Expression of lncRNA FAM95B1 in glioma and the possible mechanism of its effect on the proliferation and migration of LN382 cells / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨lncRNA FAM95B1对胶质瘤细胞增殖和迁移能力的影响并探究其相关作用机制。方法： 选取2018年1月至2020年8月于合肥市第三人民医院行手术治疗的38例胶质瘤患者的胶质瘤组织及癌旁组织标本，利用qPCR检测胶质瘤组织与4种细胞系中FAM95B1的表达水平，以表达最低的胶质瘤LN382细胞为研究对象，转染空载质粒（对照组）或pcDNA3.1-FAM95B1质粒（实验组）。MTT法和划痕实验检测FAM95B1对LN382细胞增殖和迁移能力的影响。生物信息学分析技术和双荧光素酶基因报告实验预测并验证FAM95B1与miR-26a-5p及PTEN之间的相互作用机制，应用qPCR和WB法检测FAM95B1对miR-26a-5p和PTEN表达的影响。结果： FAM95B1在胶质瘤组织中的表达明显低于癌旁组织（P<0.01）。FAM95B1在多种胶质瘤细胞系中的表达均明显低于正常脑胶质细胞（均P<0.01）。过表达FAM95B1可以下调LN382细胞的增殖（P<0.05）和迁移能力（P<0.01）。FAM95B1能够靶向结合miR-26a-5p（P<0.01），miR-26a-5p能够靶向结合PTEN mRNA（P<0.01）。过表达FAM95B1可下调LN382细胞中miR-26a-5p的表达（P<0.01），促进PTEN mRNA的表达（P<0.01）。结论：在胶质瘤组织和细胞系中异常低表达的FAM95B1通过发挥竞争性内源RNA的功能抑制miR-26a-5p的表达而增强PTEN蛋白表达，抑制胶质瘤细胞系LN382的增殖和迁移。

Metformin inhibits proliferation and functions of regulatory T cells in acidic environment / 南方医科大学学报

OBJECTIVE@#To investigate the regulatory effect of metformin on regulatory T cells (Treg) in acidic environment.@*METHODS@#CD4 CD25 Treg cells were obtained by magnetic bead sorting. Treg and conventional T cells (Tcon) cells were cultured for 24-72 h in pH 7.4 or pH 6.7 medium, and the cell proliferation, apoptosis and Foxp3 expression were detected by flow cytometry. Real-time PCR was used to detect the expression levels of the genes related with glucose metabolism. Thirty-two C57BL/6 male mouse models bearing subcutaneous prostate cancer xenograft derived from RM-1 cells were randomized into 4 equal groups for treatment with PBS, metformin, tumor vaccine, or both metformin and the vaccine. The treatment started on the 4th day following tumor cell injection, and metformin (100 mg/kg) or PBS was administered by intraperitoneal injection on a daily basis; the vaccine was intramuscularly injected every 4 days. The tumor size was continuously monitored, and the mice were euthanized on day 25 after tumor implantation to obtain tumor and blood samples. Flow cytometry was used to detect the changes in CD4, CD8, CD4Foxp3 cell subsets in the tumor tissue and peripheral blood.@*RESULTS@#Treg cells showed significantly enhanced proliferation ( < 0.05) while the proliferation of Tcon cells was suppressed in acidic medium ( < 0.001). Treg cells cultured in acidic medium showed significantly increased expressions of OXPHOS-related genes pgc1a ( < 0.001) and cox5b ( < 0.01), which did not vary significantly in Tcon cells in acidic medium. Treg cells exhibited significantly decreased apoptosis in acidic medium ( < 0.01) with increased Foxp3 cells ( < 0.001) and intracellular alkaline levels ( < 0.01). Metformin obviously reversed the acid tolerance of Treg cells without producing significant effect on Tcon cells. In the animal experiment, both metformin ( < 0.05) and vaccine ( < 0.01) alone reduced the tumor volume, but their combined treatment more potently reduced the tumor volume ( < 0.001). Metformin alone did not obviously affect CD4 cells or CD8 cells but significantly decreased the percentage of CD4Foxp3 ( < 0.05); the vaccine alone significantly increased CD4 cells and CD8 cells ( < 0.001) and also the percentage of CD4Foxp3 cells ( < 0.05). The combined treatment, while reducing the percentage of CD4Foxp3cells to a level lower than that in the vaccine group ( < 0.01), produced the strongest effect to increase CD4 cells and CD8 cells ( < 0.01).@*CONCLUSIONS@#Metformin can inhibit the proliferation and function of regulatory T cells in an acidic environment and enhance the effect of tumor vaccine by reducing the proportion of Treg cells to achieve the anti-tumor effect.

