Objective To systematically evaluate the impact of pulmonary hypertension (PH) on the prognosis of patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Methods A computerized search was conducted in CNKI, Wanfang Data, VIP, CBM, PubMed, The Cochrane Library, EMbase, and Web of Science databases from inception to June 2023 for cohort studies on the prognostic impact of PH in severe AS patients undergoing TAVR. Two researchers independently screened the literature, extracted data, and assessed the quality of included studies. Stata 17.0 software was used for meta-analysis. Results A total of 16 cohort studies were included, all with Newcastle-Ottawa Scale scores≥7. Meta-analysis results showed that, compared with AS patients without PH, those with PH had significantly higher 1-year all-cause mortality after TAVR [OR=2.10, 95%CI (1.60, 2.75), P<0.01], 30-day all-cause mortality [OR=2.09, 95%CI (1.54, 2.83), P<0.01], and cardiovascular mortality [OR=1.49, 95%CI (1.18, 1.90), P<0.01]. The differences between the two groups in major bleeding events, stroke, myocardial infarction, pacemaker implantation, and postoperative renal failure were not statistically significant. For outcome indicators with significant heterogeneity, subgroup analyses were performed based on PH measurement methods, diagnostic criteria, and different types of PH. The results showed that most subgroup combined results were consistent with the overall findings and that heterogeneity was significantly reduced. Conclusion PH significantly increases the 30-day all-cause mortality, 1-year all-cause mortality, and cardiovascular mortality in patients with severe AS undergoing TAVR.

Objective To systematically evaluate the clinical effects of remote ischaemic preconditioning (RIPC) in elective vascular surgery. Methods Electronic searches were conducted in The Cochrane Library, PubMed, EMbase, Web of Science, CNKI, Wanfang Data, VIP Database, and CBM. Relevant randomized controlled trials (RCTs) were screened according to inclusion and exclusion criteria. Meta-analysis was performed using RevMan 5.3 software, and the risk of bias was assessed using the Cochrane risk of bias tool. Results A total of 15 studies involving 1 382 patients were included. The meta-analysis results showed no statistically significant difference between RIPC and non-RIPC groups in reducing perioperative mortality in elective vascular surgery (P>0.05). There were also no statistically significant differences between the two groups of vascular surgery patients regarding the incidence of myocardial infarction, renal injury, postoperative stroke, postoperative length of hospital stay, duration of surgery or total anesthesia time, or the incidence of limb injury, arrhythmia, heart failure, and pneumonia (P>0.05). Conclusion For patients undergoing elective vascular surgery, there are no significant differences between RIPC and non-RIPC in terms of perioperative mortality and other clinical endpoint outcomes.

Objective:To analyze the predictive factors associated with late-onset sepsis(LOS) in very low birth weight infants,and to develop a risk prediction score scale applicable to these infants three days postnatal.This will provide valuable insights for early diagnosis and timely intervention.Methods:Very low birth weight infants admitted to the Children's Hospital of Fudan University from January 1,2022,to June 30,2024,were selected as research subjects.These infants were categorized into two groups:the LOS group and the non-LOS group,based on whether they developed LOS.LASSO regression analysis,alongside univariate and multivariate regression analyses,was employed to identify predictive factors for LOS in this population.A Logistic model was constructed using the optimal combination of predictive variables,and a risk assessment scale was subsequently developed.The prediction performance of the model was evaluated using the Hosmer-Lemeshow chi-square test and the receiver operating characteristic curve.Results:A total of 444 cases of very low birth weight infants were included,of which 185 had LOS and 259 did not.After screening the variables,seven independent factors were included into the model:birth weight,gestational age,tracheal intubation,abnormal skin color,abdominal distension,elevated C-reactive protein levels,and right hand perfusion index.A predictive scoring scale was developed based on the regression coefficients of each variable,with corresponding risk scores assigned as follows:1,4,3,2,1,1,and 2; a score of ≥3.5 indicated high-risk groups.The Hosmer-Lemeshow test results demonstrated that χ2 = 7.602( P = 0.473).The area under the receiver operating characteristic curve was 0.792 ( P<0.001),with a sensitivity of 73.5% and specificity of 71.0%. Conclusion:The risk score scale developed in this study exhibits significant predictive capability,providing valuable insights for clinical medical personnel to assess the risk of LOS in very low birth weight infants during the early postnatal period.

