NLRP3 Inflammasome-Mediated Neuroinflammation and Related Mitochondrial Impairment in Parkinson's Disease / 神经科学通报·英文版

Parkinson's disease (PD) is a common neurodegenerative disorder caused by the loss of dopamine neurons in the substantia nigra and the formation of Lewy bodies, which are mainly composed of alpha-synuclein fibrils. Alpha-synuclein plays a vital role in the neuroinflammation mediated by the nucleotide-binding oligomerization domain-, leucine-rich repeat-, and pyrin domain-containing protein 3 (NLRP3) inflammasome in PD. A better understanding of the NLRP3 inflammasome-mediated neuroinflammation and the related mitochondrial impairment during PD progression may facilitate the development of promising therapies for PD. This review focuses on the molecular mechanisms underlying NLRP3 inflammasome activation, comprising priming and protein complex assembly, as well as the role of mitochondrial impairment and its subsequent inflammatory effects on the progression of neurodegeneration in PD. In addition, the therapeutic strategies targeting the NLRP3 inflammasome for PD treatment are discussed, including the inhibitors of NLRP3 inflammatory pathways, mitochondria-focused treatments, microRNAs, and other therapeutic compounds.

Exploring the mechanism of Marsdenia tenacissima in the treatment of hepatocellular carcinoma based on network pharmacology / 药学实践杂志

Objective To investigate the material basis and antitumor mechanism of Marsdenia tenacissima (MT) on hepatocellular carcinoma (HCC) by bioinformatics, network pharmacology and molecular docking technology. Methods Active ingredients of MT were collected by literature search and screened by Swiss ADME website, which targets were predicted by Swiss Target Prediction. The chip data of HCC (GSE147888) were downloaded from the NCBI Gene Expression Omnibus (GEO) database. Differentially expressed genes were screened by R software. HCC-related targets were collected from the Genecards and OMIM databases. The Venny online tool was used to obtain the intersection of the herbal medicine targets and the disease targets. Subsequently, drug-target network and protein–protein interaction (PPI) network were constructed by Cytoscape software and String platform. GO enrichment analysis and KEGG pathway analysis were performed to analysis the functions and pathways enriched by key genes. The expression of key genes in HCC and its effect on survival were analyzed by the GEPIA database. The Human Protein Atlas (HPA) was used to analyze the immunohistochemical expression of key genes in HCC. Finally, molecular docking was carried out to investigate interactions between the top five targets and their related active compounds. Results A total of 50 active components were screened and 12 common targets were identified related to MT and HCC. Scutellarein-4-Methylether, Tenasogenin, Sinapic Acid, Dresgenin and Kaempferol were considered as the critical components. JUN, MMP9 and PTGS2 were recognized as key therapeutic targets. The GO analyses demonstrated that key targets mainly involved in the process of gene silencing and inflammatory response. KEGG analysis suggested that key targets were enriched in TNF signaling pathway and IL-17 signaling pathway. Survival analysis by the GEPIA showed significant differences in the expression of ESR1, MMP1, MMP9, JUN, and PPARG between high and low risk groups. Immunohistochemical results showed that ESR1 and MMP9 were differentially expressed in normal and hepatocellular carcinoma tissues. The molecular docking results verified that the drug active ingredient could be stably bound to the target protein. Conclusion This study reflected the multi-component, multi-target and multi-pathway characteristics of the MT in the treatment of HCC, which could provide a scientific basis for the clinical application of MT in HCC.

Discussion on supine time of school-aged children with acute leukemia after first lumbar puncture / 中国实用护理杂志