Preventive protection of Yingxindan on myocardial ischemia / 中国药理学通报

Aim To observe the preventive protection of Yingxindan on acute myocardial ischemia induced by sublingual injection of pituitrin ( pit) in rats.Methods Sixty rats were randomly divided into saline group , model group, nifedipine 12.6 mg · kg -1 group, and Yingxindan 25.2, 12.6, 6.3 mg · kg -1 groups.The saline group and model group were given the same vol-ume of water.After administration for 7 d, an acute myocardial ischemia model was induced by sublingual intravenous injection of pit 1 U · kg -1 in the rats 1 h after last administration .The changes of the II electro-cardiogram(ECG) ST segment at different time points , as well as the positive rate of myocardial ischemia and arrhythmia were observed .Meanwhile , the levels of serum creatine kinase ( CK ) , creatine kinase isoenzyme ( CK-MB ) , glycogen phosphorylase isoenzyme BB ( GPBB ) , cardiac troponin I ( cTnI ) and cardiac troponin T ( cTnT ) were observed .Re-sults Yingxindan could suppress the changes of ST segment of electrocardiogram in rats with acute myocar-dial ischemia induced by pit and reduce the positive rate of myocardial ischemia and arrhythmia .The con-tents of myocardial injury markers CK , CK-MB, GPBB, cTnI and cTnT in serum significantly de-creased, and the corresponding relationship existed . The greater the dose of Yingxindan , the smaller the content of myocardial injuried markers in serum .Con-clusion Yingxindan has significant preventive protec-tion effect on acute myocardial ischemia by pit .

Glutathione S-transferase P1 Ile105Val Polymorphism and Male Infertility Risk: An Updated Meta-analysis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Several studies concerning the association between glutathione S-transferase P1 (GSTP1) Ile105Val polymorphism and male infertility risk have reported controversial findings. The present study was aimed to explore this association using a meta-analysis.</p><p><b>METHODS</b>The PubMed, EMBASE, China National Knowledge Infrastructure (CNKI), and Wanfang databases were searched. Odds ratios (OR s) with 95% confidence intervals (CI s) were calculated to estimate the strength of the association.</p><p><b>RESULTS</b>A total of 3282 cases and 3268 controls in nine case-control studies were included. There was no significant association between GSTP1 Ile105Val polymorphism and male infertility in the overall population, but significant associations were found under the dominant (OR = 1.23, 95% CI = 1.04-1.46, I2 = 32.2%) and heterozygote (OR = 1.29, 95% CI = 1.08-1.53, I2 = 26.8%) models after excluding studies for which the data did not satisfy Hardy-Weinberg equilibrium (HWE). Similarly, subgroup analyses revealed no significant association in Asians or Chinese population although a significant association was apparent among Chinese population in studies with HWE under the heterozygote model (OR = 1.25, 95% CI = 1.03-1.52, I2 = 44.1%). Significant heterogeneity could be observed in some genetic models, but this heterogeneity was not significant when stratified by HWE. No evidence for publication bias was found.</p><p><b>CONCLUSIONS</b>The GSTP1 Ile105Val polymorphism might not be associated with male infertility risk, and thus additional well-designed studies with larger sample size are warranted.</p>

Primary investigation of immunoglobulin A synthesis and secretion in human mesangial cells / 北京大学学报(医学版)

Objective:To investigate the expression of immunoglobulin A (IgA) in human mesangial cells (HMCs).Methods:The HMCs were cultured.The subcellular location of IgA was detected by immunofluorescence staining;the transcripts of Ig α,Ig κ and Ig λ constant region were detected by reverse transcription-polymerase chain reaction (RT-PCR) and further analyzed by DNA sequencing.The expressions of Igαt and Ig λ were detected at transcription level by Western blot after the cytoplasmic protein extraction.The culture supernatant was collected to explore whether IgA could be secreted out of the cell and the protein was further analyzed by mass spectrometry after being purified by affinity chromatography with jacalin-sepharose.The results of DNA sequencing and mass spectrometry were aligned with the mRNA and amino acid sequences in the National Center of Biotechnology Information (NCBI) data-base.Results:By immunofluorescence staining,we detected the presence of IgA heavy chain Ig α,light chain,both Ig κ and Ig λ in expressions of transcripts of Ig α1,Ig α2,Ig κ and Ig λ in the HMCs and the alignment of the sequences of the RT-PCR products with those of the Ig Cα1,Ig Cα2,Ig κ and Ig λ mRNA in the NCBI database exhibited that the similarities were 99％,97％,98％ and 97％,respectively.Western blot showed Ig α and Ig λ expressions in the cell lysate and secretion of Ig α1 and Ig α2 heavy chains in cell culture supernatant.To further explore the protein that secreted into the supernatant,after supernatant affinity chromatography with jacalin-sepharose,the proteins were separated by sodium dodecyl sulfonate-polyacrylamide gel electrophoresis (SDS-PAGE) and the band approximating to 65 000 was cut and sent to mass spectrometry.The results were aligned with the amino acid sequences of Ig α1 and Ig α2 constant region in NCBI database,showing that amino acids between No.52 and No.104,amino acids between No.154 and No.221,amino acids between No.276 and No.327 from Ig Cα1 and amino acids between No.52 and No.113,amino acids between No.151 and No.204,amino acids between No.251 and No.314 from Ig Cα2 were the same with those derived from B cells.Conclusion:Our findings suggested that HMCs could synthesize and secret IgA.

