[Association between HLA-DRB1 gene polymorphisms and genetic susceptibility of early-onset severe preeclampsia]. / HLA-DRB1åŸºå› å¤šæ€æ€§ä¸Žæ—©å‘åž‹é‡åº¦å­ç—«å‰æœŸé—ä¼ æ˜“æ„Ÿæ€§çš„ç ”ç©¶.

OBJECTIVES: To explore the correlation between the single nucleotide polymorphisms (SNP) of rs3135388, rs114293611 and rs142804168 of HLA-DRB1 gene and early-onset severe preeclampsia (sPE). METHODS: Blood samples were collected from 102 early-onset sPE mothers and their neonates (sPE group), as well as 120 normotensive mothers and their neonates (control group). Sanger sequencing was performed to compare the genotype distribution, allele frequencies, and differences in genotype distribution after maternal-infant compatibility between the two groups. RESULTS: Statistically significant differences in genotype distribution at rs114293611 of HLA-DRB1 gene were observed between sPE and control groups in both mothers and neonates (P<0.05). The frequency of the T allele at rs114293611 was higher in the sPE group of neonates than that in the control group (P<0.05), while no significant difference was found between the two groups of mothers (P>0.05). The maternal-infant genotype compatibility analysis showed significant differences in genotype distribution between sPE and control groups (P<0.05). There were no significant differences in genotype distribution and allele frequencies at rs3135388 and rs142804168 of HLA-DRB1 gene between the two groups of mothers and neonates (P>0.05). CONCLUSIONS: The SNP at rs114293611 of HLA-DRB1 gene may be associated with the development of early-onset sPE in mothers. Maternal-infant genotype compatibility abnormality at rs114293611 of HLA-DRB1 gene may be a predisposition factor for the development of sPE.

Identification of environmental microorganism using optimally fine-tuned convolutional neural network.

To not only optimize the hyper-parameters of the classification layer of dense convolutional network with 201 convolutional layers (DenseNet-201) but also use data augmentation processes could enhance the performance of DenseNet-201, and DenseNet-201 is rarely applied to the identifications of the environmental microorganism (EM) images. Hence, this study was to propose the optimally fine-tuned DenseNet-201 (OFTD) with data augmentation to better classify the EM images on Environmental Microorganism Dataset (EMDS). The training dataset was composed of 70% Environmental Microorganism Dataset (EMDS) images and so was mainly used to fit the parameters of convolutional layers of optimally fine-tuned DenseNet-201 (OFTD). Meanwhile, the other EMDS images were considered as the testing dataset and used to qualify the performance of the OFTD. Also, gradient-weighted class activation mapping method (Grad-CAM) was adopted to visually illustrate the dominant features of the EM images. Based on the results, the OFTD model with data augmentation achieved the highest classification accuracy of 98.4%. In this case, so its stability and accuracy were guaranteed. Besides, the optimally fine-tuned classification layer is considered a more efficient method than the data augmentation technique adopted in this study when it comes to the improvement of the performance in DenseNet-201 implemented on EMDS. Grad-CAM highlighted the coarse EM features identified effectively by the OFTD; for example, foot and stalk were considered as the dominated features of Rotifera and Vorticella, respectively. In summary, the proposed OFTD with data augmentation could provide an efficient solution for the EM detection in digital microscope.

Combined stomach and duodenal perforating injury following blunt abdominal trauma: a case report and literature review.

BACKGROUND: Gastrointestinal injury following blunt abdominal trauma is uncommon; a combined stomach and duodenal perforating injury is even more rare. Because these two organs are located in different spaces in the abdomen, such injuries are difficult to identify. CASE PRESENTATION: A young woman involved in a motor vehicle crash presented to our emergency department with concerns of severe peritonitis. Contrast-enhanced computed tomography of the abdomen revealed pneumoperitoneum and retroperitoneal hematoma in zone 1. An emergency laparotomy was performed, revealing a stomach-perforating injury, which was resolved with primary repair. No obvious injury was observed on retroperitoneal exploration. However, peritonitis presented again on the second postoperative day, and a second laparotomy was performed, revealing a duodenum-perforating injury in its third portion. We performed primary repair with multi-tube-ostomy. The patient recovered well without permanent tube placement or internal bypass. CONCLUSIONS: Assessing associated injuries in blunt abdominal trauma is crucial because they may be fatal if timely intervention is not undertaken. These types of complicated injuries require a feasible surgical strategy formulated by experienced surgeons, which gives the patient a better chance of survival.

