Precision N‐glycoproteomics reveals elevated LacdiNAc as a novel signature of intrahepatic cholangiocarcinoma

Primary liver cancer, mainly comprising hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), remains a major global health problem. Although ICC is clinically different from HCC, their molecular differences are still largely unclear. In this study, precision N‐glycoproteomic analysis was performed on both ICC and HCC tumors as well as paracancer tissues to investigate their aberrant site‐specific N‐glycosylation. By using our newly developed glycoproteomic methods and novel algorithm, termed ‘StrucGP’, a total of 486 N‐glycan structures attached on 1235 glycosites were identified from 894 glycoproteins in ICC and HCC tumors. Notably, glycans with uncommon LacdiNAc (GalNAcβ1‐4GlcNAc) structures were distinguished from their isomeric glycans. In addition to several bi‐antennary and/or bisecting glycans that were commonly elevated in ICC and HCC, a number of LacdiNAc‐containing, tri‐antennary, and core‐fucosylated glycans were uniquely increased in ICC. More interestingly, almost all LacdiNAc‐containing N‐glycopeptides were enhanced in ICC tumor but not in HCC tumor, and this phenomenon was further confirmed by lectin histochemistry and the high expression of β1‐4 GalNAc transferases in ICC at both mRNA and protein expression levels. The novel N‐glycan alterations uniquely detected in ICC provide a valuable resource for future studies regarding to the discovery of ICC diagnostic biomarkers, therapeutic targets, and mechanism investigations.     

Impact of pathological response after preoperative transcatheter arterial chemoembolization (TACE) on incidences of microvascular invasion and early tumor recurrence in hepatocellular carcinoma: a multicenter propensity score matching analysis

BackgroundTo study the influence of pathological responses (PR) after transcatheter arterial chemoembolization (TACE) on incidences of microvascular invasion (MVI) and early recurrence in hepatocellular carcinoma (HCC) patients.MethodsBetween 2013 to 2015, consecutive HCC patients who underwent liver resection with “curative” intent at three hospitals were enrolled in this study. Patients with different areas of PR after preoperative TACE were compared with those without preoperative TACE on the incidences of MVI, early recurrence rates and patterns of recurrence before and after propensity score matching (PSM).ResultsOf 1,970 patients, 737 patients who received preoperative TACE were divided into three groups according to the areas of PR: ≥90% (n=226), 60–90% (n=447), and <60% (n=64). PR ≥90% was an independent protective factor of incidences of MVI [odds ratio (OR), 0.144; 95% confidence interval (CI), 0.082–0.245, P<0.001) and early recurrence (HR, 0.742; 95% CI, 0.561–0.963, P=0.032); while PR<60% was an independent risk factor of incidences of MVI (OR, 6.076; 95% CI, 3.004–11.728, P<0.001) and early recurrence (HR, 1.428; 95% CI, 1.095–1.929; P=0.009). Furthermore, patients with PR <60% were significantly more likely to develop multiple intrahepatic recurrences involving multiple hepatic segments when compared with patients without preoperative TACE.ConclusionsThis study indicated the area of PR after TACE was closely associated with the incidences of MVI and early tumor recurrence. Patients with PR <60% were at significantly higher risks of having more MVI, early and multiple tumor recurrences     

Functional mutations of SARS-CoV-2: implications to viral transmission,pathogenicity and immune escape

The pandemic of coronavirus disease 2019 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to major public health challenges globally. The increasing viral lineages identified indicate that the SARS-CoV-2 genome is evolving at a rapid rate. Viral genomic mutations may cause antigenic drift or shift, which are important ways by which SARS-CoV-2 escapes the human immune system and changes its transmissibility and virulence. Herein, we summarize the functional mutations in SARS-CoV-2 genomes to characterize its adaptive evolution to inform the development of vaccination, treatment as well as control and intervention measures.     

The value of quantitative magnetic resonance imaging signal intensity in distinguishing between spinal meningiomas and schwannomas

Background: Prior studies have suggested a number of the subjective visual characteristics that help distinguish between spinal meningiomas and schwannomas on magnetic resonance imaging and computed tomography; however, objective quantification of the signal intensity can be useful information. This study assessed whether quantitative magnetic resonance imaging (MRI) signal intensity (SI) measurements could distinguish intradural-extramedullary schwannomas from meningiomas.Methods: From July 2019 to September 2021, 54 patients with intradural-extramedullary tumors (37 meningiomas and 17 schwannomas) underwent surgery, and tumors were verified pathologically. Defined regions of interest were used to quantify SI values on T1- (T1W) and T2-weighted images (T2W). Receiver operating characteristic curve analysis was used to obtain cutoff values and calculate the area under the curve (AUC), sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV).Results: Both Maximum (T2_max) and mean (T2_mean) T2W SI values demonstrated outstanding (AUC: 0.91) abilities to differentiate meningiomas from schwannomas with Se, Sp, PPV, and NPV values of 94.6%, 70.6%, 87.5%, and 85.7%, respectively, for T2_max and 81.1%, 88.2%, 93.8%, and 68.2% for T2_mean. The maximum SI value on contrast-enhanced T1W (T1CE_max) and the T2W tumor: fat SI ratio (rTF) demonstrated acceptable abilities (AUC: 0.73 and 0.79, respectively) to differentiate meningiomas from schwannomas with Se, Sp, PPV, and NPV values of 94.6%, 70.6%, 87.5%, and 85.7%, respectively, for T1CE_max and 81.1%, 88.2%, 93.8%, and 68.2% for rTF.Conclusions: Quantitative SI values (T2_max, T2_mean, T2_min, T1CE_max, rTF) can be used to differentiate intradural-extramedullary schwannomas from meningiomas.     

