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Competing Interests: Conflicts of interest All authors declare that they have no competing interests.

Racial and ethnic disparities persist in cancer survival rates across the United States, despite overall improvements. This comprehensive analysis examines trends in 5-year relative survival rates from 2002-2006 to 2015-2019 for major cancer types, elucidating differences among racial/ethnic groups to guide equitable healthcare strategies. Data from the SEER Program spanning 2000-2020 were analyzed, focusing on breast, colorectal, prostate, lung, pancreatic cancers, non-Hodgkin lymphoma, acute leukemia, and multiple myeloma. Age-standardized relative survival rates were calculated to assess racial (White, Black, American Indian/Alaska Native, Asian/Pacific Islander) and ethnic (Hispanic, Non-Hispanic) disparities, utilizing period analysis for recent estimates and excluding cases identified solely through autopsy or death certificates. While significant survival improvements were observed for most cancers, notable disparities persisted. Non-Hispanic Blacks exhibited the largest gain in breast cancer survival, with an increase of 5.2% points (from 77.6 to 82.8%); however, the survival rate remained lower than that of Non-Hispanic Whites (92.1%). Colorectal cancer survival declined overall (64.7-64.1%), marked by a 6.2% point drop for Non-Hispanic American Indian/Alaska Natives (66.3-60.1%). Prostate cancer survival declined across all races, with Non-Hispanic American Indian/Alaska Natives showing a decrease of 7.7% points (from 96.9 to 89.2%). Lung cancer, acute leukemia, and multiple myeloma showed notable increases across groups. Substantial racial/ethnic disparities in cancer survival underscore the notable need for tailored strategies ensuring equitable access to advanced treatments, particularly addressing significant trends in colorectal and pancreatic cancers among specific minority groups. Careful interpretation of statistical significance is warranted given the large dataset., (© 2024. The Author(s).)

With advancements in genomics and immunology, immunotherapy has emerged as a revolutionary strategy for tumor treatment. However, pancreatic ductal adenocarcinoma (PDAC), an immunologically "cold" tumor, exhibits limited responsiveness to immunotherapy. This study aimed to address the urgent need to uncover PDAC's immune microenvironment heterogeneity and identify the molecular mechanisms driving immune evasion. Using single-cell RNA sequencing datasets and spatial proteomics, we discovered LIM domain only 7 (LMO7) in PDAC cells as a previously unrecognized driver of immune evasion through Treg cell enrichment. LMO7 was positively correlated with infiltrating regulatory T cells (Tregs) and dysfunctional CD8 + T cells. A series of in vitro and in vivo experiments demonstrated LMO7's significant role in promoting Treg cell differentiation and chemotaxis while inhibiting CD8 + T cells and natural killer cell cytotoxicity. Mechanistically, LMO7, through its LIM domain, directly bound and promoted the ubiquitination and degradation of Foxp1. Foxp1 negatively regulated transforming growth factor-beta (TGF-β) and C-C motif chemokine ligand 5 (CCL5) expression by binding to sites 2 and I/III, respectively. Elevated TGF-β and CCL5 levels contribute to Treg cell enrichment, inducing immune evasion in PDAC. Combined treatment with TGF-β/CCL5 antibodies, along with LMO7 inhibition, effectively reversed immune evasion in PDAC, activated the immune response, and prolonged mouse survival. Therefore, this study identified LMO7 as a novel facilitator in driving immune evasion by promoting Treg cell enrichment and inhibiting cytotoxic effector functions. Targeting the LMO7-Foxp1-TGF-β/CCL5 axis holds promise as a therapeutic strategy for PDAC. Graphical abstract revealing LMO7 as a novel facilitator in driving immune evasion by promoting Tregs differentiation and chemotaxis, inducing CD8 + T/natural killer cells inhibition., (© 2024. The Author(s).)

Background: Marginal ulcer (MU) is one of the postoperative complications of pancreaticoduodenectomy (PD), which needs particular attention in postoperative treatments., Methods: The data of 190 patients who underwent PD and follow-up gastroscopic review due to upper GI symptoms within two years were retrospectively analyzed. The incidence of MU and risk factors were analyzed based on personal history, surgical procedure, past medical history, postoperative complications, and other relevant indicators., Results: The proportion of MU in patients who underwent endoscopic follow-up for upper gastrointestinal symptoms in the postoperative period in this cohort was 10.5% (20/190). Advanced age (69y vs. 59y, P ​= ​0.012), alcohol consumption (20% vs. 8.2%, P ​= ​0.03), and cigarette smoking (35% vs. 14.7%, P ​= ​0.022) were associated with an increased incidence of MU. Longer surgery time (276.5min vs. 240min, P ​= ​0.049), postoperative bleeding (10% vs. 1.8%, P ​= ​0.030), and failure to take antacid regularly postoperatively (75% vs. 97.1%, P ​= ​0.000) would increase the risk of MU; taking antacid regularly was an independent protective factor for postoperative anastomotic ulceration (OR: 0.091, CI: 0.022-0.383, P ​= ​0.001)., Conclusion: Advanced age, alcohol consumption, smoking, longer operation time, or postoperative extraluminal hemorrhage are associated with MU. Regular use of antacids is an independent protective factor against the development of MU., Competing Interests: Declaration of competing interest All the authors have no conflicts of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This study conducted experimental analyses on a 280 Ah single lithium iron phosphate battery using an independently constructed experimental platform to assess the efficacy of compressed nitrogen foam in extinguishing lithium-ion battery fires. Based on theoretical analysis, the fire-extinguishing effects of compressed nitrogen foam at different outlet pressures from foam mixture tanks were analyzed, examining factors such as battery surface temperature, flame temperature, and thermal weight loss. The results indicate that the compressed nitrogen foam can extinguish the open flame of the battery in 14 s at 0.7 MPa, with the battery's surface temperature dropping by approximately 11 % before and after the application of the extinguishing agent. Compared with other commonly used extinguishing agents, the compressed nitrogen foam demonstrates superior extinguishing efficiency, but its cooling efficiency is somewhat lower. At pressures ranging from 0.4 to 0.6 MPa, the foam displays prolonged drainage time and sustained cooling effects, rendering it more suitable for lithium-ion battery fire scenarios. To address the issue of reduced cooling performance during later stages of fire suppression by compressed nitrogen foam, an intermittent injection approach has been proposed to effectively preserve its cooling efficacy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Cyclin-dependent kinase subunit 2 (CKS2) has been reported to promote various malignancies. This study investigated the functional role of CKS2 in pancreatic cancer (PC). An analysis of abnormally expressed genes and their prognostic value for PC was performed by using the Gene Expression Profiling Interactive Analysis (GEPIA) database and performing immunohistochemical staining on 64 samples of tumor tissue. CCK-8 assays, EdU staining, colony formation assays, flow cytometry, and a xenograft tumor model were used to analyze the biological function of CKS2 in PC. Our results revealed that CKS2 was expressed at significantly higher levels in PC tissues than in adjacent normal tissues, and a high level of CKS2 expression was associated with a poor prognosis for patients with PC. Moreover, functional assays revealed that CKS2 knockdown suppressed cell proliferation, induced cell cycle S phase, G2/M phase arrest, and apoptosis in vitro, and also reduced tumor growth in vivo. In addition, CKS2 knockdown increased the levels of Bax, caspase-3, P53, P21, and GADD45α expression, but decreased Bcl-2, Cyclin B1, CDK1, Cyclin A, and Cdc25C expression. CKS2 overexpression produced the opposite effects of CKS2 knockdown. Furthermore, we found that ELK1 protein regulated transcription of the CKS2 gene. In conclusion, our findings suggest that CKS2 expression is regulated by ELK1, which could possibly serve as prognostic indicator and therapeutic target for PC., (© 2023 Wiley Periodicals LLC.)

