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Lianyuan Tao,1,2 Li Su,3 Chunhui Yuan,1 Zhaolai Ma,1 Lingfu Zhang,1 Shiping Bo,4 Yunyun Niu,4 Sijia Lu,4 Dianrong Xiu11Department of General Surgery, Peking University Third Hospital, Beijing 100191, People’s Republic of China; 2Department of Hepatobiliary Surgery, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou, Henan 450003, People’s Republic of China; 3Medical and Health Analytical Center, Peking University Health Science Center, Beijing 100191, People’s Republic of China; 4Department of Clinical Research, Yikon Genomics Co. Ltd., Shanghai, People’s Republic of ChinaPurpose: The aim of this study was to evaluate the value of flow cytometry (FCM) detection of portal vein circulating tumor cells (CTCs) in predicting postoperative metastasis.Methods: Samples of portal venous blood and peripheral blood were collected from 39 patients during surgery, and CTCs were detected by FCM, with confirmation by laser confocal microscopy and single-cell sequencing.Results: Among all patients, a portal EpCAM+CD45- percentage ≥24.5×10−4 (P=0.06), peripheral EpCAM+CD45- count ≥97/5 mL (P=0.034), peripheral EpCAM+CD45- percentage ≥4.4×10−4 (P=0.042), and CA242≥3.5 U/mL (P=0.027) were significant predictors of metastasis. Further analysis showed that the portal EpCAM+CD45- ratio ≥24.5×10−4 is a predictor of metastasis (P=0.025) in pancreatic cancer after curative resection.Conclusion: CTCs detected by FCM in portal venous blood are of significant value for the prediction of postoperative metastasis in pancreatic or periampullary tumors.Keywords: circulating tumor cells, flow cytometry, portal vein, pancreatic cancer, metastases

Catechol-O-methyltransferase (COMT) Val158Met (rs4680) polymorphism plays a crucial role in regulating brain dopamine level. Converging evidence from Caucasian samples showed that, compared with rs4680 Val allele, the Met allele was linked to lower COMT activity, which in turn was linked to better cognitive performance such as working memory (WM) and to a larger hippocampus (a brain region important for WM). However, some behavioral studies have shown that the function of rs4680 appears to vary across different ethnic groups, with Chinese subjects showing an opposite pattern as that for Caucasians (i.e. the Val allele is linked to better cognitive functions related to WM in Chinese). Using a sample of healthy Han Chinese college students (ages from 19 to 21 years), this study investigated the association of COMT Val158Met genotype with behavioral data on a two-back WM task (n = 443, 189M/254F) and T1 MRI data (n = 320, 134M/186F). Results showed that, compared to the Met allele, the Val allele was associated with larger hippocampal volume (the right hippocampus: β = -0.118, t = -2.367, P = 0.019, and the left hippocampus: β = -0.099, t = -1.949, P = 0.052) and better WM performance (β = -0.110, t = -2.315, P = 0.021). These results add to the growing literature on differentiated effects of COMT rs4680 polymorphism on WM across populations and offer a brain structural mechanism for such population-specific genetic effects.

Lingfu Zhang,1 Lianyuan Tao,1 Limei Guo,2 Jun Zhan,3 Chunhui Yuan,1 Zhaolai Ma,1 Bin Jiang,1 Dianrong Xiu1 1Department of General Surgery, Peking University Third Hospital, Beijing, People’s Republic of China; 2Department of Pathology, Peking University Third Hospital, Beijing, People’s Republic of China; 3Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing, People’s Republic of China Background: Recent studies demonstrated that granulocyte colony-stimulating factor (G-CSF), regularly used for the prevention of neutropenia, is engaged in cancer progression. However, the role of G-CSF in pancreatic ductal adenocarcinoma (PDAC) is not clear. The aim of the present study was to investigate the expression and prognostic value of G-CSF in patients with PDAC.Materials and methods: The localization and expression of G-CSF in PDAC were examined by immunohistochemistry (IHC). The analysis of the levels of G-CSF in plasma was evaluated using ELISA kit. The correlation between G-CSF expression and patients’ survival was assessed by Kaplan–Meier analysis.Results: In IHC specimens, G-CSF was discovered predominantly in the cell cytoplasm and expressed in most of PDAC, while in plasma, the systemic level of G-CSF is no different between normal patients and pancreatic cancer patients. In 100 PDAC cases with IHC, patients with grades 2 and 3 were defined as the high expression group (41 patients, 41%), and those with grades 0 and 1 as the low expression group (59 patients, 59%). Significant correlation was noted between high G-CSF expression and neural invasion (P = 0.042) or early recurrence (P

The distribution and diversity of woody vegetation are crucial for understanding the structure and ecology of urban forests. As urbanization accelerates, the construction and composition of urban forests vary significantly along the urban-rural gradient. Qingdao's urban forests offer an opportunity to test the relationship between the diversity of woody plants and the urban-rural gradient. We classified the urban-rural gradient using imperviousness and construction time, then investigated the diversity of woody plants in Qingdao's urban forests under different urban-rural gradients and tested the reasonableness of their allocation. Correlation analysis found that the diversity index of woody plants in urban forests was highly connected to the urban-rural gradient (by imperviousness: r Margalef Index  = -0.589, r Shannon-Wiener Index  = -0.373, r Pielou Index  = -0.170, r Simpson Index  = 0.272/by construction time: r Margalef Index  = -0.530, r Shannon-Wiener Index  = -0.360, r Pielou Index  = -0.148, r Simpson Index  = 0.272/0.174). With a decrease in urbanization density, the Margalef ( H ), Shannon-Wiener ( H' ), and Simpson ( D ) indices all decreased while the Pielou ( E ) index increased. The four diversity indices showed a substantial correlation with one another, but not with the Margalef and Pielou indices. The analysis utilizing the 10/20/30 rule of empirical demonstrates a clear irrationality in allocating shrub species in Qingdao's urban forests, and the distribution of tree species is reasonable. Based on the study results, strategies for optimizing and enhancing urban forests in Qingdao are proposed for different urban-rural gradients, respectively. This study can provide a scientific framework for urban biodiversity conservation and management in Qingdao and serve as a guide for urban forests and greening with comparable climates., 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 Published by Elsevier Ltd.)