Objective:To investigate the optimal lengths of supine position after first lumber puncture for school-aged children with acute leukemia.Methods:From January 2020 to December 2021, a total of 152 children with acute leukemia who underwent first lumbar puncture were randomly divided into 1h group, 2 h group, 3 h group and 4 h group, there were 38 cases in each group. The lengths of supine position after lumber puncture were 1 h, 2 h, 3 h and 4 h in the 1h group, 2 h group, 3 h group and 4 h group, respectively. The effects of different lengths of supine position on headache, low back pain, comfort and postoperative complications were observed.Results:Finally, 38 cases were enrolled in the 1 h group, 36 cases in the 2 h group, 38cases in the 3 h group and 34 cases in the 4 h group. The scores of low back pain, sleep comfort, lying position comfort, emotional comfort as well as the incidence of limb numbness in the 1 h group were (1.71 ± 0.56), (1.95 ± 0.87), (2.74 ± 1.06), (2.63 ± 0.79), 5.3%(2/38), in the 2 h group were (1.61 ± 0.27), (2.08 ± 0.81), (2.92 ± 1.34), (2.86 ± 0.80), 2.8%(1/36), which were significant lower than those of in the 3 h group (2.32 ± 1.12), (2.92 ± 1.34), (3.71 ± 1.11), (3.55 ± 1.25), 21.1%(8/38) and 4 h group(2.74 ± 1.42), (3.06 ± 1.37), (3.85 ± 1.50), (3.88 ± 0.81), 23.5%(8/34), F=6.81 to 14.06, χ2=10.84, all P<0.05. The amount of cerebrospinal fluid exudation in 1 h group was (0.33±0.09) g, which was significantly higher than that in 2 h group(0.27±0.08) g, 3 h group (0.27±0.10) g and 4 h group (0.24±0.09) g, the difference was significant ( F=5.82, P<0.05). The incidence of pressure injury in 1 h group, 2 h group and 3 h group were 0, 2.0%(1/36), 7.9%(3/38), which were significantly lower than that in the 4 h group 23.5%(8/34), χ2=15.39, P<0.05. There was no significant difference in pain scores among the 4 groups ( P>0.05). Conclusion:Two hours for supine position after first lumber puncture does not increase cerebrospinal fluid exudation in children with acute leukemia, and effectively alleviate low back pain, improve the comfort degree.

Effect of Williams life skills training on posttraumatic growth and care ability for parents of children with leukemia / 中国实用护理杂志

Objective:To explore the effect of Williams life skills training on posttraumatic growth and care ability for parents of children with leukemia.Methods:A total of 86 parents of children with leukemia were assigned to Children′s Hospital Affiliated to Nanjing Medical University from January to December 2019 who were devided into experimental group and control group according to the enrolled time, there were 43 cases in each group. The parents in the control group recieved routine nursing, the experimental group carried out 4-week Williams life skills training. The effect was assessed by Posttraumatic Growth Inventory (PTGI) and Family Caregiver Task Inventory (FCTI), respectively.Results:Finally, 41 cases were included in the experimental group and 40 cases in the control group. After intervention, the personal strength, relating to others, spiritual change scores and total scores in PTGI were (21.10 ± 4.47), (19.95 ± 6.18), (5.12 ± 0.95), (73.41 ± 8.37) points in the experimental group, significantly higher than (18.38 ± 4.50), (17.60 ± 3.30), (4.65 ± 1.05), (66.13 ± 6.31) points in the control group, the differences were statistically significant ( t values were 2.117-4.420, P<0.05 or 0.01). The disease cognitive ability, basic care skills, emotional management ability, ability to seek support scores and total scores in FCTI were (5.41 ± 1.76), (4.10 ± 1.09), (6.71 ± 1.12), (5.56 ± 1.16), (38.00 ± 3.92) points in the experimental group, significantly lower than (6.60 ± 1.58), (4.63 ± 1.10), (7.58 ± 1.74), (6.33 ± 1.53), (41.18 ± 4.72) points in the control group, the differences were statistically significant ( t values were 2.164-3.286, P<0.05 or 0.01). Conclusions:Williams life skills training can effectively promote posttraumatic growth and care ability in parents of children with leukemia.

Efficacy of Moxifloxacin against in Zebrafish Model / 生物医学与环境科学（英文）

Objective@#Moxifloxacin (MFX) shows good activity against and can be a possible antibiotic therapy to treat infection; however, other studies have shown a lower or no activity. We aimed to evaluate MFX activity against using zebrafish (ZF) model .@*Methods@#A formulation of labeled with CM-Dil was micro-injected into ZF. Survival curves were determined by recording dead ZF every day. ZF were lysed, and colony-forming units (CFUs) were enumerated. Bacteria dissemination and fluorescence intensity in ZF were analyzed. Inhibition rates of MFX and azithromycin (AZM, positive control) were determined and compared.@*Results@#Significantly increased survival rate was observed with different AZM concentrations. However, increasing MFX concentration did not result in a significant decrease in ZF survival curve. No significant differences in bacterial burdens by CFU loads were observed between AZM and MFX groups at various concentrations. Bacterial fluorescence intensity in ZF was significantly correlated with AZM concentration. However, with increasing MFX concentration, fluorescence intensity decreased slightly when observed under fluorescence microscope. Transferring rates at various concentrations were comparable between the MFX and AZM groups, with no significant difference.@*Conclusion@#MFX showed limited efficacy against using ZF model. Its activity needs to be confirmed.

