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 provide reference for the optimization of development policy of traditional Chinese medicine. METHODS ROSTCM text mining analysis software was adopted to screen the literature preliminarily ，the PMC policy index model was built ，and the results by PMC index and visual PMC surface were analyzed. RESULTS & CONCLUSIONS A total of 33 policies related to traditional Chinese medicine were included ，and 10 primary variables and 46 secondary variables were set. The average PMC index of 33 policies was 6.15，of which 2 were excellent policies and the rest were good policies. Among the primary variables ，the scores of policy openness ，policy evaluation and policy field were relatively high ，while the scores of release time ，policy level and policy type were low. The analysis of sink index and secondary variables showed that the macro planning of national policies was not specific enough in terms of policy objectives and contents ，with low score ，while the local policies were usually planned in detail. Generally speaking ，there is still much room for improvement in the policies related to the development of traditional Chinese medicine in terms of policy system construction ，government investment ，talent construction ， financing supporting policies ，market access rules ，responsible subjects and legal guarantee.

OBJECTIVE: To investigate the effects of overexpression of long noncoding RNA (lncRNA) MEG3 on the proliferation and invasion of glioblastoma U251 cells by suppressing the expression of hypoxia inducible factor 1 METHODS: The expression of lncRNA MEG3 and HIF1 RESULTS: The expression of MEG3 was significantly lower and HIF1 CONCLUSIONS MEG3 overexpression inhibits the proliferation and invasion of U251 cells through suppressing the expression of HIF1
Apoptosis ; Cell Line, Tumor ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Gene Expression Regulation, Neoplastic ; Glioblastoma/genetics* ; Humans ; MicroRNAs ; RNA, Long Noncoding/genetics*

Objective:To explore the effect of online appointment system of standardized patients (SP) in cardiology practice teaching.Methods:The undergraduate students who entered the cardiology department of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine for clinical practice in 2018 and 2019 were selected as teaching objects, and they were divided into traditional teaching group ( n=30) and appointed SP teaching group ( n=30). After the teaching, SPSS 19.0 software was used for data analysis to compare the teaching effect of the two groups. Results:The scores of SP teaching group were higher than those of traditional teaching control group, with statistical significance ( P<0.05). Conclusion:Through constructing SP database and typical case database, online appointment system of SP for medical history inquiry and doctor-patient communication skills training can effectively solve the problems such as lack of clinical practice cases and doctor-patient contradiction, and greatly improve the teaching efficiency.

with the increasing prevalence of myopia in Chinese children, there are more methods for its prevention and control.Orthokeratology is one of the most appealing techniques for myopia correction.In recent years, an increasing number of hospitals have applied this technology, and its acceptance among patients is increasing.The safety of the orthokeratology have drawn increasing attention, especially in relation to orthokeratology-associated infectious keratitis.Acanthamoeba keratitis (AK) is one of the most worrying diseases.The onset of AK is slow, and its early clinical manifestation is particularly atypical, which often leads to incorrectly diagnosis, so as to mistreatment or delay of medical therapy, and subsequently irreversible impairment of visual function.Therefore, it is very important to reinforce the knowledge of its early symptoms in order to improve the early diagnosis level, and manage the associated risk factors.Early diagnosis and promper treatment can contribute to good visual outcomes.

Objective:To explore the effect of online appointment system of standardized patient in cardiology practice teaching.Methods:The undergraduate students who entered the cardiology department for clinical practice in 2018 and 2019 were selected as teaching objects, and they were divided into traditional teaching group ( n=30) and appointed SP teaching group ( n=30). After the teaching, SPSS 19.0 software was used for data analysis to compare the teaching effect of the two groups. Results:The scores of SP teaching group were higher than those of traditional teaching control group, with statistical significance ( P<0.05). Conclusion:Through constructing standardized patient database and typical case database, online appointment system of standardized patient for medical history inquiry and doctor-patient communication skills training can effectively solve the problems such as lack of clinical practice cases and doctor-patient contradiction, and greatly improve the teaching efficiency.

Objective:To explore the predictive factors of pathological complete response (pCR) after neoadjuvant chemoradiotherapy for middle-low rectal cancer.Methods:A case-control study was conducted. The inclusion criteria were as follows: (1) colonoscopy, digital examination or magnetic resonance imaging (MRI) showed a distance from the lower edge of the tumor to the dentate line of no more than 10 cm; (2) complete clinicopathological data were available; (3) preoperative biopsy revealed adenocarcinoma; (4) preoperative pelvic MRI or endorectal ultrasonography was performed; (5) no distant metastasis was found. Exclusion criteria: (1) preoperative radiotherapy and chemotherapy were not administrated according to the standard; (2) simultaneous multiple primary cancer and familial adenomatous polyposis were observed. According to the above criteria, clinicopathological data of 245 patients with middle-low rectal cancer undergoing preoperative neoadjuvant chemoradiotherapy in Changhai Hospital of Navy Medical University from January 2012 to December 2019 were retrospectively collected. Univariate analysis and multivariate logistic analysis were used to identify the clinical factors predicting pCR. pCR is defined as complete disappearance of cancer cells under the microscope in cancer specimens (including lymph nodes) after neoadjuvant chemoradiotherapy.Results:A total of 72 patients with pCR were enrolled in this study. Univariate analysis showed that preoperative T stage, tumor circumference, tumor morphology, carbohydrate antigen (CA) 19-9, interval between the end of neoadjuvant therapy and operation were associated with pCR (all P<0.05). The above 5 variables were included in multivariate logistic analysis and the results revealed that the T stage (OR=5.743, 95% CI: 2.416-13.648, P<0.001), tumor circumference (OR=7.754, 95% CI: 3.822-15.733, P<0.001), tumor morphology (OR=0.264, 95% CI: 0.089-0.786, P=0.017) and the interval between the end of neoadjuvant therapy and operation (OR=0.303, 95% CI: 0.147-0.625, P=0.001) were independent predictive factors of pCR, while CA 19-9 level was not an independent factor (OR=1.873, 95% CI:0.372-9.436, P=0.447). Conclusion:By knowing the clinical features of preoperative T stage, tumor circumference, tumor morphology and the interval between neoadjuvant chemoradiotherapy and operation, patients with higher likelyhood of pCR after neoadjuvant chemoradiotherapy may be identified.

