Lymph node sampling in resectable hepatocellular carcinoma: national practice patterns and predictors of positive lymph nodes

Background and objectivesRoutine lymphadenectomy (LND) for resectable hepatocellular carcinoma (HCC) remains controversial. We evaluated national LND trends to identify pre-operative factors associated with node-positive disease to determine which patients might benefit from LND.MethodsWe identified HCC patients in the National Cancer Database (NCDB) treated with surgical resection between 2004 and 2015. Demographic, operative, pathologic, and survival data were compared. Multivariable regression was performed to determine preoperative predictors of pathologic nodal disease.ResultsOf 8095 total resected patients, 1442 (17.8%) underwent hepatectomy with LND. Patients who received LND had higher preoperative clinical T (T3-T4: 20.0% vs 12.1%, p < 0.001) and N (N1: 3.3% vs 0.6%, p < 0.001) stages. The strongest independent predictor of pathologic nodal disease was clinical N stage (OR 106.54, CI 44.10–257.42). Survival was highest in patients whose surgeons omitted LND or were found with LND to be node-negative on final pathology (p < 0.001). Clinical node positivity had high negative predictive value (97.9%) but moderate positive predictive value (56.3%) in estimating pathologic nodal status. Conclusions: Defining preoperative clinical nodal status is imperative in HCC patients. Clinical node positivity was the strongest predictor of pathologic nodal disease and its associated worse prognosis. LND can be considered selectively in clinically node-positive patients.     

The CD226-ERK1/2-LAMP1 pathway is an important mechanism for Vγ9Vδ2 T cell cytotoxicity against chemotherapy-resistant acute myeloid leukemia blasts and leukemia stem cells

Vγ9Vδ2 T cells are attractive effector cells for immunotherapy with potent cytotoxic activity against a variety of malignant cells. However, the effect of Vγ9Vδ2 T cells on chemotherapy-resistant acute myeloid leukemia (AML) blasts, especially highly refractory leukemia stem cells (LSCs) is still unknown. In this study, we investigated the effect of cytotoxicity of allogeneic Vγ9Vδ2 T cells on chemotherapy-resistant AML cell lines, as well as on primary AML blasts and LSCs obtained from refractory AML patients. The results indicated that Vγ9Vδ2 T cells can efficiently kill drug-resistant AML cell lines in vitro and in vivo, and the sensitivity of AML cells to Vγ9Vδ2 T cell–mediated cytotoxicity is not influenced by the sensitivity of AML cells to chemotherapy. We further found that Vγ9Vδ2 T cells exhibited a comparable effect of cytotoxicity against LSCs to primary AML blasts. More importantly, we revealed that the CD226–extracellular signal–regulatory kinase1/2 (ERK1/2)–lysosome-associated membrane protein 1 (LAMP1) pathway is an important mechanism for Vγ9Vδ2 T cell–induced cytotoxicity against AML cells. First, Vγ9Vδ2 T cells recognized AML cells by receptor-ligand interaction of CD226–Nectin-2, which then induced ERK1/2 phosphorylation in Vγ9Vδ2 T cells. Finally, triggering the movement of lytic granules toward AML cells induced cytolysis of AML cells. The expression level of Nectin-2 may be used as a novel marker to predict the susceptibility/resistance of AML cells to Vγ9Vδ2 T cell treatment.     

立体定向体部放射治疗对原发性肝癌 合并门静脉癌栓的近期疗效

〔摘 要〕 目的：探讨肝细胞癌（HCC）合并门静脉癌栓（PVTT）行立体定向体部放射治疗（SBRT）的近期疗效。 方法：回顾性分析 2020 年 4 月至 2021 年 1 月厦门大学附属第一医院收治的 18 例原发性 HCC 合并 PVTT 患者,针对 PVTT 行 SBRT,观察放射治疗后 PVTT 退缩率及放射治疗相关不良反应。 结果：全部患者均完成放射治疗疗程,放射治疗后 4 周 评估疗效完全缓解 1 例,部分缓解 3 例,疾病稳定 13 例,疾病进展 1 例。放射治疗中急性损伤均可耐受,放射治疗后随访 中未发现上消化道出血或放射性肝病。 结论：SBRT 可作为治疗 HCC 合并 PVTT 安全有效的方法。     