Mesenchymal stem cells and immune disorders: from basic science to clinical transition / 医学前沿

As a promising candidate seed cell type in regenerative medicine, mesenchymal stem cells (MSCs) have attracted considerable attention. The unique capacity of MSCs to exert a regulatory effect on immunity in an autologous/allergenic manner makes them an attractive therapeutic cell type for immune disorders. In this review, we discussed the current knowledge of and advances in MSCs, including its basic biological properties, i.e., multilineage differentiation, secretome, and immunomodulation. Specifically, on the basis of our previous work, we proposed three new concepts of MSCs, i.e., "subtotipotent stem cell" hypothesis, MSC system, and "Yin and Yang" balance of MSC regulation, which may bring new insights into our understanding of MSCs. Furthermore, we analyzed data from the Clinical Trials database ( http://clinicaltrials.gov ) on registered clinical trials using MSCs to treat a variety of immune diseases, such as graft-versus-host disease, systemic lupus erythematosus, and multiple sclerosis. In addition, we highlighted MSC clinical trials in China and discussed the challenges and future directions in the field of MSC clinical application.

The relationship between military loyalty and both character strengths and psychological resilience / 解放军医学杂志

Objective: To explore the correlation between military loyalty and both character strengths and psychological resilience, and understand the influence of personality factor on military loyalty. Methods: The correlation between military loyalty, character strengths and psychological resilience can be found by correlation analysis. Hierarchical regression analysis explored the influence of demographic and personality factors on military loyalty. Analysis of mediating effect was conducted for finding the role that psychological resilience plays in character strengths mediating the military loyalty. Results: A total of 476 valid questionnaires were retrieved. Military personnel showed a significant positive correlation of character strengths and psychological resilience with loyalty (P=0.000); character strengths and psychological resilience had significant positive predictive effects on the loyalty of military personnel, of which character strengths had a positive predictive rate (β=0.42, P=0.000) for the loyalty of military personnel and explained 15.6% of the total variation in loyalty. The positive prediction rate (β=0.38, P=0.000) of military psychological resilience for loyalty explained 13.0% of the total variation of loyalty; psychological resilience not only has a significant positive predictive effect on the loyalty of military personnel, but also plays a partial mediating effect of character strengths on the loyalty of military personnel, with the mediating effect accounting for 29.3% of the total effect. Conclusion: Character strengths and psychological resilience can effectively and positively predict the loyalty of military personnel, while psychological resilience partially regulates the improvement of the loyalty of military personnel.

Effects of astaxanthin on the expression of NF-κB inflammatory signaling pathway related proteins in hippocampus of rats after acute carbon monoxide poisoning / 中华行为医学与脑科学杂志

