数字化技术在胰头癌手术中的应用研究

目的 探讨数字化技术在胰头癌手术中的应用价值。方法 收集10例胰头癌患者的临床资料。采用三维（3D）可视化技术观察血管的变异情况、胰头癌累及的范围、肿瘤与血管关系、胰周肿大淋巴结情况等,同时结合3D打印技术进行实时手术引导。分析术前规划结果、手术情况、手术前后肝功能及糖链抗原199（CA199）水平变化、术后并发症及近期疗效。结果 10例胰头癌患者均完成了基于数字化技术的术前规划及术中导航。所有患者均顺利完成手术。手术时间（315.1±59.5）min,术中出血量325（200,450）ml,手术切缘均达到R0切除标准。10例患者的术后总胆红素、直接胆红素、ALT、AST、CA199均比术前下降（P均< 0.05）。术后发生B级胰瘘1例,经保守治疗后痊愈,无围术期死亡病例。结论 数字化技术适用于胰头癌的术前规划和术中导航,有助于提高手术成功率,降低手术风险。     

Cerebral venous sinus thrombosis due to external compression of internal jugular vein

Cerebral venous sinus thrombosis (CVST) is a special subtype of stroke that may be life-threatening in severe cases. CVST has distinct risk factors and is frequently overlooked because of its initially nonspecific clinical presentation. We herein describe a 72-year-old man who developed CVST in the right lateral sinus. Despite the absence of common risk factors in this patient, he developed external compression of the bilateral internal jugular veins by a lateral mass of the C1 vertebra and expansion of the carotid artery. Because of his elevated D-dimer and fibrinogen concentrations, which are associated with ongoing activation of the coagulation system, the patient underwent treatment with batroxobin combined with anticoagulation. Recanalization of the sinus was achieved, and his high intracranial pressure and papilledema remarkably decreased. We conclude that external compression of the internal jugular veins, which can be identified with three-dimensional computed tomography venography, may be an important risk factor for CVST.     

Ultrastructural Changes of Mitochondria in the Cultivated Skin Fibroblasts of Patients with Point Mutations in Mitochondrial DNA

Mitochondrial disorders represent a heterogeneous group of multisystem diseases with extreme variability in clinical phenotype. The diagnosis of mitochondrial disorders relies heavily on extensive biochemical and molecular analyses combined with morphological studies including electron microscopy. Although muscle is the tissue of choice for electron microscopic studies, the authors investigated cultivated human skin fibroblasts (HSF) harboring 3 different pathologic mtDNA mutations: 3243A > G, 8344A > G, 8993T > G. They addressed to the possibility of whether mtDNA mutations influence mitochondrial morphology in HSF and if ultrastructural changes of mitochondria may be used for differential diagnostics of mitochondrial disorders caused by mtDNA mutations. Ultrastructural analysis of patients' HSF revealed a heterogeneous mixture of mainly abnormal, partially swelling mitochondria with unusual and sparse cristae. The most characteristic cristal abnormalities were heterogeneity in size and shapes or their absence. Typical filamentous and branched mitochondria with numerous cristae as appeared in control HSF were almost not observed. In all lines of cultured HSF with various mtDNA mutations, similar ultrastructural abnormalities and severely changed mitochondrial interior were found, although no alterations in function and amount of OXPHOS were detected by routinely used biochemical methods in two lines of cultured HSF. This highlights the importance of morphological analysis, even in cultured fibroblasts, in diagnostics of mitochondrial disorders.     

Adipose tissue-derived stem cells promote pancreatic cancer cell proliferation and invasion

To explore the effects of adipose tissue-derived stem cells (ADSCs) on the proliferation and invasion of pancreatic cancer cells in vitro and the possible mechanism involved, ADSCs were cocultured with pancreatic cancer cells, and a cell counting kit (CCK-8) was used to detect the proliferation of pancreatic cancer cells. ELISA was used to determine the concentration of stromal cell-derived factor-1 (SDF-1) in the supernatants. RT-PCR was performed to detect the expression of the chemokine receptor CXCR4 in pancreatic cancer cells and ADSCs. An in vitro invasion assay was used to measure invasion of pancreatic cancer cells. SDF-1 was detected in the supernatants of ADSCs, but not in pancreatic cancer cells. Higher CXCR4 mRNA levels were detected in the pancreatic cancer cell lines compared with ADSCs (109.3±10.7 and 97.6±7.6 vs 18.3±1.7, respectively; P<0.01). In addition, conditioned medium from ADSCs promoted the proliferation and invasion of pancreatic cancer cells, and AMD3100, a CXCR4 antagonist, significantly downregulated these growth-promoting effects. We conclude that ADSCs can promote the proliferation and invasion of pancreatic cancer cells, which may involve the SDF-1/CXCR4 axis.     

