Anti‐fibrotic and Anti‐tumorigenic Effects of Rhein,a Natural Anthraquinone Derivative,in Mammalian Stellate and Carcinoma Cells

Anthraquinone compounds have been recognized to possess antiinflammatory, anti‐fibrotic and anti‐tumour properties and thus applied in human and veterinary therapeutics as active substances of medicinal products. Amongst the anthraquinones isolated from Rheum palmatum, also known as da‐huang, rhein was detected as one of the highest metabolite contents in the bloodstream of mammals. The biological activities of rhein therefore deserve detailed investigation. In this study, we aimed to delineate the mechanism of inhibitory actions of rhein on fibrotic and tumorigenic processes by means of various biochemical assays, such as immunofluorescent staining, real‐time polymerase chain reaction (PCR) and western blotting analyses in rat pancreatic stellate cells (LTC‐14), human pancreatic ductal adenocarcinoma cells (PANC‐1) and human colon carcinoma cells (SW480 and SW620). Our results demonstrated that the application of rhein notably suppressed the mRNA and protein levels of various fibrotic and tumorigenic mediators including alpha‐smooth muscle actin, type I collagen, fibronectin, N‐cadherin and matrix metalloproteinases in the testing mammalian cells. The mechanism of the suppressive actions of rhein was associated with the modulation of the sonic hedgehog and serine‐threonine kinase signalling pathways. In conclusion, we suggest that rhein may serve as a therapeutic or an adjuvant agent in anti‐fibrotic and anti‐tumorigenic approaches. Copyright © 2014 John Wiley & Sons, Ltd.     

超声引导下腹部神经阻滞对老年患者术后疼痛及认知状态的影响

目的：探讨超声引导下腹部神经阻滞对老年患者术后疼痛及认知状态的影响。方法：回顾性分析本院2017年4月～2020年4月收治的80例老年腹部手术患者,根据镇痛模式的选择分为全麻-神经阻滞组(44例)和全麻组(36例)。比较两组的术中情况(麻醉时间、手术时间、术中出血量)、术后24 h内舒芬太尼自控镇痛用量与追加次数、术后24 h和术后48 h的静息状态与运动状态下疼痛程度(VAS疼痛评分)、入室时和术后24 h的血清细胞白介素6(IL-6)、超敏-C反应蛋白(Hs-CRP)水平、术后7 d内POCD发生率和不良反应发生率。结果：两组患者麻醉时间、手术时间、术中出血量的差异均无统计学意义;全麻-神经阻滞组患者的24 h内舒芬太尼用量、追加次数、术后24 h和48 h的静息疼痛评分和运动疼痛评分均低于全麻组;两组患者术后24 h的血清IL-6、Hs-CRP均较入室时升高,全麻-神经阻滞组术后24 h的血清IL-6、Hs-CRP低于全麻组;两组患者术后POCD发生率和不良反应总发生率无明显差异。结论：全麻-神经阻滞继以静脉自控镇痛用于老年腹部手术患者的镇痛效果优于全麻继以静脉自控镇痛,舒芬太尼...     

老年睑板腺功能障碍蠕形螨感染率及茶树精油联合氟米龙的疗效

目的：研究老年睑板腺功能障碍(MGD)蠕形螨感染率及茶树精油联合氟米龙的疗效。

方法：回顾性病例对照研究。选择2017-09/2018-03在宁波市眼科医院门诊就诊的老年MGD患者59例118眼。将睫毛蠕形螨镜检为阳性的38例患者76眼进行症状评分、蠕形螨数量、泪膜破裂时间(BUT)、角膜荧光素染色(FL)、Schirmer I试验(SIaT)等检查,并按不同治疗方法分成3组,A组使用0.02%氟米龙滴眼液滴眼24眼; B组使用茶树精油(TTO)湿巾敷眼26眼; C组用0.02%氟米龙滴眼液滴眼联合TTO湿巾敷眼26眼,随访4wk。

结果：118眼中76眼(64.4%)睫毛蠕形螨镜检为阳性。睫毛蠕形螨阳性的三组患者治疗后的主观症状评分均较治疗前有改善(P<0.05)。治疗后A组蠕形螨数量较治疗前无显著差异(P=0.11); B、C组较治疗前明显减少(均P<0.01)。三组患者BUT治疗前后比较,A组BUT无显著差异(P=0.22); B、C组BUT明显延长(均P<0.05)。治疗后C组的BUT较A、B组明显延长(均P<0.05)。三组患者治疗前后的FL评分均较治疗前明显改善(P<0.05)。

