Comment on “Outcomes of curative liver resection for hepatocellular carcinoma in patients with cirrhosis”

The present letter to the editor is in response to the research “Outcomes of curative liver resection for hepatocellular carcinoma in patients with cirrhosis” by Elshaarawy et al in World J Gastroenterol 2021; 13(5): 424–439. The preoperative assessment of the liver reserve function in hepatocellular carcinoma (HCC) patients with cirrhosis is crucial, and there is no universal consensus on how to assess it. Based on a retrospective study, Elshaarawy et al investigated the impact of various classical clinical indicators on liver failure and the prognosis after hepatectomy in HCC patients with cirrhosis. We recommend that we should strive to explore new appraisal indicators, such as the indocyanine green retention rate at 15 min.     

脊髓小脑共济失调2型家系ATXN2基因中间重复病例表型与分子遗传学特征

目的探讨脊髓小脑共济失调2型(SCA2)致病基因ATXN2异常等位基因中间重复个体的表型和分子遗传学特点。方法针对2005—2018年中日友好医院神经科运动障碍与神经遗传病研究中心收集的1383个常染色体显性遗传共济失调家系的先证者和部分家系成员,采用荧光标记毛细管电泳片段分析方法进行动态突变检测,对携带ATXN2基因中间重复的个体进行临床表型和遗传特征分析。结果共检出163个家系(包含先证者和家系成员共203人)携带异常扩展的ATXN2基因CAG重复序列,其中93个家系中有107例的异常扩展等位基因重复次数在29~34次之间。在其中的20个亲子对中,父系遗传16个,异常等位基因的代间扩展增加0~28次,母系遗传4个,异常等位基因的代间扩展增加0~4次。结论对于临床拟诊SCA2家系患者,需对其亲代或成年子代个体进行ATXN2基因检测,以免漏诊。动态突变基因检测有助于识别中间重复的个体,对明确家系致病基因和遗传咨询至关重要。     

Gastric Cancer and Paraneoplastic Pemphigus

Paraneoplastic pemphigus is a relatively rare but significant acquired autoimmune mucocutaneous disorder that is characterised by diffuse erythema, painful blistering and sores of the skin and mucus membranes. The underlying pathogenesis is believed to be triggered by altered immune system in response to underlying neoplasm. The manifestations can predate, occur at the same time or after the diagnosis of cancer. Associations with gastric cancer have only been reported twice. A 78-year-old lady presented with a month’s history of extensive skin lesions that started off as bullous lesions and biopsy revealed bullous pemphigus. Endoscopy for anemia revealed gastric cancer. This case reinforced the need to consider underlying malignancy in elderly patient with new onset dermatological presentation.     

Necroptotic TNFα-Syndecan 4-TNFα Vicious Cycle as a Therapeutic Target for Preventing Temporomandibular Joint Osteoarthritis

Temporomandibular joint osteoarthritis (TMJOA) is a chronic degenerative disease for which the underlying mechanism still remains unclear. Compared with apoptosis and autophagy, necroptosis causes greater harm to tissue homeostasis by releasing damage-associated molecular patterns (DAMPs). However, the role of necroptosis and downstream key DAMPs in TMJOA is unknown. Here, rodent models of TMJOA were established by the unilateral anterior crossbite (UAC). Transmission electron microscopy (TEM) and immunohistochemistry of receptor interacting protein kinase 3 (RIPK3)/phosphorylation of mixed lineage kinase domain-like protein (pMLKL) were conducted to evaluate the occurrence of necroptosis in vivo. The therapeutic effects of blocking necroptosis were achieved by intra-articularly injecting RIPK3 or MLKL inhibitors and using RIPK3 or MLKL knockout mice. In vitro necroptosis of condylar chondrocyte was induced by combination of tumor necrosis factor alpha (TNFα), second mitochondria-derived activator of caspases (SMAC) mimetics and carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone (z-VAD-fmk). The possible DAMPs released by necroptotic chondrocytes were screened by quantitative proteomics and blocked by specific antibody. Translucent cytosol, swollen organelles, and ruptured cell membranes, features of necroptosis, were frequently manifested in chondrocytes at the early stage of condylar cartilage degeneration in TMJOA, which was accompanied by upregulation of RIPK3/pMLKL. Inhibiting or knocking out RIPK3/MLKL significantly prevented cartilage degeneration. DAMPs released by necroptotic condylar chondrocytes, such as syndecan 4 (SDC4) and heat shock protein 90 (HSP90), were verified. Furthermore, blocking the function of SDC4 significantly attenuated the expression of TNFα in cartilage and synovium, and accordingly increased cartilage thickness and reduced synovial inflammation. Thus, the necroptotic vicious cycle of TNFα-SDC4-TNFα contributes to cartilage degeneration and synovitis, and can serve as a potential therapeutic target for treating TMJOA. © 2022 American Society for Bone and Mineral Research (ASBMR).     

