Microglial surveillance plays an essential role in clearing misfolded proteins such as amyloid-beta, tau, and α-synuclein aggregates in neurodegenerative diseases. However, due to the complex structure and ambiguous pathogenic species of the misfolded proteins, a universal approach to remove the misfolded proteins remains unavailable. Here, we found that a polyphenol, α-mangostin, reprogrammed metabolism in the disease-associated microglia through shifting glycolysis to oxidative phosphorylation, which holistically rejuvenated microglial surveillance capacity to enhance microglial phagocytosis and autophagy-mediated degradation of multiple misfolded proteins. Nanoformulation of α-mangostin efficiently delivered α-mangostin to microglia, relieved the reactive status and rejuvenated the misfolded-proteins clearance capacity of microglia, which thus impressively relieved the neuropathological changes in both Alzheimer's disease and Parkinson's disease model mice. These findings provide direct evidences for the concept of rejuvenating microglial surveillance of multiple misfolded proteins through metabolic reprogramming, and demonstrate nanoformulated α-mangostin as a potential and universal therapy against neurodegenerative diseases.

Objective To investigate the epidemiological characteristics of COPD in people over 60 years old in Chaohu City, Anhui Province, and explore the risk factors affecting the occurrence and development of COPD, and to provide a data basis for formulating prevention and control measures of COPD. Methods Permanent residents over 60 years old in Chaohu City were selected as the research subjects. The subjects were selected by multi-stage stratified cluster random sampling method. All research subjects were divided into two different groups according to the diagnostic criteria of COPD and received questionnaire survey and pulmonary function tests. The differences in epidemiological distribution of the two groups were compared by χ² test. Logistics regression was used to analyze the risk factors affecting COPD. Results A total of 1722 cases were investigated in this study. The prevalence of COPD in people over 60 years old was 13.47%. The average age and body mass index of all research subjects were 70.4±7.5 years old and 20.4±3.5kg/m², respectively. Among them, 49.25% were males, 20.96% had college degree or above, and 63.88% lived in cities and towns. 23.11% of the subjects still smoked, 32.58% had quit smoking, and 28.16% had a history of passive smoking or were still receiving passive smoking. 16.20% of the subjects had an occupational exposure to dust and particulate matter as coal miners and painters. 51.34% of the subjects had a family history of respiratory diseases. 83.57% of the subjects had other chronic diseases, including coronary heart disease, hypertension, and diabetes. There were 232 cases diagnosed as COPD in this study. All subjects were divided into the COPD group and control group according to the diagnostic criteria of COPD. There were no significant differences between the two groups in body mass index, marital status, education, residence, type of fuel used and family history of respiratory diseases. However, there were significant differences in age, gender, smoking status, occupational dust exposure and chronic disease complications between the two groups. Multivariate logistic regression analysis showed that age (OR70~79 vs. 60~69=2.578, P=0.024; OR≥80 vs. 60~69=4.258, P=0.018), smoking status (OR_{passive smoking vs. Active smoking}=0.683, P=0.073; OR_{quit smoking vs. active smoking}=0.365, P=0.020; OR_{Non-smoking vs. active smoking}=0.252, P=0.008) and occupational dust exposure (OR=0.158, P=0.010) were the major risk factors for COPD. Conclusion Advanced age, active or passive smoking and occupational dust exposure are important risk factors for COPD.

ObjectiveTo explore the effect of home visit based on empowerment education on psychotic symptoms， self-management ability and well-being of schizophrenia patients in home rehabilitation. MethodsA total of 87 cases of schizophrenia patients who met the diagnostic criteria of International Classification of Diseases， tenth edition （ICD-10） and were recovering at home in Caiba town， Yibin city from January to July 2021 were selected by random sampling method as research subjects. They were divided into experimental group （n=43） and control group （n=44） according to the random number table method. The two groups received routine family visits， and the experimental group received family visits based on empowerment education. The intervention cycle of the two groups was 6 months. Before and after the intervention， the severity of psychotic symptoms， self-management ability and well-being of the patients in the two groups were assessed with the Brief Psychiatric Rating Scale （BPRS）， the Schizophrenia Self-Management Instrument Scale （SSMIS） and the Index of Well-Being Scale （IWB）. ResultsAfter intervention， the intra group comparison showed that the BPRS score in the experimental group was lower than that before the intervention （t=4.550， P<0.01）， the SSMIS scores in both groups were higher than those before intervention （t=-17.107， -6.367， P<0.01）， and the IWB score in the experimental group was higher than that before intervention （t=-9.239， P<0.01）. The comparison between groups showed that the BPRS score of the experimental group was lower than that of the control group， and the SSMIS and IWB scores were higher than those of the control group （t=-3.899， 10.564， 9.690， P<0.01）. ConclusionThe implementation of family visit based on empowerment education may help to improve the psychotic symptoms of home rehabilitation schizophrenia， and improve their self-management ability and well-being.