Research progress of Epstein-Barr virus-associated gastric carcinoma / 中华胃肠外科杂志

Epstein-Barr virus-associated gastric carcinoma(EBVaGC) comprises nearly 10% of gastric carcinoma in the world. EBVaGC is supposed to have distinct clinicopathological features, including male predominance, the 'lace pattern' in the early stage, lower rate of lymph node involvement and infiltration of a large number of various inflammatory cells. EBER-ISH detection is the golden standard in the diagnosis of EBVaGC. Although there is no special therapy due to the limited understanding, EBVaGC has a better prognosis. In this paper, the relationship of EBV with gastric carcinoma, the epidemiological and clinical features of EBVaGC will be briefly introduced. In addition, the clinical diagnosis, treatment, and the prognosis of the status quo will be discussed.

Meta-analysis of Olanzapine in the Prevention and Treatment of Chemotherapy-related Nausea and Vomiting / 中国药房

OBJECTIVE:To systematically review the effectiveness and safety of olanzapine in the prevention and treatment of chemotherapy-induced nausea and vomiting(CINV),and provide evidence-based reference for clinical treatment. METHODS:Re-trieved from Medline,PubMed,EMBase,Cochrane Library,Clinical Trials.gov,CBM,CJFD,VIP and Wanfang Database,ran-domized controlled trials (RCT) about olanzapine (test group) versus other drugs or conventional antiemetic regimen (control group)in the prevention and treatment of CINV were collected,Meta-analysis was performed by using Rev Man 5.3 software after data extraction and quality evaluation by modified Jadad. RESULTS:Totally 19 RCTs were included,involving 1 794 patients. Re-sults of Meta-analysis showed,olanzapine can significantly improve the complete control rate of patients with acute CINV [RR=1.12,95%CI(1.06,1.18),P0.05). CONCLUSIONS:Olanzapine is safe and effective in the prevention and treatment of CINV and can be recommended in treating breakthrough and refractory CINV. Besides,olanzapine in the prevention and treatment of CINV belongs to“off-label use”,so the clinicians should have a comprehensive consideration of chemotherapy and patients’consent.

Psychological stress analysis and countermeasures of a university graduate student after the full implementation of the charging system / 中华医学教育探索杂志

Objective To investigate the graduate students' mental pressure after the full im-plementation of the charging system and explore effective countermeasures of alleviating the psycho-logical pressure. Methods 413 full-time graduate students of Grade 2014 were randomly selected in a university of Shandong province. The graduate students' psychological pressure scale and self-designed questionnaire survey were used. The data were analyzed using SPSS 17.0 software, statistical descrip-tion of the survey data, independent sample t test, ANOVA. Results ①The psychological pressure of full-time graduate students at their own expense was in themedium pressure level; ②The economic pressure and academic pressure of the male graduate students were higher than those of the female graduate students (P=0.000,P=0.042), the rural economic pressures were greater than urban students graduate students graduate students (P=0.000); Professional graduate economic pressures were greater than academic graduate students (P=0.027);There is difference in the pressure of interpersonal commu-nication among different majors (P=0.016); ③78.75% (315/400) of the graduate students tuition fees, living expenses were mainly from their parents and the national and school awards; ④The percentage of those who completely agreed with the following view: full charge than at public expense is more advantageous to graduate education, comprehensive charge is advantageous to the education career development and comprehensive charge embodies the fairness of education was 84.75% (339/400), 71.25% (285/400) and 68.00% (272/400). Conclusion The full-time graduate students at their own expense have a more rational understanding of the charging policy; economic and academic pressures are the two outstanding pressure sources of the graduate students at the present stage. Graduate should improve their ability to cope with stress, and government and schools should take various measures to help students relieve stress.

Effects of lead stress on net photosynthetic rate, SPAD value and ginsenoside production in Ginseng (Panax ginseng) / 中国中药杂志