Objective@#To investigate the effects of astaxanthin on neuronal injury in hippocampus of rats after acute carbon monoxide poisoning(ACMP) and the relationship with NF-κB inflammatory signaling pathway.@*Methods@#Male SD rats screened by water maze were randomly divided into three group(n=50): control group (NC group), CO poisoning group (COP group), CO poisoning+ astaxanthin group (AST group) . ACMP rat model was established by static inhaled exposure method. Meanwhile, rats in AST group were further given astaxanthin twice a day by gavage.At 1 day, 7 days, 14 days, 21 days and 28 days after CO poisoning (10 rats in each group were selected), the learning and memory abilities were evaluated by Morris water maze test. The pathological changes of the neurons in hippocampal CA1 region were observed by hematoxylin-eosin(HE) staining.The expression and activation of NF-κB in hippocampus were detected by immunoblotting and immunofluorescence, and the expression of TNF-α and IL-6 protein in hippocampus were examined by ELISA.@*Results@#Morris water maze test showed that there were no significant difference in escape latency and crossing platform times between the three groups (P>0.05). Compared with NC group, the escape latency of COP group was prolonged at 14, 21 and 28 days after CO poisoning (t=-6.04, -6.28, -8.18, all P<0.05), and the number of crossing platform was decreased (t= 5.96, 7.85, 6.51, all P<0.05). Compared with the COP group, the escape latency of the rats in AST group at the 14, 21 and 28 days was shortened (t=4.74, 4.82, 5.98, all P<0.05), and the number of crossing platform was increased (t=-3.72, -4.45, -6.53, all P<0.05). Compared with NC group, the number of NF-κ B positive cells in CA1 area of hippocampus in COP group increased at every time point (t=-8.62, -18.00, -16.67, -11.15, -6.22, all P<0.05); the number of NF-κ B positive cells in CA1 area in AST group decreased at 7 d, 14 d, 21 d and 28 d after CO poisoning, the difference was statistically significant (t= 6.55, 6.96, 4.40, 4.17; all P<0.05). Western blot showed that the changes of NF-κB protein was similar to that of immunofluorescence. After 7 days of CO poisoning, the level of NF-κB protein in hippocampus of COP group was (1.44±0.08), it was higher than that of NC group (t=-20.07, P<0.05), while that of AST group was (0.68±0.10), it was lower than that of COP group (t=10.23, P<0.05). The results of Elisa showed that TNF-α and IL-6 in the hippocampus of COP group were higher than those of NC group at every time point(all P<0.05), while compared with COP group, TNF-α and IL-6 in AST group were lower (all P<0.05). After 7 days of CO poisoning, TNF -α in COP group ((39.04±5.29) pg/ml)was higher than that in NC group ((14.13±2.12) pg/ml) (t=-7.58, P<0.05); TNF -α in AST group ((25.77±3.31) pg/ml) was lower than that in COP group (t=3.69, P<0.05). After 7 days of CO poisoning, the level of IL-6 in COP group ((181.79±9.12) pg/ml)was higher than that in NC group ((73.12±11.04) pg/ml) (t=-8.24, P<0.05), and the level of IL-6 in AST group ((121.47±9.80) pg/ml) was lower than that in COP group (t=7.80, P<0.05).@*Conclusion@#The excessive inflammatory response which mediated by NF-κB signaling pathway is involved in ACMP-induced neuronal damage in hippocampus.Astaxanthin can down-regulate the expression of NF-κB inflammatory signaling pathway related proteins, and pave a way for the treatment of ACMP brain damage and cognitive dysfunction.

Resveratrol inhibited hepatic granulama in mice with schistosomiasis by modulating Thl7 and treg responses / 中国药理学通报

Aim To observe the anli-granuloma of resveratrol in mice with schistosomiasis japonica and its effect on Thl7 and Treg responses. Methods Forty- five mice infected with S. japonieum cercariae for three weeks were randomly divided into three groups named as infected group ( A ) , resveratrol group ( H ) and praziquantel group ( C). Fifteen normal mice were taken as normal control group (D). At the 9th week post-infection, the granuloma of the liver tissues was observed using HE staining, and the number of neutrophils was calculated. IL-17A, CXCL1, CXCL2, Foxp3 levels in liver tissues were delected by RT-PCR. Thl 7 and Treg responses in spleen were determined by FCM respectively. Splenocytes from healthy mice were stimulated by PBS and SEA respectively. After SEA stimulation, resveratrol and praziquantel were added respectively, and Thl7 and Treg responses were detec ted by FCM. Results Compared to group A, the granuloma was alleviated ( P < 0. 01 ) , the number of neutrophils in single granuloma was reduced ( P < 0.01), Thl7 response significantly decreased (P < 0. 05) and Treg response increased markedly in group B ( P <0.05). The hepatic expression of IL-17A, CXCL1 , CXCL2 levels in group B was lower than that of group A (P< 0.05), and Foxp3 level in group B were higher than in group A(P <0. 01 ). In vitro, resveratrol inhibited the differentiation of Thl7 cells (P < 0. 05 ) and enhanced that of Treg cells after SEA treatment ( P < 0. 05 ). Conclusion Resveratrol inhibits the heptic granulomatous response through down-rcgu- lating Thl7 res()onse and up-regulating Treg response in mice with schistosomiasis.

Quercetin inhibits proliferation of human cervical carcinoma HeLa cells through affecting tryptophan metabolism / 中国药理学通报

Aim To investigate the mechanism of inhibition on the proliferation of human cervical carcinoma HeLa cells by quercetin.Methods Cell proliferation was detected by CCK-8 method.Flow cytometry was used to detect the cell cycle changes.OD480 values which reflected the metabolism of tryptophan and the production of kynurenine were measured by UV-Vis spectrophotometer.The mRNA levels of IDO1 were detected by qPCR.The expression and purification of IDO1 protein were detected by Western blot.Enzyme activity reaction was performed in vitro,and the content changes of tryptophan and kynurenine were detected by HPLC.Results Quercetin inhibited the proliferation of HeLa cells and led to cell cycle arrest.Quercetin inhibited the metabolism of tryptophan.Quercetin significantly inhibited the enzymatic activity of IDO1 in vitro,but did not affect the expression of IDO1.The addition of kynurenine could reverse the inhibition of cell proliferation induced by quercetin.Conclusion Quercetin affects tryptophan metabolism through inhibiting the enzymatic activity of IDO1.This may be one of the mechanisms by which quercetin exerts its effect on the proliferation of HeLa cells.