AIM: To observe the effects of cyclooxygenase-2 (COX-2) inhibitors on the levels of inflammatory factors, nerve damage-related factors and antioxidant factors, as well as pain and delirium scores in the plasma of elderly patients with orthopaedic surgery, to clarify the role of COX-2 inhibitors in the prevention and treatment of POD and explore its possible mechanism. METHODS: Eighty patients undergoing elective hip arthroplasty were randomly divided into parecoxib sodium group (P group, n =40) and control group (C group, n = 40). Group C was injected with the same volume of normal saline at the same time point, and the preoperative cognitive function was screened 1 d (T

This paper focuses on the practical necessity of discipline-integrated PBL curriculum in cultivating clinical thinking ability of college students majoring in clinical medicine. Through the teaching process of group discussion of some real and complete cases, this paper explains in detail how to cultivate medical students' clinical thinking ability by discipline-integrated PBL curriculum, discusses the implementation of ideological and political education associated with clinical medicine by heuristic teaching from close touching with clinical case and implicitly infiltration of the socialist core values such as dedication and integrity, and elaborates the humanistic quality and psychological comfort levels of medical students by being close to clinical patients. After five years of teaching practice, the teaching effect of discipline-integrated PBL curriculum has been approved by the national clinical medicine professional certification experts and praised by students. We believes that the development of discipline integrated PBL curriculum in medical college can strengthen students' problem-based autonomous learning ability, significantly improve the two-way integration ability between basic medical courses and basic medicine, and significantly build students' clinical thinking and clinical decision-making ability.

Multi-gene assays have emerged as crucial tools for risk stratification in early-stage breast cancer. This study aimed to evaluate the prognostic significance of the 21-gene recurrence score (RS) in Chinese patients with pN0-1, estrogen receptor-positive (ER
Biomarkers, Tumor/genetics* ; Breast Neoplasms/pathology* ; Female ; Humans ; Neoplasm Recurrence, Local/pathology* ; Neoplasm Staging ; Prognosis ; Receptor, ErbB-2/genetics* ; Receptors, Estrogen

Objective:To analyze the value of serum ceruloplasmin (CP) levels in predicting the outcome of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF).Methods:The clinical data of 1 751 patients with HBV-ACLF treated in the Third Affiliated Hospital of Sun Yat-sen University from January 2010 to March 2018 were retrospectively analyzed. According to 30-day outcomes, 1 220 survival patients were classified into group A; 465 fatal patients and 46 patients receiving liver transplantation were classified into group B (total 531 cases). Risk factors associated with 30-day survival were estimated using Cox proportional hazards regression. ROC curve analysis was performed to evaluate the predictive value of CP on the 30-day outcome of patients with HBV-ACLF.Results:Multivariate analysis indicated that CP, albumin and alpha fetoprotein were independent protective factors for 30-day survival of HBV-ACLF patients ( P<0.05 or <0.01), while age, white blood cell count, AST, total bilirubin, INR, serum creatinine, HBV DNA, hepatorenal syndrome and hepatic encephalopathy were independent risk factors ( P<0.01). The area under the ROC curve (AUC) of CP was 0.570 (95% CI 0.540-0.599, P<0.01); while AUC of MELD score was 0.783 (95% CI 0.759-0.807, P<0.01) and MELD-Na score was 0.774 (95% CI 0.750-0.798, P<0.01). Compared with MELD score and MELD-Na score, the value of CP in predicting the 30-day prognosis of HBV-ACLF patients was lower ( P<0.01). The cut-off value of CP for predicting 30-day outcome of HBV-ACLF patients was 0.173 g/L, with the sensitivity of 69.4%, and the specificity of 41.6%. According to the cut-off value, the patients were divided into low CP level group (level of CP<0.173 g/L) and high CP level group (level of CP≥0.173 g/L); the 30-day cumulative survival rate of low CP level group was lower than that of high CP level group ( χ2=17.75, P<0.01). Conclusions:Serum CP level can predict the 30-day outcome of HBV-ACLF patients to a certain extent.

