Tegillarca granosa extract Haishengsu (HSS) suppresses expression of mdr1, BCR/ABL and sorcin in drug-resistant K562/ADM tumors in mice

PurposeTo evaluate the effect of Haishengsu (HSS), a protein extract from Tegillarca granosa, on multidrug-resistance genes mdr1, BCR/ABL and sorcin in transplanted tumors.Material/MethodsMice were inoculated subcutaneously with a drug resistant leukemia cell line K562/ADM. Tumor-bearing animals were divided into control, adriamycin, HSS and combination therapy (adriamycin plus HSS) groups. Flow cytometry was used to detect apoptosis of tumor cells, and RT-PCR was used to evaluate the expression of mdr1, BCR/ABL and sorcin.ResultsThe apoptosis rate in the high (71.8%), medium (72.3%) and low doses HSS group (72.4%) was higher than in control (1.2%, p<0.01), adriamycin (34.4%, p<0.05) or combination therapy group (46.4%, p<0.05). The mean optical density of mdr1, BCR/ABL and sorcin in HSS groups was lower than in control, adriamycin and combination therapy group (p<0.01). The optical density of the three genes in high HSS group was lower than in medium and low HSS group (p<0.01).ConclusionsHaishengsu promotes apoptosis of drug-resistant K562/ADM tumors in mice in a dose-dependent manner. The pro-apoptotic effect of Haishengsu may be related to a reduced expression of multidrug-resistance genes mdr1, BCR/ABL and sorcin.     

Post-synthetic modification of imine linkages of a covalent organic framework for its catalysis application

Post-synthetic modification has been the most powerful strategy for covalent organic frameworks (COFs) for their functionalization in many fields. This strategy is typically achieved through the quantitative reaction between existing reactive sites on the linkers (building units) and incoming functional groups. However, usage of linkages (bonds formed to construct COFs) for the post-synthetic modification still remains limited. Herein, we develop a new post-synthetic modification route that is based on the modification of linkages. With this strategy, the imine linkages of a two-dimensional (2D) COF, TFPPy–PyTTA–COF, have been transformed into amine linkages to give the amine-linked isostructure with retention of crystallinity and porosity. The subsequent aminolysis of the amine linkages with 1,3-propane sultone and further metathetical reaction with cobalt acetate [Co(OAc)₂] enable the introduction of cobalt alkyl sulfonate to the one-dimensional (1D) channel walls of the COF. The resulting ionic COF with coupled Co²⁺ in the frameworks shows excellent catalytic activity and good recyclability towards the cycloaddition reactions of epoxides and CO₂. This strategy is of interest as it opens a way to use linkage modification for exploring the potential of COFs for different applications.

A new approach for post-synthetic modification of covalent organic frameworks has been developed based on the modification of the linkages and the resulting COF exhibited excellent catalytic performance towards cycloaddition of epoxides and CO₂.     

GP73在肝癌组织中的表达及其与临床病理特征的关系

目的：探讨GP73在肝癌组织中的表达及其与患者临床病理特征的关系。方法：采用RT-PCR及Western blot方法检测20例肝癌、相应癌旁组织和10例正常肝组织中GP73 mRNA及蛋白的表达情况,并分析其表达水平与临床病理特性的关系。结果：肝癌组织中,GP73 mRNA与蛋白表达水平均明显高于癌旁组织和正常肝组织（1.25±0.17 vs. 0.62±0.06,0.46±0.03;2.20±0.26 vs. 0.87±0.07,0.26±0.04）（均P<0.05）;GP73 mRNA及蛋白的表达水平在血管有无侵犯及肿瘤分化程度分组间差异有统计学意义,有血管侵犯和肿瘤分化低者GP73表达水平高于无侵犯及分化高者（均P<0.05）,而与患者年龄、性别、肿瘤大小、肿瘤数目及血清甲胎蛋白（AFP）水平无明显关系（均P>0.05）。结论：GP73在肝癌组织中高表达,其表达水平与肝癌侵袭性密切相关;它有望成为新的判断肝癌侵袭性及术后转移复发的标志物。     

Erythropoietin reduces white matter damage in two-day-old rats exposed to hypoxic/ischemia injury

Objective: The aim of the study was to investigate whether erythropoietin (EPO) could protect against white matter damage (WMD) in a preterm equivalent neonatal rat hypoxic-ischemia (HI) model.

