Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract, which increases the incidence of colorectal cancer (CRC). In the pathophysiology of IBD, ubiquitination/deubiquitination plays a critical regulatory function. Josephin domain containing 2 (JOSD2), a deubiquitinating enzyme, controls cell proliferation and carcinogenesis. However, its role in IBD remains unknown. Colitis mice model developed by dextran sodium sulfate (DSS) or colon tissues from individuals with ulcerative colitis and Crohn's disease showed a significant upregulation of JOSD2 expression in the macrophages. JOSD2 deficiency exacerbated the phenotypes of DSS-induced colitis by enhancing colon inflammation. DSS-challenged mice with myeloid-specific JOSD2 deletion developed severe colitis after bone marrow transplantation. Mechanistically, JOSD2 binds to the C-terminal of inosine-5'-monophosphate dehydrogenase 2 (IMPDH2) and preferentially cleaves K63-linked polyubiquitin chains at the K134 site, suppressing IMPDH2 activity and preventing activation of nuclear factor kappa B (NF-κB) and inflammation in macrophages. It was also shown that JOSD2 knockout significantly exacerbated increased azoxymethane (AOM)/DSS-induced CRC, and AAV6-mediated JOSD2 overexpression in macrophages prevented the development of colitis in mice. These outcomes reveal a novel role for JOSD2 in colitis through deubiquitinating IMPDH2, suggesting that targeting JOSD2 is a potential strategy for treating IBD.

Objective To investigate the relationship between frailty and readmission during vulnerable periods in elderly patients with chronic heart failure.Methods Using convenience sampling method,290 elderly patients with chronic heart failure admitted to Department of Cardiovascular,the People's Hospital of Guangxi Zhuang Autonomous Region from December 2022 to August 2023 were selected as the research subjects.They were followed up for three months and surveyed using general information questionnaire,frailty scale,and Barthel index.Results Spearman correlation analysis showed a positive correlation between readmission during the vulnerable period and frailty(r=0.266,P＜0.05).The readmission rate during the vulnerable period was 28.6％,and the results of multivariate Logistic regression analysis showed that frailty(OR=2.561,95％CI:1.409-4.654),age(OR=1.113,95％CI:1.067-1.161),and renal dysfunction(OR=2.903,95％CI:1.559-5.406)were independent risk factors for unplanned readmission during the vulnerable period in elderly patients with chronic heart failure.Conclusion There is a positive correlation between frailty and readmission during the vulnerable period in elderly patients with chronic heart failure.Frailty,age,and renal dysfunction are independent risk factors for decompensated admission events in vulnerable elderly patients with chronic heart failure.

Objective To analyze the diagnostic process and clinical characteristics of autoimmune gastritis(AIG)in order to improve the awareness and diagnostic proficiency of this disease.Methods A retrospective cohort study was conducted on 114 patients diagnosed with AIG in Army Medical Center of PLA between January 2021 and June 2024.Comprehensive statistical analysis was performed on clinical data,including demographic characteristics(age,sex),clinical symptoms,comorbidities,diagnostic process,Helicobacter pylori(H.pylori)infection and treatment history,laboratory indicators[results of routine blood test,anemia-related indices,thyroid function,anti-parietal cell antibody(APCA),intrinsic factor antibody(IFA)],and gastrointestinal endoscopic findings(frequency and endoscopic features).Results Among the 114 patients,males accounted for 28.1%(32/114)and females for 71.9%(82/114),and they were at a mean age of 56.3±8.4 years.Predominant symptoms included epigastric/upper abdominal pain(47.4%,54/114)and postprandial fullness(43.0%,49/114),while 24.6%(28/114)reported acid reflux or heartburn.Diagnostic delay occurred in 76.4%(87/114)of patients,with a median delay duration of 11.5 months.Primary diagnostic clues were endoscopic reverse gradient atrophy(significantly more severe mucosal atrophy in the gastric corpus/fundus versus antrum;53.5%,61/114)and repeated H.pylori eradication failure(≥2 attempts;22.8%,26/114).Positivity rate of thyroid peroxidase antibody(TPOAb)and thyroglobulin antibody(TgAb)was 56.9%(33/58)and 36.2%(21/58),respectively.APCA positive rate was 98.8%(81/82),IFA positive rate was 34.1%(28/82),and dual-antibody rate was 32.9%(27/82).Anemia was present in 25.7%(26/101)of the patients.Gastric neuroendocrine tumors(NET)were found in 12.2%(14/114),intraepithelial neoplasia in 5.3%(6/114),and gastric adenocarcinoma in 0.9%(1/114).Among colonoscopy-examined patients,tubular adenomas occurred in 25.0%(13/52)and colorectal malignancies in 3.4%(2/58).There were 18.4%(21/114)patients having gallbladder-related diseases,7.9%(9/114)having diabetes mellitus,and 1.8%(2/114)of subacute combined degeneration of the spinal cord.Conclusion AIG is frequently associated with diagnostic delay.The reverse pattern of atrophy on endoscopy serves as a critical diagnostic clue,necessitating enhanced recognition in endoscopists.Patients with recurrent H.pylori eradication failure(≥2 attempts)should be evaluated for AIG.

