Combined detection tumor markers for diagnosis and prognosis of gallbladder cancer

AIM:To clarify the value of combined use of markers for the diagnosis of gallbladder cancer and prediction of its prognosis.METHODS:Serum cancer antigens(CA)199,CA242,carcinoembryonic antigen(CEA),and CA125 levels were measured in 78 patients with gallbladder cancer(GBC),78 patients with benign gallbladder diseases,and 78 healthy controls using electrochemiluminescence.CA199,CA242,CEA,and CA125 levels and positive rates were analyzed and evaluated pre-and postoperatively.Receiver operator characteristic curves were used to determine diagnostic sensitivity and specificity of GBC.Survival time analysis,including survival curves,and multivariate survival analysis of a Cox proportional hazards model was performed to evaluate independent prognostic factors.RESULTS:Serum CA242,CA125,and CA199 levels in the GBC group were significantly higher when compared with those in the benign gallbladder disease and healthy control groups(P<0.01).With a single tumor marker for GBC diagnosis,the sensitivity of CA199 was the highest(71.7%),with the highest specificity being in CA242(98.7%).Diagnostic accuracy was highest with a combination of CA199,CA242,and CA125(69.2%).CA242 could be regarded as a tumor marker of GBC infiltration in the early stage.The sensitivity of CA199 and CA242 increased with progression of GBC and advanced lymph node metastasis(P<0.05).The78 GBC patients were followed up for 6-12 mo(mean:8 mo),during which time serum CA199,CA125,and CA242 levels in the recurrence group were significantly higher than in patients without recurrence(P<0.01).The post-operative serum CA199,CA125,and CA242levels in the non-recurrence group were significantly lower than those in the GBC group(P<0.01).Multivariate survival analysis using a Cox proportional hazards model showed that cancer of the gallbladder neck and CA199 expression level were independent prognostic factors.CONCLUSION:CA242 is a marker of GBC infiltration in the early stage.CA199 and cancer of the gallbladder neck are therapeutic and prognostic markers.     

Anti-inflammatory effect of cannabinoid agonist WIN55, 212 on mouse experimental colitis is related to inhibition of p38MAPK

AIM To investigate the anti-inflammatory effect and the possible mechanisms of an agonist of cannabinoid(CB) receptors, WIN55-212-2(WIN55), in mice with experimental colitis, so as to supply experimental evidence for its clinical use in future. METHODS We established the colitis model in C57BL/6 mice by replacing the animals' water supply with 4% dextran sulfate sodium(DSS) for 7 consecutive days. A colitis scoring system was used to evaluate the severity of colon local lesion. The plasma levels of proinflammatory cytokines, such as tumor necrosis factor-alpha(TNF-α) and interleukin-6(IL-6), and the myeloperoxidase(MPO) activity in colon tissue were measured. The expressions of cannabinoid receptors, claudin-1 protein, p38 mitogen-activated protein kinase(p38MAPK) and its phosphorylated form(p-p38) in colon tissue were determined by immunohistochemistry and Western blot. In addition, the effect of SB203580(SB), an inhibitor of p38, was investigated in parallel experiments, andthe data were compared with those from intervention groups of WIN55 and SB alone or used together. RESULTS The results demonstrated that WIN55 or SB treatment alone or together improved the pathological changes in mice with DSS colitis, decreased the plasma levels of TNF-α, and IL-6, and MPO activity in colon. The enhanced expression of claudin-1 and the inhibited expression of p-p38 in colon tissues were found in the WIN55-treated group. Besides, the expression of CB1 and CB2 receptors was enhanced in the colon after the induction of DSS colitis, but reduced when p38 MAPK was inhibited. CONCLUSION These results confirmed the anti-inflammatory effect and protective role of WIN55 on the mice with experimental colitis, and revealed that this agent exercises its action at least partially by inhibiting p38 MAPK. Furthermore, the results showed that SB203580, affected the expression of CB1 and CB2 receptors in the mouse colon, suggesting a close linkage and cross-talk between the p38 MAPK signaling pathway and the endogenous CB system.     