A highly accurate classification of diabetes mellitus (DM) with the synthetic impacts of several variables is first studied via optoacoustic technology in this work. For this purpose, an optoacoustic measurement apparatus of blood glucose is built, and the optoacoustic signals and peak-peak values for 625 cases of in vitro rabbit blood are obtained. The results show that although the single impact of five variables are obtained, the precise classification of DM is limited because of the synthetic impacts. Based on clinical standards, different levels of blood glucose corresponding to hypoglycaemia, normal, slight diabetes, moderate diabetes and severe diabetes are employed. Then, a wavelet neural network (WNN) is utilized to establish a classification model of DM severity. The classification accuracy is 94.4 % for the testing blood samples. To enhance the classification accuracy, particle swarm optimization (PSO) and quantum-behaved particle swarm optimization (QPSO) are successively utilized to optimize WNN, and accuracy is enhanced to 98.4 % and 100 %, respectively. It is demonstrated from comparison between several algorithms that optoacoustic technology united with the QPSO-optimized WNN algorithm can achieve precise classification of DM with synthetic impacts., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Background: For infected necrotizing pancreatitis (INP), percutaneous catheter drainage (PCD) is now widely acknowledged as the initial intervention in a step-up approach, followed, if necessary, by minimally invasive necrosectomy or even open pancreatic necrosectomy. However, an overemphasis on PCD may cause a patient's condition to deteriorate, leading to missed surgical opportunities or even death. This study aimed to develop a simple and convenient scoring tool for assessing the need for surgery in INP patients who received PCD procedures., Methods: In an observational study conducted between April 2015 and December 2020, PCD was utilized as the initial step to treat 143 consecutive INP patients. A surgical necrosectomy was performed when the patient failed to respond. Risk factors of PCD failure (i.e., need for surgical necrosectomy) were identified by multivariate logistic regression models. An integer-based risk scoring tool was developed using the β coefficients derived from the logistic regression model., Results: In 62 (43.4%) patients, PCD was successful, while the remaining 81 (56.6%) individuals required subsequent surgical necrosectomy. In the multivariate model, organ failure, percentage of pancreatic necrosis, extrapancreatic necrosis volume, and mean CT density of extrapancreatic necrosis volume were associated with a need for surgical necrosectomy. A predictive scoring tool based on these four factors demonstrated an area under the receiver operating characteristic curve (AUC) of 0.893. Under the scoring tool, a total score of 4 or more indicates a high possibility of surgical necrosectomy being required (at least 80%). Using the coordinates of the receiver operating characteristic curve (ROC), the sensitivity and specificity at this threshold are 0.802 and 0.903, respectively., Conclusions: A risk score model integrating organ failure, percentage of pancreatic necrosis, extrapancreatic necrosis volume, and mean CT density of extrapancreatic necrosis volume can identify INP patients at high risk for necrosectomy. The straightforward risk assessment tool assists clinicians in stratifying INP patients and making more judicious medical decisions., (© 2023. The Society for Surgery of the Alimentary Tract.)

Background/aim: Curcumin may have potential as a therapy for wound healing, but the underlying mechanism remains unclear. It is not known whether curcumin can promote wound healing by activating Nrf2 signaling pathway and inducing apoptosis. This study determined the role of Nrf2 signaling pathway and apoptosis in curcumin-promoting skin wound healing., Materials and Methods: The full-thickness skin defect model of mice was made and randomly divided into a control group and a curcumin group. The mice in the curcumin group and in the control group received respectively a daily topical treatment of Vaseline cream with or without 5 mg curcumin. The wound healing of mice was observed daily. The mice in two groups were killed respectively on postinjury days 3, 7, and 14, and the wound tissues were collected, with 5 mice in each group. Pathological change and formation of collagen fibers were observed by HE and Masson staining respectively. The expression of caspase-3 was observed by immunohistochemistry. Western blot was used to examine the protein levels of Nrf2 and HO-1, and ELISA assay and colorimetry assay were used to check the contents of ROS, MDA, SOD, and GSH., Results: The wound healing rates of curcumin group were higher than those of control group (p < 0.05), and the pathological changes were also significantly better than those in the control group (p < 0.05). Collagen fiber synthesis in curcumin group was higher than that in control group (p < 0.05). Moreover, the expression of caspase-3 in curcumin group was higher than that in control group on 7th day post wound (p < 0.05). Furthermore, the levels of ROS and MDA in curcumin were lower than those in control group (p < 0.05), and the level of Nrf2, HO-1, SOD and GSH were higher than those in control group (p < 0.05)., Conclusion: Curcumin improves skin wound healing by activating the Nrf2 signaling pathway and inducing apoptosis in mice., Competing Interests: Conflict of interest: The authors declare no conflicts of interest relevant to this study., (© TÜBİTAK.)

Background: Delayed gastric emptying (DGE) is a common complication after pancreaticoduodenectomy (PD) or pylorus-preserving pancreaticoduodenectomy (PPPD). However, its risk factors are still unclear. This meta-analysis aimed to identify the potential risk factors of DGE among patients undergoing PD or PPPD., Materials and Methods: We searched PubMed, EMBASE, Web of Science, Cochrane Library, Google Scholar, and ClinicalTrial.gov for studies that examined the clinical risk factors of DGE after PD or PPPD from inception through 31 July 2022. We pooled odds ratios (ORs) with 95% CIs using random-effects or fixed-effects models. We also performed heterogeneity, sensitivity, and publication bias analyses., Results: The study included a total of 31 research studies, which involved 9205 patients. The pooled analysis indicated that out of 16 nonsurgical-related risk factors, three risk factors were found to be associated with an increased incidence of DGE. These risk factors were older age (OR 1.37, P =0.005), preoperative biliary drainage (OR 1.34, P =0.006), and soft pancreas texture (OR 1.23, P =0.04). On the other hand, patients with dilated pancreatic duct (OR 0.59, P =0.005) had a decreased risk of DGE. Among 12 operation-related risk factors, more blood loss (OR 1.33, P =0.01), postoperative pancreatic fistula (POPF) (OR 2.09, P <0.001), intra-abdominal collection (OR 3.58, P =0.001), and intra-abdominal abscess (OR 3.06, P <0.0001) were more likely to cause DGE. However, our data also revealed 20 factors did not support stimulative factors influencing DGE., Conclusion: Age, preoperative biliary drainage, pancreas texture, pancreatic duct size, blood loss, POPF, intra-abdominal collection, and intra-abdominal abscess are significantly associated with DGE. This meta-analysis may have utility in guiding clinical practice for improvements in screening patients with a high risk of DGE and selecting appropriate treatment measures., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is a foodborne pathogen that specifically colonizes and infects the human large intestine. EHEC O157:H7 engages intricate regulatory pathways to detect host intestinal signals and regulate virulence-related gene expression during colonization and infection. However, the overall EHEC O157:H7 virulence regulatory network in the human large intestine remains incompletely understood. Here, we report a complete signal regulatory pathway where the EvgSA two-component system responds to high-nicotinamide levels produced by microbiota in the large intestine and directly activates loci of enterocyte effacement genes to promote EHEC O157:H7 adherence and colonization. This EvgSA-mediated nicotinamide signaling regulatory pathway is conserved and widespread among several other EHEC serotypes. Moreover, disruption of this virulence-regulating pathway by the deletion of evgS or evgA significantly decreased EHEC O157:H7 adherence and colonization in the mouse intestinal tract, indicating that these genes could be potential targets for the development of new therapeutics for EHEC O157:H7 infection., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Exploring a cost-effective and high-accuracy optical detection method is of great significance in promoting fruit quality evaluation and grading sales. Apples are one of the most widely economic fruits, and a qualitative and quantitative assessment of apple quality based on soluble solid content (SSC) was investigated via visible (Vis) spectroscopy in this study. Six pretreatment methods and principal component analysis (PCA) were utilized to enhance the collected spectra. The qualitative assessment of apple SSC was performed using a back-propagation neural network (BPNN) combined with second-order derivative (SD) and Savitzky-Golay (SG) smoothing. The SD-SG-PCA-BPNN model's classification accuracy was 87.88%. To improve accuracy and convergence speed, a dynamic learning rate nonlinear decay (DLRND) strategy was coupled with the model. After that, particle swarm optimization (PSO) was employed to optimize the model. The classification accuracy was 100% for testing apples via the SD-SG-PCA-PSO-BPNN model combined with a Gaussian DLRND strategy. Then, quantitative assessments of apple SSC values were performed. The correlation coefficient ( r ) and root-square-mean error for prediction (RMSEP) in testing apples were 0.998 and 0.112 °Brix, surpassing a commercial fructose meter. The results demonstrate that Vis spectroscopy combined with the proposed synthetic model has significant value in qualitative and quantitative assessments of apple quality.

