Ag85B with c-di-AMP as mucosal adjuvant showed immunotherapeutic effects on persistent Mycobacterium tuberculosis infection in mice

Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains the leading cause of mortality by a single infectious agent in the world. M. tuberculosis infection could also result in clinical chronic infection, known as latent TB infection (LTBI). Compared to the current limited treatment, several subunit vaccines showed immunotherapeutic effects and were included in clinical trials. In this study, a subunit vaccine of Ag85B with a novel mucosal adjuvant c-di-AMP (Ag85B:c-di-AMP) was delivered intranasally to a persistent M. tuberculosis H37Ra infection mouse model, which also presented the asymptomatic characteristics of LTBI. Compared with Ag85B immunization, Ag85B:c-di-AMP vaccination induced stronger humoral immune responses, significantly higher CD4+ T cells recruitment, enhanced Th1/Th2/Th17 profile response in the lung, decreased pathological lesions of the lung, and reduced M. tuberculosis load in mice. Taken together, Ag85B:c-di-AMP mucosal route immunization provided an immunotherapeutic effect on persistent M. tuberculosis H37Ra infection, and c-di-AMP, as a promising potential mucosal adjuvant, could be further used in therapeutic or prophylactic vaccine strategies for persistent M. tuberculosis infection as well as LTBI.

Regulatory factor X5 promotes hepatocellular carcinoma progression by transactivating tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta and suppressing apoptosis / 中华医学杂志(英文版)

BACKGROUND@#Our previous studies have shown that regulatory factor X5 (RFX5), a classical transcription regulator of MHCII genes, was obviously overexpressed in hepatocellular carcinoma (HCC) tumors. However, the role of RFX5 in the carcinogenesis and progress of HCC remains unknown. This study aimed to reveal its biological significance and the underlying mechanism in HCC.@*METHODS@#RFX5 mRNA expression level and copy number variation in HCC tumors and cell lines were determined by analyzing deposited data sets in the Cancer Genome Atlas and Gene Expression Omnibus database. The biological significance of RFX5 in HCC was investigated by monitoring the colony formation and subcutaneous tumor growth capacity when RFX5 was silenced with lentiviral short hairpin RNA and CRISPR/Cas9 system in HCC cell lines. The downstream gene transcriptionally activated by RFX5 in HCC cells was determined by chromatin immunoprecipitation and luciferase reporter assay. The involvement of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta (YWHAQ) in HCC development was further determined by performing colony formation rescue assay and subcutaneous tumor growth rescue experiment. The association of YWHAQ with recurrence-free survival of patients with HCC was assessed by Kaplan-Meier analysis. Moreover, apoptosis level and the protein level of p53 pathway were determined to reveal the mechanism of RFX5 in driving HCC development.@*RESULTS@#RFX5 was amplified and highly overexpressed in HCC tumor tissues compared with the corresponding non-tumor tissues. The mRNA expression level of RFX5 was significantly correlated with its DNA copy number (r = 0.4, P < 0.001). Functional study demonstrated that RFX5 was required for both clonogenic forming in vitro and subcutaneous tumor growth in vivo of HCC cells. Further study identified YWHAQ, namely 14-3-3 tau, as a key downstream transcriptional target gene of RFX5, which was tightly regulated by RFX5 in HCC. Moreover, overexpression of YWHAQ largely rescued the clonogenic growth of HCC cells that was suppressed by RFX5 knockdown. In addition, overexpression of YWHAQ in primary tumor was linked to poor prognosis of patients with HCC. These results demonstrated that YWHAQ was a downstream effector of RFX5 in HCC. Notably, RFX5-YWHAQ pathway could protect cells from apoptosis by suppressing the p53 and Bax in HCC.@*CONCLUSION@#RFX5 is a putative HCC driver gene that plays an important role in the development and progression of HCC by transactivating YWHAQ and suppressing apoptosis.

Regulatory factor X5 promotes hepatocellular carcinoma progression by transactivating tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta and suppressing apoptosis / 中华医学杂志(英文版)