创伤性枢椎滑脱的临床诊治分析

目的 探讨创伤性枢椎滑脱(Hangman骨折)的损伤机制、临床表现及治疗方法。方法 回顾1988年6月-2001年3月收治的hangman骨折患者10例,对其影像学表现、损伤机制及治疗方法进行分析。结果 10例患者男9例,女1例,平均年龄40岁,致伤原因为车祸7例,原木砸伤颈部1例,高处坠落1例,另1例患强直性脊柱炎因摔跤致伤,其中Ⅰ型1例,Ⅱ型5例,Ⅱa型2例,Ⅲ型2例;4例保守治疗,6例手术治疗。结论 车祸和坠落为创伤性枢椎滑脱的主要致伤因素,其临床表现多为颈椎局部疼痛、拒动等症状,少有神经系统的损伤;影像学诊断依据颈椎侧位X光片和颈椎CT;创伤性枢椎滑脱Ⅰ型、Ⅱ型及Ⅱa型可保守治疗,Ⅲ型和伴有C2-3间盘突出损伤脊髓的患者应采取手术治疗。     

Ilizarov外固定技术在复杂性踝关节融合术中的应用

目的 介绍Ilizarov外固定技术在合并有严重的病理改变的踝关节融合手术和翻修融合手术中的应用经验及临床结果。方法 总结分析1999年5月至2002年1月在澳大利亚皇家布里斯本医院进行的9例复杂性踝关节融合手术患者的病案记录和影象资料,并对患者进行随访评定,平均随访时间18．1个月。结果 9例患者均未出现血管神经损伤,伤口感染,伤口裂开不愈合等并发症,5例患者获得好结果,即关节融合稳定,残留轻度疼痛和功能限制,4例患者获得良结果,即关节融合稳定,残留中度疼痛,中度跛行或功能限制。结论 Ilizarov外固定技术即细针环形外固定架是进行复杂的踝关节融合手术时有效的固定方法之一,包括合并感染的踝关节和翻修的踝关节融合。     

异种脱细胞真皮基质与自体皮复合移植后基底膜重塑的实验观察

目的　观察异种 (猪 )脱细胞真皮基质与薄自体皮复合移植模型中基底膜重塑的变化规律。　方法　将异种 (猪 )脱细胞真皮基质与薄自体皮复合移植于大鼠创面 ,分别于移植后 1、2、3、4、8、12、16周留取标本 ,采用免疫组化、透射电镜等方法 ,观察基底膜中层粘连蛋白的变化规律及 12周时基底膜的超微结构 ,同时以单纯薄自体皮移植进行对照。　结果　异种脱细胞真皮基质与薄自体皮复合移植后 ,层粘连蛋白的表达高于单纯薄自体皮移植。 12周时复合移植组基底膜清晰连续 ,半桥粒较多且分布均匀 ;薄自体皮组基底膜致密板模糊、不连续 ,半桥粒减少且分布不均。　结论　异种脱细胞真皮基质与薄自体皮复合移植后 ,基底膜中层粘连蛋白表达增高 ,可能有利于复合皮移植后基底膜的重塑 ,增强表皮和真皮之间的连接 ,进而改善创面愈合质量     

颈椎不稳在交感型颈椎病发病中的作用

目的：研究交感型颈椎病的病理因素及治疗方法。方法：回顾分析了1988-2000年收治的20例手术治疗的交感型颈椎病患者。根据术前及术后颈椎伸屈侧位X光片判断有无颈椎不稳。结果：20例患者术前均有颈椎不稳,颈椎不稳主要发生在C3-C4和C4-C5,颈椎高位硬膜外封闭对大部分患者有短期效果。每例患者均于不稳节段行颈前路融合术,手术有效率为90％。结论：颈椎不稳是导致交感型颈椎病发病的重要因素;颈椎高位硬膜外封闭可有短期疗效因此具有重要的诊断价值;颈椎前路植骨融合术是治疗交感型颈椎病的有效方法。     

Effects of the 532-nm and 1,064-nm Q-switched Nd:YAG lasers on collagen turnover of cultured human skin fibroblasts: a comparative study

Cultured human skin fibroblasts were irradiated twice successively with the 1.5 J/cm² of 532-nm and 1,064-nm lasers, respectively. The mRNA of procollagen, matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), heat-shock protein 70 (Hsp70), interleukin-6 (IL-6) and transforming growth factor beta (TGF-β) were analyzed at 24 and 48 h post-irradiation by using RT-PCR. Both lasers significantly increased the expression of type I and III procollagen, TIMP1, and TIMP2, but decreased MMP1 and MMP2 expression. The 1,064-nm laser initiated TGF-β expression while the 532-nm laser elicited the increase of Hsp70 and IL-6. The increase/decrease rates of procollagen, TIMPs and MMPs for the 1,064-nm laser were higher than that of the 532-nm laser. Thus, both lasers effectively accelerated collagen synthesis and inhibited collagen degradation. Collagen synthesis induced by the 1,064-nm laser might be partly due to the upregulation of TGF-β expression, while the increase of Hsp70 and IL-6 might be partly responsible for collagen synthesis stimulated by the 532-nm laser. With the parameters used in this study, the 1,064-nm infrared laser is more effective in promoting the beneficial molecular activities than the 532-nm visible laser.