The SNARE-associated protein Sft2 functions in Imh1-mediated SNARE recycling transport upon ER stress.

Vesicular trafficking involving SNARE proteins play a crucial role in the delivery of cargo to the target membrane. Arf-like protein 1 (Arl1) is an important regulator of the endosomal trans-Golgi network (TGN) and secretory trafficking. In yeast, ER stress-enhances Arl1 activation and Golgin Imh1 recruitment to the late-Golgi. Although Arl1 and Imh1 are critical for GARP-mediated endosomal SNARE-recycling transport in response to ER stress, their downstream effectors are unknown. Here, we report that the SNARE-associated protein Sft2 acts downstream of the Arl1-Imh1 axis to regulate SNARE recycling upon ER stress. We first demonstrated that Sft2 is required for Tlg1/Snc1 SNARE-recycling transport under tunicamycin-induced ER stress. Interestingly, we found that Imh1 regulates Tlg2 retrograde transport to the late-Golgi under ER stress, which in turn is required for Sft2 targeting to the late-Golgi. We further showed that Sft2 with 40 amino acids deleted from the N-terminus exhibits defective mediation of SNARE recycling and decreased association with Tlg1 under ER stress. Finally, we demonstrated that Sft2 is required for GARP-dependent endosome-to-Golgi transport in the absence of Rab protein Ypt6. This study highlights Sft2 as a critical downstream effector of the Arl1-Imh1 axis, mediating the endosome-to-Golgi transport of SNAREs.

Environmental microorganism classification using optimized deep learning model.

Rapid environmental microorganism (EM) classification under microscopic images would help considerably identify water quality. Because of the development of artificial intelligence, a deep convolutional neural network (CNN) has become a major solution for image classification. Three popular CNNs, referred to as ResNet50, Vgg16, and Inception-v3, were transferred to identify the EM images present on the Environmental Microorganism Dataset (EMDS), and EMAD was the small dataset, which only has 294 EM images with 21 EM classes. Besides data augmentation, optimizing the fully connected layer of CNN, i.e., both optimally fine-tuned neuron number and dropout rate, was adopted to enhance the performance produced by CNN. The discussions on the causes of the accuracy improved by optimization are also provided. The results showed that the Inception-v3 model obtained 84.9% of the accuracy and performed better than the other two famous CNNs. Also, the implement of data augmentation enhanced the performance of Inception-v3 on EMDS. To add to that, the optimized Inception-v3 model archived 90.5% of the accuracy, and this result demonstrated the improvement effect obtained by using genetic algorithm (GA) to optimize the fully connected layer of the Inception-v3. Therefore, the optimize Inception-v3 with data augmentation process obtained the accuracy of 92.9% and improved almost 21% higher than that obtained from the famous Vgg16. In addition, the optimized Inception-v3 would need less neurons, when compared with that of the optimized Vgg16 possibly. This optimized Inception-v3 could provide a solution to the EM classification in microscope with a digital camera system.

Afamin expression in breast cancer.

BACKGROUND: Breast cancer is a collection of molecularly and clinically distinct neoplastic disease. Recent research has shown the information regarding gene expression in breast cancer could be beneficial in the designing of an optimal treatment plan and may also provide with prognostic information. The creation of tissue microarrays (TMA) allows for the rapid immunohistochemical analysis of thousands of tissue samples in parallel with minimal damage to the original blocks. This study was designed with the application of tissue microarray (TMA) to analyze the afamin status in breast cancer with the hope of elucidating the possible relationship between afamin expressions and breast cancer. METHODS: Archival tissue specimens from 106 patients with primary invasive breast cancer were analyzed for afamin expression by immunhistochemical staining with TMA. Results were compared to clinicopathologic data by multivariate analysis. RESULTS: TNM stage has shown significant relationship to the overall 5-year survival rate. However, afamin expression was not significantly related to overall five-year survival. CONCLUSION: Immunohistochemical staining with TMA was convenient and feasible for analyzing afamin expression status in breast cancer. Our preliminary results show that afamin expression showed no significant prognostic value in breast cancer.

Prospective Evaluation of Neoadjuvant Imatinib Use in Locally Advanced Gastrointestinal Stromal Tumors: Emphasis on the Optimal Duration of Neoadjuvant Imatinib Use, Safety, and Oncological Outcome.