The paper aimed to evaluate the effects of lead stress on photosynthetic performance and ginsenoside content in ginseng (Panax ginseng). To accomplish this, three years old ginseng were cultivated in pot and in phytotron with different concentrations of lead, ranging from 0 to 1000 mg x kg(-1) soil for a whole growth period (about 150 days). The photosynthetic parameters in leaves and ginsenoside content in roots of ginseng were determined in green fruit stage and before withering stage, respectively. In comparison with the control, net photosynthetic rate and SPAD value in ginseng leaves cultivated with 100 and 250 mg x kg(-1) of lead changed insignificantly, however, ginseng supplied with 500 and 1 000 mg x kg(-1) of lead showed a noticeably decline in the net rate of photosynthesis and SPAD value (P < 0.05), the lowest net photosynthetic rate and SPAD value showed in the treatment supplied with 1 000 mg x kg(-1) of lead, with decline of 57.8%,11.0%, respectively. Total content of ginsenoside in ginseng roots cultivated with 100 mg x kg(-1) of lead showed insignificantly change compared to the control, but the content increased remarkably in treatments supplied with 250, 500, 1 000 mg x kg(-1) of lead (P < 0.05), and highest content appeared in these ginsengs exposed to 1000 mg x kg(-1) of lead. The net photosynthetic rate and SPAD value in leaves of ginseng both showed significantly negative linear correlations with lead stress level (P < 0.01), and significant positive linear correlations between total content of ginsenoside and lead concentration was also observed (P < 0.05). These results strongly indicate that exposing to high level of lead negatively affects photosynthetic performance in ginseng leaves, but benefits for accumulation of secondary metabolism (total content of ginsenoside) in ginseng root.

Changes in clinicopathological features and survival after surgical resection for gastric cancer over a 20-year period at a single institution / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate changes in clinicopathological features and survival of patients with gastrectomy at a single institution in China.</p><p><b>METHODS</b>From January 1990 to December 2009, clinicopathological data of 2518 cases of gastric cancer patients who underwent surgical resection in the Sun Yat-sen University Cancer Center were analyzed retrospectively. The overall survival rate was determined using Kaplan-Meier method and log-rank test was used to determine significance. The prognosis was analyzed using univariate analysis and multivariate analysis by Cox proportional hazards model. Clinical features, pathological findings and survival differences were compared in this cohort between two consecutive periods(1990-1999 and 2000-2009).</p><p><b>RESULTS</b>The 5-year survival rates for the whole cohort and those undergoing radical resection was 48.1% and 53.7%, respectively. In the first period, the 5-year survival rate for the whole cohort and for patients undergoing radical resection was 40.1% and 45.7%. In the second period, the 5-year survival rates for whole cohort and for patients undergoing radical resection was 51.5% and 57.1%, respectively. For those who underwent radical resection, the mean number of lymph node dissection was significantly higher in the recent period (20.1±8.3 vs. 9.5±6.0, P<0.01). On multivariate analysis by means of the Cox proportional hazard model, age, location, tumor size, histological type, radical resection, lymphatic/venous invasion, depth of invasion, nodal status, number of retrieved lymph nodes, and treatment period were independent factors (P<0.05). The constitution, number of retrieved lymph nodes, and survival rate were all improved between the two intervals (P<0.05).</p><p><b>CONCLUSION</b>The overall survival rate has gradually increased in gastric cancer patients over the past 20 years.</p>

Changes of AFP and beta-hCG in testicular tumors analyzed by a function method / 中华男科学杂志

<p><b>OBJECTIVE</b>To establish a new function method for the analysis of a-fetoprotein (AFP) and beta-hCG in testicular tumors.</p><p><b>METHODS</b>We reexamined the serum levels of AFP and beta-hCG after radical orchiectomy, and calculated the measured coordinate, with the abscissa representing the number of the half-lives of tumor markers, and the ordinate representing the measured value of tumor markers. Referring to the measured value of tumor markers before surgery as a, the number of half-lives as x, and their theoretical value over a period of x elimination half-lives as y (logarithm to the base 2 of y), we calculated the predicted coordinate according to the formula y = log2(a/2x) ==> x + y = log2a (function 1). Then we assessed tumor residue and metastasis by analyzing the relationship between the measured and predicted coordinates.</p><p><b>RESULTS</b>The pathological examination of case 1 revealed a germ cell tumor of a mixed histological pattern of syncytiotrophoblast and yolk sac tumor. The measured coordinates of AFP and beta-hCG were (2.22, 6.21) and (10, 8.38), and the predicted coordinates (2.22, 6.34) and (10, 4.41) , indicating the elimination of the yolk sac tumor and metastasis of the syncytiotrophoblast tumor. Case 2 demonstrated the mixed pathological nature of teratocarcinoma and yolk sac tumor. The measured coordinates of AFP and beta-hCG were (2.67, -1.03) and (12, -3.32), and the predicted coordinates (2.67, 1.41) and (12, -5.80). But the review times of AFP and beta-hCG were out of the effective range of half-lives, with the measured values below the normal, which suggested no tumor residue or metastasis. Case 3 was found to be embryonal carcinoma. The measured coordinate of AFP was (0.22, 9.25) , and the predicted coordinate (0.22, 9.55) , indicating the elimination of tumor.</p><p><b>CONCLUSION</b>The change of the tumor markers predicted by the function method coincided with the natural course of disease in the three cases. The coincidence of the measured with the predicted coordinate after radical orchiectomy indicates no metastasis, while their disagreement suggests possible residue and metastasis of the tumor.</p>

