The innate immune sensor NLRP3 inflammasome overactivation is involved in the pathogenesis of ulcerative colitis. PGAM5 is a mitochondrial phosphatase involved in NLRP3 inflammasome activation in macrophages. However, the role of PGAM5 in ulcerative colitis and the mechanisms underlying PGAM5 regulating NLRP3 activity remain unknown. Here, we show that PGAM5 deficiency ameliorates dextran sodium sulfate (DSS)-induced colitis in mice via suppressing NLRP3 inflammasome activation. By combining APEX2-based proximity labeling focused on PGAM5 with quantitative proteomics, we identify NEK7 as the new binding partner of PGAM5 to promote NLRP3 inflammasome assembly and activation in a PGAM5 phosphatase activity-independent manner upon inflammasome induction. Interfering with PGAM5-NEK7 interaction by punicalagin inhibits the activation of the NLRP3 inflammasome in macrophages and ameliorates DSS-induced colitis in mice. Altogether, our data demonstrate the PGAM5-NEK7 interaction in macrophages for NLRP3 inflammasome activation and further provide a promising therapeutic strategy for ulcerative colitis by blocking the PGAM5-NEK7 interaction.

Psoriasis is an incurable chronic inflammatory disease that requires new interventions. Here, we found that fibroblasts exacerbate psoriasis progression by promoting macrophage recruitment via CCL2 secretion by single-cell multi-omics analysis. The natural small molecule celastrol was screened to interfere with the secretion of CCL2 by fibroblasts and improve the psoriasis-like symptoms in both murine and cynomolgus monkey models. Mechanistically, celastrol directly bound to the low-density lipoprotein receptor-related protein 1 (LRP1) β-chain and abolished its binding to the transcription factor c-Jun in the nucleus, which in turn inhibited CCL2 production by skin fibroblasts, blocked fibroblast-macrophage crosstalk, and ameliorated psoriasis progression. Notably, fibroblast-specific LRP1 knockout mice exhibited a significant reduction in psoriasis like inflammation. Taken together, from clinical samples and combined with various mouse models, we revealed the pathogenesis of psoriasis from the perspective of fibroblast-macrophage crosstalk, and provided a foundation for LRP1 as a novel potential target for psoriasis treatment.

Objective:To investigate the effect of the magnetic stimulation of the sacral nerve on detrusor weakness after spinal cord injury. Method:36 individuals with detrusor weakness after spinal cord injury were divided into experimental group and control group after randomization.Both groups received conventional rehabilitation treatment,besides,the experimental group received repetitive functional magnetic stimulation(rFMS)on S3 nerve roots.Before treat-ment and after 4-weeks treatment,the simple bladder capacity,bladder ultrasound,self-rating anxiety scale were observed. Result:The maximum automatic micturition volume,average automatic micturition volume,residual urine vol-ume,initial uriesthesis,and anxiety self-evaluation score of the two groups were improved after intervention.And the improvements are more in experimental group(P＜0.05). Conclusion:The effect of the rFMS on individuals with detrusor weakness after spinal cord injury is signifi-cantly better than conventional intervention,which provides a new idea for the clinical treatment of neurogenic bladder with detrusor weakness.

Objectives:To investigate the clinical feasibility of three-dimensional(3D)high-resolution late gadolinium enhancement(LGE)MRI in accessing left atrial myocardial fibrosis in patients with atrial fibrillation(AF). Methods:A total of 34 AF patients referred for hybrid surgical ablation were retrospectively enrolled in this study.3D-LGE-MRI images were acquired by Siemens 3.0 T machine and analyzed by ADAS post-processing software by two experienced radiologists to obtain parameters such as the area and the area percentage of LGE.Regional analysis was performed by one of the two radiologists at ten left atrial segments.The Kappa test was used to assess the agreement for scoring image quality,and the interclass correlation coefficient(ICC)was used to evaluate the interobserver agreement of LGE parameters.The parameters of left atrial morphology,area(and area percentage)of LGE,and location of LGE were compared between patients with persistent AF and paroxysmal AF. Results:Images of all 34 patients were considered to have diagnostic value.The scores of the overall image quality and the clarity of the left atrial wall evaluated by two radiologists were(2.88±0.64)points and(3.26±0.75)points(radiologist 1),(2.97±0.58)points and(3.24±0.70)points(radiologist 2),respectively.The corresponding Kappa values were 0.724 and 0.859.Both the area and the area percentage of LGE showed good consistency among observers,and the ICCs were 0.969 and 0.950,respectively.The difference in the area of LGE and the area percentage of LGE between patients with paroxysmal and persistent atrial fibrillation was similar(both P＞0.05).Compared with patients with paroxysmal AF,patients with persistent AF had a higher Utah stage and more severe myocardial fibrosis in the right inferior pulmonary vein antrum and the left atrial septum(all P＜0.05). Conclusions:3D high-resolution LGE-MRI provides a non-invasive way to visualize and quantify left atrial myocardial fibrosis.The extent of left atrial fibrosis in patients with persistent AF is more severe than that in patients with paroxysmal AF,with a preferential distribution in the right inferior pulmonary vein antrum and the left atrial septum.