BACKGROUND: Neoadjuvant imatinib therapy has been proposed for routine practice with favorable long-term results for patients with locally advanced gastrointestinal stromal tumors (GISTs). However, clarification of the optimal duration, safety, and oncological outcomes of neoadjuvant imatinib use before surgical intervention remains necessary. METHODS: We prospectively analyzed the treatment outcomes of 51 patients with locally advanced, nonmetastatic GISTs treated with neoadjuvant imatinib followed by surgery. The optimal duration was defined as the timepoint when there was a <10% change in the treatment response or a size decrease of less than 5 mm between two consecutive computed tomography scans. RESULTS: Primary tumors were located in the stomach (23/51; 45%), followed by the rectum (17/51; 33%), ileum/jejunum (9/51; 18%), and esophagus (2/51; 4%). The median maximal shrinkage time was 6.1 months, beyond which further treatment may not be beneficial. However, the maximal shrinkage time was 4.3 months for the stomach, 8.6 months for the small bowel and 6.9 months for the rectum. The R0 tumor resection rate in 27 patients after neoadjuvant imatinib and surgery was 81.5%, and 70.4% of resection procedures succeeded in organ preservation. However, 10 of 51 patients (19.6%) had complications following neoadjuvant imatinib use (six from imatinib and four from surgery). CONCLUSION: Our analysis supports treating GIST patients with neoadjuvant imatinib, which demonstrated favorable long-term results of combined therapy. However, careful monitoring of complications is necessary. The optimal duration of neoadjuvant imatinib use before surgical intervention is, on average, 6.1 months.

Surgical Margin Status of Patients with Pancreatic Ductal Adenocarcinoma Undergoing Surgery with Radical Intent: Risk Factors for the Survival Impact of Positive Margins.

BACKGROUND: For pancreatic ductal adenocarcinoma (PDAC), surgical margin status is an important pathological factor for evaluating surgical adequacy. In this study, we attempted to investigate predictive factors for the survival impact of positive surgical margins. MATERIALS AND METHODS: From February 2004 to December 2013, 204 patients were diagnosed with PDAC and underwent surgery with radical intent; 189 patients fulfilled our selection criteria and were enrolled for analysis. RESULTS: For the 189 enrolled patients with PDAC, we found male predominance (112/189, 59%) and a median age of 64 years; most patients were diagnosed with stage IIB disease (n=115, 61%). The positive surgical margin rate was 21% (n=40). Carbohydrate antigen 19-9 (CA19-9) level higher than 246 U/ml (odds ratio (OR)=2.318; 95% confidence interval (CI)=1.037-5.181 p=0.040) and lesion location in the uncinate process (OR=2.996; 95% CI=1.232-7.284 p=0.015) were the only two independent risk factors for positive surgical margins. Positive retroperitoneal soft-tissue margins were the most frequently observed (24/40, 60%). Overall, positive surgical margins had no survival impact in the 189 patients with PDAC who underwent surgery; however, positive surgical margins had an unfavorable survival impact on patients with stage IIA PDAC who underwent surgery. CONCLUSION: Retroperitoneal soft-tissue was the most common site for positive surgical margins. Additionally, surgical margin positivity was more likely for tumors located in the uncinate process than for other tumors. Positive surgical margins had an unfavorable survival impact on patients with stage IIA PDAC who underwent surgery.

Whole-exome sequencing to identify a novel LMNA gene mutation associated with inherited cardiac conduction disease.

BACKGROUND: Inherited cardiac conduction diseases (CCD) are rare but are caused by mutations in a myriad of genes. Recently, whole-exome sequencing has successfully led to the identification of causal mutations for rare monogenic Mendelian diseases. OBJECTIVE: To investigate the genetic background of a family affected by inherited CCD. METHODS AND RESULTS: We used whole-exome sequencing to study a Chinese family with multiple family members affected by CCD. Using the pedigree information, we proposed a heterozygous missense mutation (c.G695T, Gly232Val) in the lamin A/C (LMNA) gene as a candidate mutation for susceptibility to CCD in this family. The mutation is novel and is expected to affect the conformation of the coiled-coil rod domain of LMNA according to a structural model prediction. Its pathogenicity in lamina instability was further verified by expressing the mutation in a cellular model. CONCLUSIONS: Our results suggest that whole-exome sequencing is a feasible approach to identifying the candidate genes underlying inherited conduction diseases.