Objective: To explore the effectiveness of minimally invasive surgical treatment for pancreatic acinar cell carcinoma (PACC). Methods: Six patients with PACC diagnosed in Peking University Third Hospital from January 2010 to September 2022 were retrospectively selected. Preoperative evaluation was performed on whether the lesions were eligible for surgery, including whether radical resection of liver metastases could be performed. Laparoscopic or Da Vinci robot-assisted resection was performed on six patients, and spleen retention was determined according to the original lesions and the relationship with peripheral blood vessels and tissues, while simultaneous resection was performed on cases of peripheral organ tissue invasion. The patients' basic information, preoperative general conditions, preoperative diagnosis and tumor stage, minimally invasive surgery methods, postoperative complications, pathological results, tumor stage and follow-up data were collected and analyzed to explore the effectiveness of minimally invasive surgery. Results: Among the six patients, four were males and two were females, with the age of 25-69 years. Five patients had abdominal pain and distension before surgery, five patients had tumors located at the tail of the pancreatic body, and one patient had tumors located at the head of the pancreas. Preoperative imaging (enhanced CT and MRI) was performed to measure the tumor diameter (2.8-10.0 cm). Tumor markers were elevated in two patients before surgery, and six patients underwent surgery through laparoscopy or robotic platform. No complications such as postoperative pancreatic fistula and bleeding were clinically relevant during and after surgery. There were two cases with concurrent or heterochronous liver metastasis, two cases with lymph node metastasis and nodular metastasis, four cases with tumor invasion of surrounding organs (stomach, spleen or duodenum), and three cases with vascular cancer thrombi. The follow-up time of the six patients was 12 to 165 months, and one patient underwent three operations due to postoperative liver metastasis and residual pancreatic recurrence, and the results were satisfactory. All the six patients survived at the last follow-up. Conclusions: PACC is prone to invade the surrounding organs, and has a large tumor diameter. Radical surgery for PACC can be completed through minimally invasive surgery, and satisfactory oncology prognosis can be obtained. In addition, some PACC patients with recurrence and metastasis can still be treated by surgery.

Objective: Currently, pre-treatment prediction of patients with pancreatic neuroendocrine tumors with liver metastases (PNELM) receiving surufatinib treatment was unsatisfying. Our objective was to examine the association between radiological characteristics and efficacy/prognosis., Methods: We enrolled patients with liver metastases in the phase III, SANET-p trial (NCT02589821) and obtained contrast-enhanced computed tomography (CECT) images. Qualitative and quantitative parameters including hepatic tumor margins, lesion volumes, enhancement pattern, localization types, and enhancement ratios were evaluated. The progression-free survival (PFS) and hazard ratio (HR) were calculated using Cox's proportional hazard model. Efficacy was analyzed by logistic-regression models., Results: Among 152 patients who had baseline CECT assessments and were included in this analysis, the surufatinib group showed statistically superior efficacy in terms of median PFS compared to placebo across various qualitative and quantitative parameters. In the multivariable analysis of patients receiving surufatinib (N=100), those with higher arterial phase standardized enhancement ratio-peri-lesion (ASER-peri) exhibited longer PFS [HR=0.039; 95% confidence interval (95% CI): 0.003-0.483; P=0.012]. Furthermore, patients with a high enhancement pattern experienced an improvement in the objective response ratio [31.3% vs . 14.7%, odds ratio (OR)=3.488; 95% CI: 1.024-11.875; P=0.046], and well-defined tumor margins were associated with a higher disease control rate (DCR) (89.3% vs . 68.2%, OR=4.535; 95% CI: 1.285-16.011; P=0.019) compared to poorly-defined margins., Conclusions: These pre-treatment radiological features, namely high ASER-peri, high enhancement pattern, and well-defined tumor margins, have the potential to serve as predictive markers of efficacy in patients with PNELM receiving surufatinib., (Copyright ©2023 Chinese Journal of Cancer Research. All rights reserved.)

Multicolor two-photon endomicroscopy has become a highly competitive tool for functional imaging in biomedical researches. However, to make the imaging system miniature and applicable for freely behaving animal brain activity, metalenses have received much attention in compact imaging systems. For high resolution multicolor imaging and maximizing fluorescence collection, there is a challenge metalenses faced to achieve large numerical aperture (NA) and focus the NIR excitation and VIS emission lights of multiple fluorophores to the same distance simultaneously because of the limitation of the group delay range of the meta-units. In this paper, we proposed a high NA and polarization-insensitive ultra-broadband achromatic metalens specifically for achromatically focusing the excitation and emission light of multiple fluorophores commonly used in neuroscience studies. TiO 2 and Si meta-unit libraries composed of heights, widths and the corresponding phase and group delay were constructed, and the optimal meta-units were selected by particle swarm optimization algorithm to engineer the dispersion of metalens in the VIS band and NIR band, respectively. Combining dispersion engineering with spatial multiplexing, the proposed metalens achieved the maximal effective NA up to 0.8 and large achromatic bandwidth ranging from 500 nm to 1050 nm, which exhibited the coefficient of variation of focal lengths was only 3.41%. The proposed achromatic metalens could successfully achromatically focus different fluorescence with any polarization, which was suitable for most fluorophores. Our results firmly establish that the proposed metalens can open the door to high resolution and minimally invasive multicolor two-photon functional imaging in intravital deep brain.

Introduction: Postoperative pancreatic fistula (POPF) remains one of the main complications following pancreatic resection. Despite pancreatic fistula having a low postoperative mortality rate, the readmission and intervention rates in patients with pancreatic fistula are still considerable. Although there are several studies on pancreatic fistula development after pancreaticoduodenectomy, there are only a few studies on the feeding protocols applied after distal pancreatectomy or enucleation of pancreatic tumours. We designed this trial to test the hypothesis that early feeding does not increase the incidence of POPF and positively influences the long-term prognosis in patients who undergo distal pancreatectomy or enucleation of pancreatic tumours., Methods and Analysis: This is a prospective randomised controlled trial that will be conducted in a single centre. A total of 106 patients undergoing distal pancreatectomy or enucleation of pancreatic tumours will be recruited after providing informed consent. They will be randomly assigned to either an early or late feeding group. The early feeding group will begin enteral nutrition on postoperative day (POD) 3, and the late feeding group will begin enteral nutrition on POD7. The primary outcome is the incidence of POPF. The secondary outcomes include the length of postoperative hospital stay, postoperative complications, and indicators of long-term prognosis., Ethics and Dissemination: Peking University Third Hospital Medical Science Research Ethics Committee approved the study (M2021395). Findings will be disseminated in a peer-reviewed journal and in national and/or international meetings to guide future practice., Trial Registration Number: ChiCTR2100053978., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