Efficacy of Gastrosis No.1 compound on functional dyspepsia of spleen and stomach deficiency-cold syndrome: a multi-center, double-blind, placebo-controlled clinical trial / 中国结合医学杂志

<p><b>OBJECTIVE</b>To assess the efficacy and safety of Gastrosis No.1 compound in the treatment of functional dyspepsia with Spleen (Pi) and Stomach (Wei) deficiency-cold syndrome.</p><p><b>METHODS</b>A randomized, double-blind, placebo-controlled trial was performed in 5 centers. Patients with functional dyspepsia (FD) of Spleen-deficiency and qi-stagnation syndrome (162 cases) were randomly assigned to groups given Chinese herbal medicine (CHM) Gastrosis No.1 compound or placebo in a 2:1 ratio. This trial included a 4-week treatment period and a 4-week follow-up period. The outcomes were the dyspepsia symptom scores (measured by total dyspepsia symptom scale and single dyspepsia symptom scale) and syndromes of traditional Chinese medicine score (measured by traditional Chinese medicine syndrome scale). The outcomes were noted at weeks 0, 4 and 8.</p><p><b>RESULTS</b>Compared with patients in the placebo group, patients in the CHM group showed significant improvement in the dyspepsia symptom scores as rated by patients and investigators (P <0.01), and also showed improvement in syndromes of traditional Chinese medicine score (P <0.01). No serious adverse event was reported. Safety tests obtained after 4 weeks of treatment showed no abnormal values.</p><p><b>CONCLUSION</b>CHM Gastrosis No.1 compound was effective and safe in the treatment of functional dyspepsia with Spleen and Stomach deficiency-cold syndrome.</p>

CT-Guided Core Needle Biopsy of Deep Suprahyoid Head and Neck Lesions

OBJECTIVE: To evaluate the efficacy of computer tomography (CT)-guided core needle biopsy (CNB) in the diagnosis of deep suprahyoid lesions in patients with treated head and neck cancers. MATERIALS AND METHODS: Between December, 2003 and May, 2011, 28 CT-guided CNBs were performed in 28 patients with deep suprahyoid head and neck lesions. All patients had undergone treatment for head and neck cancers. Subzygomatic, paramaxillary, and retromandibular approaches were used. The surgical results, response to treatment, and clinical follow-up were used as the diagnostic reference standards. RESULTS: All biopsies yielded adequate specimens for definitive histological diagnoses. A specimen from a right parapharyngeal lesion showed atypia, which was deemed a false negative diagnosis. Diagnostic accuracy was 27/28 (96.4%). Two minor complications were encountered: a local hematoma and transient facial palsy. Between the 18 or 20 gauge biopsy needles, there was no statistical difference in the diagnostic results. CONCLUSION: CT-guided core needle biopsy, with infrequent and minor complications, is an accurate and efficient method for the histological diagnosis of deep suprahyoid lesions in post-treated head and neck cancer patients. This procedure can preclude an unnecessary surgical intervention, especially in patients with head and neck cancers.

Effects of heme oxygenase-1 gene modulated mesenchymal stem cells on vasculogenesis in ischemic swine hearts / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Mesenchymal stem cells (MSCs) transplantation may partially restore heart function in the treatment of acute myocardial infarction (AMI). The aim of this study was to explore the beneficial effects of MSCs modified with heme xygenase-1 (HO-1) on post-infarct swine hearts to determine whether the induction of therapeutic angiogenesis is modified by the angiogenic cytokines released from the implanted cells.</p><p><b>METHODS</b>In vitro, MSCs were divided into four groups: (1) non-transfected MSCs (MSCs group), (2) MSCs transfected with the pcDNA3.1-Lacz plasmid (Lacz-MSCs group), (3) MSCs transfected with pcDNA3.1-hHO-1 (HO-1-MSCs group), and (4) MSCs transfected with pcDNA3.1-hHO-1 and pretreatment with an HO inhibitor, tin protoporphyrin (SnPP) (HO-1-MSCs + SnPP group). Cells were cultured in an airtight incubation bottle for 24 hours, in which the oxygen concentration was maintained at < 1%, followed by 12 hours of reoxygenation. After hypoxia/reoxygen treatment, ELISA was used to measure transforming growth factor (TGF-β) and fibroblast growth factor (FGF-2) in the supernatant. In vivo, 28 Chinese mini-pigs were randomly allocated to the following treatment groups: (1) control group (saline), (2) Lacz-MSCs group, (3) HO-1-MSCs group, and (4) HO-1-MSCs + SnPP group. About 1 × 10(7) of autologous stem cells or an identical volume of saline was injected intracoronary into porcine hearts 1 hour after MI. Magnetic resonance imaging (MRI) assay and postmortem analysis were assessed four weeks after stem cell transplantation.</p><p><b>RESULTS</b>Post hypoxia/reoxygenation in vitro, TGF-β in the supernatant was significantly increased in the HO-1-MSCs ((874.88 ± 68.23) pg/ml) compared with Lacz-MSCs ((687.81 ± 57.64) pg/ml, P < 0.001). FGF-2 was also significantly increased in the HO-1-MSCs ((1106.48 ± 107.06) pg/ml) compared with the Lacz-MSCs ((853.85 ± 74.44) pg/ml, P < 0.001). In vivo, at four weeks after transplantation, HO-1 gene transfer increased the capillary density in the peri-infarct area compared with the Lacz-MSCs group (14.24 ± 1.66/HPFs vs. 11.51 ± 1.34/HPFs, P < 0.001). Arteriolar density was also significantly higher in HO-1-MSCs group than in the Lacz-MSCs group (7.86 ± 2.00/HPFs vs. 6.45 ± 1.74/HPFs, P = 0.001). At the same time, the cardiac function was significantly improved in the HO-1-MSCs group compared with the Lacz-MSCs group ((53.17 ± 3.55)% vs. (48.82 ± 2.98)%, P < 0.05). However, all these effects were significantly abrogated by SnPP.</p><p><b>CONCLUSION</b>MSCs provided a beneficial effect on cardiac function after ischemia/reperfusion by the induction of therapeutic angiogenesis, and this effect was amplified by HO-1 overexpression.</p>

