Effects of electro-scalp acupuncture on inflammatory response and microglial polarization in the ischemic cortex of rats with ischemic stroke / 中国针灸

OBJECTIVE@#To observe the effects of electro-scalp acupuncture （ESA） on the expression of microglial markers CD206 and CD32, as well as interleukin (IL)-6, IL-1β, and IL-10 in the ischemic cortex of rats with ischemic stroke, and to explore the mechanisms of ESA on alleviating inflammatory damage of ischemic stroke.@*METHODS@#Sixty 7-week-old male SD rats were randomly selected, with 15 rats assigned to a sham surgery group. The remaining rats were treated with suture method to establish rat model of middle cerebral artery occlusion (MCAO). The rats with successful model were randomly divided into a model group, a VitD3 group, and an ESA group, with 15 rats in each group. In the ESA group, ESA was performed bilaterally at the "top-temporal anterior oblique line" with disperse-dense wave, a frequency of 2 Hz/100 Hz, and an intensity of 1 mA. Each session lasted for 30 min, once daily, for a total of 7 days. The VitD3 group were treated with intragastric administration of 1,25-dihydroxyvitamin D3 (1,25-VitD3) solution (3 ng/100 g), once daily for 7 days. The neurological deficit scores and neurobehavioral scores were assessed before and after the intervention. After the intervention, the brain infarct volume was evaluated using 2,3,5-triphenyltetrazolium chloride (TTC) staining. Immunofluorescence double staining was performed to detect the protein expression of CD32 and CD206 in the ischemic cortex. Western blot analysis was conducted to measure the protein expression of IL-6, IL-1β, and IL-10 in the ischemic cortex.@*RESULTS@#Compared with the sham surgery group, the model group showed increased neurological deficit scores and neurobehavioral scores (P<0.01), increased brain infarct volume (P<0.01), increased protein expression of CD32, IL-6, and IL-1β in the ischemic cortex (P<0.01), and decreased protein expression of CD206 and IL-10 in the ischemic cortex (P<0.01). Compared with the model group, both the ESA group and the VitD3 group showed decreased neurological deficit scores and neurobehavioral scores (P<0.01), reduced brain infarct volume (P<0.01), decreased protein expression of CD32, IL-6, and IL-1β in the ischemic cortex (P<0.01), and increased protein expression of CD206 and IL-10 in the ischemic cortex (P<0.01). Compared with the VitD3 group, the ESA group had lower neurological deficit score (P<0.05), larger brain infarct volume (P< 0.05), and lower protein expression of CD32, CD206, IL-1β, and IL-10 in the ischemic cortex (P<0.01, P<0.05).@*CONCLUSION@#ESA could improve neurological function in MCAO rats, and its mechanism may be related to promoting microglial M1-to-M2 polarization and alleviating inflammatory damage.

Tumor-associated antigen-based personalized dendritic cell vaccine in solid tumor patients.

Tumor-associated antigens (TAAs) have been tested in various clinical trials in cancer treatment but the patterns of specific T cell response to personalized TAA immunization remains to be fully understood. We report antigen-specific T cell responses in patients immunized with dendritic cell vaccines pulsed with personalized TAA panels. Tumor samples from patients were first analyzed to identify overexpressed TAAs. Autologous DCs were then transfected with pre-manufactured mRNAs encoding the full-length TAAs, overexpressed in the patients' tumors. Patients with glioblastoma multiforme (GBM) or advanced lung cancer received DC vaccines transfected with personalized TAA panels, in combination with low-dose cyclophosphamide, poly I:C, imiquimod and anti-PD-1 antibody. Antigen-specific T cell responses were measured. Safety and efficacy were evaluated. A total of ten patients were treated with DC vaccines transfected with personalized TAA panels containing 3-13 different TAAs. Among the seven patients tested for anti-TAA T cell responses, most of the TAAs induced antigen-specific CD4+ and/or CD8+ T cell responses, regardless of their expression levels in the tumor tissues. No Grade III/IV adverse events were observed among these patients. Furthermore, the treated patients were associated with favorable overall survival when compared to patients who received standard treatment in the same institution. Personalized TAA immunization-induced-specific CD4+ and CD8+ T cell responses without obvious autoimmune adverse events and was associated with favorable overall survival. These results support further studies on DC immunization with personalized TAA panels for combined immunotherapeutic regimens in solid tumor patients.Trial registration ClinicalTrials.gov, NCT02709616 (March, 2016), NCT02808364 (June 2016), NCT02808416 (June, 2016).

A Multi-Element Expression Score Is A Prognostic Factor In Glioblastoma Multiforme.