Comparing the diagnostic value of bronchoalveolar lavage fluid galactomannan,serum galactomannanan,and serum 1,3-β-d-glucan in non-neutropenic respiratory disease patients with invasive pulmonary aspergillosis

The incidence of invasive pulmonary aspergillosis (IPA) is increasing higher in non-neutropenic patients. This study aimed to assess the diagnostic performance of bronchoalveolar lavage fluid (BALF). Galactomannan (GM), serum GM, and 1,3-β-d-glucan (BDG) in non-neutropenic respiratory disease patients with IPA.A total of 333 non-neutropenic patients suspected IPA were recruited from Xiamen University Zhong Shan hospital between January 2016 and February 2019. One, 33, and 92 cases were diagnosed with proven, and possible IPA.BALF and serum GM were both elevated in the possible IPA group and the probable/proven IPA group (p < 0.001). BALF and serum GM showed a fair correlation in the possible IPA group (r = 0.286, p = 0.008), and moderate correlation in the probable/proven IPA group (r = 0.466, p = 0.005). When the cutoff value was 0.5, the sensitivity and negative likelihood ratio of BALF GM were superior to serum GM (78.3% vs 47.8%, 96.7% vs 91.6%). The specificity and positive likelihood ratio of BALF GM were slightly weaker than serum GM (91.8% vs 95.4%, 56.7% vs 85.0%). When the cutoff value was 1.0, the sensitivity and negative predictive value of BALF GM were better than serum GM (73.9% vs 26.1%, 94.5% vs 88.8%), and the specificity of were equivalent (99.2%). The optimal cutoff value of BALF GM was 0.6, wherein the sensitivity reached 78.3% and the specificity reached 95.4%. Given the extremely low sensitivity of serum BDG at different cutoff values (≥10 μg/mL = 5.3%, ≥20 μg/mL = 2.1%), it cannot be used as a preferred biomarker.The diagnostic performance of BALF GM was superior to other biomarkers and the optimal cutoff value was 0.6.     

糖尿病老年患者行人工髋关节置换术的围手术期护理干预效果观察

目的观察围手术期护理干预在糖尿病老年患者行人工髋关节置换术中的护理效果及影响。方法2017年2月—2019年3月间纳入该院行人工髋关节置换术的老年糖尿病患者共74例为护理研究对象,开展回顾性分析,将其分为对照组与干预组,各组均为37例。对照组接受常规围手术期护理,干预组接受围手术期护理干预。对比两组手术前后血糖指标变化、髋关节功能评分变化,术后恢复指标及手术并发症情况。结果血糖指标及髋关节功能评分术前检验、测评结果组间对比差异无统计学意义(P>0.05)。术后,干预组血糖指标、髋关节功能评分、术后恢复指标均明显优于干预组,干预组手术并发症率低于对照组(P<0.05)。结论围手术期护理干预的应用,可实现对糖尿病老年患者血糖变化及髋关节置换术预后效果的有效改善,护理效果显著。     

Novel bi-allelic variants in DNAH2 cause severe asthenoteratozoospermia with multiple morphological abnormalities of the flagella

Research questionMultiple morphological abnormalities of the flagella (MMAF) is characterized by excessive immotile spermatozoa with severe flagellar abnormalities in the ejaculate. Previous studies have reported a heterogeneous genetic profile associated with MMAF. What other genetic variants might explain the cause of MMAF?DesignWhole-exome sequencing was conducted in a cohort of 90 Chinese patients with MMAF. The pathogenicity of identified mutations was assessed through electron microscopy and immunofluorescent examinations.ResultsThree unrelated men with bi-allelic DNAH2 variants were identified. Sanger sequencing verified that the six novel variants originated from every parent. All these variants were located at the conserved domains of DNAH2 and predicted to be deleterious by bioinformatic tools. Haematoxylin and eosin staining and scanning electron microscopy revealed that spermatozoa harbouring DNAH2 variants displayed severely aberrant morphology mainly with absent and short flagella (≥78%). Moreover, transmission electron microscopy revealed the obvious absence of a central pair of microtubules and inner dynein arms in the spermatozoa with mutated DNAH2. Immunofluorescence data further validated these findings, showing reduced DNAH2 protein expression in the spermatozoa with DNAH2 variants, compared with normal spermatozoa. Intracytoplasmic sperm injection using spermatozoa from the three men with mutated DNAH2 resulted in blastocyst formation in all cases. Embryo transfer was carried out in two couples, both resulting in clinical pregnancy.ConclusionsThese experimental and clinical data suggest that bi-allelic DNAH2 variants might induce MMAF-associated asthenoteratozoospermia, which can be overcome through intracytoplasmic sperm injection. These findings contribute to the knowledge of the genetic landscape of asthenoteratozoospermia and clinical counselling of male infertility.     

