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BACKGROUND: Exosomes are nano-scale vesicles that can be secreted by almost all types of cells in the body, which can participate in multiple cell signaling pathways by transporting signal molecules, such as proteins, lipids and miRNAs to perform intercellular communication, immune responses, and antigen presentation. Therefore, exosomes have a great value in the clinical diagnosis and treatment of diseases. Of the cell types known to produce exosomes, mesenchymal stem cells are currently the most prolific producer closely related to the occurrence and development of neurodegenerative diseases. OBJECTIVE: To review the origin and biological characteristics of mesenchymal stem cell-derived exosomes, the isolation and identification methods of exosomes, and the progress of mesenchymal stem cell-derived exosomes in the treatment of neurodegenerative diseases. METHODS: The literature search was performed in PubMed and CNKI databases, and the keywords were "mesenchymal stem cells; exosomes; MSC-exosomes; neurodegenerative diseases" in Chinese and English, respectively. RESULTS AND CONCLUSION: A total of 61 eligible literatures were enrolled. Mesenchymal stem cell-derived exosomes have low immunogenicity and long-circulating half-life and can carry small molecular substances across the blood-brain barrier, which can promote nerve cell growth and neuronal differentiation. Mesenchymal stem cell-derived exosomes help damaged nervous system function and enhance vascular neurogenesis, which is becoming an emerging treatment for neurodegenerative diseases.
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BACKGROUND: Exosomes are nano-scale vesicles that can be secreted by almost all types of cells in the body, which can participate in multiple cell signaling pathways by transporting signal molecules, such as proteins, lipids and miRNAs to perform intercellular communication, immune responses, and antigen presentation. Therefore, exosomes have a great value in the clinical diagnosis and treatment of diseases. Of the cell types known to produce exosomes, mesenchymal stem cells are currently the most prolific producer closely related to the occurrence and development of neurodegenerative diseases. OBJECTIVE: To review the origin and biological characteristics of mesenchymal stem cell-derived exosomes, the isolation and identification methods of exosomes, and the progress of mesenchymal stem cell-derived exosomes in the treatment of neurodegenerative diseases. METHODS: The literature search was performed in PubMed and CNKI databases, and the keywords were "mesenchymal stem cells; exosomes; MSC-exosomes; neurodegenerative diseases" in Chinese and English, respectively. RESULTS AND CONCLUSION: A total of 61 eligible literatures were enrolled. Mesenchymal stem cell-derived exosomes have low immunogenicity and long-circulating half-life and can carry small molecular substances across the blood-brain barrier, which can promote nerve cell growth and neuronal differentiation. Mesenchymal stem cell-derived exosomes help damaged nervous system function and enhance vascular neurogenesis, which is becoming an emerging treatment for neurodegenerative diseases.
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Objective@#To investigate the clinical effect and safety of entecavir (ETV) versus tenofovir disoproxil fumarate (TDF) in the treatment of previously untreated HBeAg-positive chronic hepatitis B (CHB) patients with a high viral load.@*Methods@#A retrospective analysis was performed for the clinical data of 152 HBeAg-positive CHB patients with a high viral load (HBV DNA≥106 IU/ml) who were firstly treated with ETV (ETV group) or TDF (TDF group), with 76 patients in each group. The serum levels of alanine aminotransferase (ALT), HBV DNA, HBeAg, anti-HBe, creatinine, and creatine kinase were measured at baseline, and the patients were followed up and evaluated at weeks 4, 12, 24, 36, 48, 60, 72, 84, and 96 of treatment. The Kaplan-Meier survival curves were used to analyze cumulative complete virologic response, HBeAg seroconversion, and ALT normalization rate. The Cox proportional hazards regression model was used to identify the influencing factors for virologic response. P < 0.05 was considered statistically significant.@*Results@#There were no significant differences in ALT normalization rate between the ETV group and the TDF group at weeks 4, 12, 24, 48, 72, and 96 of treatment (18.1%/55.6%/83.3%/90.3%/93.1%/97.2% vs 16.0%/53.6%/75.4%/94.2%/100%/100%, P > 0.05). There were also no significant differences in virologic response rate between the ETV group and the TDF group at weeks 48 and 96 of treatment (89.5%/97.3% vs 93.4%/98.7%, P > 0.05). The multivariate analysis showed that the baseline parameters were not predictive factors for virologic response. At week 48 of treatment, the TDF group had a significantly higher HBeAg seroconversion rate than the ETV group (14.5% vs 3.9%, P = 0.048); at week 96 of treatment, there was no significant difference in HBeAg seroconversion rate between the two groups (15.8% vs 7.9%, P = 0.132). The Kaplan-Meier survival analysis showed that there were no significant differences between the two groups in cumulative ALT normalization rate, cumulative HBV DNA undetectable rate, and cumulative seroconversion rate. Only one patient in the ETV group experienced virologic breakthrough from weeks 60 to 72 of treatment, and there were no serious adverse reactions.@*Conclusion@#TDF and ETV had similar clinical effects, HBeAg seroconversion rate, and safety in previously untreated HBeAg-positive CHB patients with a high viral load.