Relationship between High-risk HPV Infection and Cervical Lsesions in Cervical Cancer Opportunistic Screening / 实用妇产科杂志

Objective:To analyze the infection rate of high-risk HPV(hr-HPV) and its relationship with cervical intraepithelial neoplasms in cervical cancer screening population.Methods:The positive rate of HPV 16,18 and other 12 kinds of HPV subtypes from 2015.Jun to 2016 Nov was calculated and the infection rate in CIN Ⅱ+ population were analysed.Results:In the cervical cancer screening population,the total HPV positive rate was 19.0％,the positive rate of HPV 16,HPV 18 and other 12 kinds of HPV were 5.0％,1.6％ and 15.2％ respectively The risk to develop CIN Ⅱ + in HPV 16,HPV 18 and 12 other hr-HPV positive TCT ASCUS/LSlL population was 55.2％,35.5％ and 38.9％ respectively The risk to develop CIN Ⅲ+ was 25.3％,7.7％ and 6.9％ in HPV 16,HPV 18 and other 12 kinds of hr-HPV positive TCT ASCUS/LSIL population respectively In the CIN Ⅱ + population,45.0％ cases were 12 other hr-HPV positive while 46.3％ were HPV 16 positive and the positive rate of HPV 18 was 8.7％.Conclusions:In the cervical cancer screening population,the rate of HPV 18 positive was low,the rate of other 12 kinds of HPV positive was high.It's necessary to establish exact classification for the positive rate of each subtype.hr-HPV genotyping plays an important role in cervical cancer screening.In the referral to colposcope population,the rate of HPV 18 positive was low,the TCT results showed ASCUS/LSIL risk of HPV 18 positive and other 12 kinds of HPV positive was low.Consider using shunt detection to improve screening specificity.

Exosome extracted from hAMSCspromotes neurological function recovery after traumatic brain injury in rats / 基础医学与临床

Objective To investigate the therapeutic effect of exosomes extracted from human adipose-derived mesenchymal stem cells(hAMSCs) on traumatic brain injury (TBI) and its possible mechanism.Methods Mesenchymal stem cells(MSCs) were isolated from healthy human adipose tissue and the exosomes were extracted by ultrafiltration.Rats were divided into four groups: sham group, PBS control group, MSCs treatment group and exosomes treatment group.24 h After TBI, the treatment group was locally injected along the lesion area, 30 μL of PBS, 2×105 MSC, 25 μg protein of exosomes respectively, the total volume was 30 μL.We performed the Modified Neurological Severity Score(mNSS) and the forelimb Foot-Fault Test in all rats before injury and at 1, 3, 7, 10, 13, 16, 21 and 30 days after TBI.The rats were sacrificed at 3 and 7 days after TBI respectively,total RNA was extracted from rat brain tissue.The expression of TNF-α and IL-1β were detected by quantitative PCR.The rats were also killed at 30 days after TBI for testing the neuronal apoptosis in lesion area by tunel-neun double imm-unofluorescence.Results Exosomes treatment significantly promotes the recovery of neurological deficits caused by TBI,and the therapeutic effect is similar to MSCs, its possible mechanism may be the inhibition of the acute inflammation and the reducing of the neurons apoptosis after TBI.Conclusions Exosomes extracted from human adipose-derived mesenchymal stem cellshas promoted neurological functionrecovery after traumatic brain injury, which will provide a new and safer TBI treatment for clinical practice.