结论：老年MGD患者睫毛蠕形螨感染率较高,睑板腺热疏通后TTO湿巾联合0.02%氟米龙滴眼液能有效驱螨、缓解MGD患者局部症状。     

Tisotumab vedotin in Japanese patients with recurrent/metastatic cervical cancer: Results from the innovaTV 206 study

New treatments, particularly second‐line options, are needed to improve outcomes for patients with recurrent/metastatic cervical cancer (r/mCC). Tisotumab vedotin (TV) is an antibody–drug conjugate directed to tissue factor, a transmembrane protein commonly expressed in cancer cells, to deliver cytotoxic monomethyl auristatin E. This single‐arm, open‐label phase 1/2 trial evaluated the consistency of safety and efficacy outcomes of TV in Japanese patients with r/mCC to bridge the current findings with those reported in previous trials in non‐Japanese patients in the United States and Europe. In part 1 (dose escalation; N = 6), patients with advanced solid tumors received TV 1.5 or 2.0 mg/kg once every 3 weeks to determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D). Part 2 (dose expansion; N = 17) evaluated the RP2D in r/mCC patients with 1–2 prior lines of therapy. In part 1, no dose‐limiting toxicities were observed, the MTD was not reached, and TV 2.0 mg/kg was established as the RP2D. In part 2, the most common treatment‐emergent adverse events were anemia (58.8%), nausea (58.8%), alopecia (47.1%), epistaxis (47.1%), and diarrhea (35.3%); adverse events of special interest were bleeding (76.5%), ocular events (35.3%), and peripheral neuropathy (17.6%), and were mostly grade 1/2. In part 2, confirmed objective response rate was 29.4%, median duration of response was 7.1 months, and median time to response was 1.2 months. In Japanese patients with r/mCC, TV demonstrated a manageable and tolerable safety, pharmacokinetics, and efficacy profile consistent with that observed in non‐Japanese patients.     

Analgesic and anti-arthritic effects of Lingzhi and San Miao San supplementation in a rat model of arthritis induced by Freund's complete adjuvant

Aim of study

In this study, we have investigated the analgesic and anti-arthritic effects of a traditional Chinese medicine (TCM) combination of Lingzhi and San Miao San (SMS) in a rat model of arthritis induced by Freund's complete adjuvant (FCA).

Materials and methods

Sprague–Dawley rats were induced with monoarthritis by single unilateral injection of FCA into the knee joint. The TCM combination was administered to the rats daily by intraperitoneal injection (50 mg/(kg day)) or via oral administration (500 mg/(kg day)) for 7 days before induction of arthritis and 7 days after. Extension angle that provoked struggling behavior, and size and blood flow of the rat knees were measured to give indexes of allodynia, edema, and hyperemia, respectively. The extent of cell infiltration, tissue proliferation, and erosions of joint cartilage provided additional indexes of the arthritis condition.

Results

FCA injection produced significant allodynia, edema, hyperemia, immune cell infiltration, synovial tissue proliferation, and erosions of joint cartilage in the ipsilateral knees compared with the contralateral saline-injected knees. Intraperitoneal injection of the TCM combination (50 mg/(kg day)) suppressed allodynia, edema, and hyperemia in the inflamed knees, and oral administration (500 mg/(kg day)) suppressed edema and hyperemia. Histological examination showed that the TCM administered by either route reduced immune cell infiltration and erosion of joint cartilage.

Conclusions

These findings suggest the Lingzhi and SMS formulation has analgesic and anti-inflammatory effects in arthritic rat knees, and concur to previous clinical studies that showed the TCM combination reduced pain in rheumatoid arthritis patients, and extends its possible benefit to suppression of inflammatory symptoms in these patients.     