Background/objectives: To evaluate perioperative safety and outcome of parenchyma-preserving pancreatectomy and risk factors of metastasis and recurrence for patients with solid pseudopapillary neoplasm (SPN)., Methods: Demographic data, operative and pathological parameter, follow-up data of patients with SPN undergoing their first operation were collected in our single center from May 2016 to October 2021 and compared between regular pancreatectomy group and parenchyma-preserving surgery group. Risk factors for metastasis and recurrence were investigated., Results: A total of 194 patients were included, 154 of whom were female and the average age of all patients was 33 years old. Most patients were asymptomatic, with the most common complaint being abdominal pain or discomfort. Of them, 62 patients underwent parenchyma-preserving pancreatectomy including middle segment pancreatectomy and enucleation, and 132 patients underwent regular pancreatectomy including pancreaticoduodenectomy, distal pancreatectomy and total pancreatectomy. Patients in the parenchyma-preserving surgery group had a shorter duration of operation, less intraoperative bleeding, and decreased risk of combined organ removal and blood transfusion, with no statistical significance yet. The two groups exhibited a similar incidence of postoperative complications including grade B and C pancreatic fistula, delayed gastric emptying, postoperative pancreatic hemorrhage, and other complications, as well as radiological intervention, relaparotomy and the length of postoperative hospital stay. There were no perioperative deaths. All the patients, except 18 of those who discontinued follow-up, were alive with a median follow-up time of 31 months. Three patients in the regular pancreatectomy group were observed to have liver metastasis, and no metastasis was observed in the parenchyma-preserving surgery group. Significant risk factors for tumor metastasis and recurrence were tumor size, angioinvasion, and nerve infiltration., Conclusions: Parenchyma-preserving surgery did not significantly increase the frequency of perioperative complications or recurrence and might be preferable if comprehensive conditions allow., (© 2023. The Author(s).)

In this work, the photoacoustic (PA) quantitative measurement of blood glucose concentration (BGC) influenced by multiple factors was firstly investigated. A set of PA detection system of blood glucose considering the comprehensive influence of five factors was established. The PA signals and peak-to-peak values (PPVs) of 625 rabbit whole blood were obtained under 625 influence combinations. Due to the accurate measurement of BGC limited by the overlap PA signals, wavelet neural network (WNN) was utilized to train the PPVs of blood glucose for 500 rabbit blood. The mean square error (MSE) of BGC for 125 testing blood was approximately 6.5782 mmol/L. To decrease the MSE, the parameters of WNN were optimized by particle swarm optimization (PSO), that is, PSO-WNN algorithm was employed. Under the optimal parameters, MSE of BGC was decreased to approximately 0.48005 mmol/L. To further improve the prediction accuracy of BGC, an improved nonlinear dynamic inertia weight (NDIW) strategy of PSO was proposed, and compared with other two kinds of dynamic inertia weight strategies. Under the optimal parameters, the MSE of BGC was decreased to approximately 0.2635 mmol/L. The comparison of nine algorithms demonstrate that the PA technique combined with PSO-WNN and the improved NDIW strategy is significant in the quantitative measurement of blood glucose influenced by multiple factors., (© 2022 Wiley-VCH GmbH.)

An effective method for separating and purifying critical saponins (polyphyllin II and polyphyllin VII) from a Paris polyphylla var. yunnanensis extract was developed in this study which was environmentally friendly and economical. Static adsorption kinetics, thermodynamics, and the dynamic adsorption-desorption of macroporous resins were investigated, and then the conditions of purification and separation were optimized by fitting with an adsorption thermodynamics equation and a kinetic equation. Effective NKA-9 resin from seven macroporous resins was screened out to separate and purify the two saponins. The static adsorption and dynamic adsorption were chemical and physical adsorption dual-processes on the NKA-9 resin. Under the optimum parameters, the contents of polyphyllin II and polyphyllin VII in the product were 17.3-fold and 28.6-fold those in plant extracts, respectively. The total yields of the two saponins were 93.16%. This research thus provides a theoretical foundation for the large-scale industrial production of the natural drugs polyphyllin II and polyphyllin VII.

Background: Pancreatojejunostomy stricture (PJS) is a rare long-term complication of pancreaticojejunal anastomosis. This study aimed to investigate the role of surgery in the management of pancreatojejunostomy strictures., Methods: The database of the Pancreas Center of Nanjing Medical University was retrospectively screened for patients who underwent a surgical revision for PJS between June 2012 and August 2019, and their clinical characteristics and management modalities were reviewed., Results: Fourteen consecutive cases were retrieved, the median age at index operation was 41.1 years (19-71). The average time between the two operations was 70.6 months (8-270 months). Index procedures included pancreaticoduodenectomy (PD) (7/14, 50%), pylorus-preserving PD (4/14, 28.6%), Berger procedure (2/14, 14.3%), and middle pancreatectomy (1/14, 7.1%). The diameter of the main pancreatic duct was < 4 mm in all 14 cases, and nine underwent pancreaticojejunostomy (PJ) stenting during the index operation. The most frequent complaints were abdominal pain (6/14, 42.9%), recurrent acute pancreatitis (6/14, 42.9%), pancreatic fistula (1/14, 7.1%), and abdominal distention (1/14, 7.1%). The diagnosis of PJ stricture was confirmed by computed tomography or magnetic resonance imaging in all cases. All patients had a main duct diameter > 5 mm before surgical revision. All patients underwent wedge excision with interrupted one-layer suturing with absorbable sutures and without stent placement. In this series, only one patient required reoperation. Upon follow-up, 11 of 12 patients had complete resolution of the PJ stricture., Conclusion: PJS is a long-term complication of pancreatojejunostomy. Surgical revision of the anastomosis is a safe and effective treatment modality., (© 2022. The Author(s).)

To accurately identify the blood authenticity, a set of photoacoustic detection system was established. In experiments, five kinds of blood in total of 125 groups were used, the time-resolved photoacoustic signals and peak-to-peak spectra were obtained in 700 to 1064 nm. Experimental results showed the accurate identification of blood authenticity was limited due to overlap of signals and spectra. To solve the problem, wavelet neural network (WNN) was employed to supervised train peak-to-peak spectra of 100 samples. The correct rate was 72% for 25 test samples. To improve correct rate, the parameters of WNN were optimized by quantum-behaved particle swarm optimization (QPSO) algorithm. Meanwhile, the effects of neurons number, learning rate factors, iteration times and training times on correct rate were studied and compared with WNN and WNN-PSO algorithms. Results showed the correct rate of WNN-QPSO was increased to 96%. Then, three kinds of dynamic contraction-expansion coefficients were used. Under the optimal dynamic coefficient, the correct rate reached 100%. Moreover, the truncated mean stabilization strategy (TMSS) was coupled to improve the convergent speed. Finally, 10 algorithms were compared. Results demonstrated that photoacoustic spectroscopy combined with WNN-QPSO coupled with TMSS and dynamic contraction-expansion coefficient had an excellent performance in the identification of blood authenticity., (© 2022 Wiley-VCH GmbH.)

Background: BRAF and MEK inhibitors significantly prolonged the progression-free survival of patients with BRAF mutant melanoma, but their long-term efficacy was limited by drug resistance. Our previous studies found that targeted inhibition of the mitogen-activated protein kinases (MAPK) pathway promotes the activation of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway in BRAF-mutant melanoma cells. Whether dual inhibition of MAPK and JAK2/STAT3 pathways can reverse drug resistance in melanoma remains unclear., Methods: This study verified whether morusin could enhance the inhibitory effect of MAPK pathway inhibitors on BRAF mutant melanoma by inhibiting the feedback activation of STAT3 at the cellular and animal levels., Results: We demonstrated that morusin could enhance the inhibitory effect of MAPK pathway inhibitors on BRAF mutant melanoma cells by inhibiting the feedback activation of the STAT3/SOX2 pathway. Moreover, our study showed morusin combined with MAPK pathway inhibitors specifically inhibited BRAF-mutant melanoma cells to a greater extent than wild-type cells. Our results also showed that the combination of morusin and BRAF inhibitors could jointly inhibit BRAF mutant melanoma in vivo. Finally, our experiment also revealed that the combination therapy of morusin and MAPK pathway inhibitors jointly inhibited drug-resistant melanoma in vitro and in vivo., Conclusion: Our results suggested that the combination of morusin and MAPK pathway inhibitors may be a more effective treatment strategy for BRAF-mutant melanoma than MAPK pathway inhibitors alone., Competing Interests: Conflict of interest statement The authors declare no competing interests., (Copyright © 2022 Southwest Medical University. Published by Elsevier Ltd.. All rights reserved.)

