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In this research, canola meal was densified using bio-additives including alkali lignin, glycerol, and l -proline. The fuel pellet's formulation was optimized. The best fuel pellet demonstrated relaxed density and mechanical durability of 1015 kg/m3 and 99.0%, respectively. Synchrotron-based computer tomography technique indicated that lack of water in pellet formulation resulted in a twofold increase in pellet porosity. Thermogravimetric analysis showed that ignition temperature (240 °C) and burn-out temperature (640 °C) for fuel pellet were smaller than those for coal. Impacts of process parameters were evaluated on the quality of the gas product obtained from pellet's steam gasification and hydrothermal gasification. The gasification experiments showed production of untreated syngas with a suitable range of H2/CO molar ratio (1.3–1.6) using steam gasification. Hydro-thermal gasification produced a larger molar ratio of H2/CO (1.8–51.2) for the gas product. Modeling of pellet's steam gasification showed an excellent agreement with experimental results of steam gasification.

In this paper, an integrated drive converter of segmented-double-stator switched reluctance machine (SDS-SRM) with isolation and non-isolation charging capabilities for electric vehicle (EV) is presented. The proposed converter can not only reduce the number of the power switches, but also implement multiple operation modes. In non-isolation charging mode, the motor windings and existing power switches constitute a buck/boost converter to charge the battery. The appropriate rotor positions are obtained to achieve torque-free control, and the interleaved phase currents control method is introduced to reduce the charging current ripples. In isolation charging mode, the inner-stator is powered by the utility grid to drive the middle-rotor, and converts electrical energy into mechanical energy. While, the outer-stator is operated in generation mode to convert mechanical energy into electrical energy. The SDS-SRM is served as a rotating transformer to transfer the electric power to charge the battery with the galvanic isolation function. A low power proof-of-concept prototype platform is built and experiments are carried out to verify the effectiveness of the proposed integrated drive converter and the corresponding control schemes.

This paper proposes an integrated multifunctional power converter topology, where a traction battery charger (TBC), an auxiliary battery charger (ABC), and a motor drive converter (MDC) merge into an effective system. Traction battery charging, auxiliary battery charging, and motor driving operation modes can be realized by sharing power components. For the battery charging mode, a single-phase power supply charges the traction battery, and the circuit is capable of power factor correction (PFC) and active power decoupling (APD) (G2V mode). For the purpose of enhancing its charging power, the traction battery can also be connected to a three-phase power supply. For the battery discharging mode, the traction battery can feed energy back to a single-phase grid or a three-phase grid (V2G mode). When necessary, the traction battery can charge an auxiliary battery through a DC–DC converter (T2A mode). In the motor driving mode, the energy of the traction battery is used to drive a motor (T2M mode). Each of the charging modes can be implemented under the galvanic isolated condition. Power relays are used to switch the operating modes of the proposed topology.

Cyclophilin A (CypA) is a ubiquitous and highly conserved protein. CypA, the intracellular target protein for the immunosuppressant cyclosporine A (CsA), plays important cellular roles through peptidyl-prolyl cis-trans isomerase (PPIase). Increasing evidence shows that CypA is up-regulated in a variety of human cancers. In addition to being involved in the occurrence and development of multiple tumors, overexpression of CypA has also been shown to be strongly associated with malignant transformation. Surgery, chemotherapy and radiotherapy are the three main treatments for cancer. Chemotherapy and radiotherapy are often used as direct or adjuvant treatments for cancer. However, various side effects and resistance to both chemotherapy and radiotherapy bring great challenges to these two forms of treatment. According to recent reports, CypA can improve the chemosensitivity and/or radiosensitivity of cancers, possibly by affecting the expression of drug-resistant related proteins, cell cycle arrest and activation of the mitogen-activated protein kinase (MAPK) signaling pathways. In this review, we focus on the role of CypA in cancer, its impact on cancer chemotherapeutic and radiotherapy sensitivity, and the mechanism of action. It is suggested that CypA may be a novel potential therapeutic target for cancer chemotherapy and/or radiotherapy.

