BACKGROUND: Pre-transplant exposure to immune checkpoint inhibitors (ICIs) significantly increases the risk of allograft rejection after liver transplantation (LT); however, whether ICI-related rejection leads to increased graft loss remains controversial. Therefore, this study aimed to investigate the association between ICI-related allograft rejection and perioperative graft loss. METHODS: This was a retrospective analysis of adult liver transplant recipients with early biopsy-proven T-cell-mediated rejection (TCMR) at Liver Transplantation Center of Sun Yat-sen Memorial Hospital from June 2019 to September 2024. The pathological features, clinical characteristics, and perioperative graft survival were analyzed. RESULTS: Twenty-eight patients who underwent early TCMR between June 2019 and September 2024 were included. Based on pre-LT ICI exposure, recipients were categorized into ICI-related TCMR (irTCMR, n = 12) and conventional TCMR (cTCMR, n = 16) groups. Recipients with irTCMR had a higher median Banff rejection activity index (RAI) (6 vs . 5, P = 0.012) and more aggressive tissue damage and inflammation. Recipients with irTCMR showed higher proportion of treatment resistance, achieving a complete resolution rate of only 8/12 compared to 16/16 for cTCMR. Graft loss occurred in 5/12 of irTCMR recipients within 90 days after LT, with no graft loss in cTCMRs recipients. Cox analysis demonstrated that irTCMR with an ICI washout period of <30 days was an independent risk factor for perioperative graft loss (hazard ratio [HR], 6.540; 95% confidence interval [CI], 1.067-40.067, P = 0.042). CONCLUSION IrTCMR is associated with severe pathological features, increased resistance to treatment, and higher graft loss in adult liver transplant recipients.
Humans ; Liver Transplantation/adverse effects* ; Male ; Female ; Middle Aged ; Retrospective Studies ; Graft Rejection/immunology* ; Immune Checkpoint Inhibitors/therapeutic use* ; Adult ; T-Lymphocytes/drug effects* ; Graft Survival/immunology* ; Aged

Chronic obstructive pulmonary disease (COPD) and pulmonary hypertension (PH) are both chronic progressive respiratory diseases that cannot be completely cured. COPD is characterized by irreversible airflow limitation, chronic airway inflammation, and gradual decline in lung function, whereas PH is characterized by pulmonary vasoconstriction, remodeling, and infiltration of inflammatory cells. These diseases have similar pathological features, such as vascular hyperplasia, arteriolar contraction, and inflammatory infiltration. Despite these well-documented observations, the exact mechanisms underlying the occurrence and development of COPD and PH remain unclear. Evidence that mitochondrial dynamics imbalance is one major factor in the development of COPD and PH. Mitochondrial dynamics is precisely regulated by mitochondrial fusion proteins and fission proteins. When mitochondrial dynamics equilibrium is disrupted, it causes mitochondrial and even cell morphological dysfunction. Mitochondrial dynamics participates in various pathological processes for heart and lung disease. Mitochondrial dynamics may be different in the early and late stages of COPD and PH. In the early stages of the disease, mitochondrial fusion increases, inhibiting fission, and thereby compensatorily increasing adenosine triphosphate (ATP) production. With the development of the disease, mitochondria decompensation causes excessive fission. Mitochondrial dynamics is involved in the development of COPD and PH in a spatiotemporal manner. Based on this understanding, treatment strategies for mitochondrial dynamics abnormalities may be different at different stages of COPD and PH disease. This article will provide new ideas for the potential treatment of related diseases.
