认知障碍的海马多模态MRI研究进展

认知障碍是一种未达到痴呆程度的疾病,不仅影响患者的日常生活能力,严重者可能发展为痴呆.海马是承载机体认知功能的重要脑区,近年来,MRI技术被广泛地应用于认知障碍患者海马的研究,因此,笔者就认知障碍的海马MRI神经影像的研究现状进行综述,以了解其最新进展.大量研究一致认为海马是认知功能损害的主要受累脑区,尤其海马CA1区,其功能和结构改变可能是认知功能损害的重要神经影像学标志物,相比于结构变化,功能改变对检测认知障碍可能更敏感.     

Effects of exercise dose and type during breast cancer chemotherapy on longer-term patient-reported outcomes and health-related fitness: A randomized controlled trial

The Combined Aerobic and Resistance Exercise (CARE) Trial compared different types and doses of exercise performed during breast cancer chemotherapy. Here, we report the longer-term follow-up of patient-reported outcomes, health-related fitness and exercise behavior at 6, 12 and 24 months postintervention. A multicenter trial in Canada randomized 301 breast cancer patients initiating chemotherapy to thrice weekly, supervised exercise consisting of a standard dose of 25–30 min of aerobic exercise (STAN; n = 96), a higher dose of 50–60 min of aerobic exercise (HIGH; n = 101) or a combined dose of 50–60 min of aerobic and resistance exercise (COMB; n = 104) performed for the duration of chemotherapy (median of 17 weeks). Primary outcomes were patient-reported outcomes including quality of life, cancer-related symptoms and psychosocial outcomes. Secondary outcomes were objective health-related fitness (assessed at 12 months only) and self-reported exercise behavior. A total of 269 (89.4%) participants completed patient-reported outcomes at all three follow-up time points and 263 (87.4%) completed the health-related fitness assessment at 12-month follow-up. COMB was significantly superior to (i) STAN for sleep quality at 6-month follow-up (p = 0.027); (ii) HIGH for upper body muscular endurance at 12-month follow-up (p = 0.020); and (iii) HIGH for meeting the resistance exercise guideline at 6-month follow-up (p = 0.006). Moreover, self-reported meeting of the combined exercise guideline during follow-up was significantly associated with better patient-reported outcomes and health-related fitness. Performing combined exercise during and after breast cancer chemotherapy may result in better longer-term patient-reported outcomes and health-related fitness compared to performing aerobic exercise alone.     

妊娠合并右心感染性心内膜炎的临床特征及母婴结局的文献分析

目的探讨妊娠合并右心感染性心内膜炎的临床特征、处理策略和母婴结局,为疾病的诊断和治疗提供理论依据。方法在中国知网、万方数据库、维普网、中国生物医学文献服务系统、PubMed、OVID、EMbase、ScienceDirect数据库检索相关文献,提取临床资料,分析妊娠合并右心感染性心内膜炎的临床表现、危险因素、赘生物位置、血培养结果、治疗策略和母婴结局等。结果纳入15篇文献,共18例患者。患者年龄为(27.7±4.8)岁,发病孕周为(27.8±6.9)周。发热(14例)、咳嗽(12例)、贫血(8例)、气短或呼吸困难(8例)是最常见的症状。心脏听诊时7例可闻及杂音,其中6例为收缩期杂音,1例未明确杂音类型,5例明确心脏听诊无杂音。9例合并肺栓塞和5例合并心力衰竭。危险因素主要为先天性心脏病(10/18)和静脉药瘾史(6/18)。赘生物附着位置以三尖瓣居多(10/18),其次为肺动脉瓣(4/18)。血培养阳性率高(15/16),主要包括葡萄球菌(9/15)及链球菌(3/15)。处理策略上,多以剖宫产适时终止妊娠,针对心内膜炎方面,在应用足量足疗程抗生素的基础上,11例患者行心脏手术,术式主要包括赘生物清除术、瓣膜修复或置换术以及先天性心脏病的手术等,根据患者的孕周、病情和心肺功能等具体情况决定手术在终止妊娠之前、之后或同期进行。18例患者全部存活,新生儿1例死亡(妊娠28周时行剖宫产分娩,因重度窒息死亡)。产妇随访情况基本良好。结论妊娠合并右心感染性心内膜炎临床少见且病情复杂,需及早诊断并实施个体化治疗方案。给予足量足疗程抗生素、选择合适的手术方案以及终止妊娠的时机,对于母婴结局具有重要意义。     

新型冠状病毒肺炎中医认识初探

新型冠状病毒肺炎中医属"寒湿疫"范畴,以湿邪为病机核心,以肺为病位中心,以脾胃盛衰为疾病进退的关键。治疗与预防调护方面,急性期,卫气同调,宜宣清和化;恢复期,肺脾同治,宜清补轻宣,注重饮食、情志调摄;谨慎使用抗病毒、抗生素、激素及液体疗法。     

Epidemiology and risk factors of colorectal cancer in China

In China, colorectal cancer (CRC) ranked fourth and fifth in the highest incidence and mortality rates of all malignancies in 2018, respectively. Although these rates are below the world average, China placed first worldwide in the number of new CRC cases and CRC-related deaths because of its comparatively large population. This disease represents a threat to the health of population and incurs a heavy economic burden on the society and individuals. CRC has various risk factors, including age, sex, lifestyle, genetic factors, obesity, diabetes, gut microbiota status, and precancerous lesions. Furthermore, incidence and mortality rates of CRC are closely related to socioeconomic development levels, varying according to regional and population characteristics. Prevention is the main strategy to reduce incidence and mortality rates of CRC. This can be achieved through strategies stimulating lifestyle changes, healthy diet habits, and early screening for high-risk individuals. To reduce the burden of CRC, public health officials should promote prevention and management of modifiable risk factors through national policies. The rising incidence and mortality rates of CRC in China may be timely curbed by clarifying specific epidemiological characteristics, optimizing early screening strategies, and strictly implementing diagnosis and treatment guidelines. Thus, this study aimed to collect and report the current research status on epidemiology and risk factors of CRC in China.     