Background::Pancreatic ductal adenocarcinoma (PDAC) is one of the main types of malignant tumor of the digestive system, and patient prognosis is affected by difficulties in early diagnosis, poor treatment response, and a high postoperative recurrence rate. Carbohydrate antigen 19-9 (CA19-9) has been widely used as a biomarker for the diagnosis and postoperative follow-up of PDAC patients. Nevertheless, the production mechanism and potential role of CA19-9 in PDAC progression have not yet been elucidated.Methods::We performed single-cell RNA sequencing on six samples pathologically diagnosed as PDAC (three CA19-9-positive and three CA19-9-negative PDAC samples) and two paracarcinoma samples. We also downloaded and integrated PDAC samples (each from three CA19-9-positive and CA19-9-negative patients) from an online database. The dynamics of the proportion and potential function of each cell type were verified through immunofluorescence. Moreover, we built an in vitro coculture cellular model to confirm the potential function of CA19-9. Results::Three subtypes of cancer cells with a high ability to produce CA19-9 were identified by the markers TOP2A, AQP5, and MUC5AC. CA19-9 production bypass was discovered on antigen-presenting cancer-associated fibroblasts (apCAFs). Importantly, the proportion of immature ficolin-1 positive (FCN1+) macrophages was high in the CA19-9-negative group, and the proportion of mature M2-like macrophages was high in the CA19-9-positive group. High proportions of these two macrophage subtypes were associated with an unfavourable clinical prognosis. Further experiments indicated that CA19-9 could facilitate the transformation of M0 macrophages into M2 macrophages in the tumor microenvironment. Conclusions::Our study described CA19-9 production at single-cell resolution and the dynamics of the immune atlas in CA19-9-positive and CA19-9-negative PDAC. CA19-9 could promote M2 polarization of macrophage in the pancreatic tumor microenvironment.

Objective:To explore the clinical efficacy of immunoadsorption in highly sensitized kidney transplant (KT) candidates.Methods:From September 2019 to April 2023, the relevant clinical data were retrospectively reviewed for 26 highly sensitized KT recipients. Protein A immunoadsorption desensitization therapy was offered after KT. The effect of immunosorbent on reducing anti-human leukocyte antigen (HLA) antibodies was summarized. And operative success rate and postoperative complication incidence were calculated.Results:The mean number of treatment session was (10.76±5.53). The highest level of HLA-Ⅰ antibody mean fluorescence intensity (MFI) dropped from (17 921±4 442) to (7 333±6 434) with a decline of 59% and HLA-Ⅱ antibody MFI decreased from (21 135±5 245) to (10 989±7 627) with a decline of 48%. The differences were statistically significant (both P<0.001). All kidneys were harvested from cadavers. The complications were acute antibody mediated rejection (7 cases), perioperative pulmonary infection (3 cases) and myelosuppression (2 cases). The average follow-up period was (30.8±12.6) month. The graft survival rate was 88.5% (23/26) and the recipient survival rate 100% (26/26) . Conclusions:Immunoadsorption therapy can effectively reduce HLA antibody in highly sensitized KT candidates, thereby increasing the probability of successful KT. In terms of safety, immunosorbent therapy may boost the potential risks of infection and myelosuppression. It requires heightened attention.

Objective    To analyze the correlation between the gray value of epicardial fat and the prognosis of patients with atrial fibrillation (AF) treated by thoracoscopic radiofrequency ablation. Methods    The clinical data of 97 patients, including 75 males and 22 females with an average age of 57.8±9.4 years, who underwent thoracoscopic radiofrequency ablation in Fuwai Hospital from 2017 to 2018 were analyzed retrospectively. The left atrial fat volume and average gray scale were calculated by left atrial enhanced CT. According to the average gray scale of left atrial fat tissue, the patients were divided into three groups: a high gray scale group, a medium gray scale group and a low gray scale group. The patients were followed up at 3, 6 and 12 months after operation. The end point of follow-up was the recovery rate of sinus rhythm. Survival analysis was used to analyze the correlation between CT features of epicardial fat enhancement and prognosis. Results    After adjustment of body mass index, body surface area, gender and left atrial end diastolic diameter, regression analysis showed that the fat gray of left atrial enhanced CT was correlated with the type of AF (OR=0.30, 95%CI 0.12-0.79, P=0.014). Cox regression analysis showed that the fat gray value of left atrial CT predicted the recurrence of AF after thoracoscopic radiofrequency ablation (OR=0.92, 95%CI 0.85-0.99). The Kaplan-Meier curve showed significant difference in the long-term recurrence rate of AF among the three groups (P=0.011). The lower left atrial fat enhanced CT gray scale was, the higher long-term recurrence rate of AF was. Conclusion    The gray value of left atrial fat enhanced CT can effectively predict the recurrence of AF after radiofrequency ablation in thoracoscopic surgery.