Humans ; Mitochondrial Dynamics/physiology* ; Pulmonary Disease, Chronic Obstructive/metabolism* ; Hypertension, Pulmonary/metabolism* ; Mitochondria/metabolism* ; Animals

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Within traditional teaching models,students frequently assume a passive role in acquiring knowledge,potentially resulting in diminished motivation and limited engagement,particularly within the realm of Medical Immunology education.The inte-gration of role-playing,informed by constructivist learning theory,situated learning theory,and multiple intelligences theory,has demonstrated encouraging outcomes within clinical medical education settings.However,the extent to which this approach has been explored within the context of Immunology instruction remains insufficiently examined.This study investigates the utilization of role-playing as a pedagogical approach in Medical Immunology education,wherein students are assigned specific scenarios to simulate the functions of various immune components.The primary objective is to augment interactivity and the overall appeal of the learning pro-cess.Efficacy of this instructional method was evaluated through in-class quizzes,surveys,and performance analysis.The findings demonstrate that role-playing substantially enhances student engagement,comprehension,knowledge retention,and examination per-formance.In practical application,the integration of role-playing with ideological and political elements has the potential to enhance learning outcomes and foster students'enthusiasm for engaging in cutting-edge literature and immunological research.This approach also necessitates greater proficiency in teachers'professional competencies and organizational skills,as well as increased allocation of class time and spatial resources.Future research should investigate the applicability of role-playing across various educational levels and examine its potential integration with classroom ideological and political education.

Objective:To explore the outcomes and problems of the Beijing Nursing Association Emergency Specialist Nurse Training Course, so as to provide reference for improving the training of emergency specialist nurses.Methods:Convenience sampling was used to select 75 trainees from the 2023 Beijing Nursing Association Emergency Specialist Nurse Training Course as survey subjects. Beijing Nursing Association Emergency Specialist Nurse Training Scoring Criteria was used to score trainees from four aspects of theoretical knowledge, skill operation, case analysis, and review defense, and to summarize and analyze the existing problems.Results:A total of 75 questionnaires were distributed, and 75 valid questionnaires were collected, with a valid response rate of 100.0%. The theoretical knowledge score was (68.4±10.7), with a minimum of 38.0 and a maximum of 91.0, and the pass rate (number of passing trainees divided by the total number of trainees) was 81.3%. The score for the review defense was (78.8±5.7), with a minimum of 65.0 and a maximum of 94.0, and a pass rate of 100.0%. The skill operation score was (93.5±3.7), with a minimum of 85.0 and a maximum of 99.0, and a pass rate of 100.0%. The score for the case analysis was (90.2±5.6), with a minimum score of 80.0 and a maximum score of 100.0, and a pass rate of 100.0%. The main reasons for losing points in the theoretical knowledge were mechanical ventilation and cardiopulmonary resuscitation. The main reasons for losing points in the review defense were topic selection and paper writing. The main reasons for losing points in skill operation were preparation before operation and key points after operation. The main reasons for losing points in the case analysis were the consultation ideas and treatment measures.Conclusions:The trainees of the emergency specialist nurse training course currently have a relatively good overall professional practical skills, but there are significant differences in theoretical knowledge, weak scientific research capabilities, and room for improvement in triage decision-making. It is suggested to give full play to the advantages of teachers and set up a variety of Internet courses for trainees to learn on their own to meet the personalized needs of trainees and improve teaching homogeneity.

