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Objectives. Recently, it has been demonstrated that patients with subtle preexisting cognitive impairment were susceptible to delayed neurocognitive recovery (DNR). This present study investigated whether preoperative alterations in gray matter volume, spontaneous activity, or functional connectivity (FC) were associated with DNR. Methods. This was a nested case-control study of older adults (≥60 years) undergoing noncardiac surgery. All patients received MRI scan at least 1 day prior to surgery. Cognitive function was assessed prior to surgery and at 7-14 days postsurgery. Preoperative gray matter volume, amplitude of low-frequency fluctuation (ALFF), and FC were compared between the DNR patients and non-DNR patients. The independent risk factors associated with DNR were identified using a multivariate logistic regression model. Results. Of the 74 patients who completed assessments, 16/74 (21.6%) had DNR following surgery. There were no differences in gray matter volume between the two groups. However, the DNR patients exhibited higher preoperative ALFF in the bilateral middle cingulate cortex (MCC) and left fusiform gyrus and lower preoperative FC between the bilateral MCC and left calcarine than the non-DNR patients. The multivariate logistic regression analysis showed that higher preoperative spontaneous activity in the bilateral MCC was independently associated with a higher risk of DNR (OR=3.11, 95% CI, 1.30-7.45; P=0.011). A longer education duration (OR=0.57, 95% CI, 0.41-0.81; P=0.001) and higher preoperative FC between the bilateral MCC and left calcarine (OR=0.40, 95% CI, 0.18-0.92; P=0.031) were independently correlated with a lower risk of DNR. Conclusions. Preoperative higher ALFF in the bilateral MCC and lower FC between the bilateral MCC and left calcarine were independently associated with the occurrence of DNR. The present fMRI study identified possible preoperative neuroimaging risk factors for DNR. This trial is registered with Chinese Clinical Trial Registry ChiCTR-DCD-15006096.

Objective The aim of the study was to analyze the outcomes of patients who have undergone laparoscopic pancreaticoduodenectomy (LPD) in China. Summary background data LPD is being increasingly used worldwide, but an extensive, detailed, systematic, multicenter analysis of the procedure has not been performed. Methods We retrospectively reviewed 1029 consecutive patients who had undergone LPD between January 2010 and August 2016 in China. Univariate and multivariate analyses of patient demographics, changes in outcome over time, technical learning curves, and the relationship between hospital or surgeon volume and patient outcomes were performed. Results Among the 1029 patients, 61 (5.93%) required conversion to laparotomy. The median operation time (OT) was 441.34 minutes, and the major complications occurred in 511 patients (49.66%). There were 21 deaths (2.43%) within 30 days, and a total of 61 (5.93%) within 90 days. Discounting the effects of the early learning phase, critical parameters improved significantly with surgeons' experience with the procedure. Univariate and multivariate analyses revealed that the pancreatic anastomosis technique, preoperative biliary drainage method, and total bilirubin were linked to several outcome measures, including OT, estimated intraoperative blood loss, and mortality. Multicenter analyses of the learning curve revealed 3 phases, with proficiency thresholds at 40 and 104 cases. Higher hospital, department, and surgeon volume, as well as surgeon experience with minimally invasive surgery, were associated with a lower risk of surgical failure. Conclusions LPD is technically safe and feasible, with acceptable rates of morbidity and mortality. Nonetheless, long learning curves, low-volume hospitals, and surgical inexperience are associated with higher rates of complications and mortality.

The etiology of 80% of patients with primary antibody deficiency (PAD), the second most common type of human immune system disorder after human immunodeficiency virus infection, is yet unknown. Clinical/immunological phenotyping and exome sequencing of a cohort of 126 PAD patients (55.5% male, 95.2% childhood onset) born to predominantly consanguineous parents (82.5%) with unknown genetic defects were performed. The American College of Medical Genetics and Genomics criteria were used for validation of pathogenicity of the variants. This genetic approach and subsequent immunological investigations identified potential disease-causing variants in 86 patients (68.2%); however, 27 of these patients (31.4%) carried autosomal dominant (24.4%) and X-linked (7%) gene defects. This genetic approach led to the identification of new phenotypes in 19 known genes (38 patients) and the discovery of a new genetic defect (CD70 pathogenic variants in 2 patients). Medical implications of a definite genetic diagnosis were reported in ~50% of the patients. Due to misclassification of the conventional approach for targeted sequencing, employing next-generation sequencing as a preliminary step of molecular diagnostic approach to patients with PAD is crucial for management and treatment of the patients and their family members.