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OBJECTIVE:To optimize the ultrasonic extraction technology for Tianshu capsules. METHODS:Using the transfer rate of active ingredient ferulic acid in Ligusticum chuanxiong and gastrodin in Gastrodia elata of Tianshu capsules as investigation indexes,L9(34)orthogonal design test was adopted to investigate the effects of ethanol volume fraction,ethanol amount,extraction time and ultrasonic power on the extraction rate. Ultrasonic extraction technology for Tianshu capsules was optimized,and verifica-tion test was carried out. RESULTS:The optimized extraction technology for Tianshu capsules was as follow as 8-fold 70% etha-nol,extracting twice under 350 W,extracting 1.5 h every time. Results of verification test showed the average transfer rate was 94.06% for ferulic acid(RSD=0.18%,n=3)and 95.02% for gastrodin(0.47%,n=3). CONCLUSIONS:The optimized tech-nology is rapid,simple,stable and feasible,and can be used for extracting the active ingredients in Tianshu capsules.
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[Objective]To study the association between the polymorphisms in the promoter region of Osteopontin(OPN)with hepatitis B virus(HBV)-related HCC.[Methods]A total of 225 cases diagnosed with hepatitis B virus(HBV)-related HCC and 200 age-matched patients with HBV infection without HCC were collected. Three polymorphisms(-156delG/G,-443T/C and-616T/G)in the Osteopontin promoter were genotyped using direct sequencing.[Results]The frequency of-156delG/delG genotype in the HCC group was higher than that of in the control group (P = 0.003). There was a significantly increased frequency of the allele-156delG(P<0.001)in HCC patients. Logistic regression analysis was performed to show an increase HCC risk associated with the delG variant genotype(OR1.64;95%CI 1.25~2.16). There were no differences between the groups in the genotype distributions and allele frequencies of SNP-443T/C and-616T/G.[Conclusion]Our findings suggest that allele-156delG in the Osteopontin promoter may be a marker for risk of HCC with HBV infection in Chinese Han population.
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<p><b>OBJECTIVE</b>To investigate the dynamic changes in serum levels of hepatitis B surface antigen (HBsAg) and their relation to hepatic parenchyma cell volume (hepatic cell quantity) at different grades of liver inflammation and stages of hepatic fibrosis in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B.</p><p><b>METHODS</b>Serum HBsAg levels were detected by electrochemilumineseence. Serum HBsAg levels were apportioned according to the hepatic parenchyma cell volume and compared among liver histological inflammation grade (1, 2, 3 and 4) and hepatic fibrosis stage ( I, II, III and IV), respectively.</p><p><b>RESULTS</b>The levels of serum HBsAg among the four liver histological inflammation grades were:1:6,036.4+/-2,729.4 COI/ml; 2:6,704.6+/-2,457.5 COI/ml; 3:6,332.2+/-2,409.0 COI/ml; 4:6,226.2+/-2,716.0 COI/ml. There were no differences among the groups before apportion (Fbefore apportion=0.564, P=0.640).Serum HBsAg levels apportioned by the hepatic parenchyma cell volume among liver histological inflammation grades were:1:9,174.8+/-4,142.0 COI/ml; 2:10,743.1+/-3,950.3 COI/ml; 3:11,078.0+/-4 230.0COI/ml; 4:11,540.5+/-5,058.8 COI/ml. There were significant differences among the groups after apportion (Fafter apportion =27.354, P<0.001). Serum HBsAg levels among hepatic fibrosis stages were: I: 6,222.1+/-2,665.4 COI/mL; II: 6,706.8+/-2,623.8 COI/ml; III:6 004.5+/-2,625.5 COI/ml; IV:6,455.6+/-2,344.4 COI/ml. There were no differences among groups before apportion (Fbefore apportion=0.768, P=0.513).Serum HBsAg levels apportioned by the hepatic parenchyma cell volume (hepatic cell quantity) among hepatic fibrosis stages were: I :9 417.5+/-4,034.2 COI/ml; II :10,093.3+/-4,183.4 COI/ml; III:10,177.1+/-4,445.0 COI/ml; IV:12,166.6+/-4,418.5 COI/ml. There were significant differences among the groups after apportion (Fafter apportion=57.077, P<0.001).</p><p><b>CONCLUSION</b>Serum HBsAg levels apportioned by the same hepatic parenchyma cell volume (hepatic cell quantity), rather than serum HBsAg levels, increased with hepatic pathological progress.</p>