Importance: A higher incidence of pancreatic cancer has been reported in the Chinese population compared with the White population, but genetic differences are unknown to date. Large-sample germline testing for both familial and sporadic pancreatic cancers has been conducted predominantly in White populations, whereas similar studies in Chinese populations are limited., Objective: To assess the prevalence of germline sequence variations in patients with pancreatic diseases in China., Design, Setting, and Participants: This genetic association study was a case series that included genetic data from patients with pancreatic ductal adenocarcinoma (PDAC) or non-PDAC pancreatic diseases seen at The First Affiliated Hospital of Nanjing Medical University in Nanjing, China, between January 2006 and December 2017 (Nanjing cohort). Comparator group data were obtained for a US cohort from Johns Hopkins Hospital (JHH), a population from East Asia from the Exome Aggregation Consortium (ExAC) database, and the larger population from China from the ChinaMAP database. Data were updated and analyzed in July 2021., Main Outcomes and Measures: Next-generation sequencing technology was used to examine the prevalence of deleterious variations in 59 genes of the included Chinese patients with DNA extracted from peripheral blood samples. The Fisher exact test was used to assess differences among the frequencies of germline variations in the study patients vs the comparator groups., Results: A total of 1009 patients with PDAC (627 [62.1%] male; mean [SD] age, 62.8 [10.2] years) and 885 with non-PDAC diseases (477 [53.9%] male; mean [SD] age, 52.0 [15.9] years) from the Nanjing cohort were included for genetic analysis; all were Han Chinese individuals. Pathogenic variations were detected in 63 patients with PDAC (6.2%; 95% CI, 4.7%-7.7%). Variations in BRCA2 (odds ratio [OR], 3.2; 95% CI, 1.4-7.7; P = .008) and PALB2 (OR, 5.2; 95% CI, 1.6-17.0; P = .007) were significantly associated with pancreatic risk in the Nanjing cohort. Pathogenic variants of genes associated with homologous recombination DNA damage repair, including ATM, BRCA1/2, PALB2, BRIP1, FANCA, FANCC, RAD51D, and XRCC2, were found in 34 patients with PDAC (3.4%). No Ashkenazi Jewish-specific BRCA2 variation (p.Ser1982fs) was detected. The odds ratio of a SPINK1 variation in patients with PDAC was 3.2 (95% CI, 1.8-5.7; P < .001) in the Nanjing cohort compared with the ExAC cohort. Variations in the pancreatic secretory enzyme genes CPA1 and CPB1 were not detected in the Nanjing cohort., Conclusions and Relevance: In this genetic association study, sporadic pancreatic cancer was associated with pathogenic germline variations in a cohort from China. These findings provide insights into the genetic background of pancreatic cancer in the Han Chinese population with PDAC.

Purpose: This study aims to integrate pancreatic cancer TCGA, GEO, and single-cell RNA-sequencing (scRNA-seq) datasets, and explore the potential prognostic markers and underlying mechanisms of the immune microenvironment of pancreatic cancer through bioinformatics methods, in vitro and in vivo assays., Methods: Expression data and clinicopathological data of pancreatic cancer TCGA, GEO (GSE131050), single cell sequencing (PAAD&#95;CRA001160) dataset were downloaded. We used R/Bioconductor edgeR for differential expression analysis. ClusterProfiler was utilized to perform GO enrichment analysis on differentially expressed genes. The online software CIBERSORT was used to reanalyze the mRNA expression data of pancreatic cancer. CellRanger, RunPCA, FindNeighbors, FindClusters, RunTSNE and RunUMAP were used to perform preprocessing, cell clustering and expression profile analysis on single-cell sequencing data sets. We analyzed intracellular pH with or without CA9 inhibitor SLC-0111. Indirect co-culture model of human pancreatic cancer cell lines and healthy individual-derived PBMCs were used to determine the effect of CA9-related Acidic Microenvironment on CD8+ T cells., Results: The CIBERSORT analysis of TCGA pancreatic cancer transcriptome sequencing data showed that among the 22 immune microenvironment components, CD8+ T cell infiltration was significantly correlated with the prognosis of pancreatic cancer patients. The differential expression analysis of the TCGA data grouped by the level of CD8+ T cell infiltration indicates that the expression of carbonic anhydrase 9 (CA9) is the most significant, and the survival analysis suggests that CA9 is associated with the overall survival of pancreatic cancer. TCGA data and GEO data set GSE131050 expression correlation analysis suggests that CA9 and CD8 expression are closely related. Pancreatic cancer single-cell sequencing data set PAAD&#95;CRA001160 analysis results show that CA9 is mainly expressed in pancreatic cancer cell clusters, and the expression of the cancer cell subgroup CA9 in the single-cell data set is correlated with CD8+ T cell infiltration., Conclusion: Pancreatic cancer cells may inhibit the infiltration of CD8+ T cells through CA9. Further exploration of its related mechanisms can be used to explore the immune escape pathway of pancreatic cancer and provides new perspectives immune targeted therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yin, Lu, Cao, Lu, Wei, Zhu, Chen, Guo, Tu, Xi, Zhang, Wu, Gao, Jiang, Miao, Li and Peng.)

Background: Postoperative pancreatic fistula (POPF) is the major complication following pancreaticoduodenectomy (PD). We sought to develop and validate a risk prediction model for POPF after PD with the aim of determining personal risk probability and proposing a novel strategy for intraoperative placement and/or early-removal of prophylactic drainage., Methods: Data from 993 patients undergoing PD from January 2012 to December 2016 were retrospectively analyzed. Patients were randomly assigned to either training cohort or validation cohort. A nomogram was formulated based on the results from multivariable regression model for prediction of POPF. Internal and external validation were carried out with calibration plot respectively., Results: POPF occurred in 162 (16.3%) patients. The final pre-/intra-operative prediction model included alanine transaminase level [odds ratio (OR) 1.00, 95% confidence interval (CI): 1.00-1.00, P=0.023], combined portal-superior mesenteric vein resection (OR 0.22, 95% CI: 0.05-0.95, P=0.043), pancreatic duct diameter (OR 1.48, 95% CI: 1.11-1.96, P=0.007), intraoperative colloid infusion (OR 1.00, 95% CI: 1.00-1.00, P=0.001), pathology (OR 1.71, 95% CI: 1.09-2.66, P=0.018). The area under the curve (AUC) was 0.667 in the training cohort and 0.621 in the validation cohort. The final postoperative prediction model included pancreatic duct diameter (OR 1.58, 95% CI: 1.14-2.19, P=0.006), intraoperative colloid infusion (OR 2.52, 95% CI: 1.26-5.06, P=0.009), drainage fluid amylase on postoperative day 3 (POD3) (OR 4.70, 95% CI: 3.30-6.70, P<0.001), and neutrophil count on POD3 (OR 2.83, 95% CI: 1.63-4.93, P<0.001). The AUC was 0.809 in the training cohort and 0.797 in the validation cohort. Based on these variables, two nomogram prediction models were developed respectively. The calibration plot of the two models showed a good correlation between the expected risk and the actual risk in the low-risk range. Our risk-stratified strategy for drain management according to nomograms may be beneficial for 34.5% of patients., Conclusions: Our study formulated and validated two nomogram models for predicting POPF that performed particularly well in the low-risk range. This tool may allow surgeons to propose a risk stratified strategy for intraoperative drain placement and early drain removal, which may be beneficial for a substantial proportion of patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://gs.amegroups.com/article/view/10.21037/gs-21-550/coif). The authors have no conflicts of interest to declare., (2022 Gland Surgery. All rights reserved.)

Purpose: To introduce sub-adventitial divestment technique (SDT), a procedure to remove the tumor while preserving the artery during curative pancreatectomy. Peri-operative safety profile was also evaluated., Methods: In a single center consecutive series of pancreatectomy for pancreatic cancer, the outcome of patients who had pancreatectomy with SDT was compared to standard pancreatic surgery., Results: From June 2014 to June 2016, 72 patients had pancreatectomy with SDT and 235 had standard surgery. Tumor stage was T4 in all 72 (100%) tumors removed using SDT compared to four (2%) with standard pancreatectomy (p < 0.001). All 72 (100%) tumors in the SDT group were stage III compared to 24 (10%) in the standard surgery group (p < 0.001). Both groups had a high proportion of poorly differentiated tumors (52 (72%) and 163 (69%) respectively) and perineural tumor invasion (62 (86%) and 186 (79%) respectively). R1 (< 1 mm) was found in 24 (86%) of 28 tumors in the SDT group, and in 72 (60%) out of 120 standard pancreatectomy tumors (p = 0.01). Complications occurred in 29 (40%) of the SDT group and in 88 (37%) of the standard group. The in-hospital mortality was four (6%) in the SDT group and one (0.4%) in the standard group (p = 0.01), with a 90-day mortality of 5 (8%)/60 and 6 (3%)/209 (p = 0.07) respectively., Conclusions: The sub-adventitial divestment technique appeared to be an effective surgical technique to remove the tumor while preserving the artery. This approach warrants further validation in prospective studies.