补充维生素D预防骨折——随机对照试验汇总分析

背景：对于脊椎以外的骨折而言，补充口服维生素D的预防作用和用量仍无定论。 目的：评估补充维生素D在预防老年髋骨骨折和非脊椎骨折方面的效果。 数据来源：使用MEDLINE、Cochrance对照试验记录（1960～2005年）以及EMBASE（1991-2005年），对英文和非英文文章进行系统回顾。通过与临床专家接触，通过检索美国社会骨和骨矿研究协会提供的参考文献和摘要（1995～2004年）．进一步寻找更多的研究。检索词包括随机对照试验（randomized controlled trial，RCT）、临床对照试验、随机分配、双盲法、维生素D3、维生素D2；25-羟基维生素D、骨折、人类、老年、摔倒和骨密度。 研究选取：纳入的研究仅限于口服补充维生素D（维生素D3、维生素D2、补钙或不补钙）与补钙或安慰剂比较的双盲RCTs。试验于检查髋部骨折或非脊椎骨折的老年人（年龄≥60岁）中进行。数据提取：两位作者根据预先规定独立提取相关数据，其中包括研究质量指标。 数据综合：所有的汇总分析均以随机效应模型为基础。5项有关髋部骨折的RCTs（n=9294）和7项有关非脊椎骨折危险的RCTs（n=9820）符合我们的纳入标准。所有试验均使用了维生素D3。对髋部和非脊椎骨折预防研究的异质性亦进行观察，用低剂量（400IU／d）和高剂量（700～800IU／d）分别合并RCTs后异质性消失。与补钙或安慰剂相比，每天服700～800IU的维生素D可使髋部骨折的相对危险（relative risk，aa）下降26％（3项RCTs共计5572人；RR，0．74；95％可信区间[confidence interval，CI]，0．61～0．88），使非脊椎骨折的相对危险下降23％（5项RCTs共计6098人；RR，0．77；95％CI，0．68～0．87）。每天服400IU的维生素D（2项RCTs共计3722人；髋部骨折RR，1．15；95％CI，0．88～1．50；非脊椎骨折RR，1．03；95％CI，0．86—1．24）未见明显获益。 结论：口服补充维生素D（700～800IU／d）可以降低尚能活动的老人或慈善机构收容的老年人发生髋部骨折和脊椎以外骨折的危险，每天口服400IU维生素D并不足以预防骨折。     

阿尔茨海默病患者的执行功能障碍

目的了解阿尔茨海默病(A lzhe im er d isease,AD)患者执行功能损害状况及对于生活能力的影响,探讨执行功能障碍与记忆等AD常见认知功能损害的相关性。方法运用神经心理学测验的方法对40例AD患者及30例轻度认知功能损害(m ild cogn itive impairm ent,MC I)患者进行执行功能、记忆及其他认知功能检查,同时进行生活能力评定。另外选择40名健康老人作对照。结果AD组的执行功能测验成绩均显著低于健康对照组(P<0.01),其中额叶功能评定量表(FAB)(5.29±2.47)分,执行性画钟作业(CLOX1)(4.63±3.56)分,Stroop测验错误次数(Stroop1)(14.17±8.99)分,词语流畅性测验(RVR)(17.56±10.51)分。除Stroop测验反应时间(Stroop2)外,MC I组的其他执行功能测验成绩显著低于健康对照组(P<0.05),其中FAB为(7.67±2.44)分,CLOX1为(7.86±3.78)分,Stroop1为(7.21±8.07)分,RVR为(30.86±8.38)分。用多元逐步回归方法分析不同认知功能对生活能力的影响,结果为反映执行功能的FAB测验成绩处于第一位,独立与操作性日常生活能力(IADL)相关(β=-0.778,t=-7.079,P<0.01)。各项执行功能测验与年龄相关性不明显(r=0.026~0.250,P>0.05),与简易精神状态量表(MMSE)、记忆测验成绩相关性好(r=0.438~0.786,P<0.01)。结论AD患者具有明显的执行功能障碍;在尚未到达痴呆水平的MC I阶段也可发现执行功能损害。执行功能和整体认知功能及记忆等认知域功能具有良好的相关性。AD患者的执行功能障碍是导致生活能力下降的重要因素。