Ubiquitination is a crucial post-translational modification process that can degrade proteins within cells and plays a vital role in maintaining protein homeostasis and abundance.Deubiquitinating enzymes(DUBs)are important proteases in the ubiquitin system.They reverse the ubiquitination process by cleaving protein chains and recycling ubiquitin molecules to regulate protein stability.Abnormal deubiquitinating enzyme activity is related to the occurrence and development of many malignant tumors.JOSD2,a DUB,is a member of the Machado-Joseph disease protein domain protease(MJD)family and characterized by a single highly conserved catalytic Josephin domain.Increasing studies have revealed a connection between JOSD2 and malignant tumors.This article elaborates on the current research status of DUBs,particularly JOSD2,in malignant tumors.Results suggest that JOSD2 is a potential target for the treatment of malignant tumors.

Objective To explore the effects of four extralevator abdominoperineal excision(ELAPE)procedures on the biomechanics of female pelvic floor through finite element analysis.Methods Six finite element models of the female pelvic floor were established,including a normal model,an ELAPE model,and four individual models.The maximum stress in each model was measured under the same pressure,and the stress distribution was observed.Results The maximum stress of non-levator ani muscle tissues on the partially reserved side and totally removed side of the levator ani muscle were 3.101±0.133 and 4.868±0.123 MPa in individual model 1,respectively,which were lower than the maximum stress in the ELAPE model(5.111±0.081 MPa;both P<0.01).The maximum stress in the non-levator ani muscle tissue were 5.138±0.091 MPa on both sides in individual model 2,which were not significantly different from that in the ELAPE model(P>0.05).The maximum stress of non-levator ani muscle tissues were 4.700±0.105 and 3.653±0.156 MPa in individual models 3 and 4,respectively,which were lower than the maximum stress in the ELAPE model(both P<0.01).Conclusion Three ELAPE procedures,including ELAPE with unilateral levator ani muscle resection plane close to the rectum,and the bilateral pubococcygeal muscle lateral resection of levator ani muscle and levator ani muscle in front of the rectum preserved could decrease stress in the non-levator ani muscle tissue on both sides.The effect is evident on the levator ani muscle partially reserved side of ELAPE with unilateral levator ani muscle resection plane close to the rectum.ELAPE with unilateral levator ani muscle resection plane close to the pelvic wall has no significant reduction effect on the non-levator ani muscle tissue on either side.ELAPE模型(均P<0.01).

Objective To explore the public's cognition and attitude towards general medicine,general practitioners,and pre-hospital first-aid knowledge in Ludian County,Yunnan Province,to find out the training and learning methods that are more acceptable to the public for this kind of related knowledge,and to propose targeted solutions.Methods A complete random sampling survey was conducted among the nucleic acid collection office at the gate of the vegetable market from October 15,2022,to December 30,2022,and the outpatient clinic of Wenping Street Health Center from January 1,2023,to February 28,2023,by using electronic questionnaire and paper questionnaire.Results Nearly 50%of the people in Ludian County of Yunnan Province lack the knowledge of general medicine and pre-hospital emergency care,especially the knowledge of electrical defibrillation.People with higher education and the medical profession have a higher understanding of general medicine,and people with a higher understanding of general medicine are more willing to participate in pre-hospital emergency care.The average Ridit value is:very familiar with general medicine(0.774)>Knowledge of some general practices(0.565)>Never heard of general practice(0.400).The higher education level and the more comprehensive understanding of general medicine had a positive impact on participation in pre-hospital emergency care,with B values of 0.624 and 0.619,OR 95%CI of 1.867(1.544～2.257)and 1.857(1.298～2.657),respectively.Taking medical staff as a reference,the B value of medical students was = 0.942,P = 0.234,the difference was not significant,and the B value of non-medical professional population was all less than 0,the effect is negative.In addition,most people have a positive attitude towards learning pre-hospital first aid,and more than 70%of people are willing to learn and train related knowledge of pre-hospital first aid.Conclusions People in urban areas of Ludian County,Yunnan Province have poor understanding of general practice,low recognition of general practitioners,low demand for general practitioners,and lack of awareness of the importance of pre-hospital emergency treatment.Because of the cognitive differences among different groups,it is necessary to conduct specific training for different groups.