Objective: The aim of this study was to test the hypothesis that early oral feeding (EOF) is superior to early nasojejunal nutrition (ENN) after pylorus-preserving pancreaticoduodenectomy (PPPD) in terms of delayed gastric emptying (DGE)., Background: DGE is a common complication after PPPD. Although EOF after PPPD is recommended by several international guidelines, there is no randomized trial to support this recommendation., Methods: From September 2016 to December 2017, a total of 120 patients undergoing PPPD were randomized into the ENN, EOF, or saline groups at a 1:1:1 ratio (40 patients in each group). The primary endpoint was the rate of clinically relevant DGE. Secondary endpoints included overall morbidity, postoperative pancreatic fistula, post-pancreatectomy hemorrhage, abdominal infection, length of hospital stay, reoperation rate, and in-hospital mortality., Results: The baseline characteristics and operative parameters were comparable between the groups. The incidence of clinically relevant DGE varied significantly among the three groups (ENN, 17.5%; EOF, 10.0%; saline, 32.5%; p =0.038). The saline group had a higher clinically relevant DGE rate than the EOF group (p = 0.014). The saline group also had greater overall morbidities than the ENN and EOF groups (p = 0.041 and p = 0.006, respectively). There were no significant differences in other surgical complication rates or postoperative hospital stay. No mortality was observed in any of the groups., Conclusions: Nutritional support methods were not related to DGE after PPPD. EOF was feasible and safe after PPPD, and additional ENN should not be routinely administered to patients after PPPD., Clinical Trial Registration: ClinicalTrials.gov, identifier NCT03150615., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Liu, Chen, Fu, Lu, Chen, Guo, Li, Wu, Gao, Jiang, Dai, Miao and Wei.)

Background: Abdominal tuberculosis (TB) remains an issue as it masquerades as many malignant or benign abdominal conditions. Objective : To analyze the clinical and laboratory features of abdominal TB retrospectively and discuss its management. Methods: The data of patients with a histopathologic diagnosis of abdominal TB seen from January 1, 2008, to February 1, 2019 were collected in The First Affiliated Hospital of Nanjing Medical University. Nodal, visceral, peritoneal, and mixed TB cases were included while excluding other forms of extra-pulmonary TB (EPTB). Results: A total of 21 patients presented having a median age of 49 years (interquartile range 33-57 years) with 12 females and 9 males. Ten presented with abdominal pain, whereas four had abdominal pain and distention. Weight loss was present in five and type 2 diabetes mellitus (DM) in three. Every patient received contrast-enhanced computed tomography (CE-CT) with positive results in all the cases. Seven patients received endoscopic ultrasound-guided fine-needle aspiration cytology examination (EUS-FNAC) and five had results positive for TB. Pre-operative diagnosis of abdominal TB was possible in seven; however, the majority (n = 14) underwent exploratory laparotomy, and all obtained a definitive diagnosis of TB. No deaths occurred. Conclusions: Both CE-CT and EUS-FNAC can aid in the timely diagnosis. Laparotomy is an invasive but efficient tool for the final diagnosis of abdominal TB.

Modification of outer membrane proteins (OMPs) is the first line of Gram-negative bacteria defence against antimicrobials. Here we point to Proteus mirabilis OMPs and their role in antibiotic and phage resistance. Protein profiles of amikacin (AMKrsv), phage (Brsv) and amikacin/phage (AMK/Brsv) resistant variants of P. mirabilis were compared to that obtained for a wild strain. In resistant variants there were identified 14, 1, 5 overexpressed and 13, 5, 1 downregulated proteins for AMKrsv, Brsv and AMK/Brsv, respectively. Application of phages with amikacin led to reducing the number of up- and downregulated proteins compared to single antibiotic treatment. Proteins isolated in AMKrsv are involved in protein biosynthesis, transcription and signal transduction, which correspond to well-known mechanisms of bacteria resistance to aminoglycosides. In isolated OMPs several cytoplasmic proteins, important in antibiotic resistance, were identified, probably as a result of environmental stress, e.g. elongation factor Tu, asparaginyl-tRNA and aspartyl-tRNA synthetases. In Brsv there were identified: NusA and dynamin superfamily protein which could play a role in bacteriophage resistance. In the resistant variants proteins associated with resistance mechanisms occurring in biofilm, e.g. polyphosphate kinase, flagella basal body rod protein were detected. These results indicate proteins important in the development of P. mirabilis antibiofilm therapies.

Pancreatic cancer (PC) is one of the most malignant gastrointestinal tumors and the 5-year survival is only 9%. The expression of miRNAs in serum has been proved to be related to tumorigenesis and development of cancers. The miRNA targets and gene targets were predicted in microRNA.org, miRDB, TargetScan, and RNAInter. The expression data of STK31 (Serine/Threonine Kinase 31) and miRNAs generated from PC samples was from TCGA and the relationship of expression of STK31 and miR-543 was confirmed in PC samples from our center. Double luciferase reporter gene assay was used to demonstrate the direct binding between miR-543 and STK31. The effect of expression level of miRNAs on survival time was assessed by Kaplan-Meier curves. The Go Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of miR-543-related genes were performed. The results showed that miR-543 had a statistically significant correlation with the expression of STK31 and contained the direct binding site with STK31. The expression level of miR-543 may affect the survival of PC. The results of GO and KEGG pathway analysis showed that miR-543 might play a key role in Insulin signaling pathway. MiR-543 could be combined with STK31 and affect the expression of STK31. The expression of miR-543 could also predict the survival of patients with PC, which suggested that miR-543 might play an important role in PC. The GO and KEGG pathway analysis also displayed that miR-543 was involved in several other pathways of pancreas., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Contrast-enhanced computed tomography (CT) contributes to the increasing detection of pancreatic neuroendocrine neoplasms (PNENs). Nevertheless, its value for differentiating pathological tumor grades is not well recognized. In this report, we have conducted a retrospective study on the relationship between the 2017 World Health Organization (WHO) classification and CT imaging features in 94 patients. Most of the investigated features eventually provided statistically significant indicators for discerning PNENs G3 from PNENs G1/G2, including tumor size, shape, margin, heterogeneity, intratumoral blood vessels, vascular invasion, enhancement pattern in both contrast phases, enhancement degree in both phases, tumor-to-pancreas contrast ratio in both phases, common bile duct dilatation, lymph node metastases, and liver metastases. Ill-defined tumor margin was an independent predictor for PNENs G3 with the highest area under the curve (AUC) of 0.906 in the multivariable logistic regression and receiver operating characteristic curve analysis. The portal enhancement ratio (PER) was shown the highest AUC of 0.855 in terms of quantitative features. Our data suggest that the traditional contrast-enhanced CT still plays a vital role in differentiation of tumor grades and heterogeneity analysis prior to treatment.

Background: Prognostic prediction had been widely used in various cancer entities, from early screening to end-stage patient caring. Currently, there is hardly any well-validated nomogram which exists for long-term survival prediction in pancreatic adenocarcinoma (PC) patients in a post-surgery setting. Our objectives are to identify possible prognostic factors in PC patients following radical resection and to develop a prognostic nomogram based on independent survival predictors., Methods: From 2009 to 2014, a total of 432 PC patients who underwent curative intended surgeries with complete follow-up data were included in this current retrospective long-term survival analysis. Clinicopathological data were extracted from medical records, and all missing values (percentage 0.9-8.3%) were imputed five times with the "PMM" method. Cox proportional hazards models were utilized. A nomogram was formulated based on results from the multivariate regression model so as to predict OS at 1-, 2- and 3-year as well as median OS. Validations, including discrimination and calibration, were carried out with 1000 bootstrap resamples. External validation was conducted in order to verify the accuracy of our nomogram at 1 and 2 years by utilizing the clinicopathological data of 122 PC patients who underwent curative intended surgeries in 2015 in our centre., Results: Age, abdominal pain, back pain, tumour location, preoperative neutrophil-lymphocyte ratio, preoperative CA19-9, tumour differentiation, microscopic nerve invasion, microscopic vascular invasion, T stage, lymph node ratio, M stage and adjuvant chemotherapy were all assembled into nomogram. The concordance index (C-index) of internal and external validation was 0.702 and 0.688, respectively. The C-index of the TNM staging system was 0.572 (P < 0.001 vs. nomogram)., Conclusion: Our prognostic nomogram based on clinicopathological parameters shows good performance in long-term survival prediction in PC patients following radical surgery and could play a role in further clinical utilization.