Serum HIF-1alpha and VEGF levels pre- and post-TACE in patients with primary liver cancer / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To investigate the expression levels of serum hypoxia inducible factor 1 alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) pre- and post-transcatheter arterial chemoembolization (TACE) in patients with primary liver cancer (PLC), and correlations between prognosis factors and serum HIF-1alpha as well asVEGF levels.</p><p><b>METHODS</b>Forty consecutive patients fulfilling diagnostic criteria for PLC undergoing TACE from March 2008 to May 2009 were enrolled into the study. The serum HIF-1alpha and VEGF levels of PLC patients pre- and 1 day, 1 week, 1 month post-TACE were analyzed using ELISA, and compared with that of 20 healthy volunteers. Patients were divided into complete response (CR) and partial response (PR), stable disease (SD), progressive disease (PD) groups according to the therapeutic efficacy. Pearson correlation was used to analyze the correlation between different clinical variables and serum HIF- 1alpha and VEGF levels before TACE, and correlation between serum HIF-1alpha and VEGF levels was also evaluated.</p><p><b>RESULTS</b>The expression levels of serum HIF-1alpha and VEGF in PLC patients were 154.94 +/- 83.29 and 264.00 +/- 148.10 pg/mL pre-TACE, and both of them were significantly higher than those in control group (23.84 +/- 8.15 and 69.78 +/- 21.42 pg/mL, all P<0.01). One day after TACE, both serum HIF-1alpha (570.64 +/- 230.87 pg/mL) and VEGF levels (362.07 +/- 102.25 pg/mL) reached the peak values (all P<0.01). One week post-TACE, expression levels of them were decreased (198.62 +/- 92.11 and 283.52 +/- 145.46 pg/mL respectively), but still significantly higher than those before TACE (all P<0.01). The levels of both HIF-1alpha (133.96 +/- 57.02 vs. 255.74 +/- 123.44 pg/mL) and VEGF (150.96 +/- 84.89 vs. 368.95 +/- 161.90 pg/mL) in CR group 1 month post-TACE were significantly lower than those in PR+SD+PD group (all P<0.01). The level of serum HIF-1alpha was positively correlated with serum VEGF level (r=0.42, P<0.001). Both serum HIF-1alpha and VEGF levels were observed to be correlated with portal vein tumor thrombi (P<0.05) and metastasis (P<0.05).</p><p><b>CONCLUSION</b>The HIF- 1alpha and VEGF might play an important role in relapse of PLC. They might be considered as predictors of the efficacy ofTACE and metastasis of PLC.</p>

Efficiently tracking of stem cells in vivo using different kinds of superparamagnetic iron oxide in swine with myocardial infarction / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Superparamagnetic iron oxide (SPIO) particles have shown much promise as a means to visualize labeled cells using molecular magnetic resonance imaging (MRI). Micrometer-sized superparamagnetic iron oxide (MPIO) particles and nanometer-sized ultrasmall superparamagnetic iron oxide (USPIO) are two kinds of SPIO widely used for monitoring stem cells migration. Here we compare the efficiency of two kinds of SPIO during the use of stem cells to treat acute myocardial infarction (AMI).</p><p><b>METHODS</b>An AMI model in swine was created by 60 minutes of balloon occlusion of the left anterior descending coronary artery. Two kinds of SPIO particles were used to track after intracoronary delivered 10(7) magnetically labeled mesenchymal stem cells (MR-MSCs). The distribution and migration of the MR-MSCs were assessed with the use of 3.0T MR scanner and then the results were confirmed by histological examination.</p><p><b>RESULTS</b>MR-MSCs appeared as a local hypointense signal on T₂*-weighted MRI and there was a gradual loss of the signal intensity after intracoronary transplantation. All of the hypointense signals in the USPIO-labeled group were found on T₂*-weighted MRI, contrast to noise ratio (CNR) decreased in the MPIO-labeled group (16.07 ± 5.85 vs. 10.96 ± 1.34) and USPIO-labeled group (11.72 ± 1.27 vs. 10.03 ± 0.96) from 4 to 8 weeks after transplantation. However, the hypointense signals were not detected in MPIO-labeled group in two animals. MRI and the results were verified by histological examination.</p><p><b>CONCLUSIONS</b>We demonstrated that two kinds of SPIO particles in vitro have similar labeling efficiency and viability. USPIO is more suitable for labeling stem cells when they are transplanted via a coronary route.</p>