To improve prognosis of cancer patients and determine the integrative value for analysis of disease-free survival prediction, a clinic investigation was performed involving with 146 non-small cell lung cancer (NSCLC) patients (83 men and 73 women; mean age: 60.24 years ± 8.637) with a history of surgery. Their computed tomography (CT) radiomics, clinical records, and tumor immune features were firstly obtained and analyzed in this study. Histology and immunohistochemistry were also performed to establish a multimodal nomogram through the fitting model and cross-validation. Finally, Z test and decision curve analysis (DCA) were performed to evaluate and compare the accuracy and difference of each model. In all, seven radiomics features were selected to construct the radiomics score model. The clinicopathological and immunological factors model, including T stage, N stage, microvascular invasion, smoking quantity, family history of cancer, and immunophenotyping. The C-index of the comprehensive nomogram model on the training set and test set was 0.8766 and 0.8426 respectively, which was better than that of the clinicopathological-radiomics model (Z test, P =0.041<0.05), radiomics model and clinicopathological model (Z test, P =0.013<0.05 and P =0.0097<0.05). Integrative nomogram based on computed tomography radiomics, clinical and immunophenotyping can be served as effective imaging biomarker to predict DFS of hepatocellular carcinoma after surgical resection., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Dianhui Xiu et al.)

Background & Aims: Tumor-initiating cells (TICs) drive pancreatic cancer tumorigenesis, therapeutic resistance, and metastasis. However, TICs are highly plastic and heterogenous, which impede the robust identification and targeted therapy of such a population. The aim of this study is to identify the surface marker and therapeutic target for pancreatic TICs., Methods: We isolated voltage-gated calcium channel α2δ1 subunit (isoform 5)-positive subpopulation from pancreatic cancer cell lines and freshly resected primary tissues by fluorescence-activated cell sorting and evaluated their TIC properties by spheroid formation and tumorigenic assays. Coimmunoprecipitation was used to identify the direct substrate of CaMKⅡδ., Results: We demonstrate that the voltage-gated calcium channel α2δ1 subunit (isoform 5) marks a subpopulation of pancreatic TICs with the highest TIC frequency among the known pancreatic TIC markers tested. Furthermore, α2δ1 is functionally sufficient and indispensable to promote TIC properties by mediating Ca 2+ influx, which activates CaMKⅡδ to directly phosphorylate PKM2 at T454 that results in subsequent phosphorylation at Y105 to translocate into nucleus, enhancing the stem-like properties. Interestingly, blocking α2δ1 with its specific antibody has remarkably therapeutic effects on pancreatic cancer xenografts by reducing TICs., Conclusions: α2δ1 promotes pancreatic TIC properties through sequential phosphorylation of PKM2 mediated by CaMKⅡδ, and targeting α2δ1 provides a therapeutic strategy against TICs for pancreatic cancer., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To explore the feasibility and efficacy of laparoscopic transcystic drainage and common bile duct exploration in the treatment of patients with difficult biliary stones., Methods: Between April 2020 and December 2021, eighteen patients with difficult biliary stones received laparoscopic transcystic drainage (C-tube technique) and common bile duct exploration. The clinical characteristics and outcomes were retrospectively collected. The safety and effectiveness of laparoscopic transcystic drainage and common bile duct exploration were analyzed., Results: Among the eighteen patients with difficult biliary stones, thirteen patients received traditional laparoscopic transcystic drainage, and the remaining five received modified laparoscopic transcystic drainage. The mean surgical duration were (161±59) min (82-279 min), no bile duct stenosis or residual stone was observed in the patients receiving postoperative cholangiography via C-tube. The maximum volume of C-tube drainage was (500±163) mL/d (180-820 mL/d). Excluding three patients with early dislodgement of C-tube, among the fifteen patients with C-tube maintained, the median time of C-tube removal was 8 d (5-12 d). The duration of hospital stay was (12±3) d (7-21 d) for the 18 patients. Five C-tube related adverse events were observed, all of which occurred in the patients with traditional laparoscopic transcystic drainage, including two abnormal position of the C-tube, and three early dislocation of the C-tube. All the 5 adverse events caused no complications. Only one grade one complication occurred, which was in a patient with modified laparoscopic transcystic drainage. The patient demonstrated transient fever after C-tube removal, but there was no bile in the drainage tube and the subsequent CT examination confirmed no bile leakage. The fever spontaneously relieved with conservative observation, and the patient recovered uneventfully with discharge the next day. All the 18 patients were followed up for 1-20 months (median: 9 months). Normal liver function and no recurrence of stone were detected with ultrasonography or magnetic resonance cholangiopancreatography (MRCP)., Conclusion: Laparoscopic transcystic drainage combined with common bile duct exploration is safe and feasible in the treatment of patients with difficult biliary stones. The short-term effect is good. Modified laparoscopic transcystic drainage approach may reduce the incidence of C-tube dislocation and bile leak.