Previous studies have reported that increased glycolytic activity enhances chemotherapy resistance in some types of malignancies. However, whether glycolysis influences the curative effect of gemcitabine (GEM) on pancreatic cancer (PC) cells remains unclear. The aim of this study was to investigate the status of glycolysis in PC and its association with tolerance to GEM. Data from The Cancer Genome Atlas (TCGA) were used to analyze the correlation between glycolysis-related gene (GRG) expression and PC progression and prognosis. 2-Deoxy-D-glucose (2-DG) was applied to assess the effect of glycolysis inhibition on PC cell death and GEM tolerance. Expression of some GRGs, such as HK1, GAPDH, PKM2, and LDHA, was significantly associated with the prognosis of PC. Furthermore, HK1, PKLR, and LDHA expression correlated positively with PC progression. Further analysis revealed that cancer cell death was markedly enhanced following glycolysis inhibition and that the sensitivity of cancer cells to GEM was notably increased in the presence of 2-DG. Our findings indicate that abnormally increased glycolytic activity promotes the development of PC and enhances drug tolerance to GEM. 2-DG combined with GEM is a potential therapy for PC., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Vibrio parahaemolyticus is a major food-borne pathogen. V. parahaemolyticus infections are associated with various serotypes; to date, 71 K-serogroups of V. parahaemolyticus have been determined based on capsular polysaccharide (CPS) diversity. In this study, the capsular polysaccharide gene clusters (CPSgcs) of 55 K-serogroups were identified by whole-genome sequencing and analysis. These CPSgcs exhibit a high level of genetic diversity. A microsphere-based suspension array (MSA) was established for the detection and identification of 55 V. parahaemolyticus K-serogroups based on CPSgc-specific genes. To evaluate our array, a double-blind test with 120 clinical isolates was carried out. In addition, an in silico K-serotyping system was established based on V. parahaemolyticus CPSgc-specific genes. This system was then used to examine 845 publicly available V. parahaemolyticus genomes; the results demonstrated that 813 isolates belong to one of 43 K-serogroups. Taken together, these results demonstrate that the molecular system developed in this study is suitable for rapid serotyping of V. parahaemolyticus isolates from environmental and clinical samples. In addition, the system could be applied to epidemiological investigations of this important food-borne pathogen., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Our previous finding demonstrated that chronic corticosterone (CORT) may be involved in mediating the pathophysiology of premature aging in rats. Frequent jet lag increases the risk for many diseases, including obesity and type 2 diabetes, and is associated with the aging processes. However, the effect of jet lag on CORT-induced depression and its association with aging phenotypes remain unclear. In this study, the rats were exposed to both CORT and jet lag treatment, and the differences were analyzed and compared to rats with single CORT treatment. Our results showed that jet lag treatment aggravated CORT-induced depression-like behavior evidenced by sucrose intake test, forced swimming test, and open field test. Additionally, this treatment aggravated the shortening of telomeres, which possibly resulted in decreased telomerase activity, and downregulated the expression of telomere-binding factor 2 (TRF2) and telomerase reverse transcriptase compared to that in CORT rats, as revealed by quantitative real-time-polymerase chain reaction and western blot analysis, respectively. The shortening of telomeres may have been caused by increased oxidative stress, which was associated with the inhibition of sirtuin 3. Exposure to jet lag also aggravated the degeneration of mitochondrial functions, as shown by the decreases in the mRNA expression of COX1, ND1, and Tfam. Our findings provide physiological evidence that jet lag exposure may worsen stress-induced depression and age-related abnormalities., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

In this study, a thermophilic facultative anaerobic strain Geobacillus thermoglucosidasius W-2 was found to degrade nitroalkane under both aerobic and anaerobic conditions. Bioinformatical analysis revealed three putative nitroalkane-oxidizing enzymes (Gt-NOEs) genes from the W-2 genome. The three identified proteins Gt2929, Gt1378, and Gt1208 displayed optimal activities at high temperatures (70, 70, and 80 °C, respectively). Among these, Gt2929 exhibited excellent degradation capability, pH stability, and metal ion tolerance for nitronates under aerobic condition. Interestingly, under anaerobic condition, only Gt1378 still maintained high activity for 2-nitropropane and nitroethane, indicating that the W-2 strain utilized various pathways to degrade nitronates under aerobic and anaerobic conditions, respectively. Taken together, the first revelation of thermophilic nitroalkane-degrading mechanism under both aerobic and anaerobic conditions provides guidance and platform for biotechnological and industrial applications., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: Central pancreatectomy (CP) has been applied for treating benign and low-grade malignant tumors in pancreatic neck, but studies regarding CP for pancreatic ductal adenocarcinoma (PDAC) are quite limited. We aimed to investigate the role of central pancreatectomy in the treatment of PDAC in the neck of the pancreas., Methods: Patients who underwent CP at our hospital between 2009 and 2016 were identified. Patients treated by distal pancreatectomy (DP) were matched according to the tumor size, location, and staging. The surgical and survival outcomes were compared between the CP and DP groups., Results: Nine patients had CP. Five (56%) had postoperative complications and three (33%) had clinically significant (grade B + C) fistula. No significant difference was found between the CP and DP groups for the rate of overall morbidity, pancreatic fistula, reoperation, and readmission. Tumor size was smaller in the CP group compared to the DP group. The mortality of both groups was zero. The median postoperative survival was similar between the two groups (20.4 months for CP vs 19.4 months for DP, P = 0.842)., Conclusions: CP is safe for patients with small PDAC at the neck of the pancreas. Considering the good preservation of pancreatic endocrine and exocrine functions, CP could be considered as an alternative procedure for single small PDAC in pancreatic neck.

Background: Patients with potentially resectable pancreatic ductal adenocarcinoma (PDAC) are frequently found to be unresectable on exploration due to small distant metastasis. This study was to investigate predictors of small distant metastasis in patients with potentially resectable PDAC., Methods: Patients who underwent surgical exploration for potentially resectable PDAC from 2013 to 2014 were reviewed retrospectively and divided into two groups according to whether distant metastases were encountered on exploration. Then, univariate and multivariate logistic regression analyses were used to identify predictors of distant metastasis. A scoring system to predict distant metastasis of PDAC on exploration was constructed based on the regression coefficient of a multivariate logistic regression model., Results: A total of 235 patients were included in this study. Mean age of the study population was 61.7 ± 10.4 years old. Upon exploration, distant metastases were found intraoperatively in 62 (26.4%) patients, while the remaining 173 were free of distant metastases. Multivariate logistic regression analysis identified that age ≤ 62 years old (p < 0.001), male sex (p = 0.011), tumor size ≥4.0 cm (p < 0.001), alanine aminotransferase level (ALT) < 125 U/L (p < 0.001), and carbohydrate antigen (CA19-9) level ≥ 385 U/mL (p < 0.001) were independent risk factors for occult distant metastasis of PDAC. A preoperative scoring system (0-8 points) for distant metastasis on exploration was constructed using these five factors. The receiver operating characteristic curves showed that the area under the curve of this score was 0.85. A score of 6 points was suggested to be the optimal cut-off value, and the sensitivity and specificity were 85% and 69%, respectively., Conclusions: Distant metastasis is still frequently encountered on exploration for patients with potentially resectable PDAC. Younger age, male sex, larger tumor size, low ALT level and high CA19-9 level are independent predictors of unexpected distant metastasis on exploration.

Objectives: Postoperative pancreatic fistula (POPF) is a major complication and main cause of mortality after pancreaticoduodenectomy (PD). Afferent loop decompression technique (ALDT) has theoretical feasibility to reduce the rate of POPF. The aim of this study is to determine whether ALDT is a protective factor for POPF., Methods: A total of 492 consecutive patients who underwent PD between January 2012 and December 2014 were identified from a prospective database. All data were extracted and events were judged based on medical records. Propensity score matching was conducted to balance several variables. Univariate and multivariate analyses were performed, respectively, to investigate the independent risk factors for pancreatic fistula. ALDT required a nasogastric tube with multiple side holes to be placed deep into the afferent jejunal limb. The rationale for this technique was to prevent pancreatic fistula by decreasing intraluminal pressure in the afferent jejunal loop by placement of the nasogastric tube and the application of continuous low-pressure suction after surgery., Results: The total rate of POPF for the entire cohort was 30.7%, and ISGPS grade-A/B/C POPF rates were 18.1, 10.6 and 2.0%, respectively. In-hospital mortality was 1.6%. Among the 331 patients who received ALDT, 89 developed pancreatic leakage (26.9 vs. 38.5% for non-ALDT; P = 0.009) and eight developed biliary leakage (2.4 vs. 6.2% for non-ALDT; P = 0.035). Apart from ALDT, decreased preoperative ALT, soft pancreas, long operative time and tumour presence in the lower common bile duct (as opposed to the pancreas) were identified as other independent risk factors for POPF following multivariate logistic regression analysis., Conclusions: ALDT may reduce the incidence of POPF after PD.