Objective Epigenetics,which changes the expression of DNA or protein by chemical modification,affects the regulation of genes and plays an important role in the interaction between genetic and environmental factors in diseases.This review focuses on the development trend and research hotspots of epigenetic modification in ulcerative colitis from 2003 to 2023.Methods Literature related to epigenetic modification in UC was obtained from the Web of Science Core Collection database,and bibliometric analyses and visualization were performed using VOSviewer,CiteSpace and R software.Results 1359 papers published from 2003-2023 were retrieved for inclusion in the analysis.The United States dominated the field of epigenetic modification,with the University of Chicago being the most published and cited institution,and Wu Feng of the Meyerhoff Center for Inflammatory Bowel Disease being the most cited author.The journals Inflammatory Bowel Diseases and Gastroenterology have high influence,screening for high-frequency keywords related to UC epigenetic modifications,including microRNA,inflammation,biomarker,azathioprine,DNA methylation,long noncoding RNA,circular RNA,received wide attention.Conclusion Epigenetics continues to evolve in the field of UC,providing important avenues in elucidating the pathogenesis of UC,in elucidating the interactions between genetics and the environment,and in giving new ideas for simplifying diagnosis,improving inflammation,and developing new drugs.

Objective To investigate the relationship between frailty and readmission during vulnerable periods in elderly patients with chronic heart failure.Methods Using convenience sampling method,290 elderly patients with chronic heart failure admitted to Department of Cardiovascular,the People's Hospital of Guangxi Zhuang Autonomous Region from December 2022 to August 2023 were selected as the research subjects.They were followed up for three months and surveyed using general information questionnaire,frailty scale,and Barthel index.Results Spearman correlation analysis showed a positive correlation between readmission during the vulnerable period and frailty(r=0.266,P＜0.05).The readmission rate during the vulnerable period was 28.6％,and the results of multivariate Logistic regression analysis showed that frailty(OR=2.561,95％CI:1.409-4.654),age(OR=1.113,95％CI:1.067-1.161),and renal dysfunction(OR=2.903,95％CI:1.559-5.406)were independent risk factors for unplanned readmission during the vulnerable period in elderly patients with chronic heart failure.Conclusion There is a positive correlation between frailty and readmission during the vulnerable period in elderly patients with chronic heart failure.Frailty,age,and renal dysfunction are independent risk factors for decompensated admission events in vulnerable elderly patients with chronic heart failure.

