The resistance of non-small cell lung cancer (NSCLC) to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) has been brought into focus. COX-2 signal pathway was found to be closely related to EGFR signal pathway by recent researches, and there has been a growing interest to focus the researches on whether COX-2 pathway inhibition improves the efficacy of EGFR-TKIs in treating advanced NSCLC. In this review, we will illustrate recent advances of combined inhibition of EGFR and COX-2 signal pathways in NSCLC therapy.
Objective To compare proton pump inhibitors (PPI) and H2 receptor antagonists (H2RA) for both the prevention of bleeding and the healing of ulcer after endoscopic submucosal dissection (ESD), so as to provide best evidence for treating ESD-induced ulcer in clinic. Methods Databases including PubMed, CENTRAL, EMbase, ISI Web of Knowledge, VIP, CNKI, CBM and WanFang Data were searched from the date of their establishment to October 26, 2012 to collect the randomized controlled trials (RCTs) about comparison of PPI and H2RA on the prevention of bleeding and the healing of ulcer after ESD. Meanwhile the references of the included studies were also retrieved manually. According to the inclusion and exclusion criteria, literature selection, data extraction and quality assessment were performed by four reviewers independently, and meta-analysis was performed using RevMan 5.1 software. Results A total of 6 studies involving 616 patients were included finally. The results of meta-analysis showed that: for the prevention of ulcer bleeding after ESD, PPI preceded H2RA apparently (OR=0.51, 95%CI 0.29 to 0.89, P=0.02), especially when the treatment course was 8-week (OR=0.43, 95%CI 0.22 to 0.82, P=0.01); but among the merged, 8-week and 4-week groups, there were no significant differences between PPI and H2RA in the healing of ESD-induced ulcer (OR=0.85, 95%CI 0.39 to 1.86, P=0.69; OR=1.33, 95%CI 0.28 to 6.27, P=0.72; OR=0.75, 95%CI 0.31 to 1.79, P=0.52). Conclusion PPI is superior to H2RA for the prevention of ulcer bleeding induced by ESD, but there is no significant difference between them in the healing of ulcer, so PPI is recommended to prevent ESD-induced ulcer bleeding in clinic. Due to the limitation of quantity and quality of the included studies, the safety of PPI has to be further proved by conducting more high quality, large scale and multicenter RCTs.
Objective To systematically evaluate the effectiveness and safety of fluoxetine in treating premature ejaculation (PE). Methods All randomized controlled trials (RCTs) on fluoxetine treating PE published from July 1996 to May 2012 were collected in the following databases: MEDLINE, EMbase, PubMed, Ovid, The Cochrane Central Register of Controlled Trials, CBM and CKNI. According to the inclusion and exclusion criteria, literature screening, data extraction and quality assessment were conducted independently by two reviewers. Then meta-analysis was performed using RevMan 5.0 software. Results A total of 6 RCTs involving 221 patients were included finally. The results of meta-analysis showed that, as for effectiveness, there was no significant difference in the intravaginal ejaculatory latency time (IELT) between the two groups before the treatment (WMD=–0.21, 95%CI −4.79 to 4.37, P=0.93), but the IELT of the fluoxetine group was obviously longer than that of the control group after the treatment, with a significant difference (WMD=134.54, 95%CI 79.78 to 189.30, Plt;0.000 01). The results of sensitivity analysis indicated that the IELT of the fluoxetine group was longer than that of the control group, with a significant difference (WMD=155.19, 95%CI 130.64 to 179.75, Plt;0.000 01). As for safety, the fluoxetine group was higher in the incidence of adverse reaction than the control group, with a significant difference (OR=5.49, 95%CI 2.43 to 12.38, Plt;0.000 1). Conclusion Current evidence indicates that fluoxetine can improve the symptoms of PE patients, obviously prolong the IELT, and improve the quality of sexual life; and it is tolerable to patients with mild adverse reactions and is suitable for long-term intake. For the limited quantity of the included studies, we herein believe that, to obtain more evidence, it is necessary to further confirm the diagnosis and therapeutic criteria of PE, to design and conduct more multicenter and large scale clinical studies by adopting the internationally recognized indexes, and to perform a long-term follow-up．
Angiotensin converting enzyme inhibitor (ACEI) is an important type of antihypertensive drug. Much evidence shows that ACEI not only decreases the blood pressure but also has the protective effect on the cardiac and cerebral vessels. ACEI may prevent the stroke. To provide the best evidence for the clinical practice, we electronically searched RCTs and systematic reviews from MEDLINE and The Cochrane Library to evaluate the mechanisms and the effects of ACEI in stroke treatment and prevention.