Background Intraductal papillary mucinous neoplasms (IPMNs) are characterized by their abundant mucin production and malignant potential. IPMNs of the pancreas are mainly managed according to their radiographic indications, but this approach lacks accuracy with regard to IPMN grading. Therefore, serological biomarkers such as CA19-9 and CA125 (MUC16) should be employed to assist in predicting the invasiveness of IPMNs. Methods We investigated the preoperative serum levels of CA19-9, CA125 and CEA in 381 surgical patients with a definite pathological diagnosis of IPMN from July 2010 to December 2019 at the Shanghai Cancer Center. We calculated the Youden indices of each point on the receiver operating characteristic (ROC) curves to identify the most appropriate cut-off values of CA19-9, CA125 and CEA for recognizing malignant IPMNs. Serological biomarker differences were correlated with clinicopathological features of IPMNs, and diagnostic indices of different scenarios were calculated to find the optimum strategy. Results The malignant group had higher serum levels of CA19-9, CA125 and CEA. According to the ROC curves, the cut-off values of CA19-9, CA125 and CEA were readjusted to 38.3 U/ml, 13.4 U/ml and 5.3 μg/L. CA19-9 elevation was significantly associated with vascular invasion and perineural infiltration. CA125 showed good efficacy in predicting invasive IPMN in the CA19-9-negative subgroup. Conclusions Serological biomarkers are useful and sensitive indicators for recognizing invasive IPMNs. CA19-9 is the most important diagnostic index among all routinely measured serum biomarkers for differentiating malignant from benign IPMNs. CA19-9 should be combined with CA125 to enable more accurate predictions of IPMN malignancy.

To evaluate the clinical value of preoperative markers in predicting occult metastases in resectable pancreatic body and tail cancer judged by a recent multidetector computed tomography (MDCT) scan of the abdomen. The data from a retrospective collected database from 2010 to 2019 with 699 patients who had MDCT scan predicted resectable mass in pancreatic body and tail and were pathological confirmed as adenocarcinoma after surgery. Receiver operating characteristic (ROC) curve was plotted for serum CA19-9, CA125, CEA and tumor size measured by MDCT. The optimal cut-off point-related sensitivity and specificity were calculated, respectively. Occult metastases were found in 73 (73/699, 10.4%) pancreatic body and tail cancer patients underwent exploration. The area under curve (AUC) for CA19-9, CA125, CEA and tumor size were 0.624, 0.733, 0.561 and 0.697, respectively. The optimal cut-off for CA19-9, CA125 and tumor size is 226 U/ml, 22.1 U/ml and 3.3 cm, respectively. The sensitivity and specificity of CA19-9 for predicting occult metastases were 67.1% and 60.4%, 72.6% and 64.7% for CA125, 80.8% and 51.4% for tumor size. CA125 is superior to CA19-9 and tumor size for predicting occulting metastases in MDCT scan suggested resectable pancreatic body and tail cancer. The high level of CA125 (≥ 22.1 U/ml) is regarded as high risk for occulting metastases, and laparoscopy should be applied for these patients.

Developing advanced negative and positive electrode materials for asymmetric supercapacitors (ASCs) as electrochemical energy storage devices can enable the device to reach high energy/power densities resulting from the cooperative effect of the two electrodes. In this work, a nanochain-like hybrid nanostructured composite of MoO3 with rich oxygen vacancies (MoO3−x) in situ grown on N-doped graphene nanotubes (N-GNTs) is synthesized as the negative electrode for an ASC. It can deliver a large specific capacitance (591 F g−1 at 2 A g−1), as well as an outstanding rate capability. Simultaneously, N-GNTs@Na+-preinserted MnO2 (NaxMnO2) nanosheet arrays are fabricated as the positive electrode of the ASC, which can exhibit an enhanced specific capacitance of 429 F g−1 with a wide potential window of 0–1.2 V. When these two different electrodes are assembled in an ASC, a maximum energy density of 105 W h kg−1 at 2.2 kW kg−1, and an ultralong lifespan with 95.4% capacitance retention after 10 000 cycles are achieved, which are superior to those of the reported ASC devices to date. Density functional theory (DFT) calculations show that benefitting from the designed vacancy defects and unique N-GNT skeleton, the electronic structure and adsorption energy can be adjusted to greatly boost the electrical conductivity and ion adsorption efficiency and subsequently enhance the capacitive properties of the electrodes in the ASC.

