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.

During coronavirus disease 2019 epidemic, the treatment of severe trauma has been impacted. The Consensus on emergency surgery and infection prevention and control for severe trauma patients with 2019 novel corona virus pneumonia was published online on February 12, 2020, providing a strong guidance for the emergency treatment of severe trauma and the self-protection of medical staffs in the early stage of the epidemic. With the Joint Prevention and Control Mechanism of the State Council renaming "novel coronavirus pneumonia" to "novel coronavirus infection" and the infection being managed with measures against class B infectious diseases since January 8, 2023, the consensus published in 2020 is no longer applicable to the emergency treatment of severe trauma in the new stage of epidemic prevention and control. In this context, led by the Chinese Traumatology Association, Chinese Trauma Surgeon Association, Trauma Medicine Branch of Chinese International Exchange and Promotive Association for Medical and Health Care, and Editorial Board of Chinese Journal of Traumatology, the Chinese expert consensus on emergency surgery for severe trauma and infection prevention during coronavirus disease 2019 epidemic ( version 2023) is formulated to ensure the effectiveness and safety in the treatment of severe trauma in the new stage. Based on the policy of the Joint Prevention and Control Mechanism of the State Council and by using evidence-based medical evidence as well as Delphi expert consultation and voting, 16 recommendations are put forward from the four aspects of the related definitions, infection prevention, preoperative assessment and preparation, emergency operation and postoperative management, hoping to provide a reference for severe trauma care in the new stage of the epidemic prevention and control.

Objective: To investigate the clinical efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) for gallbladder cancer with peritoneal metastasis. Methods: Data of 84 patients, who were admitted to Shanghai Eastern Hepatobiliary Surgery Hospital from January 2015 to January 2018, were retrospectively analyzed. Of the total patients, 31 received HIPEC combined with cytoreductive surgery (CRS) plus postoperative systemic chemotherapy one month after surgery as the study group (Group A), and the other 53 underwent CRS plus postoperative systemic chemotherapy one momth after surgery as the control group (Group B). The clinical effects and adverse reactions in the two groups were observed and compared. Results: The median survival time in the Group A was (21.72±2.96) months, significantly longer than that of (14.93±2.09) months in Group B (P<0.05). There were no statistically significant differences in leukopenia, hemoglobinemia, thrombocytopenia, gastrointestinal reaction, liver function injury and renal function injury-between the two groups (P>0.05). Conclusions: HIPEC has significant clinical efficacy for gallbladder cancer with peritoneal metastasis. HIPEC can prolong the survival time and have less side effects.

Objective:To explore the expression of Aurora Kinase A (AURKA) in hepatocellular carcinoma (HCC) and its prognostic value.Methods:mRNA expression profiles and clinical data of HCC patients were downloaded from the Cancer Genome Atlas (TCGA) database. Expression of AURKA mRNA in HCC patients of TCGA database from normal liver tissue and all tumor tissues, normal tissues adjacent to cancer and matched tumor tissues were analyzed, and then expression of AURKA to was investigated in HCC tissues and normal liver tissues in the Human Protein Atlas (HPA) database. According to the TNM stage information of HCC patients in TCGA database, expression of AURKA in different stages was analyzed. Kaplan-Meier method was used to analyze whether the high and low expression of AURKA in HCC patients of TCGA database (with the median as the cut-off value) was significantly related to the length of survival. The RNA-seq expression profile data of HCC patients in the public resource platform of the Kaplan-Meier Plotter website was used for external verification. Cox univariate and multivariate analysis were performed on the age, sex, degree of differentiation, TNM stage, and AURKA mRNA expression of TCGA database patients.Results:374 cases of HCC tumor tissues and 50 cases of adjacent normal liver tissues in the TCGA database were included. All HCC tumor tissues in the TCGA database compared with the paired adjacent tissues mRNA level of AURKA was significantly increased, and the protein level was also increased, the difference was statistically significant ( P<0.05); With the tumor TNM stage increase of AURKA mRNA expression showed a gradual upward trend, and the difference was statistically significant ( P<0.05); in the TCGA database HCC cohort, high expression of AURKA mRNA was associated with poor HCC prognosis, and was obtained in Kaplan Meier Plotter database. The difference was statistically significant ( P<0.05); Cox multivariate regression analysis showed that TNM stage ( HR=1.69, 95% CI: 1.37-2.10) and AURKA mRNA expression level ( HR=1.03, 95% CI: 1.01-1.10) are the independent prognostic factors of HCC patients. Conclusions:AURKA is highly expressed in HCC, which is associated with the poor prognosis of HCC. AURKA is an independent prognostic factor of HCC.

Objective To observe Hedgehog signaling pathways of liver cancer cell growth and the influence of the metastatic potential targeted inhibit Hedgehog.Methods Construction of Smo shRNA plasmid,The stable and low-expressed Smo-expressing HCC QGY-7701 cell line was screened after lipofection.The stable and low-expressed Smo-expressing HCC QGY-7701 cell line was screened,The cell cycle,apoptosis,invasion and metastasis of QGY-7701 cells were detected by Western blot,flow cytometry,CCK8 and transwell assay.Subcutaneous implantation of hepatocarcinoma cells in nude mice.Study on the growth and metastasis of hepatocarcinoma cells with low expression of Smo in.The ultrastructural changes of hepatoma cells with low expression of Smo were observed under electron microscope.Results RT-PCR and Western blot showed stable shR-Smo cell line was successfully constructed.Cell cycle test showed that compared with the control group,G0/G1 cells increased in shR-Smo,cells in S phase decreased;apoptosis,CCK8 and Transwell tests showed that Smo-gene silencing could significantly increase the apoptosis percentage of the hepatic cancer cells to (5.46％ ± 1.46％),proliferation activity decreasedand and the migration rates reduced to (7.82％ ±2.14)％;nude mice model showed that Smo-gene silencing could inhibit the growth of hepatocellular carcinoma cells in vivo,electron microscopy revealed that lysosomes increased significantly in Smo-gene silence cells.Conclusions Blocking Hh signaling pathways,liver cancer cells in vitro malignant degree of decline.Hedgehog in treating liver cancer have hidden meaning.