Zhijin County is a typical mineral resource-based city in Southwest China. The problem of heavy metals (HM) in the soil in Zhijin County must be considered during regional economic and ecological development. A total of 2436 soil samples (0‒20 cm depth) were collected to analyze the soil pH, organic matter content, and HM spatial distribution and sources. The HM concentrations in the surface soil were found to be higher than the national surface soil background values. Absolute principal component sore-multivariate linear regression (APCS-MLR) showed that the HM sources in the surface soil of Zhijin County were industrial and agricultural activities (48.09%), natural sources (34.47%), and atmospheric deposition (17.43%); 65.53% of HM were produced by anthropogenic activities, which were mainly associated with the mineral industry. The impact of anthropogenic pollution decreased in the following order: paddy field (66.45%) > rainfed cropland (65.91%) > barren land (61.98%) > garden land (61.82%) > forest land (59.11%) > grassland (53.31%). The potential ecological risk of surface soil is moderate, while low-risk areas were mainly distributed in mountainous regions in the north, southwest, and east. The study emphasizes the source and risk assessment of HM in the surface soil of Zhijin County. The results can be used for environmental management planning, decision-making, and risk assessment., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: There is little evidence regarding the optimal surgical sequence for colorectal cancer liver metastasis (CRLM) patients undergoing colorectal resection with simultaneous liver metastasis resection., Methods: CRLM patients from five centers were retrospectively evaluated. The short-term outcomes included intraoperative and postoperative outcomes. Postoperative complications were measured according to the Clavien-Dindo classification. Grade I to II complications were defined as minor postoperative complications. The long-term outcomes were progression-free survival (PFS) and overall survival (OS). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to overcome the selection bias between colorectal resection first and liver resection first., Results: A total of 1255 CRLM patients were included. In the multivariable logistic regression analysis, a body mass index (BMI) < 24 kg/m 2 , primary site in the left hemicolon, non-bilobar distribution of liver metastases and no preoperative chemotherapy were significantly associated with the likelihood of colorectal resection first. After 1:1 PSM, there was no significant difference between the colorectal resection first group and the liver resection first group. Compared with patients with colorectal resection first, patients with liver resection first had a comparable postoperative infection rate (15.0% vs. 16.0%, P = 0.735), a longer operation time (305.0 [231.3-416.0] vs. 300.0 [225.0-374.0], P = 0.033), more intraoperative blood loss (200.0 [150.0-400.0] vs. 100.0 [100.0-300.0], P < 0.001), a higher postoperative minor complication rate (28.7% vs. 20.7%, P = 0.023) and a higher postoperative ICU rate (14.7% vs. 8.7%, P = 0.022). IPTW-adjusted Kaplan-Meier analysis showed that patients who underwent colorectal resection first had a similar PFS (P = 0.702, median: 20.6 months vs. 16.6 months) and unfavourable OS (P = 0.014, median: 48.5 months vs. 67.0 months) compared with patients who underwent liver resection first. In the IPTW-adjusted Cox proportional hazards regression analysis, colorectal resection first was an unfavourable risk factor for OS (hazard ratio [HR] = 1.301, 95% CI 1.048-1.616, P = 0.017) and was not an independent predictor for PFS (HR = 0.986, 95% CI 0.831-1.170, P = 0.874). IPTW-adjusted Cox proportional hazards regression analysis, including postoperative complications, operation time, intraoperative blood loss and postoperative chemotherapy, produced consistent results., Conclusion: Although violating the "sterility principle", patients who underwent colorectal resection first did not have an increased postoperative infection rate and had some better short-term outcomes and comparable PFS than those who underwent liver resection first., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Radical antegrade modular pancreatosplenectomy (RAMPS) has been proven to improve R0 resection and lymph harvest in treating patients with distal pancreatic cancer. The development of minimally invasive surgery has advantages in postoperative recovery. Therefore, minimally invasive (MI-) RAMPS may combine the advantages of both benefits to improve survival. Nevertheless, evidence to validate the safety and efficacy of MI-RAMPS is limited., Method/design: The MIRROR trial will be the first multicenter prospective randomized clinical trial to investigate the outcome of MI-RAMPS. The hypothesis is that MI-RAMPS is superior in postoperative recovery. The primary outcome is the length of postoperative stay. Based on the hypothesis and primary outcome, the sample size is 250 patients (125 participants in each group). The trial will investigate factors related to surgical safety, short-term outcome, pathological assessment, and survival as secondary outcomes., Conclusion: This study will offer a relatively higher level of evidence to further illustrate the accessibility and benefits of MI-RAMPS for the treatment of distal pancreatic cancer., Clinical Trial Registration: Clinicaltrials.gov, NCT03770559., 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 Dai, Zhang, Yang, Xiu, Peng, Sun, Cao, Wu, Wang, Yuan, Chen, Wang, Tian, Wang, Liu, Xu, Liu, Zhao and MIRROR study group.)

Magnetic resonance imaging (MRI) has been shown to be associated with prognosis in some tumors; however, the correlation in pancreatic ductal adenocarcinoma (PDAC) remains inconclusive. In this retrospective study, we ultimately included 136 patients and analyzed quantitative MRI parameters that are associated with prognosis and recurrence patterns in PDAC using survival analysis and competing risks models; all the patients have been operated on with histopathology and immunohistochemical staining for further evaluation. In intravoxel incoherent motion diffusion-weighted imaging (DWI), we found that pure-diffusion coefficient D value was an independent risk factor for overall survival (OS) (HR: 1.696, 95% CI: 1.003-2.869, p = 0.049) and recurrence-free survival (RFS) (HR: 2.066, 95% CI: 1.252-3.409, p = 0.005). A low D value (≤1.08 × 10 -3 mm 2 /s) was significantly associated with a higher risk of local recurrence (SHR: 5.905, 95% CI: 2.107-16.458, p = 0.001). Subgroup analysis revealed that patients with high D and f values had significantly better outcomes with adjuvant chemotherapy. Distant recurrence patients in the high-D value group who received chemotherapy may significantly improve their OS and RFS. It was found that preoperative multiparametric quantitative MRI correlates with prognosis and recurrence patterns in PDAC. Diffusion coefficient D value can be used as a noninvasive biomarker for predicting prognosis and recurrence patterns in PDAC.

Background: The incidence of nonfunctional pancreatic neuroendocrine neoplasms (NF-pNENs) has been increasing annually. This study is aimed at investigating the clinicopathological characteristics and high-risk factors of NF-pNENs and the influence of surgical treatment on the prognosis of NF-pNEN patients with liver metastases., Methods: pNEN patients in this study were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. This study analyzed patients diagnosed with NF-pNENs from 2000 to 2017 who met the inclusion criteria. A retrospective analysis of the clinicopathological characteristics of NF-pNEN patients was conducted. Kaplan-Meier method was used to calculate the survival time. A multivariate Cox regression model was used to analyze the survival outcomes and risk factors., Results: From 2000 to 2017, the SEER database registered 10576 patients with pNENs and 1774 patients with liver metastases. Cox analysis revealed that age, sex, primary site, grade, tumor stage, surgery, tumor size, and liver metastasis were risk factors of prognosis, with grade being the most influential index. Patients with NF-pNENs with liver metastasis and no metastasis had different primary site, grade, and tumor size. In general, a higher grade was associated with a larger tumor and a greater risk of liver metastasis. Meanwhile, patients with liver metastasis showed that those with tumors originated from the tail of the pancreas had better prognoses than those with tumors originated from other parts. Surgical treatment can improve the prognosis of patients with liver metastases, despite the tumor grade., Conclusions: The incidence of pNENs has been increasing annually, and the liver has been the most common site of metastasis. Liver metastasis in patients with NF-pNENs, related to tumor size and grade, affected their long-term survival. Surgery significantly improved the prognosis of patients with liver metastases secondary to NF-pNENs with different grades., Competing Interests: The authors declare no competing interests., (Copyright © 2022 Abuduhaibaier Sadula et al.)

