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.

ObjectiveTo study the mechanism of Shenbai Jiedu prescription inhibiting the proliferation of HCT116 colorectal cancer （CRC） cells by regulating the phosphatase and tensin homolog deleted on chromosome ten （PTEN）/phosphatidylinositol 3-kinase （PI3K）/ protein kinase B （Akt） signaling pathway. MethodShenbai Jiedu prescription was extracted by water extraction and alcohol precipitation to prepare freeze-dried powder. HCT116 cells were cultured in vitro， and treated with different concentrations of Shenbai Jiedu prescription （2， 4， 8， 16 g·L^-1）. The inhibitory effect of Shenbai Jiedu prescription on the proliferation of HCT116 cells was tested by methyl thiazolyl tetrazolium （MTT）. Real-time quantitative PCR was used to detect the mRNA expression levels of PTEN， PI3K， Akt， glycogen synthase kinase-3β （GSK-3β）， c-Myc， survivin and Cyclin D₁. Western blot was employed to measure the protein expression levels of PTEN， phosphorylated PTEN （p-PTEN）， PI3K， Akt， phosphorylated Akt （p-Akt）， GSK-3β， phosphorylated GSK-3β （p-GSK-3β）， c-Myc， survivin and Cyclin D₁， β-catenin nuclear import was explored by immunofluorescence assay. ResultCompared with the control group， Shenbai Jiedu prescription inhibited the proliferation of HCT116 cells in a dose-dependent manner （P<0.01）. Compared with the control group， the mRNA expression levels of PTEN and GSK-3β were up-regulated whereas those of PI3K， Akt， c-Myc， survivin and CyclinD₁ were down-regulated after treatment with Shenbai Jiedu prescription （P<0.01）. The protein expression levels of PTEN， p-PTEN and GSK-3β were up-regulated whereas those of PI3K， Akt， p-Akt， GSK-3β， p-GSK-3β， c-Myc， survivin and CyclinD₁ were down-regulated （P<0.05， P<0.01）. Immunofluorescence assay showed that Shenbai Jiedu prescription suppressed β-catenin nuclear import in HCT116 cells. ConclusionShenbai Jiedu prescription inhibited the proliferation of HCT116 cells via the mechanism of regulating the PTEN/PI3K/Akt signaling pathway.

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 study the role of Nrf2/ARE signaling pathway in cypermethrin-induced oxidative stress and apoptosis of cerebral cortex neurons in C57BL/6 mice. METHODS: The cortical neurons of C57BL/6 mice were cultured and identified, and a cypermethrin-induced cell injury model was established by treating the cells with 0, 25, 50 and 100 μmol/L of cypermethrin for 48 h. CCK-8 assay was used to analyze the effects of cypermethrin on the cell viability, and the fluorescence probe DCFH-DA was used for detecting intracellular reactive oxygen species (ROS); flow cytometry was performed for determining the apoptosis rate of the cells. The mRNA and protein expression levels of Nrf2 and its downstream genes HO-1 and NQO1 were detected using qPCR and Western blotting. RESULTS: Exposure to cypermethrin at different doses inhibited the viability of the cultured cortical neurons. With the increase of cypermethrin dose, the viability of the neurons decreased progressively, the intracellular ROS and the cell apoptosis rate increased, and the neuronal injury worsened. At the dose of 50 and 100 μmol/L, cypermethrin significantly down-regulated the expressions of HO-1, NQO1 and Nrf2 at both the mRNA and protein levels in the cells ( < 0.01). CONCLUSIONS Cypermethrin exposure shows a dose-dependent neurotoxicity by inhibiting Nrf2/ARE signaling pathway, down-regulating the expression of Nrf2 and its downstream genes HO-1, NQO1 mRNA and protein, and inducing oxidative damage and apoptosis in primary mouse cortical neurons, .
Animals ; Carboxylic Ester Hydrolases ; Cerebral Cortex ; Mice ; Mice, Inbred C57BL ; NF-E2-Related Factor 2 ; Neurons ; Pyrethrins ; Signal Transduction