Background@#Our previous studies have shown that regulatory factor X5 (RFX5), a classical transcription regulator of MHCII genes, was obviously overexpressed in hepatocellular carcinoma (HCC) tumors. However, the role of RFX5 in the carcinogenesis and progress of HCC remains unknown. This study aimed to reveal its biological significance and the underlying mechanism in HCC.@*Methods@#RFX5 mRNA expression level and copy number variation in HCC tumors and cell lines were determined by analyzing deposited data sets in the Cancer Genome Atlas and Gene Expression Omnibus database. The biological significance of RFX5 in HCC was investigated by monitoring the colony formation and subcutaneous tumor growth capacity when RFX5 was silenced with lentiviral short hairpin RNA and CRISPR/Cas9 system in HCC cell lines. The downstream gene transcriptionally activated by RFX5 in HCC cells was determined by chromatin immunoprecipitation and luciferase reporter assay. The involvement of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta (YWHAQ) in HCC development was further determined by performing colony formation rescue assay and subcutaneous tumor growth rescue experiment. The association of YWHAQ with recurrence-free survival of patients with HCC was assessed by Kaplan-Meier analysis. Moreover, apoptosis level and the protein level of p53 pathway were determined to reveal the mechanism of RFX5 in driving HCC development.@*Results@#RFX5 was amplified and highly overexpressed in HCC tumor tissues compared with the corresponding non-tumor tissues. The mRNA expression level of RFX5 was significantly correlated with its DNA copy number (r = 0.4, P < 0.001). Functional study demonstrated that RFX5 was required for both clonogenic forming in vitro and subcutaneous tumor growth in vivo of HCC cells. Further study identified YWHAQ, namely 14-3-3 tau, as a key downstream transcriptional target gene of RFX5, which was tightly regulated by RFX5 in HCC. Moreover, overexpression of YWHAQ largely rescued the clonogenic growth of HCC cells that was suppressed by RFX5 knockdown. In addition, overexpression of YWHAQ in primary tumor was linked to poor prognosis of patients with HCC. These results demonstrated that YWHAQ was a downstream effector of RFX5 in HCC. Notably, RFX5-YWHAQ pathway could protect cells from apoptosis by suppressing the p53 and Bax in HCC.@*Conclusion@#RFX5 is a putative HCC driver gene that plays an important role in the development and progression of HCC by transactivating YWHAQ and suppressing apoptosis.

Effect of exercise on adiponectin in aged obese rats / 中国应用生理学杂志

OBJECTIVE@#To explore effects of exercise on the expression of adiponectin mRNA and protein in visceral adipose tissue, plasma adiponectin concentration, and insulin resistance of aged obese rats.@*METHODS@#Male SD rats age to 21 days old were fed with high-fat diet (fat percentage was 36.3% to 40.0%) for three stages of adolescence, maturity and old age to establish elderly obesity rats model. When the rats aged to 60 weeks old, natural growing elderly rats were randomly divided into control group (C) and aged exercise group (AE), =6; elderly obesity rats were randomly divided into obesity control group (OC) and obesity exercise group (OE), =6. The treadmill grade was 0°, the exercise speed and time were 15 m/min×15 min, 4 groups each time, between consecutive groups the rats had 5 minutes rest, the rats were exercised for 60 minutes every day, five days a week, continuous exercise for 8 weeks. Then, the expressions of adiponectin mRNA and protein in visceral adipose tissue were determined. The concentrations of blood glucose, plasma adiponectin and insulin were measured. Insulin resistance was calculated.@*RESULTS@#Comparison with control group, the expressions of adiponectin mRNA and protein were obviously decreased, the concentration of blood glucose and insulin resistance were significantly increased in obesity control group, while the expressions of adiponectin mRNA and protein were obviously increased. Comparison with obesity control group, the expressions of adiponectin mRNA and protein, the concentration of plasma adiponectin were obviously increased, the concentration of blood glucose and insulin resistance were significantly decreased in obesity exercise group.@*CONCLUSIONS@#Adiponectin mRNA and protein expression in visceral adipose tissue is decreased and accompanied by high blood glucose and insulin resistance in elderly obesity rats. Exercise can increase the adiponectin mRNA and protein expression in visceral adipose tissue, elevate levels of plasma adiponectin, and decrease the level of blood glucose and insulin resistance in elderly obesity rats.

S100A4 Gene is Crucial for Methionine-Choline-Deficient Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice

