Objective:To investigate the differences in brain age and brain age gap (BAG) between patients with prolonged disorders of consciousness (pDoC) and healthy controls (HC).Methods:A retrospective cross-sectional study was performed; 43 patients with pDoC admitted to Rehabilitation Medicine Center, Zhujiang Hospital, Southern Medical University from January 2020 to October 2022 were enrolled; 26 healthy volunteers recruited at the same time and 187 healthy subjects from the publicly available healthy control dataset Nathan Kline Institute-Rockland Sample (NKI-RS) were chosen as HC group. The clinical and imaging data of these subjects were collected. A brain age estimation model was constructed based on amplitude of low-frequency fluctuation (ALFF) in resting-state functional magnetic resonance imaging (rs-fMRI) for healthy individuals, and the pDoC group was used as the test set. A two-sample t-test was used to compare the brain age and BAG differences between the pDoC group and HC group. Pearson correlation analysis was used to explore the correlation between BAG and coma recovery scale-revised (CRS-R) in the pDoC group. Results:The chronological age and estimated brain age in the HC group were (41.54±9.61) and (42.32±10.65) years, respectively, without significant difference ( t=-0.254, P=0.801). The chronological age and estimated brain age in the pDoC group were (49.91±12.03) and (62.79±15.00) years, respectively, with significant difference ( t=-4.341, P<0.001). The BAG in the HC and pDoC groups were (0.78±4.59) and (12.88±7.17) years, respectively, with significant difference ( t=-7.822, P<0.001). Correlation analysis results showed that in the pDoC patients, no correlation was noted between BAG and CRS-R score on the day of imaging scan or 6 months after the day of imaging scan ( r=0.090, P=0.738; r=0.205, P=0.674); no correlation was noted between BAG and difference in CRS-R score (difference value of CRS-R score 6 months after the day of imaging scan-CRS-R score on the day of imaging scan, r=0.246, P=0.687). Conclusion:Compared with the HC subjects, patients with pDoC exhibit an abnormal increase in brain age, suggesting that pDoC caused by severe brain injury may lead to accelerated brain aging.

Objective To analyze the differences in structural integrity of cerebral white matter fiber bundles in vegetative state(VS)patients with different prognoses,and to construct an early-stage prognostic prediction model for 1-year post-stabilization prognosis.Methods A retrospective analysis was conducted on 52 VS patients admitted to the Department of Rehabilitation Medicine at Zhujiang Hospital of Southern Medical University.Patients were stratified into good prognosis(n=22)and poor prognosis(n=30)at 1-year follow-up based on Coma Recovery Scale-Revised(CRS-R)scores.The fractional anisotropy values of cerebral white matter fiber bundles were derived from diffusion tensor imaging,and for the first time,the scores of the visual subscales of CRS-R were combined with FA values as input features for the prognostic model.To optimize model construction,the least absolute shrinkage and selection operator regression was employed for feature screening,and synthetic minority over-sampling technique for data balancing.The prognostic prediction model was subsequently developed using a support vector machine algorithm and validated via leave-one-out cross-validation.Model performance was evaluated using area under receiver operating characteristic curve,along with accuracy,sensitivity,specificity,and F1 score metrics.Results Following LASSO regression feature screening,the pontine crossing tract,medial lemniscus,tapetum,splenium of corpus callosum,and visual subscale scores were identified as key predictors.A multimodal SVM-based prediction model constructed with the above features could effectively predict the 1-year prognosis of VS patients,achieving a high predictive performance(AUC=0.894).Conclusion The SVM-based model integrating FA values of specific white matter fiber bundles and visual subscale scores demonstrates excellent predictive performance in predicting the 1-year prognosis of VS patients.

