人参皂苷Rh2对人黑色素瘤A375—S2细胞的促凋亡作用

目的;研究人参皂苷G－Rh2诱导人黑色素肿瘤细胞A375－S2凋亡的分子生物学机制。方法：用结晶紫染色的方法测定细胞的死亡率。用置显微镜观察细胞形态学的变化。用琼脂糖凝胶电泳检测核酸片断。用流式细胞仪检测细胞凋亡和细胞周期。结果：G－Rh2抑制A375－S2细胞增殖并在20μmol/L可以诱导A375－S2细胞产生凋亡,Caspase抑制剂z-VAD-fmk(caspase家族）,z-DEVD-fmk(caspase-3)或z-IETD-fmk(caspase-8)能部分抑制细胞凋亡,但是Ac-YVAD-cmk(caspase-1)不能抑制A375－S2细胞凋亡。结论：GRh2在体外抑制A375－S2细胞的增殖,通过细胞形态学和核酸片断分析,G－Rh2能够诱导A375－S2细胞产生凋亡。这种作用是通过细胞内caspase一类半胱氨酸蛋白酶进行传导的,G－Rh2对A375－S2细胞的周期没有影响。     

Promoter methylation of tumor suppressor genes in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma(ESCC) is a prevalent and fatal cancer in China and other Asian countries.Epigenetic silencing of key tumor suppressor genes(TSGs) is critical to ESCC initiation and progression.Recently,many novel TSGs silenced by promoter methylation have been identified in ESCC,and these genes further serve as potential tumor markers for high-risk group stratification,early detection,and prognosis prediction.This review summarizes recent discoveries on aberrant promoter methylation of TSGs in ESCC,providing better understanding of the role of disrupted epigenetic regulation in tumorigenesis and insight into diagnostic and prognostic biomarkers for this malignancy.     

Global trends and performances of acupuncture research

This study was designed to evaluate the global scientific output of acupuncture research in the Science Citation Index-Expanded and to assess the tendencies and research performances of leading countries/territories and institutes. Articles referring to acupuncture were assessed by distribution of document types, languages, journals, subject categories, source countries, and source institutes. Results showed that 15 languages were represented in articles from 65 countries/territories. Journal of Alternative and Complementary Medicine published the most articles, followed by American Journal of Chinese Medicine and Acupuncture & Electro-Therapeutics Research which were listed in category of integrative & complementary medicine. In the study period of 1991-2009, USA was the top producing country, followed by China (mainland) with a sharply growth trend. In 2009, publication of China (mainland) ranked top one in the world. In addition, an acupuncture research trend was found in two phases in terms of the increase of number of SCI-expanded journals’ articles. Among the acupuncture research, pain control has been the most prevalent direction of study, and brain imaging is attracting the most recent attention.     

Axonal accumulation of hyperpolarization-activated cyclic nucleotide-gated cation channels contributes to mechanical allodynia after peripheral nerve injury in rat

Peripheral nerve injury causes neuropathic pain including mechanical allodynia and thermal hyperalgesia due to central and peripheral sensitization. Spontaneous ectopic discharges derived from dorsal root ganglion (DRG) neurons and from the sites of injury are a key factor in the initiation of this sensitization. Numerous studies have focused primarily on DRG neurons; however, the injured axons themselves likely play an equally important role. Previous studies of neuropathic pain rats with spinal nerve ligation (SNL) showed that the hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel in DRG neuronal bodies is important for the development of neuropathic pain. Here, we investigate the role of the axonal HCN channel in neuropathic pain rats. Using the chronic constriction injury (CCI) model, we found abundant axonal accumulation of HCN channel protein at the injured sites accompanied by a slight decrease in DRG neuronal bodies. The function of these accumulated channels was verified by local application of ZD7288, a specific HCN blocker, which significantly suppressed the ectopic discharges from injured nerve fibers with no effect on impulse conduction. Moreover, mechanical allodynia, but not thermal hyperalgesia, was relieved significantly by ZD7288. These results suggest that axonal HCN channel accumulation plays an important role in ectopic discharges from injured spinal nerves and contributes to the development of mechanical allodynia in neuropathic pain rats.     

Translocator protein 18 kDa: a potential therapeutic biomarker for post traumatic stress disorder

Metabolic Brain Disease - Post traumatic stress disorder (PTSD) is widely regarded as a stress-related and trauma disorder. The symptoms of PTSD are characterized as a spectrum of vulnerabilities...     

肝干细胞的研究进展

干细胞具有多向分化潜能、自我更新及分裂增殖能力，来自胚胎、胎儿及成体组织，在现代分子生物学等的推动下应用于临床医学相关疾病的治疗，展现了广阔前景。本文就肝干细胞的研究现状、认识、争论及应用前景作一综述。     

Selection, proliferation and differentiation of bone marrow-derived liver stem cells with a culture system containing cholestatic serum in vitro