Objectives: This study aimed to investigate the pharmacokinetic characteristics of siponimod in healthy volunteers and patients with MS based on aggregated data from published clinical trials, and to explore the factors influencing siponimod exposure. Methods: A total of 476 siponimod plasma concentrations aggregated from 28 dosage groups (corresponding to 294 healthy volunteers and 207 patients with MS) were collected from published clinical trials. Population pharmacokinetic (PPK) analysis was performed using a nonlinear, mixed-effect modeling approach. The pharmacokinetic properties of siponimod in healthy volunteers and patients with MS were compared, and the influence of covariates on siponimod exposure was evaluated using both PPK analysis and noncompartmental analysis (NCA). Results: A one-compartment model with first-order absorption and elimination adequately described siponimod pharmacokinetics. The typical population parameter estimates of clearance (CL/F), apparent volume of distribution (V/F), and absorption rate constant (ka) were 3.17 L/h, 112.70 L, and 0.38 h -1 , respectively. An 11.85% lower siponimod clearance was estimated for patients with MS relative to healthy volunteers. Subgroup analyses using NCA assessments revealed that siponimod presented an accumulation index of approximately 2 after multiple administration. Compared with nonobese participants, obese participants had a relatively lower dose-corrected area under the concentration-time curve (AUC 0-∞ /D) (0.31 vs. 0.42 h/L) and V/F (120.95 vs. 133.75 L), and a relatively higher CL/F (3.25 vs. 3.21 L/h). Participants with CYP2C9*2/*3, *1/*3, and *3/*3 genotypes experienced an increased (1.3- and 3.4-fold, respectively) AUC 0-∞ /D and a decreased (0.7- and 0.3-fold, respectively) CL/F compared with those in participants with the CYP2C9*1/*1, *1*2, and *2*2 genotypes. Fluconazole combination led to a decrease in CL/F (approximately 0.5 times) and an increase in AUC 0-∞ /D (approximately 1.3 times). Conclusion: Siponimod pharmacokinetic properties in healthy volunteers and patients with MS were explored using complementary model-based meta-analysis (MBMA) and NCA approaches. A slightly lower siponimod clearance was observed in patients with MS than in healthy volunteers. The dosage regimen, body mass index, CYP2C9 genetic polymorphism and fluconazole combination may had influences on siponimod pharmacokinetics. Such model paves the road to more population-based analyses in different patient populations with MS to quantify the effect of any influencing factors on siponimod pharmacokinetics., 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 Chaoyang, Xiu, Ran, Lingyun, Simiao, Ruoming, Enyao, Ying, Yimin and Zhenming.)

Background: This study aimed to investigate the work status of clinicians in China and their management strategy alteration for patients with hepatocellular carcinoma (HCC) during the COVID-19 pandemic., Methods: A nationwide online questionnaire survey was conducted in 42 class-A tertiary hospitals across China. Experienced clinicians of HCC-related specialties responded with their work status and management suggestions for HCC patients during the pandemic., Results: 716 doctors responded effectively with a response rate of 60.1%, and 664 were included in the final analysis. Overall, 51.4% (341/664) of clinicians reported more than a 60% reduction of the regular workload and surgeons declared the highest proportion of workload reduction. 92.5% (614/664) of the respondents have been using online medical consultation to substitute for the "face-to-face" visits. Adaptive adjustment for the treatment strategy for HCC was made, including the recommendations of noninvasive and minimally invasive treatments such as transcatheter arterial chemoembolization for early and intermediate stage. Targeted therapy has been the mainstay for advanced stage and also as a bridge therapy for resectable HCC., Discussion: During the COVID-19 pandemic, online medical consultation is recommended to avoid social contact. Targeted therapy as a bridge therapy is recommended for resectable HCC considering the possibility of delayed surgery., (Copyright © 2021. Published by Elsevier Ltd.)

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Recent evidence has shown that circular RNAs (circRNAs) play important roles in tissue development, gene transcription, signal regulation and tumorigenesis. However, whether circRNAs are involved in HCC progression and encode functional proteins remains largely unknown. In the present study, we aimed to explore the function and molecular mechanism of circRNAs in HCC. First, many circRNAs were found to be differentially expressed in HCC samples and paired adjacent normal liver tissues. The validation of dysregulated circRNAs by qRT-PCR revealed that circEPS15 expression was downregulated in HCC tissues, and the survival curves showed that low circEPS15 levels were associated with poor overall survival in HCC patients. Then, the overexpression of circEPS15 suppressed tumor cell invasion and migration by inhibiting the TJP1/CDH2/VIM signaling pathway and retarded cell cycle progression, which was confirmed by the Transwell culture system, wound healing assays, flow cytometry and western blot assays. After that, the spanning junction open reading frame in circEPS15 driven by IRES was shown to encode a novel protein, which was verified by western blotting with full-length, mutated, and truncated sequences of circEPS15 with a FLAG tag. Moreover, ceRNA analysis and qRT-PCR results suggest a possible circRNA (circEPS15)-miRNA-mRNA network in HCC. Collectively, our study reveals that endogenous circEPS15 plays a novel role in repressing HCC through the ceRNA network and encodes a functional protein., 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 Jiang, Tian, Li, Sadula, Xiu, Yuan and Bing.)

