Effect of neoadjuvant chemoradiotherapy on prognosis and surgery for esophageal carcinoma

AIM:To investigate the role of neoadjuvant chemoradiotherapy in prognosis and surgery for esophageal carcinoma by a meta-analysis.METHODS:PubMed and manual searches were done to identify all published randomized controlled trials(RCTs) that compared neoadjuvant chemoradiotherapy plus surgery(CRTS) with surgery alone(S) for esophageal cancer.According to the test of heterogeneity,a fi xed-effect model or a random effect model was used and the odds ratio(OR) was the principal measure of effects.RESULTS:Fourteen RCTs that included 1737 patients were selected with quality assessment ranging from A to C(Cochrane Reviewers' Handbook 4.2.2).OR(95% CI,P value),expressed as CRTS vs S(values>1 favor CRTS arm),was 1.19(0.94-1.48,P=0.28) for 1-year survival,1.33(1.07-1.65,P=0.69) for 2-year survival,1.76(1.42-2.19,P=0.11) for 3-year survival,1.41(1.06-1.87,P=0.11) for 4-year survival,1.64(1.28-2.12,P=0.40) for 5-year survival,0.82(0.39-1.73,P<0.0001) for rate of resection,1.53(1.33-2.84,P=0.007) for rate of complete resection,1.78(1.14-2.78,P=0.79) for operative mortality,1.12(0.89-2.48,P=0.503) for all treatment mortality,1.33(0.94-1.88,P=0.04) for the rate of adverse treatment,1.38(1.23-1.63,P=0.0002) for local-regional cancer recurrence,1.28(0.85-1.58,P=0.60) for distant cancer recurrence,and 1.27(0.86-1.65,P=0.19) for all cancer recurrence.A complete pathological response to chemoradiotherapy occurred in 10%-45.5% of patients.The 5-year survival benefi t was most pronounced when chemotherapy and radiotherapy were given concurrently(OR:1.45,95% CI:1.26-1.79,P=0.015) instead of sequentially(OR:0.85,95% CI:0.64-1.35,P=0.26).CONCLUSION:Compared with surgery alone,neoadjuvant chemoradiotherapy can improve the long-term survival and reduce local-regional cancer recurrence.Concurrent administration of neoadjuvant chemoradiotherapy was superior to sequential chemoradiotherapy.

右美托咪定的实验研究和临床应用(英文)

右美托咪定(DEX)是高选择性α2肾上腺素受体激动药,起效快,作用时间短、兼具有镇静、镇痛作用、且无呼吸抑制,近来在临床上越来越受到重视。研究证明,右美托咪定在达到并维持足够的镇静水平的同时,具有独特的易于唤醒的特点,同时可减少其他镇静药物的用量。右美托咪定诱导的镇静类似于非快速动眼睡眠,故可提高睡眠质量,有利于免疫系统恢复。右美托咪定的镇痛作用呈剂量依赖性,且有封顶效应。右美托咪定和阿片类药物联合应用,不仅增强阿片类药物的镇痛作用,还可以减少阿片类药物的用量,有效预防阿片类药物过量所致的不良反应。右美托咪定有血流动力学稳定作用,但也可以引起心动过缓和低血压;右美托咪定还可降低术后躁动、恶心、呕吐的发生率。右美托咪定用于长期使用阿片类药物的患者,未出现明显的撤药反应,同时可以治疗阿片类药物引起的痛觉过敏。右美托咪定和布比卡因混合液用于骶管阻滞,提供足够的镇痛作用同时,显著延长骶管阻滞时间。对于神经外科手术患者,右美托咪定不抑制体感诱发电位,不影响术中神经系统功能评估。由于右美托咪定独特的无呼吸抑制的显著特点,在众多需要保持患者自主呼吸的临床麻醉应用中是一种较理想的药物。总之,右美托咪定这些特性将使得其在未来的临床工作中有更加广阔的应用。