Objective:To analyze the predictive factors associated with late-onset sepsis(LOS) in very low birth weight infants,and to develop a risk prediction score scale applicable to these infants three days postnatal.This will provide valuable insights for early diagnosis and timely intervention.Methods:Very low birth weight infants admitted to the Children's Hospital of Fudan University from January 1,2022,to June 30,2024,were selected as research subjects.These infants were categorized into two groups:the LOS group and the non-LOS group,based on whether they developed LOS.LASSO regression analysis,alongside univariate and multivariate regression analyses,was employed to identify predictive factors for LOS in this population.A Logistic model was constructed using the optimal combination of predictive variables,and a risk assessment scale was subsequently developed.The prediction performance of the model was evaluated using the Hosmer-Lemeshow chi-square test and the receiver operating characteristic curve.Results:A total of 444 cases of very low birth weight infants were included,of which 185 had LOS and 259 did not.After screening the variables,seven independent factors were included into the model:birth weight,gestational age,tracheal intubation,abnormal skin color,abdominal distension,elevated C-reactive protein levels,and right hand perfusion index.A predictive scoring scale was developed based on the regression coefficients of each variable,with corresponding risk scores assigned as follows:1,4,3,2,1,1,and 2; a score of ≥3.5 indicated high-risk groups.The Hosmer-Lemeshow test results demonstrated that χ2 = 7.602( P = 0.473).The area under the receiver operating characteristic curve was 0.792 ( P<0.001),with a sensitivity of 73.5% and specificity of 71.0%. Conclusion:The risk score scale developed in this study exhibits significant predictive capability,providing valuable insights for clinical medical personnel to assess the risk of LOS in very low birth weight infants during the early postnatal period.

Objective:This study aimed at investigating the efficacy and safety of eltrombopag in the treatment of adult primary immune thrombocytopenia (ITP) and evaluated the factors influencing its efficacy and side effects.Methods:A total of 198 patients with adult ITP who were admitted to Tianjin Medical University General Hospital between January 2018 and March 2022 were retrospectively analyzed. The efficacy of each starting dose of eltrombopag was evaluated, and adverse events were analyzed. The factors influencing efficacy were investigated, including sex, age, adult ITP type, platelet antibodies, and combined drug treatments.Results:Of the 198 patients, 70 males and 128 females with a median age of 45 years (18-88 years) were included; 130 (65.7%) had newly diagnosed adult ITP, 25 (12.6%) had persistent adult ITP, and 43 (21.7%) had chronic adult ITP. The bleeding event scores at baseline were assessed; 84.3% had scores of<4 and 15.7% had scores of ≥4. The eltrombopag response rate (initial response) at 6 weeks was 78.8% (complete response [CR]: 49.0%; CR1: 14.6%; CR2: 15.2%). The median response time to eltrombopag was 7 (7, 14) days. The initial response rates to 25, 50, and 75 mg eltrombopag were 74.1%, 85.9%, and 60.0%, respectively ( P=0.031). The initial response rate to the 50 mg dose was significantly higher than that of the 25-mg and 75-mg doses. Two patients received 100 mg as the starting dose, and their initial response was 0. Regarding dose adjustment, 70.7% of the patients remained on the starting dose, 8.6% underwent dose adjustment to 50 mg, and 6.1% underwent dose adjustment to 75 mg. Another two patients underwent dose adjustment to 100 mg. After dose adjustment, the persistent response rates were 83.6%, 85.3%, and 85.7% for the 25-, 50-, and 75-mg doses, respectively, with no significant difference. After dose adjustment, the sustained efficacy rate for the 100-mg dose (4 patients) was 100.0%. After 6 weeks of treatment with eltrombopag, the overall bleeding score of patients with ITP decreased. The number of patients with a score of ≥4 decreased to 0, the number of patients with a score of<4 decreased, and there was no significant change in the number of patients with a score of 1-2. The most common adverse event associated with eltrombopag was impaired liver function (7.7%). No thrombosis events or other adverse events were observed. ITP type and number of megakaryocytes significantly affected the initial response to eltrombopag. The initial response rates to eltrombopag for newly diagnosed adult ITP, persistent adult ITP, and chronic adult ITP were 85.3%, 56.0%, and 76.2%, respectively ( P=0.003). For megakaryocytes, the initial response rates were 61.8%, 87.1%, and 84.3% ( P=0.009) for the decreased, normal, and increased megakaryocyte groups, respectively. Conclusion:Eltrombopag, as a second-line or higher treatment for adult ITP, has a rapid onset of action and good safety. The initial response rate is significantly higher with a dose of 50 mg than with a dose of 25 mg. Patients with newly diagnosed ITP and those with normal or increased megakaryocyte numbers have a higher initial response rate to eltrombopag.