Tau Accumulation via Reduced Autophagy Mediates GGGGCC Repeat Expansion-Induced Neurodegeneration in Drosophila Model of ALS

Expansions of trinucleotide or hexanucleotide repeats lead to several neurodegenerative disorders, including Huntington disease [caused by expanded CAG repeats (CAGr) in the HTT gene], and amyotrophic lateral sclerosis [ALS, possibly caused by expanded GGGGCC repeats (G4C2r) in the C9ORF72 gene], of which the molecular mechanisms remain unclear. Here, we demonstrated that lowering the Drosophila homologue of tau protein (dtau) significantly rescued in vivo neurodegeneration, motor performance impairments, and the shortened life-span in Drosophila expressing expanded CAGr or expanded G4C2r. Expression of human tau (htau4R) restored the disease-related phenotypes that had been mitigated by the loss of dtau, suggesting an evolutionarily-conserved role of tau in neurodegeneration. We further revealed that G4C2r expression increased tau accumulation by inhibiting autophagosome–lysosome fusion, possibly due to lowering the level of BAG3, a regulator of autophagy and tau. Taken together, our results reveal a novel mechanism by which expanded G4C2r causes neurodegeneration via an evolutionarily-conserved mechanism. Our findings provide novel autophagy-related mechanistic insights into C9ORF72-ALS and possible entry points to disease treatment.Electronic supplementary materialThe online version of this article (10.1007/s12264-020-00518-2) contains supplementary material, which is available to authorized users.     

Melatonin reduces oxidative stress and improves vascular function in pulmonary hypertensive newborn sheep

Pulmonary hypertension of the newborn (PHN) constitutes a critical condition with severe cardiovascular and neurological consequences. One of its main causes is hypoxia during gestation, and thus, it is a public health concern in populations living above 2500 m. Although some mechanisms are recognized, the pathophysiological facts that lead to PHN are not fully understood, which explains the lack of an effective treatment. Oxidative stress is one of the proposed mechanisms inducing pulmonary vascular dysfunction and PHN. Therefore, we assessed whether melatonin, a potent antioxidant, improves pulmonary vascular function. Twelve newborn sheep were gestated, born, and raised at 3600 meters. At 3 days old, lambs were catheterized and daily cardiovascular measurements were recorded. Lambs were divided into two groups, one received daily vehicle as control and another received daily melatonin (1 mg/kg/d), for 8 days. At 11 days old, lung tissue and small pulmonary arteries (SPA) were collected. Melatonin decreased pulmonary pressure and resistance for the first 3 days of treatment. Further, melatonin significantly improved the vasodilator function of SPA, enhancing the endothelial‐ and muscular‐dependent pathways. This was associated with an enhanced nitric oxide‐dependent and nitric oxide independent vasodilator components and with increased nitric oxide bioavailability in lung tissue. Further, melatonin reduced the pulmonary oxidative stress markers and increased enzymatic and nonenzymatic antioxidant capacity. Finally, these effects were associated with an increase of lumen diameter and a mild decrease in the wall of the pulmonary arteries. These outcomes support the use of melatonin as an adjuvant in the treatment for PHN.     

Systematic review of drug–drug interactions between rifamycins and anticoagulant and antiplatelet agents and considerations for management

Rifamycins (rifampin, rifabutin, and rifapentine) play an essential role in the treatment of mycobacterial and some nonmycobacterial infections. They also induce the activity of various drug transporting and metabolizing enzymes, which can impact the concentrations and efficacy of substrates. Many anticoagulant and antiplatelet (AC/AP) agents are substrates of these enzymes and have narrow therapeutic indices, leading to risks of thrombosis or bleeding when coadministered with rifamycins. The objective of this systematic review was to evaluate the effects on AC/AP pharmacokinetics, laboratory markers, and clinical safety and efficacy of combined use with rifamycins. A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidance was performed. The PubMed, Embase, and Web of Science databases were queried for English-language reports on combination use of rifamycins and AC/AP agents from database inception through August 2021. The 29 studies identified examined warfarin (n = 17), direct oral anticoagulants (DOACs) (n = 8), and antiplatelet agents (n = 4) combined with rifampin (n = 28) or rifabutin (n = 1). Eleven studies were case reports or small case series; 14 reported on pharmacokinetic or laboratory markers in healthy volunteers. Rifampin-warfarin combinations led to reductions in warfarin area under the curve (AUC) of 15%–74%, with variability by warfarin isomer and study. Warfarin dose increases of up to 3–5 times prerifampin doses were required to maintain coagulation parameters in the therapeutic range. DOAC AUCs were decreased by 20%–67%, with variability by individual agent and with rifampin versus rifabutin. The active metabolite of clopidogrel increased substantially with rifampin coadministration, whereas prasugrel was largely unaffected and ticagrelor saw decreases. Our review suggests most combinations of AC/AP agents and rifampin are problematic. Further studies are required to determine whether rifabutin or rifapentine could be safe alternatives for coadministration with AC/AP drugs.