Isolating culture of adipose mesenchymal stem cells in psoriasis vulgaris patients and differentiation into immune regulation function / 基础医学与临床

Objeetive To study the differences of the biological characteristics and immune regulation function of adipose mesenchymal stem cells (AMSCs)from psoriasis patients and healthy people.Methods AMSCs were isolated and cultured from human psoriatic and healthy adipose tissue,the phenotypes and cell cycle of AMSCs taken from three generation were detected by flow eytometry.Alkaline phosphate enzyme staining and oil red o staining were used respectively to identify their adipogenic and osteogenic capacity.Next,the levels of inflammation antimicrobial proinflammatory factor were detected by PCR and ELISA.Then gene expression profile of AMSCs were screen by gene expression profile chip,as so to bolting the the gene array related with immunology gene.Results There was no significant change in cell morphology,and cell surface markers were expressed high for CD29,CD44,CD73,while lower for CD31,CD45 and HLA-DR.AMSCs of psoriasis patients and healthy people both had the ability of adipogenic and osteogenic differentiation.But the cell cycle showed the third generation AMSCs proliferation rates were slower than that of normal control,as compared with healthy controls,adipogenic differentiation ability was stronger.What'more,the level of inflammatory cytokines in psoriasis group was lower than that in controls such asIL-10,IDO,TGF-β,on the contrary the levels of proinflammatory factor in psoriasis group were higher than that in controls,such as TNF-α,IFN-γ.In addition,gene chip results suggested that psoriasis group AMSCs had obvious expression differences on JAK-STAT pathway with healthy controls.Conclusions Compared with the control,there are significant differences in patients AMSCs proliferation and adipogenic differentiation ability,immune inflammation suppression control ability is weaken,this phenomenon may be associated with JAK-STAT immune pathways related to downgrade.

Study on Myelopoietic Functions of miR-191 by Using Zebrafish Model / 中国实验血液学杂志

<p><b>OBJECTIVES</b>To establish a method of gene analysis via zebrafish model to explore the effect of microRNA-191(miR-191) on myelopoiesis.</p><p><b>METHODS</b>The hsa-miR-191 or cel-miR-67 was microinjected into the fertilized eggs of zebrafish, then the total RNA of embryos was extracted at 10 s, 24, 36 and 48 hpf for qRT-PCR to detect the expression levels of erythroid and granulocytic genes. Then embryos at the time-point of 24 hpf were collected for whole mount in situ hybridization to detect spatiotemporal expression of those genes.</p><p><b>RESULTS</b>The antisense RNA probes with high sensitivity and specificity of erythroid genes (gata 1, scl, hbbe 3, lmo 2) and myelomonocytic genes (pu.1, L-plastin, mpx, cebpα) in zebrafish were obtained by molecular cloning and T7 RNA polymerase reaction; the expression levels of the erythroid and myelomonocytic genes of zebrafish microinjected with miR-191 mimics displayed higher than those in control group at the time-points of 24 hpf and 36 hpf. The spatiotemporal expression level of L-plastin at the time-point of 24 hpf was up-regulated, and the other genes were not significantly changed. It was worth mentioning that the mRNA expression level of mpx was significantly up-regulated by 10-20 times at the time-point of 10 s.</p><p><b>CONCLUSION</b>The genetic analysis method of embryonic myeloid differentiation has been set up via zebrafish. Preliminary analysis of regulation in zebrafish myelopoiesis shows that miR-191 may be involved in the regulation of erythroid and myelomonocytic differentiation. The mechanism and corresponding function of mpx regulated by the other factors need to be further studied.</p>

Effect of Human Hepatocellular Carcinoma HepG2 Cell-derived Exosome on the Differentiation of Mesenchymal Stem Cells and Their Interaction / 中国医学科学院学报

Objective To investigate the effect of human hepatocellular carcinoma HepG2 cell-derived Exosome on the differentiation of mesenchymal stem cells(MSC)into cancer-associated myofibroblasts(CAF)and the impacts of CAF on liver cancer cell proliferation,migration,and invasion. Methods The protein expression of HepG2 cell-derived Exosome was detected by Western blotting. MSCs were separated from human adipose tissue and cultured with HepG2 cell-derived Exosome(100 ng/nl)to initiate differentiation. The expressions of mesenchymal markers and several interleukins were also detected by Western blotting. HepG2 cells were co-cultured with the conditioned media(CM),in which HepG2 Exosome induced the differentiation of MSC into CAF. The expressions of epithelial and mesenchymal markers were detected by real-time polymerase chain reaction(PCR)and Western blotting. Cell proliferation was assessed using MTS assay. Transwell chambers were used in the in vitro migration and invasion assay. Results HepG2 cell-derived particles expressed CD63,70 kilodalton heat shock proteins,and 90 kilodalton heat shock proteins. With the treatment of HepG2 cell-derived Exosome,the expressions of mesenchymal marker α-smooth muscle actin,fibroblast activation protein α,interleukin(IL)-6,IL-8,and IL-1β were up-regulated,while vascular endothelial growth factor had no significant change. The conditioned media which HepG2 Exosome induced MSC differentiation CAF(CAF-CM)could significantly promote HepG2 cells proliferation(1.075±0.104),compared to BSA control(0.874±0.066,P=0.023)and MSC-CM(0.649±0.034,P=0.0005). CAF-CM could significantly enhance cell migration [(42.5±9.1) cells vs.(18.5±3.1) cells,P=0.001] and invasion [(29.0±3.5) cells vs.(13.1±3.7) cells,P=0.009] compared to its control group. Moreover the conditioned medium which HepG2 Exosome induced MSC to differentiate into CAF could also promote the expressions of mesenchyme-related genes Smad interacting protein 1(P=0.040),β-catenin(P=0.038),fibronectin(P=0.029),and Vimentin(P=0.013)and inhibit the expression of epithelial related genes zonula ocdudens-1(P=0.010).Conclusions Exosome extracted from HepG2 cells can induce human adipose-derived MSC to differentiate into cancer-associated myofibroblasts. CAF-like cells can promote the migration of the liver cancer cell line HepG2.