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Humans , Hepatitis B , Hepatitis B Surface Antigens , Hepatitis B e Antigens , Hepatitis B virus , Hepatocytes , Inflammation , Liver CirrhosisABSTRACT
Objective To investigate the expression of p73 gene and its protein and their relation with clinicopathologic features in nasopharyngeal carcinoma (NPC) tissues.Methods Expression of p73 mRNA and protein in 52 NPC and 25 normal nasopharyngeal tissues was detected by real-time fluorescent quantitative PCR and immunohistochemistry.Results Expression of p73 mRNA and protein was significantly higher in NPC than that in normal nasopharyngeal tissues (mRNA:73.1％ vs 24.0 ％,protein:71.2 ％ vs 36.0 ％),there were significant statistical differences between the two groups (P ＜ 0.05),and their expression was closely related to tumor invasion depth,degree of differentiation and clinical stage (P ＜ 0.05).Expression of p73 gene and protein was not closely related to age and gender (P ＞ 0.05).Conclusion Detection expression of p73 mRNA and its protein can be helpful in the diagnosis and prognostic evaluation in NPC.
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<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B (CHB) after failure of nucleoside-analogues (NAs).</p><p><b>METHODS</b>A total of 30 CHB patients who had been previously treated with NAs and had subsequently completed a 48-week course of TDF were retrospectively investigated. Patients' data of HBV DNA level (log10 copies/ml) and rate of undetectable HBV DNA at treatment weeks 0 (baseline), 4, 12, 24, 36 and 48 were collected for evaluation. The lower limit of HBV DNA detection was 100 IU/ml. The serum alanine aminotransferase (ALT) normalization rate, hepatitis B e antigen (HBeAg) seroconversion rate, viral breakthrough (VBT) rate, viral response (VR) rate, and adverse events were determined upon treatment completion. Statistical analyses were carried out using the Student's t-test, the x² test or the Kaplan-Meier method.</p><p><b>RESULTS</b>Over the 48-week treatment period, HBV DNA levels declined significantly from baseline (week 4:(2.11 ± 0.38) log10 IU/ml, t =5.582; week 12:(0.93 ± 0.31) log10 IU/ ml, t =9.303; week 24:(0.75 ± 0.20) log10 IU/ml, t =3.123; week 36:(0.16 ± 0.19) log10 IU/ml, t =10.759; week 48:(0.14 ± 0.25) log10 IU/ml, t =12.202) (all P less than 0.01). However, the rates of HBV DNA reduction and of cumulative reduction were comparable at weeks 24, 36 and 48 (all P more than 0.05). The most robust decline in HBV DNA levels was observed at week 4 ((2.11 ± 0.38) log10 IU/ml) and the highest cumulative HBV DNA reduction was observed at week 24 ((3.79 ± 0.37) log10 IU/ml). The rate of undetectable HBV DNA at week 4 (26.7%) was significantly lower than that at weeks 24 (87.5%, P less than 0.01), 36 (80.0%, P=0.007), and 48 (88.9%, P=0.001). The median time to achieving undetectable HBV DNA was 10.4 weeks (range:3.43-34.0 weeks). At week 48, the rates of VR, HBeAg seroconversion, and VBT were 88.9% ,6.7%, and 0% respectively. During treatment, the levels of creatine kinase were more than two times the upper limit normal in 9.2% of the patients, and were comparable at each time point examined (all P more than 0.05). All patients showed a normal level of serum creatinine throughout the treatment period.</p><p><b>CONCLUSION</b>For CHB patients with non-response to NAs, TDF can suppress HBV DNA replication very quickly and achieve a high rate of ALT normalization with a low rate of adverse events.</p>
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Adult , Female , Humans , Male , Middle Aged , Young Adult , Adenine , Therapeutic Uses , Antiviral Agents , Therapeutic Uses , DNA, Viral , Blood , Hepatitis B e Antigens , Blood , Hepatitis B, Chronic , Drug Therapy , Organophosphonates , Therapeutic Uses , Retrospective Studies , TenofovirABSTRACT