Objective:To investigate the differences in brain age and brain age gap (BAG) between patients with prolonged disorders of consciousness (pDoC) and healthy controls (HC).Methods:A retrospective cross-sectional study was performed; 43 patients with pDoC admitted to Rehabilitation Medicine Center, Zhujiang Hospital, Southern Medical University from January 2020 to October 2022 were enrolled; 26 healthy volunteers recruited at the same time and 187 healthy subjects from the publicly available healthy control dataset Nathan Kline Institute-Rockland Sample (NKI-RS) were chosen as HC group. The clinical and imaging data of these subjects were collected. A brain age estimation model was constructed based on amplitude of low-frequency fluctuation (ALFF) in resting-state functional magnetic resonance imaging (rs-fMRI) for healthy individuals, and the pDoC group was used as the test set. A two-sample t-test was used to compare the brain age and BAG differences between the pDoC group and HC group. Pearson correlation analysis was used to explore the correlation between BAG and coma recovery scale-revised (CRS-R) in the pDoC group. Results:The chronological age and estimated brain age in the HC group were (41.54±9.61) and (42.32±10.65) years, respectively, without significant difference ( t=-0.254, P=0.801). The chronological age and estimated brain age in the pDoC group were (49.91±12.03) and (62.79±15.00) years, respectively, with significant difference ( t=-4.341, P<0.001). The BAG in the HC and pDoC groups were (0.78±4.59) and (12.88±7.17) years, respectively, with significant difference ( t=-7.822, P<0.001). Correlation analysis results showed that in the pDoC patients, no correlation was noted between BAG and CRS-R score on the day of imaging scan or 6 months after the day of imaging scan ( r=0.090, P=0.738; r=0.205, P=0.674); no correlation was noted between BAG and difference in CRS-R score (difference value of CRS-R score 6 months after the day of imaging scan-CRS-R score on the day of imaging scan, r=0.246, P=0.687). Conclusion:Compared with the HC subjects, patients with pDoC exhibit an abnormal increase in brain age, suggesting that pDoC caused by severe brain injury may lead to accelerated brain aging.

Objective: To evaluate the mutation rates of homologous recombination repair (HRR) genes and the impact of these mutations on the clinical characteristics of metastatic endometrial cancer (EC). Methods: Somatic DNA from 895 patients with metastatic EC in the Memorial Sloan Kettering-Metastatic Events and Tropisms cohort was assessed for mutations in 10 HRR genes (BRCA1, BRCA2, ATM, BARD1, BRIP1, PALB2, RAD51C, RAD51D, CHEK2, and CDK12).The correlation between the mutation status of HRR genes and the clinical characteristics of patients with metastatic EC was evaluated. Results: Somatic mutations in HRR genes were detected in 106 (11.8%) patients with metastatic EC. Compared with nonmutation carriers, a greater proportion of carriers had endometrioid carcinoma (76.4% vs. 50.3%, p<0.001). Regarding the TCGA classification, the proportions of the POLE-ultramutated (POLEmut) and mismatch repair-deficient (dMMR) subtypes were significantly greater among mutation carriers than noncarriers (20.8% vs.0.4%, p<0.001; 34.9% vs. 11.9%, p<0.001, respectively). The carriers had a significantly lower frequency of TP53 mutations than noncarriers (25.5% vs. 54.1%, p<0.001). Fewer mutation carriers than noncarriers had intra-abdominal and lung metastases (41.5% vs.54.2%, p=0.014; 19.8% vs. 30.3%, p=0.026, respectively). The mutation status of HRR genes did not significantly affect the overall survival of patients with metastatic EC. Conclusion Somatic HRR mutations are detected in 11.8% of metastatic EC. Compared with noncarriers, HRR mutation carriers in metastatic EC have higher proportions of endometrioid carcinoma, POLEmut, and dMMR subtypes, and unique metastatic patterns.However, the prognoses are similar regardless of HRR status.