Background/objectives: We evaluated the diagnoses and surgical management of solid pseudopapillary tumors of the pancreas (SPTP) in a single center setting., Methods: Demographic details, clinical presentations, imaging features, surgical strategies, and pathological findings of 97 consecutive patients who underwent surgery for pathologically confirmed SPTP between 2008 and 2016 were analyzed retrospectively., Results: A total of 97 patients with SPTP accounted for 2.15% of total pancreatic surgeries (N = 4508). The mean age at diagnosis was 31.6 ± 13.92 years (range: 7-83 years), and males:females were 85:12. Chief complaints were abdominal pain or discomfort (n = 50). The mean transverse tumor diameter was 53.2 ± 2.76 mm (range: 14-170 mm). Tumors were localized to the pancreatic head (38.1%; 37/97), neck (12.4%; 12/97), body and tail (49.5%; 48/97). There were no significant differences in age of onset, presenting symptoms, and sites between males and females. A significant difference was found in the maximum diameter of SPTP across different age groups. Partial pancreatectomy was performed for patient with tumor ≥ 5 cm, and enucleation was performed when tumor was smaller than 5 cm. Pancreatic fistula was the main complication. Immunohistochemical markers for endocrine, exocrine and epithelial factors were used for a final diagnosis. During a median follow-up of 54 months (range: 7-121 months), 84 patients were alive without evidence of recurrence, and 13 patients were lost to follow-up., Conclusion: SPTP surgical resection is a safe procedure with low morbidity and mortality, which is also effective even in the presence of invasiveness and metastases. Accurate initial diagnoses and follow up are essential., (Copyright © 2017. Published by Elsevier B.V.)

Pancreatic neuroendocrine neoplasms (pNENs) are a group of clinically rare and heterogeneous diseases of the pancreas. However, the prognostic factors for this disease in patients still remain controversial. The purpose of our study is to evaluate the predictive roles of those prognostic factors for pNENs. All related articles published until Sep 17, 2017 were identified via PubMed, EMBASE, Web of Science, Ovid and the Cochrane Library. Studies that examined the prognostic factors of pNENs were enrolled. 17 articles (2822 patients) were finally included in this study. The pooled data suggested that patients with positive surgical resection margin and lymph node, advanced G stage and TMN stage, organ metastasis, vascular invasion and the necrosis of specimens had a decreased overall survival for pNENs. Similarly, patients with functional tumors might have a poor prognosis. However, age, gender, surgical type and size of tumor could not be regarded as prognostic factors for pNENs. Our analytic data demonstrated that surgical resection margin, G stage, TMN stage, lymph node, metastasis, vascular invasion and the necrosis could be prognostic factors for pNENs. Our study may assist doctors to screen patients with different prognosis more efficiently during follow-up and select appropriate treatment measures.

Purpose: Glucagonoma is an extremely rare neuroendocrine tumor arising from pancreatic islet cells. Although patients with glucagonoma manifest multiple typical symptoms, early diagnosis remains difficult due to the scarcity of this disease. Methods: In this study, we retrospectively screened the database of the pancreas center of Nanjing Medical University. A total of six cases diagnosed as glucagonoma during the past 17 years were included. Their clinical characteristics and treatments were reviewed. Results: The six patients consisted of four females and two males. Their median age at diagnosis was 48.7 years (range 35-77). The time from onset of symptoms to diagnosis of glucagonoma ranged from 1.3 months to >10 years. Common symptoms included necrotizing migratory erythema shown in six of six patients (100%), diabetes mellitus in five of six patients (83%), stomatitis in four of six patients (67%), and weight loss in four of six patients (67%). Plasma glucagon levels were elevated in all patients (range 245.6-1132.2 pg/mL; n  < 200), and significantly declined after surgery (range 29-225.1 pg/mL; n  < 200). Imaging studies revealed that three of six patients had metastasis at the time of diagnosis. All patients received surgical resection. The primary lesion, liver metastases, and involved organs were resected in all patients if present. The mean survival time was 5.7 years (range 3-10.4) from diagnosis and four of six patients died of this disease by the time of follow-up. Conclusion: Our data suggest surgery is effective for symptom relief and can control the progress of glucagonoma. Early diagnosis and surgery are crucial for glucagonoma., Competing Interests: No competing financial interests exist.

Capsular polysaccharides (CPSs), or K-antigens, are the major surface antigens of Escherichia coli. More than 80 serologically unique K-antigens are classified into 4 groups (Groups 1-4) of capsules. Groups 1 and 4 contain the Wzy-dependent polymerization pathway and the gene clusters are in the order galF to gnd; Groups 2 and 3 contain the ABC-transporter-dependent pathway and the gene clusters consist of 3 regions, regions 1, 2 and 3. Little is known about the variations among the gene clusters. In this study, 9 serotypes of K-antigen gene clusters (K2ab, K11, K20, K24, K38, K84, K92, K96, and K102) were sequenced and correlated with their CPS chemical structures. On the basis of sequence data, a K-antigen-specific suspension array that detects 10 distinct CPSs, including the above 9 CPSs plus K30, was developed. This is the first report to catalog the genetic features of E. coli K-antigen variations and to develop a suspension array for their molecular typing. The method has a number of advantages over traditional bacteriophage and serum agglutination methods and lays the foundation for straightforward identification and detection of additional K-antigens in the future.

Background: Pathology is the gold standard for diagnosis of pancreatic cancer. Preoperative endoscopic ultrasound-guided biopsy is an expensive procedure that is not routine in developing countries, hence a cheap, reliable alternative is required., Aim: To evaluate the effectiveness and safety of a new technique of intraoperative biopsy from pancreatic head mass., Methods: Patients undergoing intraoperative transluminal core-biopsy (TLCB) for pancreatic head mass from January 2000 to June 2015 were included in this study. Following Kocher's maneuver, a biopsy was taken from the mass through the duodenum transluminally, using a commercial 16G automatic core-biopsy needle. Multiple tissue specimens were obtained for intraoperative frozen section examination. Depending on the pathological results, a decision was taken to either perform pancreaticoduodenectomy, duodenum-preserving pancreatic head resection, bypass surgery, or to just terminate the operation. The malignancy status of the lesion was confirmed by postoperative pathological examination and/or long-term follow-up of the patients., Results: A total of 525 patients were included. Intraoperative pathological reports revealed 436 malignant cases and 89 cases without evidence of malignancy. The sensitivity, specificity, false positive rate, and false negative rate were 97.7%, 100%, 0%, and 2.3%, respectively. Complications occurred in 2 patients., Conclusion: TLCB is a quick, safe, effective, and accurate method for intraoperative diagnosis method in patients with pancreatic head mass; it can provide reliable evidence for surgical decision-making., (Copyright © 2017. Published by Elsevier B.V.)

MicroRNAs (miRNAs) play important roles in the regulation of various tumor biological processes including proliferation and apoptosis. miR-217 has been implicated in many types of cancer, whereas its expression and potential biological function in human pancreatic adenocarcinoma (HPAC) remain unclear. We aimed to investigate the clinical significance of miR-217 in patients with pancreatic carcinoma and its role and underlying molecular mechanism in HPAC. We collected 15 pairs of pancreatic cancer and normal pancreas tissues to evaluate the expression of miR-217 and tumor protein D52-like 2 (Tpd52l2). Then, we transfected AsPC-1 cells with miR-217 mimics or Tpd52l2 siRNA to detect the effect on cell proliferation, apoptosis, invasion, migration and the cell cycle. In addition, miR-217 mimics and Tpd52l2 expression plasmids were co-transfected into AsPC-1 cells to further investigate the mechanism of miR-217 and Tpd52l2 in HPAC tumorigenesis. Finally, exploration of related signaling pathways was carried out. Herein, we found that the expression of miR-217 was significantly downregulated in HPAC tissues as compared with that observed in adjacent normal tissues. Further functional assays showed that restoration of the expression of miR-217 inhibited cell proliferation, invasion and migration, induced apoptosis, and caused cell cycle arrest of HPAC cells. Notably, Tpd52l2 was identified as a functional target of miR-217 in HPAC. Furthermore, an inverse correlation between miR-217 and Tpd52l2 expression was observed in the HPAC tissues. Downregulation of Tpd52l2 had an effect similar to that following overexpression of miR-217, and upregulation of Tpd52l2 reversed the effects of the overexpression of miR-217. Finally, we found that overexpression of miR-217 or knockdown of Tpd52l2 suppressed the PIK3CA/AKT signaling pathways. In addition, this may explain the effect of miR-217/Tpd52l2 on HPAC development. Taken together, these results suggest a critical role of miR-217 in suppressing proliferation, migration and invasion of HPAC cells by targeting Tpd52l2. Targeting the miR-217/Tpd52l2 axis may be a new therapeutic application with which to treat patients with HPAC in the future.

