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.

Medicine, Chinese Traditional ; Drugs, Chinese Herbal ; China

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths, characterized by highly hypoxic tumor microenvironment. Hypoxia-inducible factor-1α (HIF-1α) is a major regulator involved in cellular response to changes of oxygen levels, supporting the adaptation of tumor cells to hypoxia. Bruceine D (BD) is an isolated natural quassinoid with multiple anti-cancer effects. Here, we identified BD could significantly inhibit the HIF-1α expression and its subsequently mediated HCC cell metabolism. Using biophysical proteomics approaches, we identified inhibitor of β-catenin and T-cell factor (ICAT) as the functional target of BD. By targeting ICAT, BD disrupted the interaction of β-catenin and ICAT, and promoted β-catenin degradation, which in turn induced the decrease of HIF-1α expression. Furthermore, BD could inhibit HCC cells proliferation and tumor growth in vivo, and knockdown of ICAT substantially increased resistance to BD treatment in vitro. Our data highlight the potential of BD as a modulator of β-catenin/HIF-1α axis mediated HCC metabolism.

With the accelerating globalization and the implementation of "Belt and Road" initiative proposed by our government, communication and exchanges between China and foreign countries have become more and more frequent than before, and much more international students have chosen to study in China's universities as candidates of master of public health (MPH). However, because China only launched the MPH program in recent years, with the training models being highly similar to the program of master of science in China but quite different from those of main international MPH programs, hindering China's MPH program to become an international one. This paper systematically evaluated existing training models of MPH programs both at home and abroad through literature review and identified major differences and deficiencies of China's MPH program compared to those from other countries: (1) requirement for medical background only; (2) comparatively longer period to complete the program; (3) incomplete curriculum; (4) overemphasizing scientific research competencies but somewhat neglecting practical abilities; and (5) limited career choices, and put forward some suggestions to improve the MPH program of China, including removing requirement for medical background only, shortening the period of MPH program, improving the curriculum of MPH program, and enhancing the training of practical abilities.

COVID-19, an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread throughout the world. China has achieved rapid containment of this highly infectious disease following the principles of early detection, early quarantine and early treatment with integrated traditional Chinese and Western medicine. The inclusion of traditional Chinese medicine (TCM) in the Chinese protocol is based on its successful historic experience in fighting against pestilence. Current findings have shown that the Chinese medicine can reduce the incidence of severe or critical events, improve clinical recovery and help alleviate symptoms such as cough or fever. To date there are over 133 ongoing registered clinical studies on TCM/integrated traditional Chinese and Western medicine. The three Chinese patent medicines (/ (Forsythiae and Honeysuckle Flower Pestilence-Clearing Granules/Capsules), (Honeysuckle Flower Cold-Relieving Granules) and (Stasis-Resolving & Toxin-Removing) were officially approved by the National Medical Products Administration to list COVID-19 as an additional indication. The pharmacological studies have suggested that Chinese medicine is effective for COVID-19 probably through its host-directed regulation and certain antiviral effects.

Objective:To explore the prognosis of posttraumatic stress disorder (PTSD) in flood survivors 13 years after they had been diagnosed with PTSD symptoms,and investigate the relationship between their personality traits and the prognosis of PTSD.Method:In this cross-sectional study,the survivors of Dongting Lake flood in 1998-1999 in Hunan in China,who were investigated and screened as PTSD symptoms positive in 2000 were selected as the target population,from which a sample of 200subjects was drawn using amulti-stage random sampling method.The Posttraumatic Stress Disorder Scale Civilian Version (PCL-C) was used to examine and re-screen the participants of PTSD symptoms in order to explore the prognosis of PTSD.Participants whose PCL-C scores were equal to 44 or higher were classified as the PTSD symptoms positive group,while those with PCL-C scores less than 44 were classified as the recovered group.Personality traits were then assessed,using the Revised Eysenck Personality Questionnaire Short Scale for Chinese (EPQ-RSC),in both the recovered group and the PTSD symptoms positive group.Finally,the multivariate logistic regression analysis was used to investigate the relationship between the prognosis of PTSD and personality traits.Results:Totally 200 subjects were eligible for this study and completed the questionnaires,but 16 of them had their questionnaires excluded from data analysis because they provided incomplete information.Thus,the response rate was 92.0％.According to the PCL-C's cut-off score,22 participants were still screened as PTSD symptoms positive and were classified as the PTSD symptoms positive group,whereas the other 162 participants were screened as PTSD symptoms negative and were classified as the recovered group.Compared with the recovered group,the EPQ-RSC extroversion scores for the PTSD symptoms positive group were significantly lower [(51.8 ± 10.7) vs.(45.1 ± 13.2),P ＜ 0.05] and their neuroticism scores were significantly higher [(46.5 ± 10.1) vs.(58.3 ± 12.2),P ＜ 0.05].The multivariate logistic regression analysis showed,after adjusting for the variables such as gender and age,that higher neuroticism (OR ＝ 3.63,95％ CI:1.05 -12.54) was a risk factor for the persistent PTSD symptoms in the flood survivors.Conclusions:It suggests that neuroticism is associated with prognosis of PTSD in flood survivors,those with higher neuroticism scores appear to have problems to recover from PTSD.