PURPOSE: Glioblastoma multiforme (GBM) is a highly malignant tumor of the central nervous system. Although primary GBM patients receive extensive therapies, tumors may recur within months, and there is no objective and scientific method to predict prognosis. Adoptive immunotherapy holds great promise for GBM treatment. However, the expression profiles of the tumor-associated antigens (TAAs) and tumor immune microenvironment (TME) genes used in immunotherapy of GBM patients have not been fully described. The present study aimed to develop a predictive tool to evaluate patient survival based on full analysis of the expression levels of TAAs and TME genes. METHODS: Expression profiles of a panel of 87 TAAs and 8 TME genes significantly correlated with poor prognosis were evaluated in 44 GBM patients and 10 normal brain tissues using quantitative real-time polymerase chain reaction (qRT-PCR). A linear formula (the LASSO algorithm based in the R package) weighted by regression coefficients was used to develop a multi-element expression score to predict prognosis; this formula was cross-validated by the leave-one-out method in different GBM cohorts. RESULTS: After analysis of gene expression, clinical features, and overall survival (OS), a total of 8 TAAs (CHI3L1, EZH2, TRIOBP, PCNA, PIK3R1, PRKDC, SART3 and EPCAM), 1 TME gene (FOXP3) and 4 clinical features (neutrophil-to-lymphocyte (NLR), number of basophils (BAS), age and treatment with standard radiotherapy and chemotherapy) were included in the formula. There were significant differences between high and low scoring groups identified using the formula in different GBM cohorts (TCGA (n=732) and GEO databases (n=84)), implying poor and good prognosis, respectively. CONCLUSION: The multi-element expression score was significantly associated with OS of GBM patients. The improve understanding of TAAs and TMEs and well-defined formula could be implemented in immunotherapy for GBM to provide better care.

Flexibility Analysis of Bacillus thuringiensis Cry1Aa / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the flexibility and mobility of the Bacillus thuringiensis toxin Cry1Aa.</p><p><b>METHODS</b>The graph theory-based program Constraint Network Analysis and normal mode-based program NMsim were used to analyze the global and local flexibility indices as well as the fluctuation of individual residues in detail.</p><p><b>RESULTS</b>The decrease in Cry1Aa network rigidity with the increase of temperature was evident. Two phase transition points in which the Cry1Aa structure lost rigidity during the thermal simulation were identified. Two rigid clusters were found in domains I and II. Weak spots were found in C-terminal domain III. Several flexible regions were found in all three domains; the largest residue fluctuation was present in the apical loop2 of domain II.</p><p><b>CONCLUSION</b>Although several flexible regions could be found in all the three domains, the most flexible regions were in the apical loops of domain II.</p>

Secondary metabolites of Eurotium cristatum from Fu Brick Tea and their biological activities / 中草药

Objective: To study the secondary metabolites of Eurotium cristatum from Fu Brick Tea and their biological activities. Methods: The compounds were isolated by various column chromatographies on normal phase silica gel, reversed silica gel, Sephadex LH-20, preparative TLC, and recrystallization. The structures were identified by the extensive analysis on their spectroscopic data. The inhibitory effects of compounds 1-9 against SF-268, MCF-7, and NCI-H460 cell lines were tested in vitro by SRB method. The inhibitory effects of compounds 2-9 on Staphyloccocus aureus, Escherichia coli, Salmonella enterica subsp. enterica, Shigella dysenteriae, and Proteus vulgaris were tested by MTT method. Results: Nine compounds were isolated from the extract of liquid fermentation broth of E. cristatum in Fu Brick Tea and identified as physcion (1), 1, 5-dihydroxy-3-methoxy-7-methyl-anthracene-9,10-dione (2), flavoglaucin (3), 2-(2', 3-epoxy-1', 3'-heptadienyl)-6-hydroxy-5-(3-methyl-2-butenyl) benzaldehyde (4), 2-(2', 3-epoxy-1', 3', 5'-heptatrienyl)-6-hydroxy-5-(3-methyl-2-butenyl) benzaldehyde (5), isodihydroauroglaucin (6), tyrosol (7), p-hydroxybenzoic acid (8), and orcinol (9). The results of the bioactivity test showed that compounds 3-6 displayed the good cytotoxic acitivities against the three tumor cell lines, and all the compounds exhibited the strong inhibitory activities against P. vulgaris except compounds 1 and 6. Besides, compound 9 also showed the significant inhibitory effects against S. aureus and E. coli. Conclusion: The benzaldehyde compounds are considered as the main metabolites of E. cristatum, compounds 7 and 9 are reported from the species of genus Eurotium Link: Fr. for the first time and compounds 2, 3, 5, 6, and 8 are firstly isolated from the fungus.

Surgical correction of male external genitalia giant condyloma acuminata / 中华整形外科杂志

<p><b>OBJECTIVE</b>To observe the clinical efficiency of curettage combining circumcision on giant condyloma acuminata(CA) in male external genitalia, the relationship between recurrence and curettage depth, the possibility of HPV infection in PBMC after operation.</p><p><b>METHODS</b>Curettage combining circumcision was carried out on 50 cases with CA. The removed wart and wound surface tissues were examined under light microcope and for HPV-DNA detection by PCR. HPV-DNA was detected in PBMC during < or =1 and > or =2 weeks after operation.</p><p><b>RESULTS</b>(1) 46 cases were cured completely after one treating (once the cure rate is 92%), 4 cases twice(twice the cure rate is 8%); (2) The tissues were proved to be HPV-DNA positive by PCR amplification and CA relapse occurred; (3) HPV-DNA was detected in PBMC only within the week after curettage in the 19 cases.</p><p><b>CONCLUSIONS</b>(1) The clinical efficiency of curettage combining circumcision on giant condyloma acuminata in male external genitalia is sure; (2) Cure rate and relapse rate are related with curettage depth; (3) Transient positive HPV-DNA in PBMC may be detected.</p>