Hepatotoxicity of cantharidin is associated with the altered bile acid metabolism

Cantharidin (CTD) is an effective antitumor agent. However, it exhibits significant hepatotoxicity, the mechanism of which remains unclear. In this study, biochemical and histopathological analyses complemented with ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS)-based targeted metabolomic analysis of bile acids (BAs) were employed to investigate CTD-induced hepatotoxicity in rats. Sixteen male and female Sprague–Dawley rats were randomly divided into two groups: control and CTD (1.0 mg/kg) groups. Serum and liver samples were collected after 28 days of intervention. Biochemical, histopathological, and BA metabolomic analyses were performed for all samples. Further, the key biomarkers of CTD-induced hepatotoxicity were identified via multivariate and metabolic pathway analyses. In addition, metabolite–gene–enzyme network and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to identify the signaling pathways related to CTD-induced hepatotoxicity. The results revealed significantly increased levels of biochemical indices (alanine aminotransferase, aspartate aminotransferase, and total bile acid). Histopathological analysis revealed that the hepatocytes were damaged. Further, 20 endogenous BAs were quantitated via UHPLC-MS/MS, and multivariate and metabolic pathway analyses of BAs revealed that hyocholic acid, cholic acid, and chenodeoxycholic acid were the key biomarkers of CTD-induced hepatotoxicity. Meanwhile, primary and secondary BA biosynthesis and taurine and hypotaurine metabolism were found to be associated with the mechanism by which CTD induced hepatotoxicity in rats. This study provides useful insights for research on the mechanism of CTD-induced hepatotoxicity.     

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。     

逆行髓内钉辅助在儿童股骨延长中的应用

目的采用髓内钉辅助延长技术进行儿童股骨大段延长,评估其可行性,并对比同期矫正和分期手术的技术要点,明确此技术在儿童患儿中的应用价值。方法自2014年7月7日至2018年1月16日共规划完成逆行髓内钉辅助延长手术10例,其中男9例,女1例;年龄(13.10±2.18)岁。所有患儿延长截骨点均位于股骨远端干骺端,初诊至末次随访记录内容包括:性别、出生日期、不等长病因及治疗史、术时年龄、延长长度、带架时间、延长段愈合时间、屈膝角度、并发症等。比较同期延长和分期矫正的愈合时间,采用SPSS 22.0软件进行统计分析,提出合理的治疗策略。结果10例患儿患肢平均延长(7.07±1.01)cm,中位带架时间为8.5(4,16)个月,中位随访时间为39(34,54)个月。所有病例均获得了良好的临床和影像学愈合,并全部恢复正常行走功能,无延长后骨折发生。同期矫正与分期手术间在愈合速度为[(1.70±1.10)月/cm vs.(1.16±0.54)月/cm],膝关节功能(136.67°±20.82°vs.125.71°±26.37°)和并发症率方面的差异均无统计学意义。结论外固定架辅助逆行髓内钉技术进行股骨延长治疗儿童股骨短缩畸形是可行的,是股骨延长的有效手术方式之一;较轻的角度畸形和延长手术可同期进行;干骺端截骨延长成骨质量更佳,可有效减少带架时间;内生软骨瘤患儿的病变区延长是安全的。     

Metastasis of oral squamous cell carcinoma to the parotid lymph nodes

Parotid lymph node (PLN) metastasis greatly worsens the prognosis of patients with oral squamous cell carcinoma (OSCC) and poses a great challenge for further treatment of OSCC. The clinicopathological characteristics and treatment strategies for PLN metastasis from OSCC need to be comprehensively elucidated. A retrospective review of OSCC patients who experienced postoperative PLN metastasis in our department between 2000 and 2018 was performed in this study. A total of 47 OSCC patients with postoperative PLN metastasis were identified. PLN with metastasis were divided into three groups based on the location: parotid tail (PLN-t), superficial lobe (PLN-sl), and deep lobe (PLN-dl). Most of the patients experienced PLN metastasis within less than 12 months after the primary surgery for OSCC. Comparatively, patients with PLN-sl metastasis were more prone to have infiltration of the facial nerve. The tongue and buccal mucosa were the most frequent primary sites associated with PLN metastasis from OSCC. PLNs in the parotid tail were most commonly affected by the metastasized OSCC. Consequently, we recommend a series of strategies for the prevention and treatment of PLN metastasis for OSCC patients. In conclusion, PLNs should not be overlooked during preoperative evaluation and postoperative follow-up examinations for OSCC patients.     

Thinned-out skin paddle versus collagen matrix as an optimized peri-implant soft tissue following fibula osteoseptocutaneous free flap: 3-year retrospective study

The objective of this study was to compare the implant longevity following two methods of peri-implant soft tissue optimization following free fibula flap (FFF): thinning of skin paddle (SP) and collagen matrix (CM). All patients who underwent rehabilitation with dental implants after mandibular reconstruction with FFF between June 2009 to May 2014 were retrospectively reviewed. Two methods of peri-implant soft tissue optimization were applied: (1) SP group, (2) CM group. Outcome measurements were: modified plaque index (mPI), modified sulcus bleeding index (mSBI), probing depth (PD), marginal bone loss (MBL), implant success rate and complication rates. A total of 24 patients with 69 implants were included in the study, with 8.7% (n = 6) of implants lost in 3 years. No statistically significant difference was found regarding the outcome measurements in both groups. Failed implants presented with statistically significant higher mPI, mSBI, PD and MBL scores during prosthesis delivery and subsequent follow-ups (P<0.03). In the SP group, one patient experienced SP necrosis which later underwent soft tissue optimization using CM. CM is an alternative peri-implant soft tissue, while thinning of SP is feasible if thickness is well controlled.     

刺果甘草全基因组Survey及叶绿体基因组特征分析＊

目的 基于基因组Survey分析对刺果甘草Glycyrrhiza pallidiflora Maxim.基因组大小和杂合率进行估计，并通过叶绿体基因组序列特征对其在甘草属Glycyrrhiza L.中的系统发育位置进行研究。方法 使用二代测序技术对刺果甘草进行测序，采用K-mer方法对测序reads进行分析，估算刺果甘草基因组大小和杂合率，使用生物信息学方法进行叶绿体基因组组装、注释和系统发育分析。结果 Survey分析结果显示其基因组大小约为577.82 Mb，杂合度约为0.31%，重复序列比例约为53.72%。叶绿体基因组长度为127，267 bp，不具有典型的四分体结构，总GC含量为34.32%，包含110个基因，其中76个蛋白质编码基因，30个tRNA基因和4个rRNA基因。系统发育分析表明，刺果甘草与圆果甘草G. squamulosa Franch.亲缘较接近。结论 刺果甘草存在低杂合和重复序列较多的特点，为了更好地对全基因组进行序列拼接和组装，可尝试采用三代测序结合二代测序的分析策略进行基因组组装；刺果甘草叶绿体全基因组比对和系统发育分析，为后续开展甘草属遗传多样性研究和分子鉴定标记筛选提供了重要依据。