Rationale: Black pleural effusion (BPE) is an extremely uncommon type of pleural fluid, which can be due to infection, primary or metastatic malignancy, and hemorrhage. As reported in previous studies, BPE is also observed in some patients with pancreatic pseudocyst., Patient Concerns: We herein reported a case of a 14-year-old female patient who was admitted to our center with a history of cough for 1 and a half months and right chest pain for 1 month. Before this, she was consecutively hospitalized in 3 different hospitals due to the same symptoms. However, the previous treatments were ineffective due to the lack of a definitive diagnosis. Laboratory examination of the pleural effusion showed BPE with a high amylase concentration. Chest x-ray and computed tomography (CT) showed massive pleural effusion, more prominent in the right chest. CT and MRCP of the abdomen showed a cystic lesion located in the tail of the pancreas, which entered the chest cavity via an esophageal hiatal hernia. DIAGNOSES:: pancreatic pseudocyst., Interventions: After confirming that the tumor was a pancreatic pseudocyst by intraoperative biopsy, internal drainage to the jejunum was performed., Outcomes: The postoperative recovery was rapid and without complications, and the final discharge diagnosis was idiopathic pancreatic pseudocyst (without history of pancreatitis or pancreatic injuries) with BPE of the right chest., Lessons: This case demonstrates that massive BPE could present as a rare complication of pancreatic pseudocyst, and surgery is a potential treatment for such patients., (Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Vasohibin 2 (VASH2) is an angiogenic factor and cancer-related protein that acts via paracrine mechanisms. Here, we investigated the angiogenic function and mechanism of action of VASH2 in 200 human breast cancer tissues by performing immunohistochemical staining, western blot, indirect sandwich enzyme-linked immunosorbent assay (ELISA), and a semi-quantitative sandwich-based antibody array. Breast cancer cells stably overexpressing VASH2 or with knocked-down VASH2 were established and used for in vivo and in vitro models. In human luminal tissue, but not in HER2-positive or basal-like breast cancer tissues, VASH2 was positively correlated with CD31-positive microvascular density, induced angiogenesis in xenograft tumors, and promoted human umbilical vein endothelial cell tube formation in vitro. VASH2 expression was absent in the concentrated conditioned medium collected from knocked-down VASH2 and VASH2-overexpressing luminal breast cancer cells. Further, VASH2 regulated the expression of fibroblast growth factor 2 (FGF2) in human luminal breast cancer cells, and the pro-angiogenic effect induced by VASH2 overexpression was blocked by FGF2 neutralization in vitro. Additionally, dual luciferase reporter assay and Chromatin immunoprecipitation analysis results showed that FGF2 promoter was transcriptionally activated by VASH2 via histone modifications. In conclusion, VASH2 expression is positively correlated with FGF2 expression and promotes angiogenesis in human luminal breast cancer by transcriptional activation of fibroblast growth factor 2 through non-paracrine mechanisms., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Purpose: The purpose of this study was to evaluate the diagnosis and surgical management of insulinomas in a single-center setting., Methods: Demographic details, clinical presentation, preoperative diagnosis, surgical strategy, and outcomes of 33 consecutive patients who underwent surgery for insulinoma were analyzed retrospectively., Results: The median time from the first onset of symptoms to diagnosis was 24 months (range 3 days to 50 years). All cases presented with Whipple's triad and had a fasting insulin to glucose ratio higher than 0.33. The preoperative detection rates of transabdominal ultrasonography, CT, MRI, and EUS were 22 % (2/9), 72 % (23/32), 75 % (9/12), and 80 % (4/5), respectively. Intraoperative manual palpation localized all cases. Enucleation was performed in 58 % of cases (19/33), partial pancreatic resection in 39 % (13/33), and enucleation plus partial resection in 3 % (1/33). Pancreatic fistula was the most common complication and occurred in 15 patients (45 %), including seven grade A, five grade B, and three grade C fistulas. There was no mortality. When compared with partial pancreatectomy, enucleation held a significant advantage in operative time and operative bleeding, with no significant differences in demographic data and postoperative complications. During a median follow-up period of 32 months, two patients were lost to follow-up and the remaining 31 patients were without evidence of recurrence., Conclusions: A fasting insulin release index larger than 0.3 is a reliable indicator for the diagnosis of insulinoma. Intraoperative palpation by an experienced surgeon can effectively complement an uncertain preoperative localization. Compared with partial pancreatic resection, enucleation showed significant benefit in terms of intraoperative blood loss and operation time.

Introduction: Few studies have compared patency rates of the different methods of venous reconstruction (VR) during a pancreatectomy. This study aimed to evaluate the patency rates and the clinical impact of various reconstruction methods., Methods: For the meta-analysis, databases were systematically searched to identify studies reporting the outcomes of patients who underwent PVR/SMVR. For the retrospective study, clinical data were retrospectively analyzed from patients who underwent a pancreatectomy and VR between Feb. 2009 and Oct. 2015. Patency was assessed by CT and/or ultrasound., Results: For the meta-analysis, the long-term patency rates of the primary repair group and the autologous graft group were significantly higher than that of the synthetic graft group. For the retrospective study, the reconstruction consisted of primary repair in 62 cases (89.8%) and synthetic grafting in 7 cases (10.1%). Synthetic grafting was more likely to cause acute thrombosis compared with primary repair for PVR/SMVR (85.7% versus 16.7%). Acute thrombosis was associated with decreased median survival (12 versus 6 months) and increased hazard of death. Late thrombosis and stenosis were not associated with survival or serious clinical impact. Median survival for the primary repair group and the synthetic grafting group was 12 and 7 months, respectively., Conclusion: Primary repair following PVR/SMVR is preferred and can be achieved in most situations. Stenosis should be noted when with risk factors (long segmental and tension), but it produced little clinical impact. Synthetic grafting was associated with a higher thrombosis rate. Acute thrombosis is associated with increased mortality and decreased survival., (Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Middle-segment preserving pancreatectomy (MPP) is a novel procedure for treating multifocal lesions of the pancreas while preserving pancreatic function. However, long-term pancreatic function after this procedure remains unclear.The aims of this current study are to investigate short- and long-term outcomes, especially long-term pancreatic endocrine function, after MPP.From September 2011 to December 2015, 7 patients underwent MPP in our institution, and 5 cases with long-term outcomes were further analyzed in a retrospective manner. Percentage of tissue preservation was calculated using computed tomography volumetry. Serum insulin and C-peptide levels after oral glucose challenge were evaluated in 5 patients. Beta-cell secreting function including modified homeostasis model assessment of beta-cell function (HOMA2-beta), area under the curve (AUC) for C-peptide, and C-peptide index were evaluated and compared with those after pancreaticoduodenectomy (PD) and total pancreatectomy. Exocrine function was assessed based on questionnaires.Our case series included 3 women and 2 men, with median age of 50 (37-81) years. Four patients underwent pylorus-preserving PD together with distal pancreatectomy (DP), including 1 with spleen preserved. The remaining patient underwent Beger procedure and spleen-preserving DP. Median operation time and estimated intraoperative blood loss were 330 (250-615) min and 800 (400-5500) mL, respectively. Histological examination revealed 3 cases of metastatic lesion to the pancreas, 1 case of chronic pancreatitis, and 1 neuroendocrine tumor. Major postoperative complications included 3 cases of delayed gastric emptying and 2 cases of postoperative pancreatic fistula. Imaging studies showed that segments representing 18.2% to 39.5% of the pancreas with good blood supply had been preserved. With a median 35.0 months of follow-ups on pancreatic functions, only 1 patient developed new-onset diabetes mellitus of the 4 preoperatively euglycemic patients. Beta-cell function parameters in this group of patients were quite comparable to those after Whipple procedure, and seemed better than those after total pancreatectomy. No symptoms of hypoglycemia were identified in any patient, although half of the patients reported symptoms of exocrine insufficiency.In conclusion, MPP is a feasible and effective procedure for middle-segment sparing multicentric lesions in the pancreas, and patients exhibit satisfied endocrine function after surgery., Competing Interests: The authors have no conflicts of interest to disclose.