Objective: The present study aimed to isolate and characterize a cancer stem cell-like sphere-forming cell subpopula-tion. Methods: By using a spheroid culture stem cell-conditioned medium, we isolated a subgroup of cancer stem-like cells from naso-pharyngeal cancer cell lines. Chemotherapy resistance was analyzed by using methyl thiazolyl tetrazolium, and clone-forming capabili-ty was determined by using softer agar clone formation assay. Finally, we verified the expression of the stemness-specific gene andβ-catenin by using immunocytochemistry staining and RT-PCR. Results: The lower-differentiated nasopharyngeal cancer lines con-tained more sphere-forming cells, whereas sphere-forming cells were not observed in the high differentiated nasopharyngeal cancer line CNE-1. Compared with CNE-2, CNE-2S (sphere-forming cells derived from CNE-2) exhibited higher chemotherapy resistance and clone-forming ability. Interestingly, the stemness genes BMI-1, ABCG2, and ALDH1 exhibited higher expression in CNE-2S than in CNE-2. β-catenin, a vital transcription factor of the WNT pathway related to stem cells, exhibited higher expression in CNE-2s cellular nucleus and plasma than in CNE-2. Conclusion: We isolated a subgroup of stem-like nasopharyngeal cancer sphere-forming cells. This discovery paves the way for the development of therapeutic strategies aimed at eradicating tumorigenic subpopulations in nasopharyn-geal cancer.
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Objective To survey the incidence of hepatocellular carcinoma (HCC) in patients with HBV-related cirrhosis receiving nucleos(t)ide analogues treatment and to assess its risk factors.Methods A total of 141 patients with HBV-related liver cirrhosis receiving nucleos(t) ide therapy from April 2008 to June 2011 were enrolled.The clinical data including virological and biochemical tests were retrospectively analyzed.Univariate and multivariate Cox proportional hazards regression model was used to identify the risk factors of HCC occurrence.Results Patients were followed up for 6.4 to 87.6 months with a median followup time of 32.5 months.During the follow-up period,15 out of 141 patients developed HCC with an average annual incidence rate of 3.8％.HCC incidence was higher in HBeAg positive cirrhosis and in those with family history of liver cancer ( RR =4.524 and 3.858,P ＜ 0.05 ).Conclusions Patients with HBV-related cirrhosis have a high incidence rate of HCC even they recieve nucleos (t) ide analogues treatment.HBeAg positive cirrhosis and family history of liver cancer are independent risk factors for HCC.
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Objective To investigate the safety and validity of Neptune 3D-RTPS-A treatment planning system compared to Prowess TPS.Methods A total of 30 clinical tumor cases with radiotherapy planning on Prowess TPS from September 2009 to May 2010 were used.The contours, organs at risk and target volumes in Prowess TPS were transported into Neptune TPS, the same parameters setted in the two treatment planning systems.The results of comparison of the two TPS were calculated.Results All cases of clinical treatment planning were completed successfully by Neptune TPS, and the various functions of the design were achieved for fitting tumor conformal radiation therapy.The key parameters on radiation treatment were compared.The results are as follows:the differences of source skin distance ( SSD ) ＜0.5% , differences of Monitor Unites ＜0.5%, the differences of dose at isocenter ＜2%, the differences of five isodose lines surrounding area ＜ 3%, and the mean difference of distances of five isodose lines was 0.43 mm, the differences of the volume of PTV on 90% isodose line ＜ 2%, and the differences in V30of organs at risk ＜ 3%.Conclusions Neptune TPS could be qualified for clinical validity and safety by clinical verification.