Prevalence and Risk Factors Associated with Adverse Drug Reactions among Previously Treated Tuberculosis Patients in China / 生物医学与环境科学（英文）

We assessed the incidence of adverse drug reactions (ADRs) with anti-TB medications and evaluated the risk factors for developing ADRs in previously treated tuberculosis patients in China. All patients received the first-line anti-TB regimen (2HREZS/6HRE) as recommended by the national guidelines. Clinical and laboratory evaluations were performed once a month. Out of the 354 participants, 262 (74.0%) experienced ADRs such as hyperuricemia (65.0%, 230/354), hepatotoxicity (6.2%, 22/354) and hearing disturbances (4.8%, 17/354). ADRs were significantly associated with diabetes mellitus [OR (95% CI): 15.5 (2.07-115.87)]; however, weight more than 50 kg [OR (95% CI): 0.41 (0.22-0.85)] was a protective factor for occurrence of ADRs. Hyperuricemia is the most common adverse event but, most patients with hyperuricemia showed increased tolerance for high uric acid levels. Low body weight and diabetes mellitus increased the risk of the occurrence of ADRs during anti-TB treatment.

Application of MOAS for Evaluating of Violence Risk in the Inpatients with Mental Disorders / 法医学杂志

OBJECTIVES@#To explore the value of Modified Overt Aggression Scale （MOAS） on predicting serious aggressive behavior in the inpatients with mental disorders and to provide theoretical basis for violence risk assessments in the inpatients with mental disorders.@*METHODS@#Total 918 inpatients in a psychiatric hospital were evaluated by trained medical workers using MOAS in September 2009, and their serious violent behavior were followed up for 2 years. The value of MOAS on predicting violence in the inpatients with mental disorders was analyzed by SPSS 21.0.@*RESULTS@#（1） Compared to the patients without serious aggressive behaviors, the patients with serious aggressive behavior within 2 years showed significantly higher scores （P＜0.05） on verbal aggression, aggression against property, physical aggression and total weighted score of MOAS; （2） Significant correlation was found between the score of verbal aggression and the serious acts of violence within 2 years （P＜0.05）; （3） Scores of verbal aggression, physical aggression and total weighted score of MOAS had predictive value on serious aggressive behaviors within 2 years.@*CONCLUSIONS@#MOAS has certain value on predicting the serious aggressive behaviors of patients with mental disorders within 2 years.