Methods: 113 two-day-old male rat pups were divided randomly into three groups: sham-treated, bilateral carotid artery occlusion (BCAO)-treated, BCAO + EPO-treated group. EPO (50 U/10 g body weight) or saline alone was administered intraperitoneally immediately after BCAO surgery. Body weight, brain weight, brain water content, and expression of myelin basic protein (MBP) were assessed at day 1, 3, 7, and 14 after HI insult. Morris water-maze (MWM) test was used to assess neurological behavior from day 31 to 35 after HI insult.

Results: Body weights of BCAO + EPO group were greater than those of BCAO group rats (P < 0.05). Specifically, at day 3 and 7 after HI, brain weights of BCAO + EPO-treated rats were higher than BCAO-treated animals (P < 0.05); at day 7 and 14 after HI, MBP of BCAO + EPO-treated rats were higher than BCAO-treated animals (P < 0.05). Similarly, the brain water content at day 3 after HI in BCAO + EPO-treated rats was lower than BCAO-treated animals (P < 0.05). The body weight, brain weight, brain water content, and MBP expression in BCAO + EPO-treated group were comparable to those in the sham-treated group. Spatial learning and memory of BCAO + EPO-treated rats was significantly improved over the BCAO-treated group and was comparable to the sham-operated animals.

Conclusion: EPO treatment could be a potential intervention in treating WMD for preterm infants.     

阿立哌唑与奋乃静治疗女性精神分裂症对照性研究

目的比较阿立哌唑与奋乃静治疗女性精神分裂症疗效和安全性。方法将83例女性精神分裂症住院患者随机分为阿立哌唑组（研究组）41例和奋乃静组（对照组）42例。以阳性和阴性综合征量表（PANSS）评定疗效,治疗中需处理的不良反应症状量表（TESS）评定不良反应。结果治疗后第2、4、8周末两组PANSS总分及各因子分与治疗前比较均显著下降（P〈0．05,P〈0．01）。治疗后第8周末研究组PANSS量表阴性症状分显著低于对照组（P〈0．05）。两组不良反应均较轻微,不良反应发生率在两组之间无统计学差异（P〉0．05）。结论阿立哌唑治疗女性精神分裂症安全有效。     

The potential role of the 5,6-dihydropyridin-2(1H)-one unit of piperlongumine on the anticancer activity

Piperlongumine (PL), a potent anticancer agent from the plant long pepper (Piper longum), contains the 5,6-dihydropyridin-2(1H)-one heterocyclic scaffold and cinnamoyl unit. In this paper, we synthesized a series of PL analogs and evaluated their cytotoxicity against cancer cells for the sake of exploring which pharmacophore plays a more potent role in enhancing the anticancer activities of PL. These results illustrated that the position effect, not the electronic effect, of substituents plays a certain role in the cytotoxicity of PL and its analogs. More important, the 5,6-dihydropyridin-2(1H)-one unit, a potent pharmacophore in enhancing the antiproliferative activities of PL, could react with cysteamine and lead to ROS generation, and then bring about the occurrence of ROS-induced downstream events, followed by cell cycle arrest and apoptosis. This work suggests that introducing a lactam unit containing Michael acceptors may be a potent strategy to enhancing the anticancer activity of drugs.

Piperlongumine (PL) could induce A549 cells apoptosis through ROS-mediated pathway and the 5,6-dihydropyridin-2-(1H)-one unit is crucial for its anticancer activity.     