Objective Epigenetics,which changes the expression of DNA or protein by chemical modification,affects the regulation of genes and plays an important role in the interaction between genetic and environmental factors in diseases.This review focuses on the development trend and research hotspots of epigenetic modification in ulcerative colitis from 2003 to 2023.Methods Literature related to epigenetic modification in UC was obtained from the Web of Science Core Collection database,and bibliometric analyses and visualization were performed using VOSviewer,CiteSpace and R software.Results 1359 papers published from 2003-2023 were retrieved for inclusion in the analysis.The United States dominated the field of epigenetic modification,with the University of Chicago being the most published and cited institution,and Wu Feng of the Meyerhoff Center for Inflammatory Bowel Disease being the most cited author.The journals Inflammatory Bowel Diseases and Gastroenterology have high influence,screening for high-frequency keywords related to UC epigenetic modifications,including microRNA,inflammation,biomarker,azathioprine,DNA methylation,long noncoding RNA,circular RNA,received wide attention.Conclusion Epigenetics continues to evolve in the field of UC,providing important avenues in elucidating the pathogenesis of UC,in elucidating the interactions between genetics and the environment,and in giving new ideas for simplifying diagnosis,improving inflammation,and developing new drugs.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To evaluate the regeneration and biomechanical property recovery of semitendinosus tendon(ST)/gracilis tendon(GT) after anterior cruciate ligament(ACL) reconstruction using shear wave elastorgraphy (SWE) combined with high-frequency ultrasound(HFUS).Methods:Twenty-five patients who underwent ST/GT autograft reconstruction after ACL rupture at the People′s Hospital of Guangxi Zhuang Autonomous Region from January 2020 to June 2022 were prospectively enrolled. All patients underwent HFUS, SWE and flexion strength assessment at pre-operation and 1, 3, 6, 12, 24 months postoperatively. The morphology, length, cross-sectional area and SWE of ST/GT and flexion strength of knee were recorded at each time point. Repeated measures analysis of variance was employed to compare the cross-sectional area and elasticity value of regenerated ST/GT at different time points. Spearman correlation analysis was used to investigate the relationship between the elasticity value of regenerated ST/GT and flexion strength.Results:The regeneration rates of ST/GT after being harvested for ACL reconstruction were 88% and 92%. The length of the regenerated ST/GT were shorter than before operation(both P<0.05). Repeated measures analysis of variance revealed significant differences in the cross-sectional area of regenerated ST/GT, both in terms of time effect and inter-group effect ( F=27.264, 28.980; both P<0.001), but no significant difference was observed in the interaction effect ( F=0.670, P=0.652). The cross-sectional area of regenerated ST/GT was the largest at 3 months postoperatively ( P<0.05), and restored to the preoperative level at 12 and 24 months postoperatively (both P>0.05). Repeated measures analysis of variance showed that the elasticity values of the regenerated ST/GT were significantly different in terms of time effect, group effect, and interaction effect ( F=265.402, 33.015, 11.475; all P<0.001). The elasticity of regenerated ST/GT post-operation gradually increased over time. The flexion strength level of knee gradually improved post-operation(χ 2=34.83, P<0.001). The elasticity values of the regenerated ST and GT showed significant positive correlations with the flexion strength ( rs=0.755, 0.761; both P<0.001). Conclusions:HFUS discovers that most of ST/GT can be regenerated after being harvested for ACL reconstruction. The flexion strength and elasticity value of regenerated tendon recover gradually with time. It is suggested that the SWE can predict the recovery of biomechanical property of regenerated ST/GT.

AIM:To establish and evaluate a colonoids model of intestinal barrier dysfunction with irritable bowel syndrome(IBS).METHODS:The colonic recess of 20～22 g male C57BL/6 mice were isolated and cultured in ma-trix glue to proliferate and differentiate into 3D hollow spheres with colonic epithelioid structure.The following experi-ments were carried out:(1)Colonoids and colonic tissues of mice were detected by immunofluorescence to identify colo-noids.(2)Fluorescein isothiocyanate dextran 4(FD4)evaluated the epithelial barrier function of colonoids.(3)To ex-plore the changes in the epithelial barrier of colonoids induced by interferon-γ(IFN-γ)at different concentrations and time points.FD4 and HE staining were used to evaluate the barrier function.RT-qPCR was used to detect the mRNA expres-sion of occludin and zonula occludens-1(ZO-1)in tight junctions of colonoids.Immunofluorescence was used to detect the distribution and localization of occludin and ZO-1 proteins.RESULTS:(1)The expression of EdU proliferation and in-testinal epithelial cell lineage markers in colonoids was consistent with that in mouse colonic tissues.(2)In the control group,FD4 did not infiltrate the colonoids lumen,but FD4 significantly infiltrated the colonoids lumen induced by ethyl-ene glycol-bis(β-aminoethyl ether)-N,N,N',N'-tetraacetic acid(EGTA).(3)From 18 h,the IFN-γ at 60,100,200 and 240 ng/mL could significantly infiltrate into the cavity of colonoids(0.033,0.032,0.042 and 0.001),and the barri-er injury of colonoids could be seen by HE staining.After 18 h,all concentrations of IFN-γ could significantly decrease the mRNA expression of occludin and ZO-1,and the fluorescence of occludin and ZO-1 decreased significantly(P<0.05).CONCLUSION:(1)The cultured organoids are colonoids with complete epithelial barrier.(2)IFN-γ could in-duce the decrease of the transcriptional levels of occludin and ZO-1 in the tight junction of colonoids,the decrease of the expression of corresponding proteins,and the change of localization and distribution,thus increasing the epithelial perme-ability of colonoids.This model is highly consistent with the pathophysiological state of IBS colonic mucosal barrier dys-function,which provides a new tool and method for studying the direction of colonic mucosal barrier dysfunction in IBS.

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.