A survey on the status of semen analysis in 118 laboratories in China

Collecting baseline information on how laboratories perform testing is a reasonable first step towards establishing intra- and inter-laboratory standardization and quality control for semen analysis. We carried out a survey of the laboratories performing the testing in China's Mainland. A questionnaire, composed of 36 questions covering all aspects of semen analysis, was designed, and a copy was distributed to each of the 145 laboratories. Of these, 118 laboratories completed the questionnaires. The survey results showed that semen volume was measured visually in 53.6% （59/110） of the responding laboratories, and 70.9% （73/103） of laboratories analysed incompletely liquefied semen without any treatment. In addition, both manual-microscopic and computer-assisted semen-analysis systems were applied to analyse sperm concentration, motility and morphology. However, more than five methods were employed in routine sperm staining. An enzyme-linked immunosorbent assay was commonly used for determining whether antisperm antibodies were present. Several seminal biochemical markers were analysed in only 27.1% （32/118） of the responding laboratories. Generally, there was a lack of intra- and inter-laboratory quality control measures for semen analysis in all laboratories responding to this survey. In conclusion, the methods of semen analysis and the interpretation of test results in the surveyed laboratories differed markedly. In particular, many laboratories employed methods other than those recommended by the World Health Organization Laboratory Manual for the Examination of Human Semen and Sperm- cervical Mucus Interaction （1999）. These findings suggest an urgent need for the standardization of semen analysis with acceptable quality controls for each parameter to make the results repeatable and meaningful.

CagA+ H pylori infection is associated with polarization of T helper cell immune responses in gastric carcinogenesis

AIM:To characterize the immune responses including local and systemic immunity induced by infection with H pylori,especially with CagA+ H pylori strains and the underlying immunopathogenesis. METHODS:A total of 711 patients with different gastric lesions were recruited to determine the presence of H pylori infection and cytotoxin associated protein A (CagA),the presence of T helper (Th) cells and regulatory T (Treg) cells in peripheral blood mononuclear cells (PBMCs),expression of plasma cytokines,and RNA and protein expression of IFN-γ and IL-4 in gastric biopsies and PBMCs were determined by rapid urease test,urea 14C breath test,immunoblotting test,flow cytometry ,real time RT-PCR and immunohistochemistry. RESULTS:Of the patients,629 (88.47%) were infected with H pylori ; 506 (71.16%) with CagA+ and 123 (17.30%) with CagA- strains. Among patients infected with CagA+ H pylori strains,Th1-mediated cellular immunity was associated with earlier stages of gastric carcinogenesis,while Th2-mediated humoral immunity dominated the advanced stages and was negatively associated with an abundance of Treg cells. However,there was no such tendency in Th1/Th2 polarization in patients infected with CagA- H pylori strains and those without H pylori infection. CONCLUSION:Polarization of Th cell immune responses occurs in patients with CagA+ H pyloriinfection,which is associated with the stage and severity of gastric pathology during the progression of gastric carcinogenesis. This finding provides further evidence for a causal role of CagA+ H pylori infection in the immunopathogenesis of gastric cancer.

Association between Bmi1 and clinicopathological status of esophageal squamous cell carcinoma