Protection of Nerve Injury with Exosome Extracted from Mesenchymal Stem Cell / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the protective effect of Exosomes from human adipose-derived mesenchymal stem cells (hAMSCs) in neural injury induced by glutamate and its possible mechanism.</p><p><b>METHODS</b>Characteristics of Exosomes from hAMSCs were identified by electron microscopy and Western blot analysis. Cytokines that might play a major role in the protective effect were tested by enzyme-linked immunosorbent assay (ELISA). The protective action of Exosome and its possible signaling pathway were researched by the in vitro neural injury induced by glutamate, including control group (without Glu), Glu group (dealing with Glu), Glu+Exo group (dealing with Glu +100 ng/ml Exo), Glu+Exo+Akt group (dealing with Glu+100 ng/ml Exo+10 μmol/L Akt), Glu+Exo+Erk group (dealing with 100 ng/ml Glu+100 ng/ml Exo+10 μmol/L Erk), and Glu+Exo+TrkB group (dealing with Glu+100 ng/ml Exo +10 μmol/L TrkB).</p><p><b>RESULTS</b>Exosomes from hAMSCs had similar sizes to those isolated from other kinds of cells, and expressed the characteristic proteins such as CD63, CD81, HSP70, and HSP90. Cytokines that had neurotrophic effects on Exosomes were mainly insulin-like growth factor and hepatocyte growth factor, with the concentration being 9336.49±258.63 and 58,645.50±16,014.62, respectively; brain derived neurotrophic factor, nerve growth factor,and vascular endothelial growth factor had lower levels, with the concentration being 1928.25±385.47, 1136.94±5.99, and 33.34±9.43, respectively. MTS assay showed that the PC12 cell survival rates were 0.842±0.047, 0.306±0.024, 0.566±0.026, 0.461±0.016, 0.497±0.003, and 0.515±0.034 in the control group, Glu group, Glu+Exo group, Glu+Exo+Akt group, Glu+Exo+Erk group, and Glu+Exo+TrkB group; obviously, it was significantly lower in Glu group than in control group (P=0.02), significantly higher in Glu+Exo group than in Glu group (P=0.01), and significantly lower in Glu+Exo+Akt group than in Glu+Exo group (P=0.01).</p><p><b>CONCLUSION</b>Exosomes secreted from hAMSCs have protective effect against neuron damage induced by glutamate, which may be mediated through activating the PI3/K-Akt signalling pathway.</p>

Puerarin extraction and identification of solution wine to protect liver function in mice / 局解手术学杂志

Objective Pueraria extract puerarin,HPLC assay puerarin extract and compare different doses of correlation with the hang-over effect of puerarin evaluate different doses of puerarin liver hangover effect. Methods Extracted under optimal conditions obtained in the previous experiment puerarin spare,HPLC method for qualitative and quantitative detection of alcohol extract of kudzu root ( PRE) ,the male Kunming mice were randomly divided into control group,positive control group and puerarin group,each group of 10. Give mice fed pueraria extract,30 min after administration of liquor,drunk mice sobering observation time and the determination of mouse liver ADH,GOT,GPT con-tent in order to investigate the effect of puerarin on drunken mice. Results HPLC fraction was measured at 8 times the volume of 70% etha-nol,60 ℃ constant temperature water bath shaker at 30 min for optimal extraction conditions puerarin extraction. Compared with the positive control groups:low,medium and high doses of alcohol extract of pueraria can significantly shorten the time to sober up drunken mice,the dose of PRE could effectively inhibit the absorption of alcohol,reduce liver tissue ADH,GOT,GPT,the effects of high doses of PRE absorption of alcohol was small. Conclusion HPLC method capable of puerarin extract the qualitative and quantitative determination of puerarin on liver injury caused by acute alcoholism a protective regulatory role,and the hangover effect of puerarin dose showed a good positive correlation.

Lipopolysaccharide, TNFα, IL-6, dexamethasone, and insulin increase the expression of GPR54 in the MCF7 breasr cancer cell line / 中华男科学杂志

<p><b>OBJECTIVE</b>To investigate the effects of different concentrations of lipopolysaccharide (LPS), tumor necrosis factor α (TNFα), interleukin-6 (IL-6), dexamethasone (Dex), and insulin on the mRNA and protein expressions of GPR54 in the MCF7 cell line in vitro.</p><p><b>METHODS</b>MCF7 breasr cancer cells were cultured and treated with different concentrations of LPS (10 and 20 µg/ml), TNFα (20 and 100 ng/ml), IL-6 (10 and 20 ng/ml), Dex (10(-6) and 10(-7) mol/L), and insulin (0.01 and 0.1 IU/L). Those treated with culture fluid only served as controls. The mRNA and protein expressions of GPR54 were measured by real-time PCR and Western blot, respectively, after 6, 24, 48, and 72 hours of treatment.</p><p><b>RESULTS</b>Compared with the blank con- trol, LPS (10 and 20 µg/ml), TNFα (20 and 100 ng/ml), IL-6 (10 and 20 ng/ml), Dex (10(-6) and 10(-7) mol/L), and insulin (0.01 and 0.1 IU/L) significantly increased the expressions of GPR54 mRNA (P < 0.05) and protein (P < 0.05).</p><p><b>CONCLUSION</b>LPS, TNFα, IL-6, Dex, and insulin evidently increase the expression of GPR54 in the MCF7 cell line, indicating their influence on the function of gonads by regulating the GPR54 level.</p>