Objective    To evaluate short-term clinical outcomes of skeletonized bilateral internal mammary artery (sBIMA) in coronary artery bypass grafting (CABG). Methods    The clinical data of 62 patients (54 males and 8 females with an average age of 56.8±6.0 years) undergoing isolated CABG using sBIMA in our hospital from October 2016 to May 2017 were retrospectively analyzed. The coronary graft flow, perioperative clinical outcomes and CT results were reviewed. Results    All the operations were carried out under extracorporeal circulation. Anastomosis of 124 internal mammary arteries was performed and 116 great saphenous veins were used simultaneously with an average anastomosis site of 4.5±0.8 for each patient. The cardiopulmonary bypass time was 116.4±22.9 min, aortic clamping time was 83.0±18.3 min, mechanical ventilation time was 20.8±21.3 h and ICU stay was 2.7±1.7 d. The graft flow of left internal mammary artery (LIMA), right internal mammary artery (RIMA) and great saphenous vein were 28.8±12.4 mL/min, 32.8±13.8 mL/min and 41.5±21.5 mL/min, respectively. There was no significant difference in the graft flow between LIMA and RIMA (P=0.112). There was no perioperative mortality, myocardial infarction or cerebrovascular accident. Only one male patient suffered sternal complication and poor wound healing and then received debridement as well as suturing. Coronary CT angiography showed that distal anastomosis of 7 vein grafts and 5 artery grafts was demonstrated shallow and 1 vein graft was undemonstrated, suggesting occlusion. Conclusion    CABG with sBIMA is a safe and reliable technique with excellent early results.

Objective To verify whether hybrid surgical and interventional ablation(HA) for the treatment of persistent atrial fibrillation (AF) is superior to video-assisted thoracoscopic surgical radiofrequency ablation (VATS-RA). Methods From September 2010 to December 2017, 79 consecutive patients with persistent AF underwent VATS-RA or HA in Fuwai Hospital. VATS-RA was performed in sixty patients (a stand-alone surgical group, 48 males and 12 females, at average age of 56.0±7.6 years, and HA was performed in nineteen patients (a hybrid group, 14 males and 5 females, at average age of 58.0±7.3 years). Follow-up was completed at 3 months, 6 months, 1 year and annually thereafter. Postoperative sinus rhythm was defined as sinus rhythm recorded in 24-hour or 7-day Holter during follow-up, without exhibited rapid atrial tachyarrhythmia≥30 s including AF, atrial flutter, or atrial tachycardia. Results Seventy-eight patients (98.7%) completed the follow-up. Although the preoperative left atrial diameter (49.1±5.3 mm) in the hybrid group was significantly greater than that in the stand-alone surgical group (41.7±6.2 mm, P<0.001). Overall sinus rhythm maintenance rate in the hybrid group was significantly greater than that in the stand-alone surgical group (94.7% versus 64.4%, P=0.011). And sinus rhythm maintenance rate free from anti-arrhythmic drugs (AADs) and catheter ablation in the hybrid group was significantly greater than that in the stand-alone surgical group (84.2% versus 50.8%, P=0.010). Conclusion HA is superior to VATS-RA in the treatment of persistent AF, but a larger sample size is needed for further validation in prospective randomized studies.

Objective This study aimed to evaluate the safety and efficacy of video-assisted thoracoscopic bipolar radio-frequency ablation in the treatment of isolated paroxysmal atrial fibrillation.Methods From September 2010 to December 2016,Seventy-two consecutive patients with paroxysmal atrial fibrillation underwent video-assisted thoracoscopic bipolar radio-frequency ablation at Fuwai Hospital.There were 50 males and 22 females with an average age of(56.5 ± 10.5) years and duration of atrial fibrillation with (6.5 ± 4.8) years.45 patients had previous catheter ablation.The patients were followed up at postoperative 3 months,6 months,1 year and annually.Success of ablation was defined as sinus rhythm and no duration of ≥30 s for rapid atrial arrhythmias,including atrial fibrillation,atrial flutter or atrial tachycardia in 24 h Holter examination.Univariate and multivariate logistic regression models were used to analyze the risk factors for atrial fibrillation recurrence.Results One patient converted to sternotomy due to bleeding on operation.All patients were successfully discharged.69 patients completed follow-up,with an average follow-up of(28 ± 18)months(3-60 months).The overall success rate was 73.9％,and the success rate without antiarrhythmic drug was 62.3％.Subgroup analysis showed that the success rate was 80％ when left atrial anterior and posterior diameter(LAD) ≤40 mm,and 57.9％ when LAD ＞ 40 mm (P =0.035).Multivariate logistic regression analysis showed that LAD ＞40 mm was an independent risk factor for postoperative recurrence of atrial fibrillation.Conclusion Video-assisted thoracoscopic bipolar radiofrequency ablation is a safe and effective method for the treatment of paroxysmal atrial fibrillation,especially in patients with LAD≤40 mm.