Food and Drug Administration (FDA) has suspended the use of both celecoxib (Celebrex, Pfizer) and naproxen (Aleve, Bayer) in prevention large clinical trials after discovering that celecoxib and naproxen appeared to increase the risk of cardiovascular events with patients on placebo. FDA also advises patients who are currently taking over the counter naproxen products to carefully follow the instructions on the label. Pfizer suggested that alternatives to celecoxib should be considered based on individual patient needs and risk. The cardiovascular community responds differently.
Objective To make individualized evidence-based treatment for patients with diabetic peripheral neuropathy. Methods Based on the clinical questions we raised, evidence was collected and critically assessed. Patients’ preferences was also taken into consideration in the decision-making treatment. Results 157 studies were retrieved and finally 15 randomized controlled trials, 14 systematic reviews and meta-analyses, and 1 clinical guidelines were considered eligible. The evidence indicated that the first step in management of patients with diabetic peripheral neuropathy should aim for stable and optimal glycemic control; there was no statistically significant difference between aldose reductase inhibitors and placebo in the treatment of diabetic polyneuropathy, the same to nerve growth factor; alpha-lipoic acid is superior to placebo in reducing symptoms of diabetic peripheral neuropathy; 5-hydroxytryptamine and norepinephrine uptake inhibitor, tricyclic antidepressants and anticonvulsants might alleviate the pain in patients with diabetic peripheral neuropathy; vitamin B and capsaicin cream are is effective and safe in the management of diabetic peripheral neuropathic pain. The individualized treatment plans were developed based on the available evidence. After 3 month of treatment, the blood sugar returned to normal and symptoms were alleviated. Conclusion The treatment efficacy in diabetic peripheral neuropathy has been improved by determining an individulized treatment plan according to evidence-based methods.
ObjectiveTo investigate antifungal activity in vitro of single or combination of triazole and echinocandin against Aspergillus species. MethodsBased on EUCAST protocol,the susceptibilities of 62 isolates of Aspergillus spp. were determined for voriconazole (VRC),itraconazole (ICZ),caspofungin (CAS) and micafungin (MICA). For VRC and ICZ,MIC-0 and MIC-2 were determined. For CAS and MICA,minimum effective concentration (MEC) and MIC-2 were determined. The fractional inhibitory concentration (FIC) was used to evaluate the effect of combination of triazole and echinocandin. ResultsIndifference was found in 2 isolates of Aspergillus fumigatus in combination of ICZ and CAS or MICA by using MIC-0 endpoint. Synergy was found in all other isolates of Aspergillus spp.With MIC-2 and MEC endpoints,synergy for VRC and CAS,VRC and MICA,ICZ and CAS and ICZ and MICA was found in 16,21,11 and 14 isolates of Aspergillus fumigatus,9,13,9 and 11 isolates of Aspergillus flavus,0,2,1 and 1 isolates of Aspergillus niger,respectively. ConclusionThe in vitro sensitivity results of combination of triazole and echinocandin are different with different endpoints. Thus,the efficacy of combination of triazole and echinocandin can not predicted by in vitro sensitivity and should be further confirmed in invasive aspergillosis animal experiments.