Objective: To evaluate the influence of the abdominal incision length on the gastrointestinal function recovery post-operatively. Background: Gut motility recovers more quickly after the minimally invasive laparoscopic surgery compared than after the traditional open surgery; however, whether the minimal abdominal incision contributes to the faster gut motility recovery is controversial and lacks solid clinical evidence. Methods: A registry-based secondary cohort analysis was conducted to evaluate the association between the abdominal incision length and gut motility recovery post-operatively based on a multicenter, prospective, and observational study of the prolonged post-operative ileus (PPOI) incidence and the risk factors in the patients with the major abdominal surgery. The incision length, in the centimeters, was the exposure. The primary outcome measures were the PPOI incidence and its association with the incision length. The secondary outcome included the days to the first passage of flatus and the days to the first passage of stool. Results: Overall, 1,840 patients, including 287 (15.7%) patients with the PPOI, were recruited. The PPOI incidence was 17.6% and 13.3% in the long-incision (>18 cm) and short-incision patients ( ≤ 18 cm), respectively. The incidence of the PPOI increased by 1.1% (1.0-1.1) by each centimeter increment of the incision length after adjusting for the confounding factors. In comparison to the short-incision patients, the long-incision patients had prolonged passage of stool (4.46 vs. 4.95 days, p < 0.001). Each centimeter increment of the incision length contributed to a 2% increased risk of delay in the first bowel movement [hazard ratio (HR) 0.980 (0.967, 0.994)]. Conclusion: A long abdominal incision length independently contributed to the prolonged gut function recovery post-operatively mainly by delaying the time to the first bowel movement, but not influencing the time to first passage of flatus., 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 Song, Yang, Guan, Jin, Yang, Chen, Wan, Li, He, Zhang, Zhu, Chen, Xiu, Tian, Yang, Lou and Zhang.)

We designed and realized highly fluorescent nanostructures composed of Eu 3+ complexes under a protein coating. The nanostructured material, confirmed by photo-induced force microscopy (PiFM), includes a bottom fluorescent layer and an upper protein layer. The bottom fluorescent layer includes Eu 3+ that is coordinated by 1,10-phenanthroline (Phen) and oleic acid (O). The complete complexes (OEu 3+ Phen) formed higher-order structures with diameter 40-150 nm. Distinctive nanoscale striations reminiscent of fingerprints were observed with a high-resolution transmission electron microscope (HRTEM). Stable fluorescence was increased by the addition of Eu 3+ coordinated by Phen and 2-thenoyltrifluoroacetone (TTA), and confirmed by fluorescence spectroscopy. A satisfactory result was the observation of red Eu 3+ complex emission through a protein coating layer with a fluorescence microscope. Lanthanide nanostructures of these types might ultimately prove useful for biometric applications in the context of human and non-human tissues. The significant innovations of this work include: (1) the structural set-up of the fluorescence image embedded under protein "skin"; and (2) dual confirmations of nanotopography and unique nanofingerprints under PiFM and under TEM, respectively.

Background: Surgical resection is the only potentially curative treatment for pancreatic ductal adenocarcinoma (PDAC). However, most of patients lose the chance of surgery due to the unresectable disease at the time of diagnosis. Despite the improvement of radiological imaging, a portion of patients intended for radical resection were proven to be unresectable at surgical exploration due to occult metastasis., Methods: Patients who were aimed to undergo radical pancreatectomy for PDAC from 2010 to 2019 were reviewed retrospectively. All patients included underwent diagnostic laparoscopic exploration. Patients were divided into two groups depending on whether distant metastasis were encountered during exploration. Univariate and multivariate logistic regression analyses were used to identify risk factors for occult metastasis. A nomogram to predict occult metastasis of PDAC on exploration was developed and evaluated., Results: A total of 273 patients who underwent diagnostic laparoscopic exploration were included in this study. Nineteen (7.0%) patients were found with distant metastasis during exploration. Multivariate logistic regression analysis showed that ALT>40U/L, CA19-9, CA125 and regional nodes enlargement were independent predictors for occult metastasis. Incorporating these four factors, the nomogram achieved concordance index of 0.799, with a well-fitted calibration curve., Conclusions: Occult metastasis is not unusual during surgical exploration in patients with resectable or borderline resectable PDAC. The nomogram could achieve a personal prediction of unexpected distant metastasis on exploration. It may help to sift through patients with PDAC who would benefit from laparoscopic exploration., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/gs-20-605). The authors have no conflicts of interest to declare., (2021 Gland Surgery. All rights reserved.)

Background: Information on incidence of gastrointestinal stromal tumor (GIST), the most common type of mesenchymal tumor in gastrointestinal tract, was limited in China. This study aimed to estimate the incidence of GIST in urban population from mainland China in 2016., Methods: Urban Employee Basic Medical Insurance (UEBMI) and Urban Residence Basic Medical Insurance (URBMI) in China were used. The denominator of incidence was the total person-years of insured individuals in 2016 in the database, covering approximately 0.43 billion individuals. The numerator was the number of incident GIST cases in 2016., Results: The crude incidence in 2016 was 0.40 per 100,000 person-years (95% CI, 0.06-1.03). Male incidence was higher than female incidence (0.44 vs. 0.36, rate ratio: 1.22, p < 0.001). The mean age at diagnosis was 55.20 years (SD = 14.26) and the incidence among those aged 50 years or older was 2.63 times (0.84 vs. 0.32, p < 0.001) higher than those aged under 50. The highest incidence was observed in East China (2.29, 95% CI: 0.46-5.54)., Conclusions: The incidence of GIST in mainland China was lower than Europe, North America and Korea. The mean age at diagnosis of GIST in China was younger than that of Europe and Canada. This study provides useful information to further research, policy formulating and management of GIST., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: Laparoscopic surgery plays an important role in the treatment of splenichematologic pathologies and solid lesions. Splenic hemangioma is the most common benign tumor of the spleen. In patients with benign splenic space-occupying lesions, laparoscopic partial splenectomy (LPS) has a lower incidence of postoperative complications than laparoscopic total splenectomy (LTS). Currently, no uniform standard for the indication of LPS is available., Presentation of Case: Herein, we report a case of hemangioma in a 23-year-old woman treated with LPS. After multidisciplinary evaluation, laparoscopic splenectomy was indicated in this case; upon evaluating the age of the patient and the affected spleen portion, a middle segment splenectomy was proposed, with preservation of the upper and lower pole. The intraoperative frozen section of the specimen was negative for malignancies., Discussion: Surgery remains the first choice in the treatment of solid lesions of the spleen. In this case, the volume of splenic hemangioma was large and accumulated in the upper and lower segments of the spleen. After the middle branch of splenic artery was cut off, the tumor was completely contained in the middle of upper and lower ischemic lines splenic segment. We think that the central type of benign splenic space occupying is not an absolute contraindication of LPS. For the patients whose splenic artery bifurcation point is far from the splenic hilus parenchyma and in those cases where the blood supply of the upper and lower poles of the splenic segments can be ensured, when the splenic tumor is resected, performing LPS and retaining some parts of the upper and lower splenic segments is possible to ensure sufficient residual spleen., (Copyright © 2020. Published by Elsevier Ltd.)