PURPOSE: To explore the influence of S100 calcium binding protein A4 (S100A4) knockout (KO) on methionine-choline-deficient (MCD) diet-induced non-alcoholic fatty liver disease (NAFLD) in mice. MATERIALS AND METHODS: S100A4 KO mice (n=20) and their wild-type (WT) counterparts (n=20) were randomly divided into KO/MCD, Ko/methionine-choline-sufficient (MCS), WT/MCD, and WT/MCS groups. After 8 weeks of feeding, blood lipid and liver function-related indexes were measured. HE, Oil Red O, and Masson stainings were used to observe the changes of liver histopathology. Additionally, expressions of S100A4 and proinflammatory and profibrogenic cytokines were detected by qRT-PCR and Western blot, while hepatocyte apoptosis was revealed by TUNEL staining. RESULTS: Serum levels of aminotransferase, aspartate aminotransferase, triglyceride, and total cholesterol in mice were increased after 8-week MCD feeding, and hepatocytes performed varying balloon-like changes with increased inflammatory cell infiltration and collagen fibers; however, these effects were improved in mice of KO/MCD group. Meanwhile, total NAFLD activity scores and fibrosis were lower compared to WT+MCD group. Compared to WT/MCS group, S100A4 expression in liver tissue of WT/MCD group was enhanced. The expression of proinflammatory (TNF-α, IL-1β, IL-6) and profibrogenic cytokines (TGF-β1, COL1A1, α-SMA) in MCD-induced NAFLD mice were increased, as well as apoptotic index (AI). For MCD group, the expressions of proinflammatory and profibrogenic cytokines and AI in KO mice were lower than those of WT mice. CONCLUSION: S100A4 was detected to be upregulated in NAFLD, while S100A4 KO alleviated liver fibrosis and inflammation, in addition to inhibiting hepatocyte apoptosis.

Microsurgical management of meningiomas in the trigone of the lateral ventricle / 医学研究生学报

Objective Meningiomas in the trigone of the lateral ventricle are characterized by deep location and low inci-dence. A few studies have been done on its treatment at home and abroad. This study was to explore the access,techniques,and clini-cal effect of microsurgery for lateral ventricular trigone meningiomas (LVTM). Methods We retrospectively analyzed the clinical data about 36 cases of LVTM treated by microsurgery in our hospital from December 2011 to December 2015. The operation involved lumbar cistern tube drainage, intraoperative drainage of cerebrospinal fluid, a unilateral parieto-occipital U-shaped cut, approach through the interparietal fissure,a sagittal incision about 3 cm long at the interparietal fissure for exposure and resection of the tumor. We followed up the patients for a mean of 17 months postoperatively and analyzed the results and complications. Results Simpson grade I removal of the tumors was achieved in all the 36 cases. Postoperative complications included homonymous hemianopia in 4 cases, central nervous system infections in 3,secondary epilepsy in 2,subcutaneous hydrops in 2,and intratumoral hemorrhage in 1 (which necessitated a second operation). Extended temporal horn of the right lateral ventricle occurred at 32 months after surgery,which was treated by fistulation. Homonymous hemianopia was improved in 2 of the 4 ca-ses. All the patients were capable of daily life activities and none experienced recurrence. Conclusion Sufficient preoperative evalu-ation of the tumor characteristics,rational selection of surgical approach,and expert operation techniques are the key factors for the mi-crosurgical treatment of meningiomas in the trigone of the lateral ventricle.

Mechanisms of anti-inflammation of taurochenodeoxycholic acid based on network pharmacology / 药学学报

To investigate the anti-inflammatory mechanisms of taurochenodeoxycholic acid (TCDCA), the molecule structure file of TCDCA was downloaded from PubChem database, PharmMapper and GeneCards were used to predict and screen the targets of TCDCA. STRING database and Cytoscape software were used to construct protein interactions network. GO and KEGG analysis was preformed through STRING database. The key targets were validated by molecular docking and the targets type was attributed by DisGeNET database. The network showed that 89 targets were involved in 68 biological processes including response to stimulus, multicellular organismal process, single-multicellular organism process, response to chemical, response to organic substance, by adjusting 51 signaling pathways, such as pathways in cancer, progesterone-mediated oocyte maturation, MAPK signaling pathway, proteoglycans in cancer. These findings provide an overview of anti-inflammation of TCDCA, which reflects the characteristic of multi-targets and multi-pathways of TCDCA. It pointed out the direction for further research on anti-inflammatory mechanism of TCDCA.

Transmission and Analysis of Drug Resistance of Acinetobacter Baumanii in ICU / 现代检验医学杂志

Objective By detecting the distribution and homology analysis of Acinetobacter baumanii in the ICU ward,to con-trol nosocomial infection,provide theoretical basis to take effective measures.Methods From January 2016,20 patients in ICU of Shaanxi Provincial People's Hospital were taken into group.The samples of sputum and surrounding environment samples were cultured.The homology of Acinetobacter baumannii was analyzed by MALDI-Biotyper software,antimicrobial susceptibility test was analyzed by K-B.Results 27 strains of Acinetobacter baumannii were detected,mainly comes from sputum,hands of medical staffs and the environment,homology analysis results showed that the 27 strains of Acinetobacter baumannii was divided into two clusters(Ⅰtype 1 1 strains,Ⅱ type 1 6 strains),most of Acinetobacter baumannii were multi-resistant bacteria,except for the polymyxin B,minocycline and SCF.Conclusion The ways of transmission of Acineto-bacter baumanii in ICU were by medical personnel hand,pollution of the medical equipment and so on,strengthening the dis-infection and reasonable application of antimicrobial agents were taken advantageous for the prevention and control of acine-tobacter baumannii infection and transmission.