Pancreatic cancer remains a challenging disease with an overall cumulative 5-year survival rate around 6%. Though significant progress has been made in the availability of diagnostic techniques and treatment strategies, pancreatic cancer remains a disease of high mortality rate. Therefore, there is an urgent need for a better understanding of the molecular mechanisms that governs the oncogenesis and metastasis process of pancreatic cancer. In the present study, by using the Cancer Genome Atlas (TCGA) dataset analysis, we demonstrated that sorting nexin 6 (SNX6) serves as a biomarker for predicting prognosis of pancreatic cancer. In vitro studies demonstrated that silencing of SNX6 expression reduced cell proliferation, colony formation, invasion, and metastasis. Higher level of SNX6 helps maintain the mesenchymal properties, which renders migration and invasive capacities to pancreatic cancer cells. Moreover, in the process of TGF-β-induced epithelial to mesenchymal transition (EMT), the expression level of SNX6 was increased, and silencing of SNX6 expression could inhibit the TGF-β-induced EMT program. These results collectively uncovered a novel predictive marker for pancreatic cancer and provided the possible underlying molecular mechanism.

// Yun Wang 1, * , Abir Garraoui 2, 3, * , Liuzhi Zeng 4, * , Mingying Lai 1 , Fen He 1 , Huaizhou Wang 5 , Chongyi Jiang 2 , Yulan Chen 2 , Lanlan Dai 2 , Ning Fan 1 , Huanming Yang 2, 6 , Jianguo Zhang 2, 7 and Xuyang Liu 1 1 Shenzhen Key Laboratory of Ophthalmology, Shenzhen Eye Hospital, Shenzhen University, Shenzhen, China 2 BGI-Shenzhen, Shenzhen, China 3 Laboratory of Human Molecular Genetics, Faculty of Medicine, University of Sfax, Sfax, Tunisia 4 The First People's Hospital of Chengdu, Chengdu, China 5 Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Beijing Ophthalmology & Visual Sciences Key Laboratory, Capital Medical University, Beijing, China 6 James D. Watson Institute of Genome Sciences, Hangzhou, China 7 Shenzhen Key Laboratory of Neurogenomics, BGI-Shenzhen, Shenzhen, China * These authors have contributed equally to this work Correspondence to: Xuyang Liu, email: xliu1213@126.com Jiangguo Zhang, email: Jianguozhang@genomics.cn Keywords: Bardet-Biedl syndrome, retinitis pigmentosa, FBN3 , whole exome sequencing Received: March 27, 2017 Accepted: August 29, 2017 Published: September 30, 2017 ABSTRACT Purpose: This study was designed to evaluate the molecular genetics of a Chinese family with Bardet-Biedl syndrome (BBS). Methods: All the family members underwent medical history evaluation, ophthalmologic and physical examinations. Whole exome sequencing was performed on two affected individuals and their parents. All variants were verified in all family members by PCR amplification and Sanger sequencing. Results: Patients in this family were diagnosed as Bardet-Biedl syndrome, with an inheritance pattern of autosomal recessive. Compound heterozygous mutations of the FBN3 gene (c.3616G>A and c.6037C>T) were identified by whole exome sequencing. Results from Sanger sequencing showed co-segregation of these compound heterozygous mutations in the FBN3 gene with BBS disease in the family. Conclusion: Novel compound heterozygous mutations c.3616G>A and c.6037C>T of FBN3 were identified in all affected individuals but not in the unaffected family members. This is the first time to the best of our knowledge, that the FBN3 gene is involved in the pathogenesis of BBS. This study will expand our understanding about the gene spectrum related to this genetically heterogeneous disorder.

Bleeding control as one of the major challenges in laparoscopic pancreaticoduodenectomy (LPD) necessitates a considerable anatomical knowledge of the blood supply to the pancreatic head so as to improve the safety of this surgery. This study aimed towards a better understanding of the anatomical features of the dorsal pancreatic artery (DPA), as well as its clinical significance in LPD. Thirteen Chinese cadaveric specimens were used to study the blood supply of the pancreatic head. Twelve of them were perfused with latex, and the other fresh one was used to build the intraorganic structure model of the pancreas by mold casting. Between July 2018 and June 2019, a total of thirty-five consecutive patients without vascular encasement, who underwent LPD in our institute, were performed with computed tomography as a preoperative detection of the DPA. The DPA was ligated prior to uncinate process dissection in seventeen patients ("early DPA ligation" group), as the others were assigned into the control group. In the thirteen cadaveric specimens, the DPA originates, respectively, from the splenic artery (46.1%), superior mesenteric artery (38.5%), common hepatic artery (7.7%) and right gastroepiploic artery (7.7%). The right branch of the DPA gives off terminal arteries to form an “inner ring” in the pancreatic head, which communicates with the pancreaticoduodenal arterial arches by plenty of collateral arteries. As compared to the control group, the “early DPA ligation" group showed a significantly lower mean blood loss (218 ± 111 vs 320 ± 162, P = 0.038), as well as shorter mean resection time (121 ± 23 vs 136 ± 22, P = 0.049). The DPA is one of the major blood supplies to the pancreatic head. A ligation of DPA prior to dissection of the uncinate process can help to completely block the blood supply to the pancreatic head, and therefore improve surgical outcome and safety in LPD.