Objective:To investigate the effects of celastrol (CSR) on dendritic cell (DC) and T follicular helper cell (Tfh) subsets in the mouse of ulcerative colitis (UC) .Methods:Forty-eight male BALB/c mice were randomly divided into healthy control group, model group, and CSR intervention group, with 16 mice in each group. The healthy control group was fed with normal purified water, while the mice in model group and CSR intervention group were fed with 3% DSS solution to induce UC model. Since the induction, the mice in CSR intervention group were gavaged with 1mg/kg of CSR, and the mice in UC group were gavaged with equal volume of saline once a day. The weight and stool characteristics of the mice were recorded, and disease activity index (DAI) were evaluated. After the 8-day intervention, the length of the mouse colon was measured, the histopathological changes were observed, and the histopathological score was evaluated. Flow cytometry was used to detect the percentage of DC, conventional DC (CD8α + cDC1, CD103 + cDC1, cDC2), plasmacytoid DC (pDC), and Tfh subsets in colon lamina propria, mesenteric lymph nodes and spleen. Cytometric bead array kit was used to detect the expression levels of DC and Tfh related cytokines [interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 21 (IL-21) ] in colon tissue. The influence of CSR on naive CD4 +T cell proliferation and Tfh differentiation were validated in vitro experiments. Results:The modelling success rate was 100% and all mice survived. Compared with model group, mice in CSR intervention group had heavier weight, lower DAI, and ameliorated colonic length shortening, with all differences being statistically significant (all P < 0.05). The intestinal mucosal structure of mice in model group was disordered, with a large number of inflammatory cell infiltration; the intestinal mucosal barrier of mice in CSR intervention group approached normal structure, with fewer inflammatory cells, and the histopathological scores were significantly decreased ( P<0.05). In the colon lamina propria, compared with model group, the percentages of DC, CD8α + cDC1 and Tfh decreased, while the percentage of CD103 + cDC1 increased in CSR intervention group, and these differences were all statistically significant (all P<0.05). In mesenteric lymph nodes, the percentage of CD8α + cDC1 decreased, while the percentages of DC, CD103 + cDC1, cDC2 and Tfh increased in CSR intervention group compared with model group, and these differences were all statistically significance (all P<0.05). In the spleen, compared with model group, the percentage of pDC was significantly reduced in CSR intervention group ( P<0.05) .The expression levels of IL-6, TNF-α and IL-21 in colon tissues of CSR intervention group were lower, while IL-10 was higher than those of model group, and these differences were statistically significant (all P<0.05). In vitro experiments, CSR could inhibit naive CD4 + T cell proliferation and Tfh differentiation, with statistically significant differences (all P < 0.05) . Conclusion:CSR can alleviate intestinal damage in UC mice, potentially by modulating the local immune microenvironment through regulating DC and Tfh subsets.

Objective:To investigate the effects of celastrol (CSR) on dendritic cell (DC) and T follicular helper cell (Tfh) subsets in the mouse of ulcerative colitis (UC) .Methods:Forty-eight male BALB/c mice were randomly divided into healthy control group, model group, and CSR intervention group, with 16 mice in each group. The healthy control group was fed with normal purified water, while the mice in model group and CSR intervention group were fed with 3% DSS solution to induce UC model. Since the induction, the mice in CSR intervention group were gavaged with 1mg/kg of CSR, and the mice in UC group were gavaged with equal volume of saline once a day. The weight and stool characteristics of the mice were recorded, and disease activity index (DAI) were evaluated. After the 8-day intervention, the length of the mouse colon was measured, the histopathological changes were observed, and the histopathological score was evaluated. Flow cytometry was used to detect the percentage of DC, conventional DC (CD8α + cDC1, CD103 + cDC1, cDC2), plasmacytoid DC (pDC), and Tfh subsets in colon lamina propria, mesenteric lymph nodes and spleen. Cytometric bead array kit was used to detect the expression levels of DC and Tfh related cytokines [interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), interleukin 21 (IL-21) ] in colon tissue. The influence of CSR on naive CD4 +T cell proliferation and Tfh differentiation were validated in vitro experiments. Results:The modelling success rate was 100% and all mice survived. Compared with model group, mice in CSR intervention group had heavier weight, lower DAI, and ameliorated colonic length shortening, with all differences being statistically significant (all P < 0.05). The intestinal mucosal structure of mice in model group was disordered, with a large number of inflammatory cell infiltration; the intestinal mucosal barrier of mice in CSR intervention group approached normal structure, with fewer inflammatory cells, and the histopathological scores were significantly decreased ( P<0.05). In the colon lamina propria, compared with model group, the percentages of DC, CD8α + cDC1 and Tfh decreased, while the percentage of CD103 + cDC1 increased in CSR intervention group, and these differences were all statistically significant (all P<0.05). In mesenteric lymph nodes, the percentage of CD8α + cDC1 decreased, while the percentages of DC, CD103 + cDC1, cDC2 and Tfh increased in CSR intervention group compared with model group, and these differences were all statistically significance (all P<0.05). In the spleen, compared with model group, the percentage of pDC was significantly reduced in CSR intervention group ( P<0.05) .The expression levels of IL-6, TNF-α and IL-21 in colon tissues of CSR intervention group were lower, while IL-10 was higher than those of model group, and these differences were statistically significant (all P<0.05). In vitro experiments, CSR could inhibit naive CD4 + T cell proliferation and Tfh differentiation, with statistically significant differences (all P < 0.05) . Conclusion:CSR can alleviate intestinal damage in UC mice, potentially by modulating the local immune microenvironment through regulating DC and Tfh subsets.