Analysis of vitrectomy combined with phacoemulsification in patients with vitreoretinal disease and cataract / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To analyze of refractive status after vitrectomy combined with phacoemulsification in patients with vitreoretinal disease and cataract.METHODS:A total of 150 patients with vitreoretinal disease and cataract were treated in our hospital from January 2014 to November 2016.According to the random number table method they were divided into two groups:combination group (75 cases) with vitrectomy combined with phacoemulsification,the control group (75 cases)with vitrectomy first,then phacoemulsification surgery.The recovery of visual acuity and the change of the axial length of the eyes were observed.The patients were followed up for 6mo,and the postoperative complications were recorded.RESULTS:After treatment,number of patients in the two groups with visual acuity ≥ 0.1 were significantly improved compared with before treatment (P＜0.05),and the percent in combination group was 95％,higher than 63％ in the control group (P＜0.05).There were no significant changes in the axial length before and after the operation in the two groups (P＞0.05),and there was no significant difference between the groups before and after treatment (P＞0.05).The refractive status of combination group shifted to myopia,that of control group shifted to hyperopia,two groups had no statistically significant difference on numerical prediction (P ＜ 0.05).The difference was statistically significant on the actual values (P＜0.05).The complication rate in the combination group was 24％,which was lower than 40％ in the control group,and the difference was statistically significant (P＜0.05).CONCLUSION:Vitrectomy combined with phacoemulsification on vitreoretinal diseases with cataract patients is effective,and safety,clinical application value is higher.

Effect of silencing the VDR gene on the migration and invasion of prostate cancer cells / 中华男科学杂志

Objective@#To investigate the effect of small interfering RNA silencing the vitamin D receptor (VDR) on the biological behavior of prostate cancer PC-3 cells.@*METHODS@#We constructed the VDR-shRNA lentiviral vector and determined the mRNA and protein expressions of VDR by RT-PCR and Western blot. Using scratch wound healing and Transwell chamber assays, we detected the changes in the migration and invasiveness of the PC-3 cells after silencing VDR.@*RESULTS@#The VDR-shRNA plasmid significantly interfered the VDR expression and successfully screened the cell lines with stable VDR-shRNA interference. The rate of scratch wound healing was markedly lower in the VDR interference group than in the blank control and LV3 negative control groups (59% vs 73.6% and 77.8%, P 0.05), and so was the count of permeable cells (P 0.05). The migration ability and invasiveness of the VDR-treated cells were remarkably decreased as compared with those of the control cells.@*CONCLUSIONS@#Down-regulated expression of the VDR gene may reduce the migration and invasiveness of prostate cancer cells.

The optimal element size, material property distributions and modeling methods for finite element modeling of lumbar vertebra / 医用生物力学

Objective To investigate the effects of element size and type, material property distributions of vertebral cancellous bone and simulation methods of cortical bone structure on the finite element (FE) results during the finite element modeling of lumbar vertebral body. Methods Based on QCT images of lumbar spine, 22 FE models of L2 without posterior structure were built by 6 element sizes (0.5, 1.0, 1.5, 2.0, 2.5, 3.0 mm), 2 heterogeneous material distribution methods of cancellous bone (300, 150) and 2 cortical bone modeling methods. The maximum displacement, strain energy, average stress and axial stiffness of these models were obtained to analyze and verify the results. Results When the element size was 0.5 mm, the axial stiffness of models with 10, 150 and 300 kinds of heterogeneous materials showed obvious differences; for the vertebral cancellous bone with 150 kinds of materials, the variation of average stress was not distinct under different element sizes; the average stress of the model using the outermost hexahedral elements to simulate the cortical bone structure was larger than that appending the skin to the outmost of the model. Conclusions It is more reasonable and effective to build the FE model of lumbar vertebral body with the method by 0.5 mm element size, 8-noded hexahedral elements, 150 kinds of heterogeneous materials, and using the outermost hexahedral elements to simulate the cortical bone structure. The research findings will lay a foundation for building subject-specific FE models of lumbar vertebral body on a large scale in future.