Objective:To investigate the value of implantable cardiac monitor (ICM) in the diagnosis and treatment of patients over 60 years old with unexplained syncope.Methods:This was a multi-center, prospective cohort study. Between June 2018 and April 2021, patients over the age of 60 with unexplained syncope at Beijing Hospital, Fuwai Hospital, Beijing Anzhen Hospital and Puren Hospital were enrolled. Patients were divided into 2 groups based on their decision to receive ICM implantation (implantation group and conventional follow-up group). The endpoint was the recurrence of syncope and cardiogenic syncope as determined by positive cardiac arrhythmia events recorded at the ICM or diagnosed during routine follow-up. Kaplan‐Meier survival analysis was used to compare the differences of cumulative diagnostic rate between the 2 groups. A multivariate Cox regression analysis was performed to determine independent predictors of diagnosis of cardiogenic syncope in patients with unexplained syncope.Results:A total of 198 patients with unexplained syncope, aged (72.9±8.25) years, were followed for 558.0 (296.0,877.0) d, including 98 males (49.5%). There were 100 (50.5%) patients in the implantation group and 98 (49.5%) in the conventional follow-up group. Compared with conventional follow-up group, patients in the implantation group were older, more likely to have comorbidities, had a higher proportion of first degree atrioventricular block indicated by baseline electrocardiogram, and had a lower body mass index (all P<0.05). During the follow-up period, positive cardiac arrhythmia events were recorded in 58 (58.0%) patients in the ICM group. The diagnosis rate (42.0% (42/100) vs. 4.1% (4/98), P<0.001) and the intervention rate (37.0% (37/100) vs. 2.0% (2/98), P<0.001) of cardiogenic syncope in the implantation group were higher than those in the conventional follow-up group (all P<0.001). Kaplan-Meier survival analysis showed that the cumulative diagnostic rate of cardiogenic syncope was significantly higher in the implantation group than in the traditional follow-up group ( HR=11.66, 95% CI 6.49-20.98, log-rank P<0.001). Multivariate analysis indicated that ICM implantation, previous atrial fibrillation, diabetes mellitus or first degree atrioventricular block in baseline electrocardiogram were independent predictors for cardiogenic syncope (all P<0.05). Conclusions:ICM implantation improves the diagnosis and intervention rates in patients with unexplained syncope, and increases diagnostic efficiency in patients with unexplained syncope.

Objective:To assess the prognostic impact of frailty on elderly inpatients with heart failure.Methods:This prospective cohort study enrolled 121 in elderly patients with heart failure from Beijing Hospital, the General Hospital of the People's Liberation Army, and Beijing Tsinghua Changgung Hospital between September 2018 and April 2019.Patients were assessed for frailty using the Fried frailty phenotype and categorized into frail and non-frail groups.Follow-ups were conducted at 3-, 6-, and 12-months post-enrollment through clinic visits or phone calls to record adverse events.Composite endpoints include all-cause mortality and rehospitalization duo to deterioration of heart failure.Results:The study included 121 patients with an average age of 78.0±7.4 years, of whom 71(58.7%)were male and 57(47.1%)were classified as frail.Compared to the non-frail group, the frail group had lower estimated glomerular filtration rates[49.5±20.7 ml/(min·1.73m 2) vs.(64.0±27.1)ml/(min·1.73m 2)], lower scores in Basic Activities of Daily Living[5.0(4.0, 6.0) vs.6.0(5.0, 6.0)], Instrumental Activities of Daily Living[2.0(1.3, 7.8) vs.7.0(5.0, 8.0)], and Mini-Mental State Examination[26.0(16.0, 28.0) vs.27.0(22.3, 29.0)], all P<0.05.They also experienced longer hospital stays[10.5(6.0, 18.8)days vs.8.0(6.0, 11.8)days, P=0.008].During the follow-up period, the incidence of composite endpoint events was significantly higher in the frail group(43.9% vs.25.0%, P=0.029).Kaplan-Meier survival analysis demonstrated that the one-year incidence of composite endpoint events was significantly higher in the frail group( P=0.013).Multivariable Cox regression analysisindicated that frailty was an independent risk factor for composite endpoint events( HR=2.201, 95% CI: 1.089-4.447, P=0.028). Conclusions:Frailty is an independent risk factor for poor outcomes in elderly hospitalized patients with heart failure and should be considered a crucial factor in clinical assessment and treatment strategies.

