慢性乙型肝炎组织中肝前体细胞的免疫组化特征

目的研究肝前体细胞（hepatic progenitor cells,HPCs）、小管样反应、中间型肝细胞在慢性乙型肝炎组织中的分布特征和数量变化,以及与肝细胞再生之间的可能联系。方法对42例慢性乙型肝炎组织行常规病理HE染色,按炎症活动度（G）分为轻、中、重三度,免疫组织化学方法观察肝胆细胞标记（AFP、GST-π、CK7、CK19）和造血干细胞标记（c-kit、CD34）的表达,并以Ki-67标记增殖的肝细胞,用CK7／CK19作为标记物对符合定义的HPCs、中间型肝细胞进行计数,小管样反应程度的判定利用彩色病理图象分析系统。结果慢性乙型肝炎的早期阶段即存在HPCs的活化和小管样反应,其数量随着炎症活动度的增加而增加,均表达CK7、CK19、GST-π和AFP,肝细胞增殖指数在轻、中度肝炎中逐渐增加,重度肝炎、肝硬化患者增殖的肝细胞数下降,而中间型肝细胞数量显著增加。小管样反应面积百分比与HPCs数目正相关（r=0．739,P〈0．05）,中间型肝细胞数目与HPCs数目正相关（r=0．614,P〈0．05）。结论慢性乙型肝炎中不仅有成熟肝细胞增殖,也存在肝前体细胞活化和分化,可能参与肝脏损伤后的再生修复。     

MR扩散加权像在急性病毒性肝炎中的初步应用

目的探讨MR扩散加权像在急性病毒性肝炎患者中对肝功能评价的价值。方法健康志愿者20例作为对照组,急性病毒性肝炎（AVH）患者56例（其中肝功能正常组26例,肝功能异常组30例）作为研究组。分别测量各例的表观扩散系数（ADC）并与转氨酶对比分析。结果在扩散敏感系数（b值）取200、400、600 s/mm2时肝功能正常组及异常组的ADC值均高于对照组,差异有统计学意义。肝功能异常组的ADC值与转氨酶呈正相关。结论在急性病毒性肝炎患者中,DWI是一种具有潜力无创的评价肝功能的重要手段,有待于进一步的探索和提高。     

L-Serine Treatment is Associated with Improvements in Behavior,EEG, and Seizure Frequency in Individuals with GRIN-Related Disorders Due to Null Variants

Pathogenic missense variants in GRIN2A and GRIN2B may result in gain or loss of function (GoF/LoF) of the N-methyl-D-aspartate receptor (NMDAR). This observation gave rise to the hypothesis of successfully treating GRIN-related disorders due to LoF variants with co-agonists of the NMDAR. In this respect, we describe a retrospectively collected series of ten individuals with GRIN2A- or GRIN2B-related disorders who were treated with L-serine, each within an independent n-of-1 trial. Our cohort comprises one individual with a LoF missense variant with clinical improvements confirming the above hypothesis and replicating a previous n-of-1 trial. A second individual with a GoF missense variant was erroneously treated with L-serine and experienced immediate temporary behavioral deterioration further supporting the supposed functional pathomechanism. Eight additional individuals with null variants (that had been interpreted as loss-of-function variants despite not being missense) again showed clinical improvements. Among all nine individuals with LoF missense or null variants, L-serine treatment was associated with improvements in behavior in eight (89%), in development in four (44%), and/or in EEG or seizure frequency in four (44%). None of these nine individuals experienced side effects or adverse findings in the context of L-serine treatment. In summary, we describe the first evidence that L-serine treatment may not only be associated with clinical improvements in GRIN-related disorders due to LoF missense but particularly also null variants.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13311-021-01173-9.     

六味银杏胶囊的毒理学研究

目的观察动物口服六味银杏胶囊的急性毒性和长期毒性反应。方法采用最大给药量法测定小鼠口服六味银杏胶囊的急性毒性;以20.0,10.0,5.0 g生药.kg-1.d-13个剂量的六味银杏胶囊(相当于临床用量68、34、17倍)灌胃SD大鼠,连续24周,观察服药24周及停药4周后,大鼠的生长发育、血液学、血液生化学、组织病理指标的变化。结果小鼠1天内口服六味银杏胶囊最大给药量为190.0 g生药/kg,相当于临床用量的700倍。长期毒性实验中,各剂量组与空白对照组比较,大鼠一般状况,体重增长,血液学、血液生化指标,主要脏器系数,肉眼观察及镜下组织形态学观察均无明显差异或异常。结论六味银杏胶囊临床用药范围内应用是比较安全的。     