Purpose: This retrospective study aimed to evaluate the distribution pattern and prognostic value of 21-gene recurrence score (RS) in Chinese patients with mucinous breast cancer (MC) and compared with infiltrating ductal carcinoma (IDC). Materials and Methods: Patients diagnosed with MC or IDC from January 2010 to January 2017 were retrospectively recruited. Reverse transcriptase–polymerase chain reaction assay of 21 genes was conducted to calculate the RS. Univariate and multivariate analyses were performed to assess the association between RS and clinicopathological factors. Survival outcomes including disease-free survival (DFS) and overall survival (OS) were estimated by Kaplan-Meier method and compared by log-rank test. Results: The MC cohort included 128 patients and the IDC cohort included 707 patients. The proportions of patients with a low (RS < 18), intermediate (18-30), or high risk (RS > 30) were 32.0%, 48.4%, and 19.5% in MC cohort, and 26.9%, 46.8% and 26.3% in IDC cohort. The distribution of RS varied significantly according to different Ki-67 index and molecular subtype in both cohorts. Moreover, the receipt of chemotherapy was associated with RS in both cohorts. Among patients with MC, tumor stage was related to the DFS (p=0.040). No significant differences in DFS and OS were found among MC patients in different RS risk groups (OS, p=0.695; DFS, p=0.926). Conclusion RS was significantly related to Ki-67 index and molecular subtypes in MC patients, which is similar in IDC patients. However, RS was not able to predict DFS and OS in patients with MC.

Objective:To explore the clinical characteristics and establish a corresponding prognostic scoring model in patients with early-stage clinical features of hepatitis B-induced acute-on-chronic liver failure (HBV-ACLF).Methods:Clinical characteristics of 725 cases with hepatitis B-related acute-on-chronic hepatic dysfunction (HBV-ACHD) were retrospectively analyzed using Chinese group on the study of severe hepatitis B (COSSH). The independent risk factors associated with 90-day prognosis to establish a prognostic scoring model was analyzed by multivariate Cox regression, and was validated by 500 internal and 390 external HBV-ACHD patients.Results:Among 725 cases with HBV-ACHD, 76.8% were male, 96.8% had cirrhosis base,66.5% had complications of ascites, 4.1% had coagulation failure in respect to organ failure, and 9.2% had 90-day mortality rate. Multivariate Cox regression analysis showed that TBil, WBC and ALP were the best predictors of 90-day mortality rate in HBV-ACHD patients. The established scoring model was COSS-HACHADs = 0.75 × ln(WBC) + 0.57 × ln(TBil)-0.94 × ln(ALP) +10. The area under the receiver operating characteristic curve (AUROC) of subjects was significantly higher than MELD, MELD-Na, CTP and CLIF-C ADs( P < 0.05). An analysis of 500 and 390 cases of internal random selection group and external group had similar verified results. Conclusion:HBV-ACHD patients are a group of people with decompensated cirrhosis combined with small number of organ failure, and the 90-day mortality rate is 9.2%. COSSH-ACHDs have a higher predictive effect on HBV-ACHD patients' 90-day prognosis, and thus provide evidence-based medicine for early clinical diagnosis and treatment.

