Use of cyproheptadine hydrochloride (HCl) to reduce neuromuscular hypertonicity in stroke survivors: A Randomized Trial: Reducing Hypertonicity in Stroke

ObjectivesThe goal of this study was to examine how the administration and dosing of the anti-serotonergic medication cyproheptadine hydrochloride (HCl) affects involuntary muscle hypertonicity of the spastic and paretic hands of stroke survivors.Materials and MethodsA randomized, double-blinded, placebo-controlled longitudinal intervention study was performed as a component of a larger clinical trial. 94 stroke survivors with chronic, severe hand impairment, rated as levels 2 or 3 on the Chedoke-McMaster Stroke Assessment Stage of Hand (CMSA-H), were block randomized to groups receiving doses of cyproheptadine HCl or matched doses of placebo. Doses were increased from 4 mg BID to 8 mg TID over 3 weeks. Outcomes were assessed at baseline and after each of the three weeks of intervention. Primary outcome measure was grip termination time; other measures included muscle strength, spasticity, coactivation of the long finger flexors, and recording of potential adverse effects such as sleepiness and depression.Results89 participants (receiving cyproheptadine HCl: 44, receiving placebo: 45) completed the study. The Cyproheptadine group displayed significant reduction in grip termination time, in comparison with the Placebo group (p<0.05). Significant change in the Cyproheptadine group (45% time reduction) was observed after only one week at the 4mg BID dosage. The effect was pronounced for those participants in the Cyproheptadine group with more severe hand impairment (CMSA-H level 2) at baseline. Conversely, no significant effect of Group * Session interaction was observed for spasticity (p=0.6) or coactivation (p=0.53). There were no significant changes in strength (p=0.234) or depression (p=0.441) during the trial.ConclusionsUse of cyproheptadine HCl was associated with a significant reduction in relaxation time of finger flexor muscles, without adversely affecting voluntary strength, although spasticity and coactivation were unchanged. Decreasing the duration of involuntary flexor activity can facilitate object release and repeated prehensile task performance.RegistrationClinical Trial number: NCT02418949     

两种相变型多功能纳米粒的制备及体外特性比较

目的制备包裹吲哚菁绿(ICG)及不同相变材料[全氟正戊烷(PFP)或全氟己烷(PFH)]的两种相变型多功能纳米粒,比较其理化性质、稳定性及体外相变特性。方法采用改良的双乳化法制备包裹ICG及液态PFP或PFH的乳酸-羟基乙酸(PLGA)纳米粒(分别称为IPNPs、IHNPs),比较两者的一般特性、稳定性及热致相变、光致相变、声致相变和光声成像能力,采用MTT法检测光致相变所需能量的细胞毒性。结果IPNPs及IHNPs粒径分别为(490.53±36.96)nm及(512.23±38.52)nm,电位分别为(-14.40±1.40)mV及(-13.97±1.61)mV,二者差异无统计学意义(P均0.05);二者形态、吸收光谱也均无明显差异,于37℃储存24h均较稳定;IPNPs热致相变、光致相变及声致相变所需能量均低于IHNPs,且IPNPs光声及超声成像增强能力高于IHNPs。经能使IPNPs及IHNPs发生相变的激光能量辐照后,MH7A细胞存活率分别为(95.34±7.96)%,(54.92±6.11)%,二者差异有统计学意义(P0.05)。结论 IPNPs是更适于诊疗一体化应用的多功能纳米粒。     

Mechanism of Regulatory Effect of MicroRNA-206 on Connexin 43 in Distant Metastasis of Breast Cancer

Background:

MicroRNA-206 (miR-206) and connexin 43 (Cx43) are related with the distant metastasis of breast cancer. It remains unclear whether the regulatory effect of miR-206 on Cx43 is involved in metastasis of breast cancer.

Methods:

Using quantitative real-time polymerase chain reaction and Western blot, the expressions of miR-206 and Cx43 were determined in breast cancer tissues, hepatic and pulmonary metastasis (PM), and cell lines (MCF-10A, MCF-7, and MDA-MB-231). MCF-7/MDA-M-231 cells were transfected with lentivirus-shRNA vectors to enhance/inhibit miR-206, and then Cx43 expression was observed. Cell counting kit-8 assay and Transwell method were used to detect their changes in proliferation, migration, and invasion activity. The mutant plasmids of Cx43-3’ untranslated region (3’UTR) at position 478–484 and position 1609–1615 were constructed. Luciferase reporter assay was performed to observe the effects of miR-206 on luciferase expression of different mutant plasmids and to confirm the potential binding sites of Cx43.