Relationship between genetic polymorphism in microRNAs precursor and genetic predisposition of hepatocellular carcinoma / 中华预防医学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between genetic polymorphism in microRNAs (miRNAs) precursor and genetic predisposition of hepatocellular carcinoma (HCC) in Chinese population.</p><p><b>METHODS</b>A case-control study including 963 HCC cases and 829 HBsAg positive controls and 852 HBsAg negative controls was conducted. hsa-mir-146a rs2910164 C→G and hsa-mir-196-a2 rs11614913 T→C were selected, where the genotypes were determined by the primer introduced restriction analysis-PCR (PIRA-PCR) assay. Odd ratios (ORs) and 95% confidence intervals (CIs) were evaluated by logistic regression analysis to investigate the relationship between onset risk of HCC and different genotypes.</p><p><b>RESULTS</b>The genotype frequencies of CC, CG and GG at rs2910164 gene locus were separately 34.5% (319/925), 48.6% (450/925) and 16.9% (156/925) in cases; 36.4% (274/753), 45.0% (339/753) and 18.6% (140/753) in HBsAg positive controls; and 36.1% (303/840), 46.0% (386/840) and 18.0% (151/840) in HBsAg negative controls. The genotype frequencies of TT, CT and CC at rs11614913 were respectively 29.7% (277/934), 48.1% (449/934) and 22.3% (208/934) in cases; 30.3% (238/785), 51.0% (400/785) and 18.7% (147/785) in HBsAg positive controls; and 28.6% (239/837), 49.8% (417/837) and 21.6% (181/837) in HBsAg negative controls. No significant relationships were observed between these two single nucleotide polymorphisms (SNPs) and onset risk of HCC after adjusting the factors as age, gender, smoking and drinking status in comparison with HBsAg positive controls: hsa-mir-146a rs2910164 (CG + GG vs CC): adjusting OR = 1.10, 95%CI: 0.90 - 1.36; hsa-mir-196-a2 rs11614913 (CC + CT vs TT): adjusting OR = 1.01, 95%CI: 0.81 - 1.25; as well as in comparison with HBsAg negative controls: hsa-mir-146a rs2910164 (CG + GG vs CC): adjusting OR = 1.06, 95%CI: 0.87 - 1.29; hsa-mir-196-a2 rs11614913 (CC + CT vs TT): adjusting OR = 0.94, 95%CI: 0.76 - 1.16. As well, no significant relationships were observed between these two SNPs and onset risk of HCC in the subgroups stratified by age, gender, smoking and drinking status.</p><p><b>CONCLUSION</b>hsa-mir-146a rs2910164 C→G and hsa-mir-196-a2 rs11614913 T→C may not play an important role in the HCC predisposition among Chinese populations.</p>

Effects of autologous mesenchymal stem cells transfected with heme oxygenase-1 gene transplantation on ischemic Swine hearts / 中华心血管病杂志

<p><b>OBJECTIVE</b>To observe the effect of intracoronary transfer of autologous HO-1 overexpressed MSCs in porcine model of myocardial ischemia (1 h)/reperfusion.</p><p><b>METHODS</b>Apoptosis was assayed and cytokine concentrations in supernatant were measured in cells exposed to hypoxia-reoxygen in vitro. In vivo, Chinese male mini-pigs were allocated to the following treatment groups: control group (saline), MSCs group (MSCs), MSCs transfected with pcDNA3.1-nHO-1 (HO-1-MSCs). 1 x 10(7) of autologous stem cells or identical volume of saline was injected intracoronary into porcine hearts 1 h after ischemia. MRI assay and postmortem analysis were assessed 3 months after stem cell transplantation.</p><p><b>RESULTS</b>In vitro, cell apoptosis rate post hypoxia-reoxygen was significantly reduced in HO-1-MSCs group (30.30% +/- 7.64%) compared with that in MSCs group (56.93% +/- 4.68%, P < 0.001) and LacZ-MSCs group (55.88% +/- 4.38%, P < 0.001), VEGF was also significantly upregulated in HO-1-MSCs group [(768.44 +/- 78.38) pg/ml] compared with that in MSCs group [(555.27 +/- 67.67) pg/ml, P < 0.001] and LacZ-MSCs group [(522.97 +/- 71.45) pg/ml, P < 0.001]. In vivo, cardiac function was significantly improved in both MSCs transplantation groups compared to saline group (all P < 0.05 vs.saline) and the left ventricular ejection fraction was significantly higher in HO-1-MSCs group compared with that in MSCs group at 3 months after transplantation (53.50% +/- 2.09% vs. 49.54% +/- 2.74%, P = 0.017), capillary density in the peri-infarct area was also significantly higher in HO-1-MSC group than that in MSCs group [(14.59 +/- 2.39)/HPF vs. (11.78 +/- 2.48)/HPF, P = 0.033].</p><p><b>CONCLUSIONS</b>Efficacy of HO-1 overexpressed MSCs on improving cardiac function and promoting angiogenesis was greater than those by MSCs in this porcine ischemia/reperfusion model.</p>