Objective To analyze the differences in structural integrity of cerebral white matter fiber bundles in vegetative state(VS)patients with different prognoses,and to construct an early-stage prognostic prediction model for 1-year post-stabilization prognosis.Methods A retrospective analysis was conducted on 52 VS patients admitted to the Department of Rehabilitation Medicine at Zhujiang Hospital of Southern Medical University.Patients were stratified into good prognosis(n=22)and poor prognosis(n=30)at 1-year follow-up based on Coma Recovery Scale-Revised(CRS-R)scores.The fractional anisotropy values of cerebral white matter fiber bundles were derived from diffusion tensor imaging,and for the first time,the scores of the visual subscales of CRS-R were combined with FA values as input features for the prognostic model.To optimize model construction,the least absolute shrinkage and selection operator regression was employed for feature screening,and synthetic minority over-sampling technique for data balancing.The prognostic prediction model was subsequently developed using a support vector machine algorithm and validated via leave-one-out cross-validation.Model performance was evaluated using area under receiver operating characteristic curve,along with accuracy,sensitivity,specificity,and F1 score metrics.Results Following LASSO regression feature screening,the pontine crossing tract,medial lemniscus,tapetum,splenium of corpus callosum,and visual subscale scores were identified as key predictors.A multimodal SVM-based prediction model constructed with the above features could effectively predict the 1-year prognosis of VS patients,achieving a high predictive performance(AUC=0.894).Conclusion The SVM-based model integrating FA values of specific white matter fiber bundles and visual subscale scores demonstrates excellent predictive performance in predicting the 1-year prognosis of VS patients.

Objective:To investigate the correlation between strong ion gap (SIG) and prognosis of adult hospitalized patients who experienced cardiac arrest (CA).Methods:A retrospective cohort study was conducted on adult CA patients (≥18 years old) who were admitted to the intensive care unit (ICU) for the first time from the Medical Information Mart for Intensive Care Ⅲ (MIMIC-Ⅲ) database from 2001 to 2012. The patients were divided into 3 groups based on the tertiles of serum SIG value. The clinical baseline characteristics and related data of CA patients were compared. Kaplan-Meier method was used to draw the 28- and 90-day cumulative survival curves of CA patients. Meanwhile, the log-rank test was used to compare the differences in the survival curves among different groups, and Cox proportional hazard regression model was established to analyze whether SIG was an independent predictor of all-cause mortality in CA patients.Results:Six hundred and six adult CA patients were eligible for final analysis. The patients were divided into 3 groups based on the tertiles of serum SIG value [<3.91 mmol/L ( n=202), 3.91~7.32 mmol/L ( n=202) and >7.32 mmol/L ( n=202)]. The mean age was (66.91±15.95) years and 382 patients (63.04%) were male. The all-cause mortality rates of ICU, 28 days and 90 days were 36.47%, 49.17% and 56.93%, respectively. There were significant differences in SOFA score, SIG, anion gap, pH, lactic acid, white blood cells, prothrombin time, creatinine, blood potassium, blood phosphorus, hypertension, coronary heart disease, cardiogenic shock, and ICU, 28-day and 90-day all-cause mortality among the 3 groups (all P<0.05). The Kaplan-Meier survival curves showed that the 28- and 90-day cumulative survival rates of CA patients decreased gradually with the increase of SIG level, and the differences were statistically significant among the 3 groups (all P<0.001). Multivariate Cox proportional hazard models showed that the increase of SIG level (>7.32 mmol/L) was an independent risk factor for 28-day ( HR=1.610, 95% CI: 1.177-2.203, P=0.003) and 90-day all-cause mortality ( HR=1.506, 95% CI: 1.123-2.019, P=0.006) among CA patients, after adjusting for the related confounders. Conclusions:The elevated SIG level (>7.32 mmol/L) is an independent predictor of 28- and 90-day all-cause mortality in CA patients. The calculation of SIG level in these patients is helpful for early identification of patients with poor prognosis.