Objective:To explore the predictive factors of pathological complete response (pCR) after neoadjuvant chemoradiotherapy for middle-low rectal cancer.Methods:A case-control study was conducted. The inclusion criteria were as follows: (1) colonoscopy, digital examination or magnetic resonance imaging (MRI) showed a distance from the lower edge of the tumor to the dentate line of no more than 10 cm; (2) complete clinicopathological data were available; (3) preoperative biopsy revealed adenocarcinoma; (4) preoperative pelvic MRI or endorectal ultrasonography was performed; (5) no distant metastasis was found. Exclusion criteria: (1) preoperative radiotherapy and chemotherapy were not administrated according to the standard; (2) simultaneous multiple primary cancer and familial adenomatous polyposis were observed. According to the above criteria, clinicopathological data of 245 patients with middle-low rectal cancer undergoing preoperative neoadjuvant chemoradiotherapy in Changhai Hospital of Navy Medical University from January 2012 to December 2019 were retrospectively collected. Univariate analysis and multivariate logistic analysis were used to identify the clinical factors predicting pCR. pCR is defined as complete disappearance of cancer cells under the microscope in cancer specimens (including lymph nodes) after neoadjuvant chemoradiotherapy.Results:A total of 72 patients with pCR were enrolled in this study. Univariate analysis showed that preoperative T stage, tumor circumference, tumor morphology, carbohydrate antigen (CA) 19-9, interval between the end of neoadjuvant therapy and operation were associated with pCR (all P<0.05). The above 5 variables were included in multivariate logistic analysis and the results revealed that the T stage (OR=5.743, 95% CI: 2.416-13.648, P<0.001), tumor circumference (OR=7.754, 95% CI: 3.822-15.733, P<0.001), tumor morphology (OR=0.264, 95% CI: 0.089-0.786, P=0.017) and the interval between the end of neoadjuvant therapy and operation (OR=0.303, 95% CI: 0.147-0.625, P=0.001) were independent predictive factors of pCR, while CA 19-9 level was not an independent factor (OR=1.873, 95% CI:0.372-9.436, P=0.447). Conclusion:By knowing the clinical features of preoperative T stage, tumor circumference, tumor morphology and the interval between neoadjuvant chemoradiotherapy and operation, patients with higher likelyhood of pCR after neoadjuvant chemoradiotherapy may be identified.

Gene therapy represents a promising treatment for the Alzheimer׳s disease (AD). However, gene delivery specific to brain lesions through systemic administration remains big challenge. In our previous work, we have developed an siRNA nanocomplex able to be specifically delivered to the amyloid plaques through surface modification with both CGN peptide for the blood-brain barrier (BBB) penetration and QSH peptide for -amyloid binding. But, whether the as-designed nanocomplex could indeed improve the gene accumulation in the impaired neuron cells and ameliorate AD-associated symptoms remains further study. Herein, we prepared the nanocomplexes with an siRNA against -site amyloid precursor protein-cleaving enzyme 1 (BACE1), the rate-limiting enzyme of A production, as the therapeutic siRNA of AD. The nanocomplexes exhibited high distribution in the A deposits-enriched hippocampus, especially in the neurons near the amyloid plaques after intravenous administration. In APP/PS1 transgenic mice, the nanocomplexes down-regulated BACE1 in both mRNA and protein levels, as well as A and amyloid plaques to the level of wild-type mice. Moreover, the nanocomplexes significantly increased the level of synaptophysin and rescued memory loss of the AD transgenic mice without hematological or histological toxicity. Taken together, this work presented direct evidences that the design of precise gene delivery to the AD lesions markedly improves the therapeutic outcome.

Objective To compare the characteristics of clinical pathology between patients with early recurrence and those with late recurrence of colorectal cancer.Methods Clinicopathological data of 391 recurrence patients after surgery from Changhai Hospital were recruited between Jan 2005 and Dec 2015.The clinical and pathological characteristics of primary cancer in early recurrence group (less than 2 years after surgery) and late recurrence group (2 year or more after surgery) were compared.Results 246 patients had early recurrence (62.9％) and 145 had late recurrence (37.1％).Liver,systemic metastases and peritoneum were the main sites of distant recurrence in the early recurrence group,whereas liver,lung and systemic metastases were the most frequent sites of metastases in the late recurrence group.Patients with the increased tumor perimeter,lymph node metastasis,increased CEA and CA19-9,without postoperative adjuvant treatment and microsatellite stability are more likely to have early recurrence.5-year overall survival rate for patients with early recurrence was significantly lower than those with late recurrence.Conclusions This study showed that clinical and pathological factors are significantly associated with recurrence of colorectal cancer.Two years after surgery is an important period for the recurrence of colorectal cancer.