Value of percutanous catheter fragmentation in the management of massive pulmonary embolism / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Acute massive pulmonary embolism (PE) is a clinical emergency requiring rapid and supportive measures. Percutanous mechanical thrombectomy is considered as a treatment option. The purpose of this study was to evaluate the clinical efficacy and safety of peructaneous mechanical catheter fragmentation in the management of acute massive PE.</p><p><b>METHODS</b>From January 2003 to June 2007, 28 patients (20 men, 8 women; mean age 64 years) with acute massive PE initially diagnosed by computed tomography and confirmed by pulmonary angiography were treated with inferior vena caval filter placement and percutaneous catheter fragmentation. Twenty-six patients received thrombolytic agents after embolus fragmentation.</p><p><b>RESULTS</b>Technical success was achieved in all patients. The improvement of clinical status and restoration of blood flow in the main branches of the pulmonary artery were seen in 27 patients. Only one case did not benefit from the percutaneous therapy and died from the failure of the surgery. Oxygen saturation increased from (86.2 +/- 4.5)% to (96.1 +/- 3.2)% (P < 0.001) after the interventional procedure. The post-procedure mean pulmonary artery pressure decreased from (34.2 +/- 4.8) mmHg to (25.2 +/- 5.1) mmHg (P < 0.001). During clinical follow-up (range, 1 - 5 years), no patients had recurrence of PE.</p><p><b>CONCLUSION</b>Percutaneous catheter fragmentation combined with thrombolysis is an effective and safe therapy in the clinical management of acute massive PE.</p>

Transplantation of magnetically labeled mesenchymal stem cells improves cardiac function in a swine myocardial infarction model / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Mesenchymal stem cells (MSCs) transplantation provides a new approach for myocardial repair. However, many important fundamental questions about MSCs transplantation remain unanswered. There is an urgent need to identify MSCs from the beating heart and analyze the efficacy of this new approach. This study aimed to localize the magnetically labeled MSCs (MR-MSCs) and monitor the restorative effects of MR-MSCs with magnetic resonance (MR) imaging.</p><p><b>METHODS</b>Acute myocardial infarction (AMI) was created in swine by a balloon occlusion of the left anterior descending coronary artery. Cells were delivered via intracoronary infusion after myocardial infarction. Infarct size change and cardiac function were assessed with 3.0T MR scanner. The results were then confirmed by histological and western blot analysis. All statistical procedures were performed with Systat (SPSS version 12.01).</p><p><b>RESULTS</b>A total of 26 swine were divided into four groups (sham-operated group, n=6; AMI group with PBS transplantation, n=6; labeled MSCs group, n=7; unlabeled MSCs group, n=7). MSCs, MR-MSCs (10(7) cells) or PBS were delivered by intracoronary injection after MI and serial cardiac MR imaging studies were performed at 0, 4 and 8 weeks after transplantation. MR imaging demonstrated MI size decreased after MSCs transplantation in labeled and unlabeled groups, however, increases were seen in the AMI group at 8 weeks after MI. The left ventricular ejection fraction (LVEF) was slightly increased in the AMI group ((41.87+/-2.45)% vs (39.04+/-2.80)%, P>0.05), but significantly improved in the MR-MSCs group ((56.85+/-1.29)% vs (40.67+/-2.00)%, P<0.05) and unlabeled group ((55.38+/-1.07)% vs (41.78+/-2.08)%, P<0.05) at 8 weeks after treatment. MR-MSCs were further confirmed by Prussian blue and immunofluorescent staining. Western blot analysis demonstrated that there was an increased expression of cardiomyocyte markers such as myosin heavy chain and troponin T in the MSCs treatment groups and the ratio of matrix metalloproteinase 2 to tissue inhibitor of metalloproteinase 1 decreased in the labeled group and unlabeled group compared with the AMI group and sham-operated group.</p><p><b>CONCLUSION</b>Transplanted MR-MSCs can regenerate new myocardium and prevent remolding in an MI model at 2-month follow-up and represent a preferred method to better understand the mechanisms of stem cell therapy in future clinical studies.</p>