A VEGFR-3 Antagonist Increases IFN-γ Expression on Low Functioning NK Cells in Acute Myeloid Leukemia

Purpose

Although the importance of vascular endothelial growth factor receptor (VEGFR)-3 has been demonstrated in acute myeloid leukemia (AML), the role of VEGFR-3 in functioning natural killer (NK) cells remains largely unexplored. NK cells can destroy cancer cells by releasing the cytokine interferon (IFN)-γ, but NK cells in AML patients (AML NK cells) have low cytolytic activity. In the present study, we investigated whether lymphatic markers including VEGFR-3 are expressed on low-functioning AML NK cells and VEGFR-3 antagonist can restore expression of IFN-γ in NK cells.

Methods

Samples from 67 de novo AML patients and 34 healthy donors were analyzed for lymphatic markers expression using RT-PCR, flow cytometry, and immunostaining. For the cytotoxicity assays, K562 cells and AML NK cells were used as target and effector cells, respectively. To block VEGFR-3, MAZ51 was added to NK cells, which were then subjected to FACS analysis.

Results

Compared with NK cells from healthy donors (healthy NK cells), AML NK cells exhibited higher levels of VEGFR-3 and lower expression of IFN-γ. VEGFR-3-expressing AML NK cells were less potent than healthy NK cells in terms of killing K562 cells. The level of IFN-γ in AML NK cells was increased by VEGFR-3 antagonist treatment, indicating the functional relevance of VEGFR-3 in IFN-γ-secreting NK cells.

Conclusion

Collectively, our data suggest a relationship between VEGFR-3 and IFN-γ expression in NK cells and raise the possibility of advanced therapeutic approaches involving VEGFR-3 antagonist treatment prior to NK immune cell therapy in AML.     

A Clinical Study of HBsAg‐Activated Dendritic Cells and Cytokine‐Induced Killer Cells During the Treatment for Chronic Hepatitis B

We aim to study the therapeutic effects of HBsAg‐activated DCs and cytokine‐induced killer (CIK) cells as adoptive immunotherapy in patients with Chronic Hepatitis B (CHB). Autologous HBsAg‐activated DC–CIK cells were infused into patients with CHB to evaluate their effect on HBV‐DNA, HBsAg, ALT, etc. The viral load in the treatment group decreased significantly (P < 0.001), while that in the control group did not decrease (P > 0.05). Twenty‐one patients (63.6% efficiency) in the treatment group had a viral response (≥2 log decrease in viral load), while four patients (14.8% efficiency) from the control group had a viral response. There were significant differences in the viral responses of the two groups (the control group 63.6% versus the control group 14.8%, P < 0.001). We concluded that the immunity was enhanced after HBsAg activation in DCs and CIK cells. Reinfusion of autologous HBsAg‐activated DC–CIK cells inhibited HBV proliferation in 21 of 33 (63.6%) patients.     

Novel Approaches to Detection of Cerebral Microbleeds: Single Deep Learning Model to Achieve a Balanced Performance

PurposeCerebral microbleeds (CMBs) are considered essential indicators for the diagnosis of cerebrovascular disease and cognitive disorders. Traditionally, CMBs are manually interpreted based on criteria including the shape, diameter, and signal characteristics after an MR examination, such as susceptibility-weighted imaging or gradient echo imaging (GRE). In this paper, an efficient method for CMB detection in GRE scans is presented.Materials and methodsThe proposed framework consists of the following phases: (1) pre-processing (skull extraction), (2) the first training with the ground truth labeled using CMB, (3) the second training with the ground truth labeled with CMB mimicking the same subjects, and (4) post-processing (cerebrospinal fluid (CSF) filtering). The proposed technique was validated on a dataset of 1133 CBMs that consisted of 5284 images for training and 1737 images for testing. We applied a two-stage approach using a region-based CNN method based on You Only Look Once (YOLO) to investigate a novel CMB detection technique.ResultsThe sensitivity, precision, F1-score and false positive per person (FP_avg) were evaluated as 80.96, 60.98, 69.57 and 6.57, 59.69, 62.70, 61.16 and 4.5, 66.90, 79.75, 72.76 and 2.15 for YOLO with a single label, YOLO with double labels, and YOLO + CSF filtering, respectively, and YOLO + CSF filtering showed the highest precision performance, F1-score and lowest FP_avg.ConclusionsUsing proposed framework, we developed an optimized CMB learning model with low false positives and a balanced performance in clinical practice.