AIM: To explore the feasibility of direct separation, selective proliferation and differentiation of the bone marrow-derived liver stem cells (BDLSC) from bone marrow cells with a culture system containing cholestatic serum in vitro. METHODS: Whole bone marrow cells of rats cultured in routine medium were replaced with conditioning selection media containing 20mL/L, 50mL/L, 70mL/L, and 100mL/L cholestatic sera, respectively, after they attached to the plates. The optimal concentration of cholestatic serum was determined according to the outcome of the selected cultures. Then the selected BDLSC were induced to proliferate and differentiate with the addition of hepatocyte growth factor (HGF). The morphology and phenotypic markers of BDLSC were characterized using immunohistochemistry, RT-PCR and electron microscopy. The metabolic functions of differentiated cells were also determined by glycogen staining and urea assay. RESULTS: Bone marrow cells formed fibroblast-like but not hepatocyte-like colonies in the presence of 20mL/L cholestatic serum. In 70mL/L cholestatic serum, BDLSC colonies could be selected but could not maintain good growth status. In 100mL/L cholestatic serum, all of the bone marrow cells were unable to survive. A 50mL/L cholestatic serum was the optimal concentration for the selection of BDLSC at which BDLSC could survive while the other populations of the bone marrow cells could not. The selected BDLSC proliferated and differentiated after HGF was added. Hepatocyte-like colony-forming units (H-CFU) then were formed. H-CFU expressed markers of embryonic hepatocytes (AFP, albumin and cytokeratin 8/18), biliary cells (cytokeratin 19), hepatocyte functional proteins (transthyretin and cytochrome P450-2b1), and hepatocyte nuclear factors (HNF-1α and HNF-3β). They also had glycogen storage and urea synthesis functions, two of the critical features of hepatocytes. CONCLUSION: The selected medium containing cholestatic serum can select BDLSC from whole bone marrow cells. It will be a new way to provide a readily available alternate source of cells for clinical hepatocyte therapy.     

CCK－8可对抗μ－阿片受体介导的对大鼠背根节神经元钙通道的抑制效应

ＣＣＫ－８在脊髓水平可对抗μ－阿片受体介导的抗伤害性作用，但其作用位，点及机制尚不清楚。本实验以急性分离的大鼠背根节（ＤＲＧ）神经元为标本，用全细胞膜片钳（ｗｈｏｌｅ－ｃｅｌｌｐａｔｃｈ－ｃｌａｍｐ）方法记录钙通道电流，观察分析特异性μ－受体激动剂羟甲芬太尼（ＯＭＦ）对电压依赖性钙通道电流的作用，以及在同一细胞上ＣＣＫ－８对此作用的影响。结果显示ＯＭＦ可明显抑制钙通道电流，其抑制作用可被μ－受体拮抗剂纳络酮或ＣＣＫ－８所翻转，而ＣＣＫ－８的作用又可被ＣＣＫ－Ｂ受体拮抗剂Ｌ３６５，２６０所对抗。结果提示：ＣＣＫ－８可在同一细胞上经ＣＣＫ－Ｂ受体对抗阿片效应。ＣＣＫ－８本身对钙通道电流并无增强效应，相反它可引起抑制作用。关于ＣＣＫ－８如何对抗μ－受体介导的机制有待进一步研究。     

Does Early Postsurgical Temozolomide Plus Concomitant Radiochemotherapy Regimen Have Any Benefit in Newly-diagnosed Glioblastoma Patients? A Multi-center,Randomized, Parallel,Open-label,Phase II Clinical Trial

Background:

The radiochemotherapy regimen concomitantly employing temozolomide (TMZ) chemotherapy and radiotherapy (RT) 4 weeks after surgery, followed by 6 cycles of TMZ is a common treatment for glioblastoma (GBM). However, its median overall survival (OS) is only 14.6 months. This study was to explore the effectiveness and safety of early TMZ chemotherapy between surgery and chemoradiotherapy plus the standard concomitant radiochemotherapy regimen.

Methods:

A randomized, parallel group, open-label study of 99 newly diagnosed GBM patients was conducted at 10 independent Chinese neurosurgical departments from June 2008 to June 2012. Patients were treated with concomitant radiochemotherapy regimen plus early postsurgical temozolomide (early TMZ group) or standard concomitant radiochemotherapy regimen (control group). Overall response was assessed based on objective tumor assessments, administration of corticosteroid and neurological status test. Hematological, biochemical, laboratory, adverse event (AE), and neurological condition were measured for 24 months of follow-up. The primary efficacy endpoint of this study was overall survival (OS). The secondary endpoint was progression free survival (PFS).

Results:

The median OS time in the early TMZ group was 17.6 months, compared with 13.2 months in the control group (log-rank test P = 0.021). In addition, the OS rate in the early TMZ group was higher at 6, 12, and 18 months than in the control group, respectively (P < 0.05). The median PFS time was 8.7 months in the early TMZ group and 10.4 months in the control group (log-rank test P = 0.695). AEs occurred in 29 (55.8%) and 31(73.8%) patients respectively in early and control groups, including nausea (15.4% vs. 33.3%), vomiting (7.7% vs. 28.6%), fever (7.7% vs. 11.9%), and headache (3.8% vs. 23.8%). Only 30.8% and 33.3% were drug-related, respectively.

Conclusions:

Addition of TMZ chemotherapy in the early break of the standard concomitant radiochemotherapy regimen was well tolerated and significantly improved the OS of the GBM patients, compared with standard concomitant radiochemotherapy regimen. However, a larger randomized trial is warranted to verify these results.     

铜陵县晚期血吸虫病人分布现状与特点

目的了解铜陵县现存晚期血吸虫病（晚血）人的分布现状及特点。方法收集整理并分析全省在册晚血病人资料。结果2006年全县现存晚血295例，较2000年下降了31．82％，新发晚血44例占现有晚血的14．92％，全县晚血患病率为0．15％。晚血病例中，湖沼型流行区占78．98％，山丘型占21．02％。疫情未控制流行区占4．41％，疫情控制地区占79．66％，传播控制区占16．61％，传播阻断区占1．02％。巨脾型占77．63％，腹水型占20．68％，结肠增厚型占1．02%，侏儒型占0．68％，巨脾型病人已切脾者占51．09％。男性占64．07％，女性占35．93％。年龄最小者20岁，最大者86岁，50～、60～岁年龄组病例占56．27％，30～、40～、70～岁年龄组占39．66％，其余年龄组占4．07％。农民占95．59％，其他职业占4．41％。结论铜陵县晚血患病率有下降趋势，但仍有不少新的晚血病例出现；晚血患者主要为湖沼地区的农民。