Objective:To explore the abundance, diversity, and structural changes of early postoperative pulmonary bacterial microbiota in lung transplant recipients.Methods:Recruiting 40 recipients who underwent lung transplantation surgery at the First Affiliated Hospital of Guangzhou Medical University from October 2020 to May 2022 for the study.All recipients did not receive antibiotic treatment within 4 weeks prior to surgery, and all recipients received a unified immunosuppressive and anti infection regimen after surgery.The bronchoalveolar lavage fluid(BALF) was collected from the amputated lung in vitro before the transplantation for 16S ribosomal RNA sequencing and flora analysis.BALF was also collected at the scheduled time from the transplanted lung on the 7th, 14th and 30th days post transplantaion for analysis.Results:The study included a total of 40 recipients who did not receive antibiotic treatment within 4 weeks before surgery, including 35 males.Among the study participants, there were 14 cases of primary obstructive pulmonary disease, 19 cases of interstitial lung disease, 3 cases of occupational lung disease, and 4 others.Microbiome in BALF of transplanted and detached autologous lungs at the first week after surgery α( P<0.05) and β diversity is statistically significant( R2=0.08, P=0.001), and the bacterial community in the transplanted lungs α Diversity is lower than that of explant lungs.Starting from the second week after surgery, the richness and species diversity of the transplanted lung microbiota gradually increase.The bacterial structure was also changed with postoperative time, and the relative abundance of the same bacterial species were varied at different time points.The bacterial community in BALF was mainly dominated by Proteobacteria both explant lungs and transplant lungs.The relative abundance of Staphylococcus and Acinetobacter genera at the BALF in transplanted lungs was higher than that in explant lung samples, but their relative abundance decreased over time after surgery. Conclusions:The α diversity of the early postoperative pulmonary microbiota after lung transplantation was lower than that of the amputated autologous lung, and the bacterial richness and species diversity in the microbiota of the transplanted lung gradually increased at the second week after the transplantation.The bacterial microbiota of the transplanted lung is changed complicatedly with time.

CCAAT enhancer binding protein β (C/EBPβ), as a nuclear transcription factor necessary for the development of liver, airway epithelium, and adipose tissue, plays a vital role in physiological processes related to cell proliferation, apoptosis, and differentiation. However, the up-regulation of C/EBPβ activates signal pathways related to inflammatory response, epithelial-mesenchymal transition, cell proliferation and invasion, immune response, and angiogenesis by regulating a series of downstream genes transcription promotes the development of lung diseases. Therefore, targeting C/EBPβ may be a potential treatment strategy for lung diseases. This paper summarizes the regulatory effects of C/EBPβ and related signaling pathways in lung infection, asthma, chronic obstructive pulmonary disease, lung injury, pulmonary fibrosis, and lung cancer to provide a theoretical basis for the precision medicine of lung diseases.

Ulcerative colitis(UC)is a chronic inflammatory bowel disease caused by many factors including colonic inflammation and microbiota dysbiosis.Previous studies have indicated that celastrol(CSR)has strong anti-inflammatory and immune-inhibitory effects.Here,we investigated the effects of CSR on colonic inflammation and mucosal immunity in an experimental colitis model,and addressed the mechanism by which CSR exerts the protective effects.We characterized the ther-apeutic effects and the potential mechanism of CSR on treating UC using histological staining,intestinal permeability assay,cytokine assay,flow cytometry,fecal microbiota transplantation(FMT),16S rRNA sequencing,untargeted metabolomics,and cell differentiation.CSR administra-tion significantly ameliorated the dextran sodium sulfate(DSS)-induced colitis in mice,which was evidenced by the recovered body weight and colon length as well as the decreased disease activity index(DAI)score and intestinal permeability.Meanwhile,CSR down-regulated the production of pro-inflammatory cytokines and up-regulated the amount of anti-inflammatory mediators at both mRNA and protein levels,and improved the balances of Treg/Thl and Treg/Th1 7 to maintain the colonic immune homeostasis.Notably,all the therapeutic effects were exerted in a gut microbiota-dependent manner.Furthermore,CSR treatment increased the gut microbiota diversity and changed the compositions of the gut microbiota and metabolites,which is probably associated with the gut microbiota-mediated protective effects.In conclusion,this study provides the strong evidence that CSR may be a promising therapeutic drug for UC.