Opportunities and challenges of using five-membered ring compounds as promising antitubercular agents

Tuberculosis (TB), a chronic infectious disease, is one of the greatest risks to human beings and 10 million people were diagnosed with TB and 1.6 million died from this disease in 2017. In addition, with the emergence of multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB), the TB situation has become even worse, which has aggravated the mortality and spread of this disease. To overcome this problem, research into novel antituberculosis agents with enhanced activities against MDR-TB, reduced toxicity, and shortened duration of therapy is of great importance. Fortunately, many novel potential anti-TB drug candidates with five-membered rings, which are most likely to be effective against sensitive and resistant strains, have recently entered clinical trials. Different five-membered rings such as furans, pyranoses, thiazoles, pyrazolines, imidazoles, oxazolidinone, thiazolidins, isoxazoles, triazoles, oxadiazoles, thiadiazoles, and tetrazoles have been designed, prepared, and evaluated for their antimycobacterial activity against Mycobacterium tuberculosis. In this article, we highlight the recent advances made in the discovery of novel five-membered ring compounds and focus on their antitubercular activities, toxicity, structure–activity relationships, and mechanisms of action.     

托拉塞米联合美托洛尔治疗老年退行性心脏瓣膜病心力衰竭的临床研究

目的探讨托拉塞米注射液联合酒石酸美托洛尔注射液治疗老年退行性心脏瓣膜病心力衰竭的临床疗效。方法选取2015年1月—2017年1月在聊城市第二人民医院心胸外科接受治疗的老年退行性心脏瓣膜病心力衰竭患者86例,入选患者采用随机数字表法分为对照组和治疗组,每组各43例。对照组静脉滴注酒石酸美托洛尔注射液,15 mL加入到0.9%氯化钠注射液500 mL中,1次/d。治疗组在对照组基础上静脉滴注托拉塞米注射液,初始剂量10 mg/d,加入到0.9氯化钠注射液250 mL,若疗效不如意可增加至20 mg/d,最大剂量为40 mg/d。两组患者均治疗1周。观察两组的临床疗效,比较两组的心功能指标和血清细胞因子情况。结果治疗后,对照组和治疗组的总有效率分别为81.39%、97.67%,两组比较差异有统计学意义(P0.05)。治疗后,两组左室射血分数(LVEF)显著上升,左室舒张末期内径(LVEDD)和左室收缩末期内径(LVESD)明显下降,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标的改善程度明显优于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,两组血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和N末端脑钠肽原(NT-pro BNP)水平均显著下降,同组治疗前后比较差异有统计学意义(P0.05);且治疗组这些观察指标明显低于对照组,两组比较差异具有统计学意义(P0.05)。结论托拉塞米注射液联合酒石酸美托洛尔注射液治疗老年退行性心脏瓣膜病心力衰竭具有较好的临床疗效,可有效改善心脏功能,调节血清细胞因子水平,改善炎症反应,具有一定的临床推广应用价值。     

芪骨胶囊联合骨瓜提取物注射液治疗中老年不稳定型桡骨远端骨折的疗效观察

目的探讨芪骨胶囊联合骨瓜提取物注射液治疗中老年不稳定型桡骨远端骨折的临床疗效。方法选取2015年10月—2016年12月高唐县人民医院收治的中老年桡骨远端骨折患者116例,随机分为对照组和治疗组,每组各58例。对照组静脉滴注骨瓜提取物注射液,50 mg加入5%葡萄糖溶液250 m L中,1次/d;治疗组在对照组的基础上口服芪骨胶囊,3粒/次,3次/d。两组均持续治疗4周。观察两组的临床疗效,同时比较两组治疗前后VAS评分、肿胀程度及其疼痛缓解、肿胀消除和骨折愈合的时间。结果治疗后,两组总有效率比较差异不具有统计学意义。治疗1、4周后,两组患者VAS评分和肿胀程度评分均显著降低,同组治疗前后比较差异具有统计学意义(P0.05);且治疗1周后治疗组的上述评分明显低于对照组,两组比较差异具有统计学意义(P0.05)。治疗后,治疗组疼痛缓解时间、消肿时间以及骨折愈合时间均较对照组明显缩短,两组比较差异具有统计学意义(P0.05)。结论芪骨胶囊联合骨瓜提取物注射液治疗中老年不稳定型桡骨远端骨折能有效减轻患者疼痛和肿胀情况,缩短止痛、消肿以及骨折愈合的时间,具有一定的推广应用价值。