Background Uncinate process dissection is one of the major challenges for surgeons when performing laparoscopic pancreatoduodenectomy. This study aimed to evaluate the artery first approach for handling uncinate process dissection in laparoscopic pancreatoduodenectomy. Methods Between February 2015 and June 2018, a total of 91 consecutive patients without vascular encasement underwent selective laparoscopic pancreatoduodenectomy, including the first 26 consecutive cases treated with the conventional approach and the remaining 65 with the artery first approach applied for uncinate process dissection. Here, we present and analyze the surgical outcomes and the oncological results for the two groups. Results There was no significant difference between the two groups in operative time, intraoperative blood loss, the rate of conversion to open pancreatoduodenectomy, postoperative complications, mortality, as well as the number of lymph nodes retrieved in the malignancies. In contrast, the artery first approach group showed a statistically significant shorter resection time and a higher R0 resection rate when compared with the conventional group. Conclusions The artery first approach is a safe and feasible technique that can be used for uncinate process management in laparoscopic pancreatoduodenectomy for patients without vascular encasement. It also has the advantage of increased rate of radical resection in the surgical intervention of relevant malignancies.

The objective of the study is to evaluate the safety and feasibility of laparoscopic pancreaticoduodenectomy (LPD) in elderly patients by short-term surgical effects. We retrospectively collected clinical data of 55 non-elderly patients (

// Sujie Ni 1, * , Hongwei Wang 1, 2, * , Xiaolin Zhu 3 , Chunhua Wan 4 , Junfei Xu 5 , Chen Lu 6 , Li Xiao 6 , Jiaqi He 2 , Chongyi Jiang 2 , Wei Wang 2 , Zhixian He 5 1 Department of Medical Oncology, Affiliated Hospital of Nantong University, Nantong University, Nantong 226001, China 2 Bilary and Pancreatic Center, Huadong Hospital of Fudan University, Fudan University, Shanghai 200040, China 3 Department of Gastroenterology, Affiliated Hospital of Nantong University, Nantong University, Nantong 226001, China 4 Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong 226001, China 5 Department of General Surgery, Affiliated Hospital of Nantong University, Nantong University, Nantong 226001, China 6 Department of Pathology, Huadong Hospital of Fudan University, Fudan University, Shanghai 200040, China * These authors have contributed equally to this work Correspondence to: Zhixian He, email: hezhixian@ntu.edu.cn Wei Wang, email: hdwangwei@fudan.edu.cn Keywords: CBX7, pancreatic cancer, prognosis, tumor suppression, PTEN Received: April 23, 2016 Accepted: November 21, 2016 Published: December 20, 2016 ABSTRACT Chromobox protein homolog 7 (CBX7), one of the polycomb group (PcG) proteins, is a transcriptional repressor involved in the regulation of cell proliferation and senescence. In the present study, we showed that CBX7 negatively regulates the proliferation, viability, chemoresistance, and migration of pancreatic cancer cells. Overexpression of CBX7 significantly inhibited the proliferation of pancreatic cancer cells in vitro and in vivo . Depletion of CBX7 facilitated their growth. CBX7 also impaired the viability and chemoresistance of pancreatic cancer cells. Transwell assays showed that CBX7 reduces the migratory capacity of pancreatic cancer cells. Of note, CBX7 reduced PTEN/Akt signaling in pancreatic cancer cells by increasing PTEN transcription, suggesting involvement of PTEN/Akt pathway in the tumor suppressive activity of CBX7. In addition, immunohistochemical analysis the CBX7 and PTEN expression in 74 surgically resected pancreatic ductal adenocarcinoma (PDAC) specimens revealed that CBX7 expression is significantly downregulated in pancreatic ductal adenocarcinoma, compared to normal pancreatic tissues. Reduced expression of CBX7 and PTEN was associated with increased malignancy grade in pancreatic adenocarcinoma, whereas maintenance of CBX7 and PTEN expression showed a trend toward a longer survival. These findings suggest CBX7 is an important tumor suppressor that negatively modulates PTEN/Akt signaling during pancreatic tumorigenesis.

Background: Congenital cataract is a common cause of childhood vision impairment or blindness with genetic and clinical heterogeneity. The aim of this study was to identify the disease-associated gene in a Chinese family with congenital cataract. Methods: A four-generation Chinese family with three enrolled patients suffering from congenital cataract was studied. Detailed family history and clinical data of all the members were collected and recorded. Exome sequencing was applied in the proband to screen potential genetic variants, and then Sanger sequencing was used to verify the variant within the family. Results: A heterozygous variant, c.3673G > A (p.V1225M), in the periaxin gene ( PRX ) was identified in three patients and two asymptomatic individuals of the family. The variant was absent in the other three unaffected family members and in 3290 ethnically matched in-house controls from BGI-Shenzhen. Conclusions: By utilizing both exome sequencing and Sanger sequencing, we identified a missense variant in the PRX gene that is possibly associated with disease in this family. Our finding may broaden the spectrum of genes associated with congenital cataract, and may provide insights into lens development, pathogenic mechanism, future clinical genetic diagnosis and therapy of congenital cataract.