Objective:To investigate the association between the initial red cell distribution width (RDW) and all-cause mortality in patients with cardiac arrest (CA) in intensive care unit (ICU).Methods:We conducted a retrospective cohort study and extracted the related clinical data in ICU among adult CA patients (age ≥18 years), using the Multiparameter Intelligent Monitoring Intensive Care III (MIMIC-Ⅲ, v1.4) database from 2001 to 2012. Based on whether they survived or not on 90 days, the patients were divided into the survival group and death group, and the clinical data of the two groups were compared. Meanwhile, the RDW values were divided into four parts according to quartile. The cumulative survival rate of 28-day and 90-day were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate Cox proportional hazard models were also used to reveal the association between RDW and all-cause mortality.Results:Based on the inclusion and exclusion criteria, 853 adult CA patients were finally enrolled. The mean age was (67.26±15.84) years, and 534 (62.60%) patients were male. And the mean SOFA score was (6.13±3.70). Compared with the survival group ( n=410), the patients in the death group ( n=443) were older and had a higher SOFA score, RDW, anion gap, creatinine and blood phosphorus. Moreover, the proportion of chronic obstructive pulmonary disease, acute kidney injury and sepsis in the death group were higher than those in the survival group, and the length of stay in ICU in the death group was longer than that in the survival group (all P<0.05). However, the indicators of arterial blood oxygen partial pressure, hemoglobin and total blood calcium, as well as the proportion of coronary heart disease and acute myocardial infarction were lower than those in the survival group, and a shorter duration of hospitalization in the death group was noted (all P<0.05). Kaplan-Meier survival curves demonstrated that there was a significant difference in the cumulative survival rate of 28-day and 90-day (all P<0.001). In the multivariate Cox proportional hazard models, a higher RDW at ICU admission was an independent risk factor for 28-day ( HR=1.399, 95% CI: 1.014-1.930, P=0.041) and 90-day ( HR=1.433, 95% CI: 1.064-1.929, P=0.018) all-cause mortality among CA patients. Conclusions:An elevated RDW is an independent predictor for 28-day and 90-day all-cause mortality of CA patients. As a clinical indicators, it indicates a poor prognosis for adult CA patients.

Objective:To explore the clinical application and long-term safety of hydroxychloroquine sulfate (HCQ) in the treatment of rheumatic diseases.Methods:A multi-center cross-sectional study was conducted between August 2017 and August 2018 in a random sample of eleven medical institutions of rheumatology and immunology in China. Patients who took HCQ for more than 3 months were enrolled into this study. The cumulative dose and long-term side effects of HCQ were recorded. The changes of laboratory indexes before and after treatment with HCQ were analyzed. Categorical variables were presented with counts and proportions, and evaluated by Chi-square test. Continuous parametric data were presented as Mean±standard deviation, and evaluated by Student's t test or Mann-Whitney U test. P-values less than 0.05 were considered statistically significant. Results:A total of 886 patients with rheumatic diseases were enrolled into this study, including 505 cases with systemic lupus erythematosus (57.0%), 210 cases with rheumatoid arthritis (23.7%), 80 cases with Sj?gren's syndrome (9.0%), 57 cases with undifferentiated connective tissue disease (6.4%), 12 cases of systemic vasculitis (1.4%), 10 cases of mixed connective tissue disease (1.1%), 7 cases of myositis (0.8%) and 5 cases with systemic sclerosis (0.6%). The most common long-term side effects of HCQ was skin or mucous lesions (12.4%) and vision problems (8.0%). Other adverse reactions included problems of digestive system (3.0%), nervous system (2.1%), musculoskeletal system (1.1%) and cardiovascular system (0.9%). 140 cases (15.8%) had stopped taking HCQ during the treatment. More than half of them decided to stop taking medicine by themselves. Fifty-four patients (6.1%) stopped using HCQ due to side effects while 24 of them took it again, and another 12 patients (1.4%) stopped the drug due to remission of illness. Patients were divided into three groups according to the cumulative dose of HCQ: less than 500 g, 500-1 000 g and more than 1 000 g respectively. There was significant difference in the incidence of long-term side effects among the three groups ( χ2=6.382, P=0.041). The last group (more than 1 000 g) suffered the highest incidence of long-term adverse reactions (37.1%). No severe adverse drug reactions were observed in this study. Conclusion:Hydroxychloroquine is widely used in the treatment of rheumatic diseases. The incidence of long-term side effects is 20.4%, is 6.1% lead to drug withdrawal, which are especially related to the cumulative doses. It should be adjusted properly according to the clinical application.