Results:

Cx43 protein expression in hepatic and PM was significantly higher than that in the primary tumor, while no significant difference was showed in messenger RNA (mRNA) expression. MiR-206 mRNA expression in hepatic and PM was significantly lower than that in the primary tumor. Cx43 mRNA and protein levels, as well as cell proliferation, migration, and invasion capabilities, were all significantly improved in MDA-MB-231 cells after reducing miR-206 expression but decreased in MCF-7 cells after elevating miR-206 expression, which demonstrated a significantly negative correlation between miR-206 and Cx43 expression (P = 0.03). MiR-206 can drastically decrease Cx43 expression of MCF-7 cells but exerts no effects on Cx43 expression in 293 cells transfected with the Cx43 coding region but the lack of Cx43-3’UTR, suggesting that Cx43-3’UTR may be the key in Cx43 regulated by miR-206. Luciferase expression showed that the inhibition efficiency was reduced by 46.80% in position 478–484 mutant, 16.72% in position 1609–1615 mutant; the inhibition was totally disappeared in double mutant (P = 0.02).

Conclusions:

MiR-206 can regulate the expression of Cx43, the cytobiological activity, and the metastasis of breast cancer through binding to the two binding sites in Cx43-3’UTR: position 478–484 and position 1609–1615.     

双环钢丝捆扎技术联合关节置换对转子间骨折患者快速康复的临床观察

目的  探讨交叉双环钢丝捆扎技术联合关节置换术治疗高龄股骨转子间粉碎骨折的临床疗效。方法选取本院2013～2014年行人工关节置换结合钢丝捆扎治疗转子间骨折（Evans-Jensen分型：Ⅲ型、Ⅵ型）病例进行回顾性分析,其中15例采用双环钢丝捆扎加人工关节置换术,19例采用普通环形钢丝捆扎加人工关节置换术。两组分别比较住院时间、首次行走时间、术前术后记录每日睡眠时间、每日饮食量、精神状态、髋关节Harris评分、血红蛋白、白蛋白、电解质、是否有关节脱位、呼吸及泌尿系统炎症等疾病,并进行对比分析。结果  采用交叉双环钢丝捆扎组与采用普通钢丝捆扎组比较,前者术后下床时间、住院天数及术后首月髋关节Harris评分优于后者（P <0.05）,两者血液指标出院前后无明显差异（P >0.05）,但前者恢复速度较后者更快（P <0.05）,两组术后第3个月、第6个月及1年髋关节Harris功能评分差异无统计学意义（P >0.05）。结论  交叉双环钢丝捆扎加人工关节置换术能促进患者术后快速康复,减少住院时间,提高患髋近期功能,在患者术后快速恢复方面有积极作用。

     

18β-glycyrrhetinic acid inhibits migration and invasion of human gastric cancer cells via the ROS/PKC-α/ERK pathway

Journal of Natural Medicines - 18β-glycyrrhetinic acid (18β-GA) is a bioactive component of licorice root which exerts pharmacological activities including anti-inflammatory, antiviral,...     

Killed but metabolically active Pseudomonas aeruginosa-based vaccine induces protective humoral- and cell-mediated immunity against Pseudomonas aeruginosa pulmonary infections

Pseudomonas aeruginosa (Pa) is a significant cause of morbidity and mortality, especially in cystic fibrosis patients. Its eradication is difficult due to a wide phenotypic adaptability and an increase of its resistance to antibiotics. After the failure of several recombinant vaccines which mainly triggered humoral response, live-attenuated vaccines received attention thanks to their ability to elicit a broad immunity with both humoral- and cell-mediated responses, essential to fight this pathogen. In this study, we developed an innovative and safer live-attenuated Pa vaccine based on a Killed But Metabolically Active (KBMA) attenuation method. KBMA Pa has been further rationally designed to overexpress beneficial effectors like the type 3 secretion system apparatus. We demonstrated that KBMA Pa elicits a high and broad humoral response in mice against several antigens of particular interest such as OprF and PcrV proteins. Moreover, we assessed cytokines in the serum of immunized mice and showed that KBMA Pa elicits Th1, Th2 and especially Th17 pathways of cell-mediated immune responses. Th17 pathway involvement was also confirmed after specific stimulation of helper T cells in immunized mice. Finally, we showed that this vaccine is safe and has a protective effect in a murine acute pulmonary infectious challenge. In conclusion, KBMA Pa is a new platform with high potential for the development of a vaccine against Pa.     