OBJECTIVE: To systematically evaluate the efficacy difference between warming acupuncture and other acupuncture methods in the treatment of primary obesity. METHODS: A computer-based retrieval was conducted at PubMed, EMBASE, CENTRAL, CINAHL, Alt HealthWatch, CNKI, CBM, WANFANG database and VIP database. Retrieval time was from the establishment date of database to October 4, 2017. Randomized controlled trial (RCT) of warming acupuncture comparing with other acupuncture methods for the treatment of primary obesity were included. The relative risk () and weighted mean difference ( ) were used as combined effects for categorical variables and continuous variables, respectively. RESULTS: Totally 13 RCTs were included involving 878 patients. The Meta-analysis indicated compared with other acupuncture methods, warming acupuncture could more reduce weight (: -1.49 kg, 95% : -2.53 to -0.45, =0.005), improve the total effective rate (=1.16, 95% : 1.09 to 1.24, <0.000 01), reduce BMI (: -1.24 kg/m, 95% : -2.34 to -0.14, =0.03), reduce waist circumference (: -1.65 cm, 95% : -2.53 to -0.76, =0.02) and reduce hip circumference (: -2.86 cm, 95% : -4.37 to -1.35, =0.000 2), but had no significant influence on total cholesterol (: -0.05 mmol/L, 95% :-0.98 to 0.88, =0.91). CONCLUSION The warming acupuncture has better efficacy on primary obesity than other acupuncture methods, but less effects on lipid indicators.
Acupuncture Therapy ; Databases, Factual ; Humans ; Lipids ; Obesity ; therapy ; Randomized Controlled Trials as Topic

Objective To investigate the present situation of institutes of rehabilitation medicine in Guangxi. Methods From March to July, 2015, all 287 hospitals in Guangxi were investigated with the Human Resource Statistics of Guangxi Rehabilitation Medicine Depart-ment and the Specialist Questionnaire of Guangxi Rehabilitation Medicine Department by E-mail through the local Health and Family Plan-ning Commissions. Results There were 125 rehabilitation medicine departments with 2146 personnels in Guangxi, 0.2 therapists per bed in average. The proportion was 1∶0.725 for rehabilitative physicians to therapists;1∶1.92∶3.14 for senior, intermediate and primary title for physicians;1∶8∶63 for therapists and 1∶5.6∶18.9 for nurses. About 91.3%of the department of rehabilitation medicine was in the tertia-ry hospitals and was able to provide the services of physical therapy, occupational therapy, speech therapy, swallowing rehabilitation, cogni-tive rehabilitation, psychological therapy and rehabilitation engineering, and so on. Conclusion Rehabilitation has made a big progress com-pared with that in 2009 in Guangxi, in term of institutes, human resources and the service ability. However, the distribution of institutions and human resources remains unbalanced.

Based on the conception analysis of the organizational change leadership of the upper-and mid-level nursing manager,this review described connovations of the organizational change leadership and its applications in nursing field at home and abroad,and pointed out the current research status,limitations and the inspirations we got,so as to provide references for promotion and evaluation of the upper-and midlevel nursing manager's organizational change leadership.

Objective To construct and identify recombinant vaccine Bifidobacterium bifidum (pGEX-Sj32) of Schistosomajaponicum (Sj).Methods The Sj32 gene amplified by PCR from template of plasmid pET28α-Sj32 that extracted from recombinant Escherichia coli(E.coli) BL21 (pET28α-Sj32) stored in our laboratory was cloned into E.coli-Bifidobacterium bifidum shuttle expression vector pGEX-1λT to construct recombinant plasmid pGEX-Sj32.The recombinant plasmid was transformed into E.coli BL21 (DE3).The plasmid was extracted and identified by restriction enzyme digestion.The recombinant Bifibacterium bifidum (pGEX-Sj32) vaccine was constructed by electroporating pGEX-Sj32 into Bb.The extracted plasmid was amplified and identified by PCR.Results The gene Sj32 of 1 270 bp in length was amplified by PCR.The restriction endonuclease digestion showed that the length of plasmid vector was 4 947 bp,and Sj32 gene was 1 270 bp.The Sj32 gene amplified by PCR from the template of pGEX-Sj32 extracted from recombinant Bb (pGEX-Sj32) vaccine was 1 270 bp in length which consistent with expected result.Conclusion The recombinant Bb (pGEX-Sj32) vaccine of Sj is successfully constructed.