医院人才流失浅析

人才流失问题成为掣肘提升医院整体素质的不可忽视的问题,如何有效防止人才流失,是在当前激烈的医疗市场竞争中取得胜利的关键。文章通过对医院人才流失的原因分析,提出提高医院卫生人才的稳定性,完善相应的管理机制,规范人才合理流动的对策。     

Imaging Integrin αvβ3 and NRP-1 Positive Gliomas with a Novel Fluorine-18 Labeled RGD-ATWLPPR Heterodimeric Peptide Probe

Purpose

Radiolabeled Arg-Gly-Asp (RGD) and Ala-Thr-Trp-Leu-Pro-Pro-Arg (ATWLPPR) peptide analogs have received interests for their capability to serve as radiopharmaceuticals for imaging integrin α_vβ₃ and Neuropilin-1 (NRP-1) positive tumors, respectively. In this study, we developed a RGD-ATWLPPR heterodimeric peptide which contained both RGD and ATWLPPR motifs in one molecular probe. The aim of this study was to investigate the dual receptor-targeting property and tumor diagnostic value of RGD-ATWLPPR heterodimeric peptide labeled with fluorine-18 (F-18).

Procedures

A RGD-ATWLPPR heterodimer was synthesized from c(RGDyK) and ATWLPPR through a glutamate linker. The peptide was radiolabeled by reacting the [¹⁸F]fluoride–aluminum complex with the cyclic chelator, 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA). The receptor-binding characteristics and tumor-targeting efficacy of [¹⁸F]FAl-NOTA-RGD-ATWLPPR were tested in vitro and in vivo.

Results

RGD-ATWLPPR had affinity for both integrin α_vβ₃ and NRP-1 in vitro. [¹⁸F]FAl-NOTA-RGD-ATWLPPR displayed significantly higher tumor uptake than [¹⁸F]FAl-NOTA-RGD and [¹⁸F]FAl-NOTA-ATWLPPR, both in vitro and in vivo. The uptake of the F-18 labeled heterodimer by an U87MG tumor was inhibited only partially in the presence of an excess amount of unlabeled RGD or ATWLPPR but was blocked completely in the presence of both RGD and ATWLPPR. Compared with the monomeric RGD and ATWLPPR peptides, [¹⁸F]FAl-NOTA-RGD-ATWLPPR showed improved in vivo pharmacokinetics, resulting in a more preferable imaging quality.

Conclusions

[¹⁸F]FAl-NOTA-RGD-ATWLPPR exhibited significantly improved receptor-targeting properties both in vitro and in vivo compared with the F-18 labeled RGD or ATWLPPR monomers. The improved targeting and localization exhibited by the RGD-ATWLPPR heterodimer provide a foundation for further investigations of its applicability in clinical tumor imaging.     

新生儿ABO溶血病的检测与分析

本研究了解新生儿ABO溶血病（ABO-HDN）的发病率、血型模式并对溶血三项检测结果进行分析,为临床诊断及治疗提供依据.选择2013年1月至2013年10月本院及外院送检的母婴ABO血型不合病例227例,检测患儿及母亲的ABO血型及新生儿的溶血病三项试验（直接抗人球蛋白试验、游离抗体试验、红细胞抗体释放试验）.结果表明,新生儿ABO溶血病共186例,占所有病例的81.94％ （186/227）,O-A与O-B两种母婴血型模式的发病率经卡方检验P＞0.05.186例阳性病例中,直接抗人球蛋白试验阳性者占59.14％ （110/186）,游离抗体试验阳性者占84.78％ （156/186）,红细胞抗体释放试验阳性者占94.62％ （176/186）.结论：新生儿ABO溶血病发病率高,以母亲O型、患儿A/B型为主,O-A与O-B两种母婴血型模式的发病率的差异无显著性意义.溶血三项试验敏感性高,对新生儿溶血病的早期诊断、早期治疗起着非常积极的作用.     

OGDHL silencing promotes hepatocellular carcinoma by reprogramming glutamine metabolism

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