Objective To observe the effect of multiple monitoring of total intravenous anes-thesia on postoperative cognitive function in elderly patients.Methods Elective 100 patients undergo-ing general anesthesia for abdominal operation,56 males,44 females,aged 65-80 years,ASA physi-cal status Ⅱ or Ⅲ.All patients were divided into multiple monitoring group (group M)and routine monitoring group (group R)by random digital table method,n =50 each.In group M,the anesthesi-ologists modulated anesthetic drugs to make NTI of 37-56 and rSO 2 higher than 50% or not lower than the baseline value by 20%,while in group R the infusion rate of propofol,remifentanil and cisa-tracurium was adjusted by anesthesiologists according to anesthesiologist’s experiences by the pa-tients’monitoring index.Cognitive function of patients in the two groups were evaluated using MMSE 1 d before surgery and 1 d,3 d,7 d,1 month and 3 months after surgery.The occurrence of cognitive dysfunction 7 d,1 month and 3 months after surgery,the postoperative recovery and the dosage of propofol,remifentanil and cisatracurium were recorded.Blood was randomly selected from each group to determine the serum content of S100βand Aβ1-42 by ELISA method at the time point of before surgery (T0 ),one hour after starting surgery (T1 ),the end of surgery (T2 )and postopera-tive 24 hours (T3 ).Results The incidence of postoperative cognitive decline in group M on 1 d (8%vs.22%),3 d (2% vs.1 6%)after surgery were significantly lower than that in group R (P <0.05). Postoperative cognitive dysfunction between the two groups 7 d and 1 month,3 months after surgery has no statistical significance.The dose of propofol [(3.3 ± 0.8)mg · kg-1 · h-1 vs.(3.7 ± 0.7 ) mg·kg-1 ·h-1 ,P < 0.05 ] and cisatracurium [(104 ± 47 )μg · kg-1 · h-1 vs.(124 ± 68 )μg·kg-1 ·h-1 ,P <0.05]in group M was less than that in group R.The time of eye-opening [(10 ±3)min vs.(1 6±6)min,P <0.01],extubation [(13±3)min vs.(22±7)min,P <0.01]and lo-cation [(1 7±4)min vs.(27 ±9)min,P <0.01 ]was shorter in group M.Compared with T0 ,the serum level of S100βprotein was significantly increased in group M at T1 ,T2 and group R at T1-T3 (P <0.05);The level of serum S100βprotein in group M was significantly lower than that in group R (P <0.05).Compared with T0 ,Aβ1-42 protein level was significantly reduced in two groups at T1 and T2 (P <0.05),but there was no significant difference between the two groups.Conclusion Total intravenous anesthesia with multiple monitoring can reduce neural injury and reduce the incidence of early postoperative cognitive decline in elderly patients with abdominal surgery,but has no significant effect on the incidence of POCD.

Objective To explore the long-term prognosis and influence of social support and coping style of patients with post-traumatic stress disorder (PTSD) after suffering from floods.Methods Patients suffered PTSD due to Dongting lake flood in 1998 were selected through cluster random sampling.PTSD scale civilian version (PCL-C) was used to examine and diagnose the participants in this study.PTSD was then evaluated by the social support rating scale (SSRS) and the simple coping style questionnaire (SCSQ).Results Among all the 120 subjects,14(11.67％) of them were diagnosed as having PTSD.Compared with the rehabilitation group,scores on subjective support,objective support,total social support and positive coping,total of coping style from the nonrehabilitation group all appeared significant low (P＜0.05).Data from the multivariate logistic regression showed that social support (OR=0.281,95％CI:0.117-0.678) and coping style (OR=0.293,95％ CI:0.128-0.672) were protective factors of the chronic PTSD after the floods while disaster experience (OR=1.626,95％CI:1.118-2.365) appeared as a risk factor.Conclusion Chronic PTSD developed after the floods called for attention.Better social support,positive coping style could significantly improve the long-term prognosis of patients with PTSD after the floods.

OBJECTIVETo understand the risks and associated factors of HIV transmission by sharing syringes among HIV-positive drug users.