OBJECTIVETo observe the dynamic changes of immune responses of splenocytes in mice immunized with recombinant vaccine Bifidobacterium bifidum (pGEX-Sj32) of Schistosoma japonicum and investigate the immunological mechanism of the vaccine.

METHODSEighty-eight BALB/c mice were randomized for immunization with 10⁶ CFU recombinant vaccine orally or with 10⁵ CFU recombinant vaccine intranasally. Four mice were selected from each group every two weeks to test the responses of the splenocytes to stimulations with SjAWA or ConA. MTT assay and flow cytometry were used to assess splenocyte proliferation and the distribution of CD4⁺ and CD8⁺ T cells, respectively; the levels of interleukin-10 (IL-10), IL-12 and tumor necrosis factor-α (TNF-α) in the cell culture supernatant were detected by ELISA.

RESULTSRegardless of the stimulations, the splencytes showed significantly enhanced proliferation in weeks 2-16 in oral administration group and in weeks 2-18 in intranasal group (P<0.01). CD4⁺ subsets in both two groups increased obviously in weeks 2-12 (P<0.01) but CD8⁺ subsets remained stable. In oral administration group, the levels of TNF-α, IL-10 and IL-12 increased in weeks 2-14, 2-18 and 2-14, and peaked at week 8, 10 and 6, respectively; in intranasal group, the cytokines increased in weeks 2-14, 2-18 and 2-18, and peaked at week 8, 10 and 8, respectively.

CONCLUSIONThe recombinant vaccine rBb (pGEX-Sj32) can induce effective immune responses in mice.

Animals ; Antigens, Helminth ; immunology ; Bifidobacterium ; CD4-Positive T-Lymphocytes ; immunology ; CD8-Positive T-Lymphocytes ; immunology ; Interleukin-10 ; immunology ; Interleukin-12 ; immunology ; Mice ; Mice, Inbred BALB C ; Schistosoma japonicum ; Schistosomiasis japonica ; prevention & control ; Spleen ; cytology ; immunology ; Tumor Necrosis Factor-alpha ; immunology ; Vaccination ; Vaccines, Synthetic ; immunology

Objective To evaluate the accuracy of Sysmex XT-4000i automated hematology analyzer on neonatal leukocytes count and classification results.Methods 213 cases of neonatal blood specimens were analyzed respectively by Sysmex XT-4000i automated hematology analyzer and microscope counting and staining of two categories of methods.Results The instrument that immature granulocyte,primitive cell,shift to the left,three kind of tip in any one or more specimens have 112,accounted for 52.58% (112/213),and staining immature cell or shift to the left of the specimens was 91,accounted for 42.72% (91/213).The instrument to nucleated erythrocyte specimens were 109,accounting for 51.17% (109/213),and staining of nucleated erythrocyte were 66,accounting for 30.99% (66/213).Classify or classification of incomplete instrument failed to leukocytes were 11,ac-counting for 5.16% (11/213).When the specimens without nucleated erythrocytes interference or the number of nucleated eryth-rocytes is low [≤ 10/100 white blood cells(WBC)],Instruments on leukocyte count and manual counting results,there was not statistically significant differences between the two groups(P >0.05 ),when the sample number of nucleated erythrocytes (>10/100 WBC),When the specimens were nucleated erythrocyte number for a long time(>10/100 WBC),Instruments on leukocyte count and manual counting results,there was significant difference between the two groups(P <0.05).Correlation analysis on the instrument detection and manual dyeing classification of leukocytes,neutrophils,lymphocytes,monocytes,eosinophils,basophils, the correlation coefficient is respectively 0.95,0.93,0.78,0.86,0.14.Conclusion Some errors exist in Sysmex XT-4000i auto-mated hematology analyzer to count and classification of leukocytes.On neonatal blood tests should be carried out at the same time man-ual microscopy,and on the basis of nucleated erythrocytes were corrected,to ensure the clinical blood routine reporting results.