Liver tissue separation by medical water-jet scalpel and its mechanical property study / 医用生物力学

Objective To study mechanical properties of the medical water-jet scalpel when cutting parenchyma such as liver and verify its tissue-selective cutting characteristic. Methods The tension mechanical properties of porcine liver parenchyma and its vessels with different sizes were determined. Porcine and Wistar rat liver tissues were cut with arteriovenous vessels well reserved, and pathological section of the rats were analyzed by HE staining to explain the experimental phenomena. Results When the working pressure was set at 3 MPa, the incising and separating on the right lobe of porcine liver by medical water-jet scalpel in this experiment were done with minimal vessels of 0.8 mm in diameter left. Pathological sections from ordinary scalpel and medical water-jet scalpel showed that the medical water-jet scalpel caused smaller tissue damage. Conclusions The medical water-jet scalpel could cut heterogeneity soft tissue with highly-selective characteristics, which may effectively avoid the existing “one size fits all” phenomenon caused by ordinary scalpel.

Resting functional MRI with default mode-based functional connectivity analysis for localization of epileptic activity / 中华外科杂志

<p><b>OBJECTIVE</b>Using the functional connectivity analysis based on the underlying neurophysiological characteristic that epileptic discharges can induce change of brain default mode, to develop a technique for epileptogenic localization using functional MRI (fMRI) without simultaneous electroencephalography (EEG).</p><p><b>METHODS</b>A data-driven method that jointly employed independent component analysis and functional connectivity analysis was used for the resting functional MRI data analysis of 12 focal epileptic patients. The independent components were ranged according to the coefficients of the negative correlation between independent component time course and the signal temporal course in the region of posterior cingulate cortex. The results were comparatively studied with simultaneous EEG-fMRI.</p><p><b>RESULTS</b>In the 10 successful results from 12 patients underwent EEG-fMRI examination, the outcomes of eight subjects were concordant with pathological foci. While the results of all 10 patients processed by data-driven method were concordant with pathological foci, besides the other patients who failed to perform EEG-fMRI examination. Meanwhile, the default mode was well mapped in all patients.</p><p><b>CONCLUSIONS</b>The default mode-based functional connectivity analysis can localize the epileptogenic foci effectively without simultaneous EEG, besides to detect the default mode of epileptic patients.</p>

Effects of Huangqi on phagocytic activity of peritoneal macrophage of mice / 中国中药杂志

<p><b>OBJECTIVE</b>To study the effects of Huangqi decoction (HQD) on phagocytic activity of peritoneal macrophage of mice.</p><p><b>METHOD</b>One hundred Kunming mice, whose weight varied from 18 g to 22 g, were selected and divided into 10 groups randomly in eluding contrast group, groups conducted at different doses of HQD by ig, groups conducted in various ways of taking medicine, and groups conducted with comparative treat combining Huangqi and Dexamethasone. Mice in every group were taken medicine one time daily for 6 days.</p><p><b>RESULT</b>Among the groups treated at different doses of HQD, phagocytic rate and phagocytic index of mice, which were taken HQD by ig at high, middle, and low doses, were significantly higher (P < 0.01) than that of mice in contrast group, at the same time the effect in group with high dose was the best. Among the groups treated in various ways of taking medicine, phagocytic rate of the ip group was significantly better (P < 0.01) than that of the sc group and that of the ig group respectively, but there was not significant difference (P > 0.05) of phagocytic index among them. Among the groups combining Huangqi and Dexamethasone, Huangqi could antagonize the immunosuppressive effect of Dexamethasone obviously (P < 0.01).</p><p><b>CONCLUSION</b>HQD at different doses and with various ways of taking medicine could improve phagocytic activity of peritoneal macrophage of mice at different degree, and could antagonize the immunosuppressive effect of Dexamethasone.</p>

Detection of focal epileptic activity using combined simultaneous electroencephalogram-functional MRI / 中华放射学杂志

Objective To observe the brain activation of interictal epiletiform discharges(IEDs) and to localize the epileptogenic foci of epilepsy.Methods The electroencephalogram(EEG)and functional MRI data of 12 focal epileptic patients were acquired using a combination of EEG and functional MRI simultaneously.The IEDs onset time detected with EEG were set as the time parameters in an event- related paradigm of functional MRI analysis.The spatial and temporal characters of IEDs activation were analyzed in detail.In order to confirm the consistency of this method,all patients were scanned repeatedly and the results were correlated with clinical evaluation.Results Of the 12 patients,valid data from EEG- fMRI were obtained from 10 patients in a total of 18 sessions..Compared with the structural foci,the epileptic foci localization results of eleven sessions were good,five sessions were fairly good,and two sessions were poor.The results obtained from six patients in two separate sessions were concordant.respectively.Moreover,thalamic activation was detected in ten sessions,cerebellar activation was detected in all sessions,and the deactivation was found in the default mode loci in nine sessions. Conclusion The method of performing EEG and fMRI simultaneously can potentially be a useful tool in epilepsy research.