METHODThe survey was conducted among HIV-positive injecting drug users (IDUs-HIV+) who received HIV counseling, testing and treatment in Changsha city Infectious Disease Hospital and Hengyang city No.3 People's Hospital from July 2012 to May 2013 to understand their socio-demographic characteristics, HIV prevalence and syringe sharing. A total of 503 IDUs-HIV+ were involved in and provided the contact list of 2 460 drug users who had the syringe sharing experience over one month with IDUs-HIV+. 420 IDUs-HIV+ among 503 were defined as infection sources due to sharing syringe with at least one drug user. Among them, 234 HIV-negative persons were in control group, and 186 HIV-positive were in cased group. A total of 1 220 drug users were followed up among 2 460 and defined as vulnerable population. The HIV transmission rate was calculated based on the HIV prevalence among vulnerable population. Based on the result of HIV transmission to vulnerable population from 420 infection sources, case-control study and the multivariate logistic regression analysis were adopted to explore the associated factors of HIV transmission among IDUs-HIV+.

RESULTSAs the sources of HIV transmission, 420 IDUs-HIV+ had an average duration of (4.5 ± 1.2) years for drug use. As a susceptible population, 1 220 drug users sharing syringes with the 420 IDUs-HIV+ had an average duration of (1.1 ± 0.5) years for drug use. There were 238 HIV-positive persons among 1 220 vulnerable drug users, with a transmission rate of 0.57. In the case-control study, the proportion of male subjects was 87.1% (162/186) in the case group, which was higher than that in the control group (77.8%, 182/234). The proportion of subjects who received support after knowing their HIV infection status was 51.1% (95/186) in the case group, which was lower than that in the control group (79.5%, 186/234). The proportion of subjects sharing syringes every time of using drugs was 47.8% (89/186) in the case group, which was higher than that in the control group (36.8%, 86/234). The proportion of subjects having AIDS awareness was 21.0% (39/186) in the case group, which was lower than that in the control group (64.5%, 151/234); the proportion of subjects having close contact with HIV-positive persons for more than 106 days was 60.2% (112/186) in the case group, which was higher than that in the control group (31.6%, 74/234). The proportion of subjects maintaining the original drug use method after being infected with HIV was 50.5% (94/186) in the case group, which was higher than that in the control group (16.7%, 39/234) (all P values < 0.05). The multivariate logistic regression analysis was carried out to analyse high correlate factors of HIV transmission by sources of transmission, and the AIDS awareness, duration of contact between sources of transmission and vulnerable population, access to support following confirmed HIV infection were protective factors, OR (95% CI) values were 0.155 (0.104-0.262), 0.170 (0.106-0.253), and 0.306 (0.189-0.450), respectively; while the frequency of syringe sharing and continuous drug use after being infected with HIV were risk factors, and the OR (95% CI) values were 3.06 (1.77-5.29), and 3.54 (2.16-5.80), respectively.

CONCLUSIONHIV transmission by IDUs-HIV+ might be contained by raising AIDS awareness, providing comprehensive psychological support, conducting needle exchange and methadone maintenance treatment and reducing syringe sharing.

Aged ; Case-Control Studies ; Drug Users ; HIV Infections ; Humans ; Male ; Methadone ; Needle Sharing ; Prevalence ; Risk Factors ; Substance Abuse, Intravenous

Objective To explore the association between serum vaspin levels and the severity of the lower extremity vascular lesions in type 2 diabetes mellitus (T2DM) patients.Methods According to the lower extremity artery plaque,stenosis and intima-media membrane thickening severity score,92 cases of T2DM patients were divided into three groups:simple diabetes group (DM1 group) (32 cases),mild diabetic lower limb vascular lesion group (DM2 group) (33 cases),and moderately severe diabetic lower limb vascular lesion group (DM3 group) (27 cases).Twenty-six age-and gender-matched apparently healthy controls (control group) were recruited as well.Systolic blood pressure (SBP),ankle-brachial index (ABI),insulin resistance index (HOMA-IR),and other indicators were determined,serum vaspin was measured by enzyme-linked immunosorbent assay.Results After adjustment for age and gender,the DM1 group had a significantly higher serum vaspin level than control group (P ＜0.01),while for the DM2 and DM3 groups,serum vaspin levels were significantly lower than the DM1 group (P ＜ 0.01).Partial correlation analysis showed that serum vaspin was inversely associated with HOMA-IR (r =-0.461,P =0.001)and positively correlated with ABI (r =0.462,P =0.001).Logistic regression analysis demonstrated that SBP,ABI and fasting serum vaspin levels were significantly associated with the presence of the lower extremity vascular lesions in type 2 diabetes.Conclusions Serum vaspin levels were significantly elevated in simple type 2 diabetic patients while the reduction of its level might be associated with the formation of lower extremity vascular lesions in type 2 diabetic patients.