help cope with difficulties in daily life, attach importance to patients' psychological feelings, provide multi-dimensional social support, improve patients' coping strategies, and improve their quality of life.

Objective:To construct an evaluation index system for clinical practice effectiveness of undergraduate nursing students, so as to provide a basis for the evaluation of clinical practice effectiveness of undergraduate nursing students.Methods:Based on the improved Miller's pyramid theory, a preliminary evaluation index system for clinical practice effectiveness of nursing undergraduate students was formed by literature analysis and semi-structured interview method. From April to July 2023, purposive sampling was used to select 20 experts in nursing education, clinical nursing teaching, and other fields. After two rounds of Delphi expert consultation, a final evaluation index system for clinical practice effectiveness of undergraduate nursing students was formed, and the weights of each index were determined.Results:After two rounds of consultation, the effective response rates of the questionnaire were 95.00% (19/20) and 100.00% (19/19), respectively. The expert authority coefficients were 0.86 and 0.88, and the Kendall harmony coefficients were 0.226 and 0.183 ( P<0.01). The final established evaluation index system for clinical practice effectiveness of undergraduate nursing students included five primary indicators, 13 secondary indicators, and 56 tertiary indicators. Conclusions:Based on the improved Miller's pyramid theory, the evaluation index system for clinical practice effectiveness of undergraduate nursing students constructed is scientific, reliable, and practical, which can provide reference for the evaluation of clinical practice for undergraduate nursing students.

Objective:To systematically review the transitional care experience of family caregivers for adolescents with type 1 diabetes mellitus.Methods:The qualitative research on transitional care experience of family caregivers for adolescents with type 1 diabetes mellitus was electronically searched on Web of Science, PubMed, Cochrane Library, Embase, CINAHL, EBSCO, China National Knowledge Infrastructure, WanFang Data, China Biology Medicine disc, and VIP. The search period was from database establishment to June 2023.Results:A total of 11 articles were included, and 35 research results were extracted, which were integrated into 8 new categories and 4 integration results, respectively, the complex emotional experience of family caregivers for adolescents with type 1 diabetes mellitus during the transition period, the difference in the role transformation of different caregivers, the desire for support, and the active response to the transition period.Conclusions:Medical and nursing staff should pay attention to the transitional care experience of family caregivers for adolescents with type 1 diabetes mellitus, build personalized support systems according to the needs of caregivers, improve the quality of care and life in the transition period, and provide basis for the construction of family centered intervention programs in the transition period.