Introduction: The best approach for choledocholithiasis remains a matter of debate. Choledocholithiasis is usually treated with endoscopic sphincterotomy (EST), laparoscopic common bile duct exploration (LCBDE) or laparoscopic transcystic common bile duct exploration (LTCBDE). Data pertaining to the clinical outcomes of these approaches in the management of patients with cholecysto-choledocholithiasis in China are limited. An analysis of the economic burden associated with these treatments is lacking. The Chinese REgistry Study on the Treatment of Cholecysto-Choledocholithiasis (CREST Choles) was designed to address these issues in a real-world setting., Methods and Analysis: CREST Choles was an ambispective, multicenter, observational, open-cohort study. A total of 2700 patients undergoing one of the three treatments (EST+laparoscopic cholecystectomy (LC), LCBDE+LC and LTCBDE+LC) during the period from 1 January 2013 to 1 December 2018 at participating centres were enrolled in the study. Patients with gallstones and confirmed common bile duct stones were included. Data pertaining to demographics, disease history, procedural details, imaging features and follow-up were collected. Follow-up was conducted at least 6 months after enrolment in the study and annual follow-up will be conducted until December 2020. The primary outcome is the rate of adverse outcomes within 3 years postoperatively. Economic analysis (eg, incremental cost-effectiveness ratio) would be performed to compare expense across treatments., Ethics and Dissemination: Ethical approval was obtained at all participating centres. The registry presented is the first attempt to comprehensively evaluate the cost of treatment for cholecysto-choledocholithiasis in China. Findings are expected to be available in 2020 and will facilitate clinical decision making in such cases., Trial Registration Number: NCT02554097., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To explore the feasibility and to compare the merits and demerits of laparoscopic and endoscopic approach in removing common bile duct stones in patients with gastrojejunostomy after gastrectomy., Methods: Between January 2012 and December 2016, 25 patients with common bile duct stones after gastrojejunostomy received laparoscopic or endoscopic treatment in our centers. They were divided into laparoscopic group and endoscopic group based on treatment approaches for common bile duct stones, including 15 patients in laparoscopic group and 10 in endoscopic group. The clinical characteristics and outcomes between the two groups were retrospectively analyzed., Results: Among the 25 patients with gastrojejunostomy, the method of reconstruction was Billroth II in 21 patients and Roux-en-Y in 4 patients. Six patients received laparoscopic or endoscopic treatment during the acute cholangitis state. Among the laparoscopic group, 5 patients with stones more than 1 cm, 7 patients with multiple stones, while in the endoscopic group, 3 patients with stones more than 1 cm and 4 patients with multiple stones. Fourteen patients in the laparoscopic group with coexisting gallbladder stones, and 6 of their common bile duct stones were successfully removed by transcystic approach without T tube drainage. Stone removals were successful in 4 patients of the endoscopic group by a single performance, including 3 patients with single small stone and one patient with multiple small stones. Two patients in the laparoscopic group were converted to open surgery for severe adhesion and one patient in the endoscopic group turned to laparoscopic operation for failing of finding papilla in the Roux-en-Y anastomotic status. The median hospital stays were 12 d and 10 d, respectively in the laparoscopic and endoscopic group. There were 3 patients with postoperative complications, including one patient with paralytic ileus in the laparoscopic group and 2 patients with biliary pancreatitis or bacteremia in the endoscopic group, and all of them recovered uneventfully with conservative treatment., Conclusion: Both laparoscopic and endoscopic approaches are feasible for removing stones in the common bile duct in patients with gastrojejunostomy after gastrectomy, and they complement each other. In addition, both techniques are difficult to conduct, and a technical competence should be considered in selection of each method.

The aim of the present study was to investigate the function of microRNA-543 on liver cancer cell proliferation and apoptosis, and also to identify whether the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway was a direct target of microRNA-543. When compared with paracarcinoma tissue, microRNA-543 expression in tissue samples from patients with liver cancer was identified to be decreased. Furthermore, overall survival of patients with high microRNA-543 expression was increased compared with patients with low microRNA-543 expression. Inhibition of microRNA-543 expression increased cell proliferation and decreased apoptosis of liver cancer cells. It also activated the protein expression of phosphorylated JAK2, phosphorylated STAT3, c-Myc and B-cell lymphoma 2 (Bcl-2) in liver cancer cells. However, activation of microRNA-543 expression in turn decreased cell proliferation and increased apoptosis of liver cancer cells. The results of the present study highlight the pivotal function of microRNA-543 as an inhibitor in liver cancer cell proliferation by observing JAK2/STAT3/c-Myc/Bcl-2 in liver cancer.

Non-small cell lung cancer (NSCLC) is one of leading causes of cancer-associated mortality, with a high number of cases caused by metastasis. The early diagnosis of cancer contributes to the successful treatment of patients with lung cancer. The aim of the present study was to analyze the efficacy of marker gene detection and computed tomography (CT) in diagnosing human lung cancer. Lung cancer marker genes, including carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), tissue polypeptide antigen (TPA), pro-gastrin-releasing peptide (ProGRB), cytokeratin fragment 21-1 (Cyfra21-1) and neuron-specific enolase (NSE), were analyzed in patients with lung cancer. The tumor size was evaluated using CT, and the association between lung serum levels of marker gene protein expression and tumor size was investigated. A total of 328 patients with lung cancer were identified, including 204 adenocarcinoma, 75 large cell carcinoma and 49 squamous cell carcinoma cases. All patients were indicated to have a high serum level of CEA, CA125, TPA, ProGRB, Cyfra21-1 and NSE, compared with the normal range. Immunohistochemistry demonstrated higher expression levels of CEA, CA125, TPA, ProGRB, Cyfra21-1 and NSE in lung tumor tissues, compared with the normal range. Results indicated that CT was able to diagnose tumor size for patients with lung cancer. The CEA and CA125 expression levels were associated with CT-diagnosed adenocarcinoma tumor size. Large cell carcinoma tumor size was associated with serum levels of CEA, TPA and ProGRB. Results indicated that Cyfra21-1 and NSE were associated with the squamous cell carcinoma cases, as demonstrated using CT. In conclusion, these results indicated that comprehensive analysis of marker gene detection and CT results may be used to diagnose human lung cancer.