AIM： To investigate the clinicopathological roles of Bmil in esophageal squamous cell carcinoma （ESCC）.METHODS： Quantitative real-time polymerase chain reaction and immunohistochemical staining for Broil were performed in cancerous and adjacent non-cancerous paraffin-embedded esophageal specimens.RESULTS： The Bmil expression level was unaffected by gender and age. The level of Broil mRNA in ESCC was significantly higher than that in the adjacent non-cancerous tissues （2.181 ± 2.158 vs 0.931 ± 0.894, P = 0.0152）, and its over-expression was aggressively associated with lymph node metastasis （3.580 ± 2.487 vs 1.703 ± 0.758, P = 0.0003）, poorer cell differentiation （P = 0.0000） and advanced pathological stage （3.827± 2.673 vs 1.590 ± 0.735, P = 0.0001）. The patients were divided into high-expression and low-expression groups based on the median expression level of Bmi1 mRNA, and a shorter overall survival time in the former group was observed. Immunohistochemistry for Bmi1 oncoprotein showed diffusely positive, focally positive and negative expression in 44, 16 and 10 of 70 ESCC cases, respectively, compared with three, two and five of 10 adjacent non-cancerous cases （P = 0.027）. The positive rate of the oncoprotein in samples of histological grade Ⅲ was higher than that of grade Ⅱ（P = 0.031）, but its expression had no relation to the lymph node metastasis and pathological staging. In 70 ESCC samples, Bmi1 showed high intense expression in the cytoplasm and less or even no expression in the nucleus.CONCLUSION： Bmi1 was over-expressed in ESCC. Increased Bmi1 mRNA expression was significantly associated with ESCC progression, and the oncoprotein was largely distributed in the cytoplasm of tumor cells.

Granulocyte-macrophage colony-stimulating factor-transfected bone marrow stromal cells for the treatment of ischemic stroke

Adult, male, Sprague-Dawley rats were injected with granulocyte-macrophage colony-stimulating factor-transfected bone marrow stromal cells （GM-CSF-BMSCs） into the ischemic boundary zone at 24 hours after onset of middle cerebral artery occlusion. Results showed reduced infarct volume, decreased number of apoptotic cells, improved neurological functions, increased angiogenic factor expression, and increased vascular density in the ischemic boundary zone in rats that underwent GM-CSF-BMSCs transplantation compared with the BMSCs group. Experimental findings suggested that GM-CSF-BMSCs could serve as a potential therapeutic strategy for ischemic stroke and are superior to BMSCs alone.

Tagging single nucleotide polymorphisms in the PPAR-γ and RXR-α gene and type 2 diabetes risk:a case-control study of a Chinese Han population

Peroxisome proliferator-activated receptor （PPAR-γ）,which is mainly involved in adipocyte differentiation, has been suggested to play an important role in the pathogenesis of insulin resistance and atherosclerosis. We investigated the frequencies of two common tagging polymorphisms of the PPAR-γ gene and two of PPAR-α with minor allele frequency （MAF）≥ 0.05 in the Chinese Han population and analyzed the correlation between the different genotypes and the risk of type 2 diabetes mellitus （T2DM）. TaqMan assay was performed to test the genotypes in T2DM patients （n = 1,105） and normal controls （n = 1,107）. Serum adiponectin concentration was measured by ELISA kit. The variant genotypes rs17817276GG, rs3856806CT and rs3856806CT/TT of PPAR-γ were associated with T2DM, P = 0.023,0.037 and 0.018, respectively. Furthermore, the prevalence of haplotype GT in PPAR-γ was less frequent in the case subjects （0.3%） than in the controls （1.9%） [P 0.001,OR（95%CI）=0.13 （0.06-0.31）]. Patients with genotype TT of rs3856806 had a higher serum level of adiponectin than those with the genotype CC and CT （P = 0.031 and 0.038, respectively）. There was no statistically significant difference between patients and controls in genotype distribution of rs6537944 and rs1045570 of the RXR-α gene. The present study suggests that the variant genotypes in the PPAR-γ gene could decrease the risk for the development of T2DM in the Chinese Han population.

Indirubin-3′-monoxime suppresses amyloid-beta-induced apoptosis by inhibiting tau hyperphosphorylation

Indirubin-3′-monoxime is an effective inhibitor of cyclin-dependent protein kinases, and may play an obligate role in neuronal apoptosis in Alzheimer＇s disease. Here, we found that indirubin-3′-monoxime improved the morphology and increased the survival rate of SHSY5 Y cells exposed to amyloid-beta 25–35（Aβ25–35）, and also suppressed apoptosis by reducing tau phosphorylation at Ser199 and Thr205. Furthermore, indirubin-3′-monoxime inhibited phosphorylation of glycogen synthase kinase-3β（GSK-3β）. Our results suggest that indirubin-3′-monoxime reduced Aβ25–35-induced apoptosis by suppressing tau hyperphosphorylation via a GSK-3β-mediated mechanism. Indirubin-3′-monoxime is a promising drug candidate for Alzheimer＇s disease.