The Biomarkers for Predicting Viral Hepatitis-Associated Hepatocellular Carcinoma

BackgroundHepatocellular carcinoma (HCC) is the fifth most common cancer in the world, and more than half of the newly diagnosed cases are chronic hepatitis B patients. Due to the lack of specific clinical manifestations, many patients are already at an advanced stage at the time of diagnosis and therefore have missed the best time for treatment. Organs in a pathological state usually secrete specific substances into the blood, which can indirectly indicate the pathological state of the organ, so some biological markers in the blood can be used as a tool to predict the incidence of HCC.MethodsThe Research articles related to HCC were collected by searching PubMed databases with the keywords “hepatocellular carcinoma”, “serum biomarker”, “hepatitis B”, “prediction” and “prognosis”, and Additional articles were identified by manual search of references found in the primary articles, followed by a summary and review.ResultsViral hepatitis is the main cause of HCC worldwide, and this phenomenon is particularly prominent in Asian and African populations. A variety of serological markers including M2BPGi, IL-6 and COMP can be used to predict the incidence of long-term HCC in patients. The risk of HCC is dynamic rather than constant, and dynamic detection will help improve prediction accuracy. For hepatitis B patients, HBV DNA load and HBcr Ag are important predictive markers of HCC.ConclusionFor a high-risk population of HCC, early risk prediction is helpful to guide clinical work, and timely adjustments of the screening frequency and treatment plan are helpful to prolong the survival time of HCC patients.     

银汞桩核与分体式铸造桩核用于磨牙修复的疗效对比观察

目的:比较银汞桩核和分体式铸造桩核用于修复磨牙严重缺损病例的临床疗效.方法:将78例磨牙牙体严重缺损病例随机分为银汞桩核修复组40个牙和分体铸造桩核修复组41个牙,并随访观察2～3年.结果:两种桩核修复的临床疗效无显著差异(P＞0.05).结论:银汞桩核和分体式铸造桩核用于修复牙体严重缺损的磨牙都能取得较好的临床效果.     

慢性阻塞性肺疾病急性加重期使用激素治疗与低血钾的关系分析

目的 探讨慢性阻塞性肺疾病(COPD)患者在病情加重时使用激素治疗与低血钾的关系.方法 回顾性分析73例COPD急性加重期使用激素治疗患者,按体重指数(BMI)进行分类比较,了解其与低血钾的关系.结果 超重患者低血钾发生率为31%, 不超重患者为6%,经χ2检验P＜0.05.结论 超重患者出现低血钾的机会较大,应多监测,及时补充和纠正,避免严重心律失常事件的发生.     

黄春林运用仙芪地黄汤加减治疗慢性肾病经验

黄春林教授认为脾肾气虚、湿瘀内阻是慢性肾脏疾病的常见病机,益气健脾补肾、祛湿活血是慢性肾脏疾病的治疗大法,在古方六味地黄丸的基础上自拟仙芪地黄汤为基本方,加减治疗多种慢性肾脏疾病,临床疗效良好。该文对其运用仙芪地黄汤加减治疗慢性肾脏疾病的临床经验进行了初步的总结。     

Effect of Killed PRRSV Vaccine on Gut Microbiota Diversity in Pigs

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically important pathogens affecting the global swine industry. Vaccination is still a main strategy for PRRSV control; however, host factors associated with vaccine efficacy remain poorly understood. Growing evidence suggests that mucosa-associated microbiomes may play a role in the responses to vaccination. In this study, we investigated the effects of a killed virus vaccine on the gut microbiome diversity in pigs. Fecal microbial communities were longitudinally assessed in three groups of pigs (vaccinated/challenged with PRRSV, unvaccinated/challenged with PRRSV, and unvaccinated/unchallenged) before and after vaccination and after viral challenge. We observed significant interaction effects between viral challenge and vaccination on both taxonomic richness and community diversity of the gut microbiota. While some specific taxonomic alterations appear to be enhanced in vaccinated/challenged pigs, others appeared to be more consistent with the levels in control animals (unvaccinated/unchallenged), indicating that vaccination incompletely protects against viral impacts on the microbiome. The abundances of several microbial taxa were further determined to be correlated with the level of viral load and the amount of PRRSV reactive CD4⁺ and CD8⁺ T-cells. This study highlights the potential roles of gut microbiota in the response of pigs to vaccination, which may pave the road for the development of novel strategies to enhance vaccine efficacy.