Protocadherin10 (PCDH10), a member of the nonclustered protocadherin family, functions as a tumor suppressor in many cancers. The aim of this study was to evaluate the expression level and prognostic value of PCDH10 in hepatocellular carcinoma (HCC) patients.Quantitative real-time polymerase chain reaction was used to analyze the expression level of PCDH10 in HCC tissues and adjacent nontumor tissues. The association of PCDH10 expression with clinicopathological features of patients was evaluated by chi-squared test. Overall survival was estimated using the Kaplan-Meier method. Besides, the patient prognosis was also evaluated by Cox regression analysis.PCDH10 expression was significantly lower in HCC tissues than that in adjacent nontumor tissues (P = .000). Kaplan-Meier curves showed that patients with lower PCDH10 expression had a worse overall survival. Moreover, PCDH10 expression level was associated tumor size (P = .005), tumor node metastasis stage (P = .002), smoking status (P = .000), and drinking status (P = .005). Multivariate analysis showed that the expression of PCDH10 (P = .000; hazard ratio = 4.784; 95% confidence interval: 2.550-8.977) was an independently associated with poor overall survival rates, as well as smoking status and drinking status.Our findings indicated that the decreased expression of PCDH10 was closely associated with poor prognosis of HCC patients. It might be considered as a valuable biomarker for HCC.

A common challenge in systems biology is quantifying the effects of unknown parameters and estimating parameter values from data. For many systems, this task is computationally intractable due to expensive model evaluations and large numbers of parameters. In this work, we investigate a new method for performing sensitivity analysis and parameter estimation of complex biological models using techniques from uncertainty quantification. The primary advance is a significant improvement in computational efficiency from the replacement of model simulation by evaluation of a polynomial surrogate model. We demonstrate the method on two models of mating in budding yeast: a smaller ODE model of the heterotrimeric G-protein cycle, and a larger spatial model of pheromone-induced cell polarization. A small number of model simulations are used to fit the polynomial surrogates, which are then used to calculate global parameter sensitivities. The surrogate models also allow rapid Bayesian inference of the parameters via Markov chain Monte Carlo (MCMC) by eliminating model simulations at each step. Application to the ODE model shows results consistent with published single-point estimates for the model and data, with the added benefit of calculating the correlations between pairs of parameters. On the larger PDE model, the surrogate models allowed convergence for the distribution of 15 parameters, which otherwise would have been computationally prohibitive using simulations at each MCMC step. We inferred parameter distributions that in certain cases peaked at values different from published values, and showed that a wide range of parameters would permit polarization in the model. Strikingly our results suggested different diffusion constants for active versus inactive Cdc42 to achieve good polarization, which is consistent with experimental observations in another yeast species S. pombe., Competing Interests: The authors have declared that no competing interests exist.

Background: Pancreatic duct obstructions are common in patients with pancreaticoduodenectomy. However, it is often neglected in follow up. This study was to review the outcomes of pancreatic duct obstruction and explore the prevention of pancreatic duct obstruction., Methods: A retrospective analysis of 78 patients undergoing pancreaticojejunostomy without reccurence of disease within 24 months between 2004 and 2014. Pancreatic duct obstruction and long-term pancreatic complications were analysed., Results: Twenty-five patients developed pancreatic duct obstruction following pancreaticojejunostomy, 13 of whom were found to have long-term pancreatic complications. The presence of pancreatic duct obstruction and early pancreatic obstruction were associated with long-term pancreatic complications, respectively (p = 0.002, p = 0.002). There are 10 patients with pancreatic duct stent more than 24 months, the postoperative median pancreatic parenchymal thickness in these 10 patients (17.1 mm, range 8.0 to 24.7 mm) was not significantly change than the median in them preoperative (16.4 mm, range 7.2 to 24.7 mm; p = 0.747). All of them have no long-term pancreatic complications, though the difference was not significantly (p = 0.068)., Conclusions: Early pancreatic duct obstruction is associated with postoperative pancreatic long-term complications. Sustained internal pancreatic stent may improve pancreatic duct obstruction.

Background: There were many reports suggesting that different kinds of tumors can express B7-H4; however, the prognostic value in cancer was still unclearly. Therefore, we conducted a meta-analysis to investigate the relationship between overexpression of B7-H4 with the prognostic value in pancreatic cancer patients., Materials and Methods: The Pubmed, Embase, Cochrane Library, Ovid, Web of Science, and Chinese research database (including CBM, CNKI, and WAN FANG) were searched for related literature published until October 12, 2017. The pooled odds ratios (ORs) and/or pooled hazard ratios (HRs) for clinical pathological factors and overall survival (OS) were calculated and analyzed using Stata software. To assess whether an individual study had an impact on the result, sensitivity analysis was performed for all included individual studies using the fixed-effects model. Publication bias was evaluated using Egger's and Begg's tests., Results: Data from 6 observational studies including 442 patients were summarized in this meta-analysis, and each study was eligible for inclusion based on included and exclude criteria. The pooled results indicated that the B7-H4 overexpression could predict the presentation of lymph node metastasis (OR = 3.94, 95% CI: 1.22-12.66, P = .022), advanced TNM stage (T = the extent of the primary tumor, N = regional lymph nodes, M = distant metastases) (III+IV vs I+II; OR = 7.63, 95% CI: 2.46-23.66, P < .001), and the poor OS (HR = 3.00, 95%CI = 2.20-4.10, P < .001) in PC patients., Conclusions: This study reveals that high expression of B7-H4 is an unfavorable prognostic factor for patients with pancreatic cancer. These results may guide the clinical management of this patient population.