Objective:To analyze the epidemiological distribution characteristics, influencing factors, and infection rates of pertussis in the population of Henan Province.Methods:From 2022 to 2023, a cross-sectional survey was conducted to investigate the permanent population in Henan Province. Enzyme-linked immunosorbent assay (ELISA) was used to detect anti-pertussis toxin IgG (PT-IgG), analyze the antibody positivity rate (≥20 IU/ml) and median concentration (MC), and estimate the pertussis infection rate based on PT IgG ≥40 IU/ml. The rank sum test was used to compare antibody levels among groups, and the χ2 test was used to compare antibody positive rates and infection rates among groups. Results:A total of 4 810 research subjects were included in this study. The overall positive rate of PT-IgG was 12.10% and MC was 3.04 (0.35, 10.36) IU/ml. There were significant differences both in positive rates and antibody levels of PT-IgG among different regions or age groups (region positive rate: χ2=134.06, P<0.001, MC: H=337.74, P<0.001; age group positive rate: χ2=45.27, P<0.001, MC: H=134.49, P<0.001). Both the positive rate of PT-IgG (25.26%) and MC (8.01 IU/ml) were the highest within one year after completing a full course of vaccination. There were significant differences in positive rates and antibody levels among people receiving different types of pertussis vaccines (positive rate: χ2=12.38, P=0.006, MC: H=17.93, P<0.001). The antibody positivity rate (35.71%) and MC (8.88 IU/ml) of the people who received cell-free pertussis inactivated poliomyelitis influenza type b (combined) vaccine throughout the course were higher than those who received other types of vaccines. The natural infection rate of pertussis was evaluated for individuals aged≥3 years who had no history of pertussis vaccine immunization within the year prior to sampling. With a high vaccination rate, the estimated infection rate of pertussis in the population was 5 757.22/100 000. The infection rates in the 3-year-old (1 940.16/100 000) and 4-year-old (1 765.68/100 000) populations were at a low level among the entire population, reaching their peak at the age of 6 (12 656.71/100 000). Subsequently, although the infection rate continued to decline, it remained at a high level and peaked again at the age of 40-49 years (8 740.39/100 000). There was a statistically significant difference in the estimated infection rate of pertussis among different age groups ( χ2=53.21, P<0.001). Conclusion:The PT-IgG level of pertussis in the population of Henan Province is generally at a low level. The estimated infection rate of pertussis is much higher than the reported incidence rate. A booster dose of pertussis vaccine is recommended at 6 years old.

Objective:To analyze the epidemiological distribution characteristics, influencing factors, and infection rates of pertussis in the population of Henan Province.Methods:From 2022 to 2023, a cross-sectional survey was conducted to investigate the permanent population in Henan Province. Enzyme-linked immunosorbent assay (ELISA) was used to detect anti-pertussis toxin IgG (PT-IgG), analyze the antibody positivity rate (≥20 IU/ml) and median concentration (MC), and estimate the pertussis infection rate based on PT IgG ≥40 IU/ml. The rank sum test was used to compare antibody levels among groups, and the χ2 test was used to compare antibody positive rates and infection rates among groups. Results:A total of 4 810 research subjects were included in this study. The overall positive rate of PT-IgG was 12.10% and MC was 3.04 (0.35, 10.36) IU/ml. There were significant differences both in positive rates and antibody levels of PT-IgG among different regions or age groups (region positive rate: χ2=134.06, P<0.001, MC: H=337.74, P<0.001; age group positive rate: χ2=45.27, P<0.001, MC: H=134.49, P<0.001). Both the positive rate of PT-IgG (25.26%) and MC (8.01 IU/ml) were the highest within one year after completing a full course of vaccination. There were significant differences in positive rates and antibody levels among people receiving different types of pertussis vaccines (positive rate: χ2=12.38, P=0.006, MC: H=17.93, P<0.001). The antibody positivity rate (35.71%) and MC (8.88 IU/ml) of the people who received cell-free pertussis inactivated poliomyelitis influenza type b (combined) vaccine throughout the course were higher than those who received other types of vaccines. The natural infection rate of pertussis was evaluated for individuals aged≥3 years who had no history of pertussis vaccine immunization within the year prior to sampling. With a high vaccination rate, the estimated infection rate of pertussis in the population was 5 757.22/100 000. The infection rates in the 3-year-old (1 940.16/100 000) and 4-year-old (1 765.68/100 000) populations were at a low level among the entire population, reaching their peak at the age of 6 (12 656.71/100 000). Subsequently, although the infection rate continued to decline, it remained at a high level and peaked again at the age of 40-49 years (8 740.39/100 000). There was a statistically significant difference in the estimated infection rate of pertussis among different age groups ( χ2=53.21, P<0.001). Conclusion:The PT-IgG level of pertussis in the population of Henan Province is generally at a low level. The estimated infection rate of pertussis is much higher than the reported incidence rate. A booster dose of pertussis vaccine is recommended at 6 years old.