沙库巴曲缬沙坦治疗急性失代偿射血分数降低心力衰竭患者的有效性和安全性

探讨沙库巴曲缬沙坦（S/V）治疗射血分数降低急性失代偿心力衰竭（ADHF）患者的有效性和安全性。方法 连续纳入2018年5月～2019年10月重庆4个研究中心心血管内科射血分数降低的ADHF患者,根据临床处方信息患者被分为S/V组和血管紧张素转换酶抑制剂（ACEI）/血管紧张素受体阻滞剂（ARB）组（ACEI/ARB组）。住院期间和出院后医生根据患者的一般情况和血压滴定药物剂量,随访至出院后12个月。主要有效性终点是心源性死亡和心衰（HF）住院发生率,次要有效性终点是全因死亡和全因住院发生率。安全性终点肾功能损伤、高钾血症、咳嗽、血管神经性水肿和症状性低血压发生率。结果 筛选期共纳入758例,根据入排标准排除127例,631例纳入倾向性评分,最后502例患者纳入数据分析,S/V组和ACEI/ARB组各251例。S/V组和ACEI/ARB组患者主要疗效性终点心血管死亡和HF住院发生率分别为235%和32.3%（HR:0.687; 95% CI:0.493～0.958; P=0.027）,其中心血管死亡发生率分别为48%和10.4%（HR:0.444; 95% CI: 0.235～0.840; P=0.017）,HF再住院发生率分别为18.7%和21.9%（HR:0.845; 95% CI:0.573～1.247; P=0.398）;次要疗效终点全因死亡和全因住院发生率分别为35.1%和38.2%（HR:0.891; 95% CI:0.668～1.191; P=0.4.37）,其中全因死亡发生率分别为4.8%和11.6%（HR:0.396; 95% CI:0.214～0.731; P=00005）,全因住院发生率分别为30.3%和26.7%（HR, 1.168; 95% CI:0.841～1.622; P=0.352）。安全性终点两组无显著差异。结论 与ACEI/ARB相比,S/V治疗可降低射血分数降低的ADHF患者1年心源性死亡和心衰住院复合终点,并且其安全性相当。     

消化内镜专科护士培训中应用目标反馈教学的效果研究

目的　探讨目标反馈教学在消化内镜专科护士培训中的应用效果。方法　以参加重庆市消化内镜专科护士培训的68名学员为研究对象,将2019年的30名学员作为观察组,采用目标反馈教学法进行培训;2018年的38名学员作为对照组,采用传统培训方法。培训结束后,从理论成绩、技能操作成绩及综合成绩3个方面评价并比较两组学员的培训效果,同时针对学员的满意度进行问卷调查。采用SPSS 25.0进行t检验、卡方检验和Mann-Whitney U检验。结果　观察组学员的技能操作成绩（84.90±4.92）、综合成绩（86.30±4.62）高于对照组（82.39±4.10）（83.86±5.10）,差异有统计学意义（P<0.05）;理论成绩差异不大,无统计学意义[（85.80±5.63）vs.（83.68±4.51）,P>0.05]。学员对新的培训方法满意度较高。结论　目标反馈教学能很好地提高消化内镜专科护士的操作技能和综合能力,提高培训效果,确保专科护士对培训的满意度。     

影像学云平台在医学影像学实习教学中的应用与价值

目的　探讨将影像学云平台应用于医学影像学实习教学对学生诊断思维能力和学习体验的影响。方法　将重庆医科大学2016级医学影像系88位学生分为两组,每组44人。试验组以影像学云平台开展实习教学,对照组以传统实习方式教学。4周后对比两组在诊断思维能力和学习体验间的差异。采用SPSS 22.0软件进行t检验。结果　诊断思维能力的测试总成绩试验组高于对照组[（80.63±6.10） vs. （70.36±8.09）],差异有统计学意义（P<0.05）。其中征象描述、鉴别诊断及要点、新进展与建议3项得分差异有统计学意义（P<0.05）。对学习体验问卷调查的5个方面,试验组的评分均高于对照组,差异均有统计学意义（P<0.05）。结论　在影像学实习中应用影像学云平台对提高学生的诊断思维能力、提升学习体验具有重要的价值,值得实践与推广。