Effects of p38 MAPK inhibitor on the rat pain behavior and proinflammatory cytokines in a metastatic bone cancer pain model

Objective： To observe the effects of p38 mitogen activated protein kinase （MAPK） inhibitor SB203580 by intrathecal injection on the pain behavior and the spinal proinflammatory cytokines in a rat model of bone cancer pain induced by breast cancer cells. Methods： Eleven rats were used to establish the models of bone cancer pain, six rats were treated by intrathecal SB203580 injection, and the other 5 were as the controls. The paw withdrawal latency （PWL）, histology and the spinal levels of IL-1β and TNF-α were detected. Results： All the 11 rats presented evident bone destruction and thermal hyperalgesia after intra-tibial injection of breast cancer cells. No effect of SB203580 on the bone destruction was observed. However, following intrathecal injection of SB203580, the left PWLs （12.12± 1.26 s at 16 days and 12.99 ± 1.65 s at 19 days） were significant higher than that of controls （9.05 ± 1.08 s at 16 days and 8.55 ± 1.60 s at 19 days）, P 〈 0.05. Meanwhile, inkathecal injection of SB203580 evidently reduced the levels of spinal IL-1β and TNF-α. Conclusion： Intrathecal injection of SB203580 in a rat model of bone cancer pain cannot prevent the tibial destruction but significantly depress the thermalgia sensitivity, which might result from inhibiting inkacellular p38 MAPK signaling transduction, and thereby reducing the release of the proinflammatory cytokines.

Ginkgo biloba extract improved cognitive and neurological functions of acute ischaemic stroke:a randomised controlled trial

Purpose To evaluate the efficacy and safety of Ginkgo biloba extract(GBE)in acute ischaemic stroke and its impact on the recurrence of vascular events.Methods We conducted a multicentre,prospective,randomised,open label,blinded,controlled clinical trial enrollingpatients with an onset of acute stroke within 7 days from five hospitals in China Jiangsu Province.Participants were assigned to the GBE group(450 mg GBE with 100 mg aspirin daily)or the control group(100 mg aspirin daily)for 6 months.The primary outcome was the decline in the Montreal Cognitive Assessment score at 6 months.Secondary outcomes were other neuropsychological tests of cognitive and neurological function,the the incidence of adverse events and vascular events.results 348 patients were enrolled:179 in the GBE group and 169 in the control group.With 18 patients lost to follow-up,the dropout rate was 5.17%.Admission data between two groups were similar,but in the GBE group there was a marked slow down in the decline in the Montreal Cognitive Assessment scores(−2.77±0.21 vs−1.99±0.23,P=0.0116(30 days);−3.34±0.24 vs−2.48±0.26,P=0.0165(90 days);−4.00±0.26 vs−2.71±0.26,P=0.0004(180 days))compared with controls.The National Institutes of Health Stroke Scale scores at 12 and 30 days,the modified Rankin Scale scores for independent rate at 30,90 and 180 days,and the Barthel Index scores at 30,90 and 180 days in the GBE group were significantly improved compared with controls.Improvements were also observedin GBE groups for Mini-Metal State Examination scores of 30,90 and 180 days,Webster's digit symbol test scores at 30 days and Executive Dysfunction Index scores at 30 and 180 days.No significant differences were seen in the incidence of adverse events or vascular events.conclusions We conclude that GBE in combination with aspirin treatment alleviated cognitive and neurological deficits after acute ischaemic stroke without increasing the incidence of vascular events.