Objective To investigate the characteristics of clinical cellular immunity and its relationship with prognosis in elderly patients with severe infection caused by Omicron variant.Methods The clinical data of 53 patients with Omicron variant infection admitted to the geriatric Intensive Care Unit of the First Affiliated Hospital of Kunming Medical University from December 2022 to February 2023 were retrospectively analyzed.The patients were divided into 22 survival cases and 31 death cases for comparison between the two groups.Logistic analysis is adopted to define the omicron variants of elderly severe infections prognostic factors and construct the ROC curve.Results Mu-ltivariate logistic analysis revealed that the independent risk factors were elevated IL-6(P = 0.043)and decreased absolute T lymphocyte count(P = 0.011).AUC value of ROC of IL-6,absolute T lymphocyte count and IL-6 combined with absolute T lymphocyte count was 0.818,0.796 and 0.887.Conclusion Elevated IL-6 and decreased absolute T lymphocyte count are independent risk factors for elderly severe patients with Omicron variant infections.

Objective:We evaluated frailty in elderly hospitalized patients with atrial fibrillation and analyzed the relevance, consistency, and diagnostic power of different frailty tools.Methods:From September 2018 to April 2019, a total of 197 elderly patients with atrial fibrillation aged ≥ 65 years in Beijing Hospital, Chinese PLA General Hospital, and Beijing Tsinghua Changgung Hospital were prospectively enrolled.Five frailty tools, including the clinical frailty scale(CFS), FRAIL scale(FRAIL), Fried frailty phenotype(Fried), Edmonton frail scale(EFS), and comprehensive geriatric assessment-frailty index(CGA-FI), were used for frailty assessment.Results:A total of 197 hospitalized elderly patients with atrial fibrillation were enrolled, with an average age of(77.5±7.1)years old(57.4% male). The prevalence of frailty, according to the five frailty tools, were 25.4%(FRAIL), 27.9%(EFS), 34.5%(Fried), 40.6%(CFS), and 42.6%(CGA-FI), respectively.CFS had a good correlation(correlation coefficient 0.80)and and consistency(Kappa value 0.71, 95% CI 0.61~0.81)with CGA-FI.The combined frailty index was used as the gold standard for frailty diagnosis.The results showed that CFS and CGA-FI had high diagnostic sensitivity(95.9 % and 98.0 %, respectively)and specificity(77.7 % and 75.7 %, respectively). Conclusions:Frailty is common in elderly hospitalized patients with atrial fibrillation, showing multidimensional features, and physical weakness is not prominet.CFS and CGA-FI are recommended for the assessment of frailty in patients with atrial fibrillation, which had good correlation and consistency.

Objective:To evaluate the association of different biomarkers with frailty in elderly hospitalized patients.Methods:In this cross-sectional study, a total of 319 elderly patients aged 65 years or older hospitalized in Beijing Hospital between September 2018 and February 2019 were enrolled.Patients had a mean age of(75.0±6.6)years and 151(47.3%)were women.Based on the Fried phenotype, patients were divided into a non-frail group(244 cases, 76.5%)and a frail group(75 cases, 23.5%). The clinical characteristics and biomarker levels of the two groups were compared.The association of different biomarkers with frailty was evaluated by using the receiver operating characteristic(ROC)curve.The Youden index was used for the optimal cutoff values and the area under the curve(AUC)were calculated.AUCs of different biomarkers were compared to assess their correlations with frailty.Results:Hemoglobin, lipid levels(triglycerides, total cholesterol and low-density lipoprotein cholesterol), and prealbumin were significantly lower in the frail group than in the non-frail group( P<0.05), while N-terminal pro-B type natriuretic peptide(NT-proBNP)and high-sensitivity C reactive protein(hsCRP)levels were significantly higher than in the non-frail group( P<0.05). Thyrotropin(TSH)and free triiodothyronine(FT3)levels were significantly lower( P<0.05)and trans-triiodothyronine(rT3)was significantly higher( P<0.05)in the frail group.The combination of six biomarkers[hemoglobin, prealbumin, hsCRP, 25-dihydroxy vitamin D3[25(OH)D3], rT3 and NT-pro BNP]had the most powerful correlation with frailty(AUC=0.705, 95% CI: 0.652-0.755), but the correlation was not significantly different from that of the combination of 3 markers(hemoglobin, rT3 and hsCRP)(ROC=0.010, 95% CI: -0.0106-0.0306, P>0.05). Either of the two combinations was significantly better than the combination of 2 markers(hemoglobin and rT3)(ROC=0.143, 95% CI: 0.0406-0.245; ROC=0.153, 95% CI: 0.0498-0.256; all P<0.01). Conclusions:Hemoglobin, lipids, prealbumin, TSH and FT3 levels decrease while NT-proBNP and hsCRP levels increase in elderly hospitalized frail patients.The 6-biomarker combination[hemoglobin, prealbumin, hsCRP, 25(OH)D3, rT3 and NT-pro BNP]and 3-biomarker combination(hemoglobin, rT3 and hsCRP)have better correlation with frailty than the 2-biomarker combination(hemoglobin and rT3).