OBJECTIVE： To evaluate immunomodulatory drugs （IMiDs） in the treatment of deep venous thrombosis （DVT） in patients with multiple myeloma （MM） systematically， and to provide reference for safe drug use in clinic. METHODS： Retrieved and collected randomized controlled trials （RCTs） about the risk of DVT in MM patients treated with IMiDs from PubMed， Web of Science， Cochrane library， CJFD， Wanfang database， VIP， www.ClinicalTrials.gov during database and Dec. 31， 2018. Meta-analysis was conducted for the incidence and relative risk of DVT （RR） by using Stata 12.0 statistical software. Evidence was evaluated and graded by using GRADE system. RESULTS： A total of 11 RCTs were included， involving 3 365 patients （including 3 drugs）. Results of Meta-analysis showed that the incidence of DVT was 7.3％ [95％CI （4.5％， 10.2％）] during IMiDs in the treatment of MM. Compared with conventional chemotherapy， IMiDs had a higher risk of DVT in MM patients [RR＝3.57，95％CI（2.42，5.27）， P＜0.01]. Subgroup analysis in different treatment stage showed that after IMiDs treatment for MM patients at induction stage， the risk of DVT increased by 386％ compared with conventional chemotherapy plan [RR＝4.86， 95％CI （2.85， 8.30）， P＜0.01]， which evidence was moderate. Compared with conventional chemotherapy plan， there was no significant difference in the risk of DVT among MM patients treated with IMiDs at maintenance stage [RR＝2.40， 95％CI （0.70， 8.27）， P＝0.16] and relapse stage [RR＝2.01， 95％CI （0.74， 5.46）， P＝0.17]. The incidence of severe DVT caused by thalidomide and lenalidomide were 11％ [95％CI （9％， 13％）] and 3％ [95％CI （2％， 4％）]. CONCLUSIONS： The current evidence suggests that patients with MM treated with IMiDs are at a high risk of serious DVT， and clinical medication should be cautious.

Objective To investigate the prevalence of metabolic syndrome (MS) among adults in rural areas of Ningxia Hui autonomous region.Methods A cross-sectional study was conducted in 10 639 adults enrolled with a multistage method from Jingyuan County.The MS was identified according to Chinese type 2 diabetes prevention guide (2013).Results Among all the subjects, 17.4% of them met the MS definition with the standardized prevalence of 14.7% after adjustment of sex and age.The prevalence and standardized rate of MS in men were 19.9% and 17.3%, and in women were 15.3% and 13.5%.The prevalence of MS in men was higher than that in women(P<0.001) and increased with aging in both genders.The prevalence and standardized rate of abdominal obesity,hyperglycemia,hypertension,high triglycerides,and low HDL-C were 19.5% and 16.7%, 15.0% and 12.9%, 42.0% and 37.1%, 25.8% and 23.1%, 28.5% and 27.7%,respectively.The rate of abdominal obesity was higher in women than in men (20.5% vs 18.2%, P=0.004), whereas the rate of hypertension, high triglycerides, and low HDL-C were higher in men than in women (all P<0.01).The prevalence of having one parameter of the MS was 68.4%.Conclusion The prevalence of MS is higher in rural areas of Ningxia Hui autonomous region, suggesting that a series of comprehensive prevention measures should be carried out to prevent and control the MS so as to improve the public health conditions in rural areas.