Objective: To observe the therapeutic effect of terlipressin on refractory ascites (RA) in cirrhosis, and its role and impact on acute kidney injury (AKI). Methods: A non-randomized controlled clinical trial data of 111 hospitalized cases of liver cirrhosis accompanied with RA was collected from Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Zhongshan Hospital of Hubei Province, The First Affiliated Hospital of Zhengzhou University, The First Affiliated Hospital of Medical School of Zhejiang University, and People's Hospital of Pudong New Area of Shanghai between March 2015 and March 2017. 26 cases of conventional treatment group (control group) were divided into two subgroups: RA without AKI (RA-NAKI) and RA with AKI (RA-AKI), and each subgroup consisted 13 cases. Patients with bacterial infection were treated with diuretics, albumin supplementation and antibiotics. 85 cases were presented in terlipressin combined treatment group, of which 27 cases were of RA-NAKI and 58 cases were of RA-AKI. Control group was injected terlipressin 1mg of intravenous drip or static push (once q6 h ~ 12 h) for more than 5 days. The treatment duration lasted for 2 weeks with 4 weeks of follow-up. Body weight, 24-hour urine volume, abdominal circumference, mean arterial pressure (MAP), liver and kidney function, anterior hepatic ascites, deepest point of ascites, and ultrasonographic detection of ascites in supine position before treatment, one and two weeks after treatment and 4 weeks after follow-up were compared. Count data were tested by χ ². Samples of four groups at baseline were compared. One-way analysis of variance was used for normal distribution data and Kruskal-Wallis H test for non-normal distribution data. Repeated measures analysis of variance was used to compare the difference in efficacy between different time points before and after treatment in the group. The LSD method of one-way ANOVA was used to compare the two groups. A t-test of independent samples was used to compare the efficacy of different time series between the two groups. Mann-Whitney rank- sum test was used to compare the data of non-normal distribution between the two groups. Results: (1) Baseline data were compared among 4 subgroups of terlipressin RA-NAKI and control RA-AKI. Control group age was higher than that of terlipressin group, and the serum creatinine (SCr) of the RA-AKI group was higher than RA-NAKI group, and there was no significant difference in the rest of the baseline data and the combined medication (P > 0.05). (2) An intra-group comparison between control and trelipressin before and after treatment showed that all patients had lower body mass, abdominal circumference and deepest ascites, and higher serum albumin (P < 0.05). 24-hour urine volume and MAP was significantly increased in the terlipressin group, while the pre-ascites, SCr and child Turcotte Pugh (CTP) scores were decreased. Body weight, abdominal circumference, pre-ascites, and deepest ascites of the terlipressin group were decreased, while MAP was increased during the treatment and follow-up periods. The differences were statistically significant when compared with the control group at the same time (P < 0.05). There was a statistically significant difference in the increase of 24-h urine volume in the terlipressin group compared with the control group (P < 0.05). The decrease in SCr and CTP in the terlipressin group after 2 weeks of treatment and 4 weeks of follow-up was statistically significant compared with the control group (P < 0.05). (3) Among the two subgroups of RA-AKI and RA-NAKI in the terlipressin group, the baseline SCr value of the former was higher than that of the latter. After treatment, the body weight, abdominal circumference, pre-ascites, deepest ascites and CTP scores were decreased. In the RA-AKI group, 24-hour urine volume, MAP, SCr and serum albumin concentration were significantly increased. The difference between the two subgroups before and after treatment was compared, and the body weight of RA-AKI group at 1, 2 weeks of treatment and 4 weeks of follow-up was significantly lower than RA-NAKI group, which were (- 2.3 ± 0.2 vs. - 1.5 ± 0.2) kg, (- 4.1 ± 0.2 vs. - 2.6 ± 0.2) kg, (- 4.2 ± 0.3 vs. - 2.4 ± 0.3) kg, respectively. RA-NAKI group urine volume was significantly increased at 2 weeks of treatment and 4 weeks of follow-up, which was (468 ± 42 vs. 110 ± 131) ml, (272 ± 34 ml vs. 11 ± 112) ml, respectively. SCr reduction (18.3 ± 4.7 vs. 0.9 ± 2.4) µmol/l at 4 weeks of follow-up was apparent in RA-NAKI group, and the difference was statistically significant (P < 0.05). Conclusion Addition of terlipressin to conventional treatment may significantly increase MAP, 24-h urine volume, improve renal function and promote ascites resolution in patients with refractory cirrhotic ascites. Moreover, its combination effect is more obvious in AKI patients, and adverse reactions are mild.