The overall health condition of patients significantly affects the diagnosis,treatment,and prognosis of endodontic diseases.A systemic consideration of the patient's overall health along with oral conditions holds the utmost importance in determining the necessity and feasibility of endodontic therapy,as well as selecting appropriate therapeutic approaches.This expert consensus is a collaborative effort by specialists from endodontics and clinical physicians across the nation based on the current clinical evidence,aiming to provide general guidance on clinical procedures,improve patient safety and enhance clinical outcomes of endodontic therapy in patients with compromised overall health.

Objective:To preliminary observe the clinical efficacy of vedolizumab (VDZ) in the treatment of active Crohn′s disease (CD).Methods:From March 2021 to October 2022, a total of 22 patients with active CD who received VDZ treatment at Zhongda Hospital, Southeast University were retrospectively enrolled. The general clinical data, laboratory indicators, imaging finding and endoscopic images of the patients were collected. The Crohn′s disease activity index (CDAI), hypersensitive C-reactive protein (hs-CRP), erythrocyte sedimentation rate (ESR), clinical remission rate were evaluated at week 0, 2, 6 and 14 of VDZ administration. Meanwhile, the response rate under endoscopy and remission rate under endoscopy were evaluated after 14 weeks of VDZ administration. The related factors affecting the efficacy of VDZ were further analyzed. Kruskal-Wallis H test and Mann-Whithey U test were used for statistical analysis. The multiple logistic regression analysis was used to find the related factors affecting the clinical remission after VDZ treatment. Results:The CDAI at week 0, 2, 6 and 14 after treatment were 181.01 (160.11, 231.56), 148.05 (134.88, 200.52), 127.46 (91.44, 163.62), and 82.35 (63.50, 121.84), respectively, and the differences were statistically significant ( H=34.23, P<0.001); there were statistically significant differences between week 0 and week 2, 6, 14 after treatment ( U=130.00, 80.00, 33.00; P=0.017, <0.001, and<0.001). The hs-CRP levels were 5.72 mg/L (3.59 mg/L, 11.10 mg/L), 2.86 mg/L (0.86 mg/L, 5.27 mg/L), 1.55 mg/L (0.86 mg/L, 9.89 mg/L) and 2.86 mg/L (0.86 mg/L, 3.12 mg/L), respectively, and the differences were statistically significant ( H=9.69, P=0.021); there were statistically significant differences between week 0 and week 2, 6, 14 after treatment ( U=102.00, 109.00, 98.00; P=0.026, 0.045, and 0.011) .The level of ESR after 14 weeks of VDZ treatment was 8.00 mm/1 h (4.00 mm/1 h, 17.00 mm/1 h), which significantly decreased compared with that before treatment (17.00 mm/1 h(12.25 mm/1 h, 21.75 mm/1 h)), and the difference was statistically significant ( U=132.50, P=0.020). The clinical remission rates at week 2, 6 and 14 after VDZ treatment were 54.5% (12/22), 68.2% (15/22) and 86.4% (21/22), respectively, and the clinical response rates were 18.2% (4/22), 54.5% (12/22) and 95.5% (21/22), respectively. After 14 weeks of VDZ treatment, among 17 patients who underwent endoscopic re-examination, 9 patients achieved response under endoscopy and 3 patients achieved remission under endoscopy. Stenotic type and penetrating type of CD, previous use of glucocorticoids or immunosuppressants were risk factors of no clinical remission after VDZ treatment ( β=-4.586, -5.005 and -3.371; OR=0.010, 0.007 and 0.034; P=0.010, 0.025 and 0.045). While VDZ treatment for 14 weeks was a protective factor ( β=2.475, OR=11.885, P=0.011). Conclusions:VDZ can effectively relieve disease activity in patients with active CD. The disease behavior of CD, previous medication treatment of patients, and the duration of VDZ treatment may be related to the efficacy of VDZ.