Objective:To establish a long-term mortality rate prediction model for patients aged 60 years and over with atrial fibrillation and coronary heart disease using the machine learning method, and identify the corresponding risk factors of mortality.Methods:In this retrospective cohort study, a total of 329(11 cases lost of follow-up)patients with 183 males(55.6%)and 146 females(44.4%), aged(77.8±7.3)years, and 142 patients aged 80 years or older(43.2%)were selected in our hospitals from January 2013 to March 2015.And their clinical data on atrial fibrillation and coronary heart disease were analyzed.They were divided into the death group(151 cases)and the survival group(167 cases)according to the survival outcome.In addition, 60 patients aged 60 years and over admitted to our hospitals from April to July 2015 with atrial fibrillation and coronary heart disease were selected as external data validation set.The clinical data included age, gender, body mass index, diagnosis, co-morbidity, laboratory indicators, electrocardiogram, echocardiogram, treatment data.These patients were followed up for at least 6 years, and the main adverse cardiovascular and cerebrovascular events(MACCE), including death, were recorded.Finally, the data of the enrolled patients were randomly divided into the training set and the test set according to the ratio of 9∶1, Different models were established to predict the long-term mortality of patients with atrial fibrillation and coronary heart disease by machine learning algorithm.The optimal model was established by substituting external data(60 cases)into the model for verification and comparison.The top 20 risk factors for mortality were determined by Shapley additive explanation(SHAP)algorithm.Results:A total of 329 hospitalized patients were included in this study, the overall median follow-up time was 77.0 months(95% CI: 54.0~84.0), 11 cases lost during follow-up(3.3%), and 151 cases died(45.9%). The analysis found that the areas under the ROC curve for a support vector machine(SVM)model, k-Nearest Neighbor(KNN)model, decision tree model, random forest model, ADABoost model, XGBoost model and logistic regression model were 0.76, 0.75, 0.75, 0.91, 0.86, 0.85 and 0.81, respectively.The random forest model had the highest prediction efficiency, with the accuracy of 0.789 and F1 value of 0.806, which was better than the logistic regression model[the Area Under Receiver Operating Characteristic Curve(AUC): 0.91 vs.0.81, P<0.05]. D-dimer, age, number of MACCE, left ventricular ejection fraction, serum albumin level, anemia, New York Heart Association(NYHA)grade, history of old myocardial infarction, estimated glomerular filtration rate(eGFR)and resting heart rate were important risk factors for predicting long-term mortality. Conclusions:The random forest model based on machine learning method can predict the long-term mortality of patients with atrial fibrillation and coronary heart disease aged 60 years and over, have a good identification ability.Its accuracy is higher than that of the traditional Logistic regression model.Reducing the long-term mortality and improving the long-term outcomes can be achieved by intervening on D-dimer levels, correcting hypoproteinemia and anemia, improving cardiac function and controlling resting ventricular rates.

Objective:To establish donor liver quality related risk factors for the loss of function of transplanted liver.Methods:The data of donors and recipients of liver transplantation at the Organ Donation and Transplantation Center of the First Affiliated Hospital of Sun Yat-sen University from Nov 2011 to Dec 2018 were analyzed retrospectively. Propensity score matching (PSM) was performed to evaluate and screen the data of donors and recipients, in order to balance the covariates.Results:Of the organ donation, there were 70 males and 20 females , aging (40.6±16.3) years. Of the liver transplantation recipients, there were 70 males and 20 females , aging (41.8±20.3) years. Liver dysfunction after transplantation was significantly correlated with the following variables: the donor's CPR time( t=0.429, P=0.000), 15-minute retention rate of indocyanine green ( χ2=67.151, P=0.000), liver function grading ( χ2=54.154, P=0.000), bullae fatty liver grading ( χ2=8.120, P=0.017), vesicular fatty liver grading ( χ2=16.000, P=0.001), ICU stay time ( χ2=14.900, P=0.001)and serum creatinine level ( χ2=44.685, P=0.000). The donor scoring system was established in our studying. For the 90 organ donation cases, the donated liver quality were classified into four levels,which were of good correspondence to the prognosis of the recipients. Conclusion:This donor scoring system and grading standards established by analyzing the high-risk factors of liver dysfunction after transplantation helps evaluate the quality of donor liver in China.