摘要:目的:探讨卡配因抑制剂3（MDL28170）对新生大鼠缺氧缺血性脑损伤(HIBD)神经细胞凋亡的影响。方法:建立新生SD大鼠HIBD模型,治疗组于缺养缺血后即刻、2 h、4 h腹腔内注射MDL28170,对照组及手术组同时予生理盐水。缺氧缺血后24 h用免疫组化方法观察大脑皮质及海马CA1区Caspase3 蛋白表达、TUNEL法检测细胞凋亡,观察组织病理改变并计算海马神经元死亡数,透射电镜观察细胞超微结构。结果:缺氧缺血后24 h缺血侧大脑皮质及海马CA1区Caspase3和TUNEL阳性细胞数较对照组明显增加,透射电镜证实有凋亡细胞;MDL28170可减少阳性细胞数量,抑制神经元死亡,差异有显著性(Plt;0.05)。结论:MDL28170可通过抑制神经凋亡而对新生大鼠HIBD具有一定保护作用。Abstract: Objective: To investigate the effect of (Calpain inhibitor3) MDL28170 on neural apoptosis in a neonatal model of hypoxicischemic brain damage (HIBD). Methods: A neonatal model of HIBD was established, 7dayold SD rats were divided into three groups. The treatment group received MDL28170(ip) at 0 h,2 h,4 h after HI, whereas the other two groups were administered normal saline simultaneously. The expression of caspase3 (by immunohistochemistry), neural apoptosis (by TUNEL) in cortex and hippocampus ipsilateral to the insult were observed 24 h after HI; hippocampal CA1 neural loss and electromicroscopic changes were assessed at the same time. Results: Apoptotic body was observed by electromicroscopy. Caspase3 positive cells and apoptotic cells increased significantly in the ipsilateral cortex and hippocampal CA1 region compared to the control, and MDL28170 reduced the number of positive cells, attenuated CA1 neural loss with significance (Plt;0.05). Conclusion: It is suggested that MDL28170 may protect the brain of neonatal rats after HIBD by suppressing neural apoptosis.
Objective To investigate the effects of DNA methyltransferase inhibitor (DNMTi) and histone deacetylase inhibitor (HDCAi) on expression of E-cadherin gene and invasiveness of cholangiocarcinoma cell. Methods According to different treatment, the QBC939 cells were divided into four groups: blank control group, hydralazine group, valproic acid group and hydralazine and valproic acid combined group. After 48 h, the expression of E-cadherin was evaluated by reverse transcription-PCR (RT-PCR), mehtylation specific PCR (MSP) and Western blot, the invasiveness of QBC939 cells was evaluated by Transwell method. Results There was no expression of E-cadherin mRNA and protien in blank control group and valproic acid group. The expressions of E-cadherin mRNA and protien in hydralazine and valproic acid combined group were higher than those in hydralazine group ( P ＜ 0.01), while the invasiveness of QBC939 cells of hydralazine and valproic acid combined group was much lower than that of blank control group, hydralazine group and valproic acid group ( P ＜ 0.01). Conclusion DNMTi and HDACi can synergistically re-express E-cadherin gene and weaken the invasiveness of QBC939 cell, which plays an important part in treatment of cholangiocarcinoma.
Objective To investigate the invasion ability of Panc-1 cells in vivo and in vitro af ter being t ransfected with tissue factor pathway inhibitor 2 gene ( TFPI-2) . Methods The expression vector pEGFP-C1-TFPI-2 was transfected into human pancreatic cancer line Panc-1 cells by using liposome. TFPI-2 mRNA and protein of transfected and nontransfected cells were detected by reverse t ranscription-polymerase chain reaction (RT-PCR) and Western blot respectively. The tumor cells invasive behavior of t ransfected ( Panc-1-TFPI-2) and nontransfected ( Panc-1-V and Panc-1-P) cells were assessed in vitro through Boyden Chamber method. The transfected and nontransfected cells were implanted into nude mice to observe it s growth and metastasis in vivo. Results Expressions of mRNA and protein of TFPI-2 were confirmed in transfected cells. Af ter TFPI-2 t ransfection , the number of Panc-1-TFPI-2 , Panc-1-V and Panc-1-P cells passing through membrane of Boyden Chamber were 24. 4 ±3. 5 ,61. 3 ±4. 1 and 60. 2 ±3. 9 , respectively. The number of TFPI-2-expressing cells to t raverse a Matrigel-coated membrane was obviously decreased compared with that of non-expressing cells , the invasion ability was lower than that before transfection in vitro. The subcutaneous tumor volume of the Panc-1-TFPI-2 group was (438. 0 ±69. 8) mm3 , the Panc-1-V group was (852. 0 ±102. 9) mm3 and the Panc-1-P group was (831. 0 ±78. 1) mm3 , P lt; 0. 05. The metastasis to liver and lung and muscular invasion occurred in the Panc-1-V group and the Panc-1-P group. There were no muscular invasion and metastatic lesions in the Panc-1-TFPI-2 group. Conclusion TFPI-2 gene expression may obviously inhibit the invasion ability of pancreatic cancer cells in vitro and in vivo , which provides an experimental basis for the treatment of human pancreatic cancer by gene therapy.