Limited BDNF contributes to the failure of injury to skin afferents to produce a neuropathic pain condition

Although a large body of evidence has shown that peripheral nerve injury usually induces neuropathic pain, there are also clinical studies demonstrating that injury of the sural nerve, which almost only innervates skin, fails to do so. The underlying mechanism, however, is largely unknown. In the present work, we found that the transection of either the gastrocnemius–soleus (GS) nerve innervating skeletal muscle or tibial nerve supplying both muscle and skin, but not of the sural nerve produced a lasting mechanical allodynia and thermal hyperalgesia in adult rats. High-frequency stimulation (HFS) or injury of either the tibial nerve or the GS nerve induced late-phase long-term potentiation (L-LTP) of C-fiber-evoked field potentials in spinal dorsal horn, while HFS or injury of the sural nerve only induced early-phase LTP (E-LTP). Furthermore, HFS of the tibial nerve induced L-LTP of C-fiber responses evoked by the stimulation of the sural nerve and the heterotopic L-LTP was completely prevented by spinal application of TrkB-Fc (a BDNF scavenger). Spinal application of low dose BDNF (10 pg/ml) enabled HFS of the sural nerve to produce homotopic L-LTP. Finally, we found that injury of the GS nerve but not that of the sural nerve up-regulated BDNF in DRG neurons, and that the up-regulation of BDNF occurred not only in injured neurons but also in many uninjured ones. Therefore, the sural nerve injury failing to produce neuropathic pain may be due to the nerve containing insufficient BDNF under both physiological and pathological conditions.     

共同性外斜视内直肌肌纤维超微结构观察

目的观察共同性外斜视内直肌肌纤维超微结构的特点,探讨这些改变的意义。方法选择共同性外斜视内直肌12例为斜视组,角膜移植供体内直肌7例为对照组。取1mm3内直肌组织块,行甲苯胺蓝经醋酸铀及枸棒酸铝双重染色,在JEM-1200EX型透射电镜下观察,并对主要细胞器改变例数进行统计学分析。结果外斜视组内直肌肌纤维超微结构主要表现为肌原纤维排列紊乱、稀疏甚至溶解消失以及肌小节Z带不清或者消失;线粒体增多、增大、空泡化。外斜视组中有10例肌原纤维损害而对照组中仅2例,有统计学差异(P=0.0449);外斜视组中有11例线粒体不同程度的空泡化或浓缩,而对照组中线粒体异常2例,具有显著性统计学差异(P=0.0095)。结论肌纤维的损害及线粒体的异常表明共同性外斜视患者内直肌肌纤维有组织病理学改变,导致内直肌收缩功能的下降,可能与产生外斜视的生物力学相关。     

MicroRNA-214 induces dendritic cell switching from tolerance to immunity by targeting β-Catenin signaling

MicroRNAs (miRNAs) are known to function as negative gene regulators. Recently, miRNAs have been shown to regulate immunity processes; however, the mechanism is unclear. The role of microRNA-214 (miR-214) in dendritic cell (DC) maturation has not been investigated. We found that the miR-214 level was correlated with the maturation of DCs and inflammatory cytokine secretion, as depressed miR-214 levels induced DC tolerance. We also identified β-catenin as a target gene of miR-214 and demonstrated its association with Treg cell differentiation. MiR-214 regulates gene expression by binding to the 3’UTR of β-catenin. The results suggest that β-catenin is a critical regulator of tolerance in DCs via miR-214. The expression of miR-214 could be a potential therapeutic strategy in organ transplantation or autoimmunity patients.     

P2X7受体对缺氧诱发小鼠视网膜神经节细胞凋亡的影响

目的：：探讨嘌呤受体P2X7对缺氧诱发小鼠视网膜神经节细胞凋亡的影响。方法：以小鼠视网膜神经节细胞株RGC-5为研究对象,按照不同处理因素将细胞随机分为4组：正常对照组( G1)、缺氧组( G2)、缺氧+激动剂( BzATP )组( G3)、缺氧+拮抗剂(BBG)组(G4);采用四甲基偶氮唑蓝(MTT)法检测细胞的存活率;用Annxin V/PI染色流式细胞术检测细胞凋亡率;Western Blot检测细胞内cleave-caspase-3和cleave-PARP蛋白的表达。结果：与正常对照组相比, RGC-5细胞经缺氧处理后,细胞存活率明显降低;凋亡率显著升高;细胞内 cleave-caspase-3和cleave-PARP蛋白表达增加;P2X7受体激动剂BzATP能明显加重缺氧诱发的细胞凋亡,而BBG预处理可以显著拮抗缺氧所致的细胞凋亡。结论：缺氧能激活视网膜神经节细胞嘌呤受体P2X7,并参与视网膜神经节细胞的凋亡。