Objective:To explore the mechanism of dendritic cells(DCs),novel regulatory B cells(B10 cells)and Th17/Treg imbalance in the pathogenesis of patients with chronic obstructive pulmonary disease(COPD)and their correlation with lung function.Methods:According to the"Guidelines for the Diagnosis and Treatment of Chronic Obstructive Pulmonary Disease"a total of 93 COPD patients were prospectively selected from the Ninth People's Hospital of Suzhou from May 2019 to December 2021,and 50 healthy subjects were selected as the control group.The patients were followed up for 1 year to observe the occurrence of acute exacer-bation COPD(AECOPD),and divided them into stable COPD group and AECOPD group.The course of disease,modified British Medical Research Society dyspnea index(mMRC)classification,COPD assessment test(CAT)score,BODE index score,6 min walking distance(6MWD),arterial partial pressure of oxygen(PaO2),arterial carbon dioxide Partial pressure(PaCO2)were com-pared between the two groups;compared the levels of FEV1,FVC,FEV1/FVC,and the percentage of FEV1 to predicted value(FEV1/Pred)in the three groups with peripheral blood DCs,B10 cells,Th17 cells,Treg cells and Th17/Treg,IL-12,IL-10,IL-17A and TGF-β1 levels.To analyze the correlation between peripheral blood DCs cells,B10 cells and Th17/Treg imbalance and pulmonary function indexes in AECOPD group.Logistic regression analysis of independent risk factors for AECOPD.Results:A total of COPD pa-tients had AECOPD events(40.86%).The course of disease,mMRC grade,CAT score,BODE index score,and PaCO2 in AECOPD group were significantly higher than those in COPD stable group(P<0.05),6MWD and PaO2 were significantly lower than those in COPD group.The levels of FEV1,FVC,FEV1/FVC and FEV1/Pred in the AECOPD group were significantly lower than those in the stable COPD group and control group(P<0.05);the levels of FEV1,FVC,FEV1/FVC and FEV1/Pred in the stable COPD group were significantly lower than those in control group(P<0.05).DCs,B10 cells and Treg cells in AECOPD group were significantly lower than those in stable COPD group and control group,while Th17 expression level and Th17/Treg were significantly higher than that in stable COPD group and control group(P<0.05).DCs,B10 cells and Treg cells in stable COPD phase were significantly lower than those in control group,while Th17 expression level and Th17/Treg were significantly higher than control group(P<0.05).The ex-pression levels of IL-12,IL-10 and TGF-β1 in the AECOPD group were significantly lower than those in the stable COPD group and control group(P<0.05),while IL-17A was significantly higher than that in the stable COPD group and control group.The expression levels of IL-12,IL-10 and TGF-β1 in patients with stable COPD were significantly lower than control group,while IL-17A was signifi-cantly higher than control group(P<0.05).Pearson analysis showed that peripheral blood DCs,B10 cells were positively correlated with FEV1,FVC,FEV1/FVC and FEV1/Pred levels(P<0.05),while Th17/Treg was positively correlated with FEV1,FVC,FEV1/FVC and FEV1/Pred levels all were negatively correlated(P<0.05).Logistic regression analysis found that mMRC grade and Th17/Treg were independent risk factors of AECOPD(P<0.05).Conclusion:With the progression of COPD,DCs,B10 cells,Th17 cells,Treg cells and Th17/Treg gradually become unbalanced,resulting in disordered expression levels of pro-inflammatory and anti-inflamma-tory factors.Peripheral blood DCs and B10 cells were positively correlated with lung function levels,while Th17/Treg were negatively correlated with lung function levels.mMRC grade and Th17/Treg are independent risk factors of AECOPD.Therefore,actively inter-vening in the imbalanced state of immune function in patients has specific and important clinical significance in reducing the immune damage of lung tissue and promoting the improvement of lung function.