High-density lipoproteins (HDL) are naturally-occurring nanoparticles that are biocompatible, non-immunogenic and completely biodegradable. These endogenous particles can circulate for an extended period of time and transport lipids, proteins and microRNA from donor cells to recipient cells. Based on their intrinsic targeting properties, HDL are regarded as promising drug delivery systems. In order to produce on a large scale and to avoid blood borne pollution, reconstituted high-density lipoproteins (rHDL) possessing the biological properties of HDL have been developed. This review summarizes the biological properties and biomedical applications of rHDL as drug delivery platforms. It focuses on the emerging approaches that have been developed for the generation of biomimetic nanoparticles rHDL to overcome the biological barriers to drug delivery, aiming to provide an alternative, promising avenue for efficient targeting transport of nanomedicine.

Objective To evaluate the feasibility and efficacy of preoperative sequential transcatheter arterial chemoembolization (TACE) followed by selective portal venous embolization (PVE) in patients with marginally resectable hepatocellular carcinoma (HCC).The aim was to find out whether this combined procedure helped to increase the rate of extended radical liver resection.Methods From March 2009 to November 2016,29 patients with HCC which were marginally resectable underwent preoperative TACE combined with PVE were included into this study.All these patients were subsequently assessed to undergo radical hepatectomy.The complications,laboratory results,volume changes of each liver lobe and patient survival were analyzed.Results TACE combined with PVE was successful in all the 29 patients.There were no major complications.After the procedure,the volumes of the tumor and the part of the liver to be resected decreased to certain degree.The remnant liver volume (RLV) increased remarkably.The RLV were (395.4 ±58.7) cm3 and (599.2 ±75.2) cm3 before and after the procedure,respectively.The difference was significant (P ＜ 0.05).19 patients underwent radical hemihepatectomy or trisectionectomy,with a resection rate of 65.5％ (19/29).There were sufficient surgical margins in all the resected tumors.After operation,the 1-,3-,and 5-year survival rates were 58.8％,35.5％ and 17.6％,respectively.Conclusion For HCC patients who had marginally resectable HCC,preoperative TACE combined with PVE efficiently controlled the growth of the tumors,decreased the volume of the liver lobe with tumor,increased the RLV,and made it possible for a planned two-stage radical hepatectomy with sufficient surgical margin and better survival in a significant proportion of patients.

Dental Implantation, Endosseous ; Dental Implants ; Humans ; Maxilla ; Tissue Engineering

Objective To compare effects of irbesartan and captopril on left ventricular function in elderly patients with cardiovascular disease and cardiac functional reserve .Methods 100 cases of elderly patients with car-diovascular disease were chosen ,according to a list of numbers randomly divided into the two groups ,50 cases in each group,a group with irbesartan treatment ,as the irbesartan group and the other group received captopril ,as the capto-pril group compared the two groups of patients left ventricular function and cardiac functional reserve .Results (1) Left ventricular function after the irbesartan group therapy LVDd indicators ,IVSd,LVPWd,LVEF,VE/VA,LVM was significantly better than before treatment ,the difference was statistically significant (t=31.23,18.36,28.12,46.36, 51.13,16.03,all P<0.05),the captopril group before and after treatment was significantly better than the treatment of various indicators,the difference was statistically significant (t=24.53,21.36,31.12,14.33,18.19,16.45,all P<0.05);(2) The irbesartan group of patients after treatment resting heart rate ,exercise heart rate,6min walking distance improved significantly over the treatment of former CCRI and CRI ,the difference was statistically significant (t=39.09,23.77,39.01,23.18,22.45,all P<0.05),after treatment with captopril treatment was significantly better than the indexes,the difference was statistically significant (t=91.21,37.16,26.74,46.33,36.74,all P<0.05),6min walking distance from the irbesartan group therapy ,CRI better than the captopril group ,the difference was statistically significant(t=39.02,42.14,all P<0.05).Conclusion Irbesartan and captopril on improving left ventricular function in elderly patients with cardiovascular disease and cardiac reserve function has a significant effect,irbesartan 6min walking distance test and cardiac reserve indices better .

An electrochemical aptasensor for Pb2+ was constructed based on the layer-by-layer assembly of graphene (GR) and anthraquinone -2-sulfonic acid sodium salt (AQMS) on the surface of Pb2+ aptamer. The mercapto-modified Pb2+ aptamer was first anchored on a gold electrode. Then the highly conductive material of GR was adsorbed on apt through the unique π-π stacking interaction, which was further used for the assembly and signal amplification of the electroactive AQMS. Upon interaction with Pb2+ ions, the apt on the aptasensor undergone conformational switch from a single-stranded form to the G-quadruplex structure, causing the GR assembled with AQMS releasing from the electrode surface into solution. As a result, the electrochemical signal of AQMS on the aptasensor was substantially reduced. Base on this concept, a useful platform for detection of Pb2+ ions was constructed. Under the optimal experimental conditions, the attenuation of peak currents (△Ipa ) showed linear relationship with the logarithm of Pb2+ concentrations (lgCPb2+) over the range from 5. 0×10-10 to 5. 0×10-8 mol/ L. The detection limit was estimated to be 6. 0×10-11 mol/ L.