Expectation and knowledge of pregnant women undergoing first and second trimester ultrasound examination in a Chinese population

OBJECTIVE: To evaluate expectation and knowledge on obstetric ultrasound examination in the first and second trimester in a Chinese population. METHOD: A cross-sectional survey was conducted in a university obstetric clinic in Hong Kong. Chinese pregnant women who underwent the first trimester early scan sessions, or the second trimester anomaly scan sessions were invited to complete a self-administered questionnaire, which contained items on their knowledge, expectation, and sociodemographic characteristics. RESULTS: In all 276 eligible pregnant women (117 in the first trimester and 159 in the second trimester) were recruited. Although 249 women (90.2%) claimed they understood the indication of the ultrasound examination, only 93 of them were correct (33.7%). The median perceived overall-detection rate for structural abnormalities was 66.5%. Living in Hong Kong for more than 7 years was significantly associated with higher knowledge level and expectation from ultrasound examination. Attaining tertiary education level was also significantly associated with higher knowledge level. Over 90% of the pregnant women studied wished to know the fetal gender from the anomaly scan examination. CONCLUSION: Knowledge of Chinese pregnant women on ultrasound was generally unsatisfactory. Understanding their limitation of knowledge and expectations helps to devise appropriate education in the local setting.     

血塞通在老年人急性脑梗死治疗中的临床价值分析

目的:探讨血塞通在老年人急性脑梗死治疗中的临床应用价值。方法:将本院2011年1月～2011年12月在本院诊治的82例急性脑梗死患者随机分成2组:①实验组41例;②对照组41例。对照组单纯给予阿托伐他汀治疗;实验组给予阿托伐他汀+血塞通治疗。观察比较两组的临床疗效、血凝系统和血液流变学的变化情况。结果:实验组的总有效率为82.93%,对照组的总有效率为56.09%,实验组的临床疗效明显优于对照组(P<0.05);实验组患者治疗后的Fbg、TT、PT、INR、APTT指标水平均显著性优于对照组(P<0.05);实验组患者治疗后的高切ηb、低切ηb、FIB、ηp、HCT指标水平均显著性优于对照组(P<0.05)。结论:临床应用血塞通治疗急性脑梗死的效果显著。     

RNA Interference-Mediated Knockdown of Bombyx mori Haemocyte-Specific Cathepsin L (Cat L)-Like Cysteine Protease Gene Increases Bacillus thuringiensis kurstaki Toxicity and Reproduction in Insect Cadavers

The silkworm’s Cat L-like gene, which encodes a lysosomal cathepsin L-like cysteine protease, is thought to be part of the insect’s innate immunity via an as-yet-undetermined mechanism. Assuming that the primary function of Cat L-like is microbial degradation in mature phagosomes, we hypothesise that the suppression of the Cat L-like gene expression would increase Bacillus thuringiensis (Bt) bacteraemia and toxicity in knockdown insects. Here, we performed a functional analysis of Cat L-like in larvae that were fed mulberry leaves contaminated with a commercial biopesticide formulation based on Bt kurstaki (Btk) (i.e., Dipel) to investigate its role in insect defence against a known entomopathogen. Exposure to sublethal doses of Dipel resulted in overexpression of the Cat L-like gene in insect haemolymph 24 and 48 h after exposure. RNA interference (RNAi)-mediated suppression of Cat L-like expression significantly increased the toxicity of Dipel to exposed larvae. Moreover, Btk replication was higher in RNAi insects, suggesting that Cat L-like cathepsin may be involved in a bacterial killing mechanism of haemocytes. Finally, our results confirm that Cat L-like protease is part of the antimicrobial defence of insects and suggest that it could be used as a target to increase the insecticidal efficacy of Bt-based biopesticides.     

Oliva vidua fulminans, a marine mollusc, responsible for five fatal cases of neurotoxic food poisoning in Sabah, Malaysia

This is the first report in which a marine mollusc, Oliva vidua fulminans (olives), generally not known to be poisonous, was responsible for death in five children after consuming boiled olives with tamarind. The onset of symptoms was rapid 10 to 20 min after consumption of the olives. Signs and symptoms included nausea, vomiting, abdominal pain, tingling sensation around the lips, numbness around the mouth, drowsiness, lethargy and generalized weakness with paraesthesia in the limbs. The five deaths occurred within 3 to 4 hours after eating the poisoned olives and resulted from respiratory failure. Left-over olives from the affected household and freshly collected live olives had a toxicity of 14,200 mouse units (M.U.) and 15,000 M.U. per 100 g meat respectively. No other common chemical poison and organophosphorus insecticides were detected. The neurotoxic agent was acid and heat stable and was toxic at pH less than 4. Its action was similar to that of paralytic shellfish poisoning which was caused by toxins from certain dinoflagellates.