Empirical potential structure refinement (EPSR) is a neutron scattering data analysis algorithm and a software package. It was developed by the British spallation neutron source (ISIS) Disordered Materials Group in 1980s, and aims to construct the most-probable atomic structures of disordered liquids. It has been extensively used during the past decades, and has generated reliable results. However, it is programmed in Fortran and implements a shared-memory architecture with OpenMP. With the extensive construction of supercomputer clusters and the widespread use of graphics processing unit (GPU) acceleration technology, it is now necessary to rebuild the EPSR with these techniques in the effort to improve its calculation speed. In this study, an open source framework NeuDATool is proposed. It is programmed in the object-oriented language C++, can be paralleled across nodes within a computer cluster, and supports GPU acceleration. The performance of NeuDATool has been tested with water and amorphous silica neutron scattering data. The test shows that the software could reconstruct the correct microstructure of the samples, and the calculation speed with GPU acceleration could increase by more than 400 times compared with CPU serial algorithm at a simulation box consists about 100 thousand atoms. NeuDATool provides another choice for scientists who are familiar with C++ programming and want to define specific models and algorithms for their analyses., 16 pages, 7 figures

BackgroundGerminomas (IG) account for up to 50% of all intracranial germ cell tumours. These tumours are reputed to be more prevalent in Oriental populations in comparison to Western cohorts. Biological characteristics of IG in other ethnic groups are unknown. Singapore is a multi-ethnic country with diverse cultures. Owing to inter-racial heterogeneity, the authors hypothesize there are molecular differences between paediatric IG patients in our local population. The aims of this study are exploratory: firstly, to identify molecular characteristics in this tumour type and circulating CSF unique to different racial cohorts; and next, to corroborate our findings with published literature.MethodsThis is a single-institution, retrospective study of prospectively collected data. Inclusion criteria encompass all paediatric patients with histologically confirmed IG. Excess CSF and brain tumour tissues are collected for molecular analysis. Tumour tissues are subjected to a next generation sequencing (NGS) targeted panel forKIT and PDGRA. All CSF samples are profiled via a high-throughput miRNA multiplexed workflow. Results are then corroborated with existing literature and public databases.ResultsIn our cohort of 14 patients, there areKITexon variants in the tumour tissues and CSF miRNAs corroborative with published studies. Separately, there are alsoKITexon variants and miRNAs not previously highlighted in IG. A subgroup analysis demonstrates differential CSF miRNAs between Chinese and Malay IG patients.ConclusionThis is the first in-depth molecular study of a mixed ethnic population of paediatric IGs from a Southeast Asian cohort. Validation studies are required to assess the relevance of novel findings in our study.

Pancreatic ductal adenocarcinoma (PDAC) is a malignancy characterized by a poor prognosis and high mortality rate. Genetic mutations and altered molecular pathways serve as targets in precise therapy. Using next-generation sequencing (NGS), these aberrant alterations can be identified and used to develop strategies that will selectively kill cancerous cells in patients with PDAC. The realization of targeted therapies in patients with PDAC may be summarized by three approaches. First, because oncogenes play a pivotal role in tumorigenesis, inhibition of dysregulated oncogenes is a promising method (Table 3). Numerous researchers are developing strategies to target oncogenes, such as KRAS, NRG1, and NTRK and related molecules, although most of the results are unsatisfactory. Accordingly, emerging strategies are being developed to target these oncogenes, including simultaneously inhibiting multiple molecules or pathways, modification of mutant residues by small molecules, and RNA interference. Second, researchers have attempted to reactivate inactivated tumour suppressors or modulate related molecules. TP53, CDKN2A and SMAD4 are three major tumour suppressors involved in PDAC. Advances have been achieved in clinical and preclinical trials of therapies targeting these three genes, and further investigations are warranted. The TGF-β-SMAD4 signalling pathway plays a dual role in PDAC tumorigenesis and participates in mediating tumour-stroma crosstalk and modulating the tumour microenvironment (TME); thus, molecular subtyping of pancreatic cancer according to the SMAD4 mutation status may be a promising precision oncology technique. Finally, genes such as KDM6A and BRCA have vital roles in maintaining the structural stability and physiological functions of normal chromosomes and are deficient in some patients with PDAC, thus serving as potential targets for correcting these deficiencies and precisely killing these aberrant tumour cells. Recent clinical trials, such as the POLO (Pancreas Cancer Olaparib Ongoing) trial, have reported encouraging outcomes. In addition to genetic event-guided treatment, immunotherapies such as chimeric antigen receptor T cells (CAR-T), antibody-drug conjugates, and immune checkpoint inhibitors also exhibit the potential to target tumours precisely, although the clinical value of immunotherapies as treatments for PDAC is still limited. In this review, we focus on recent preclinical and clinical advances in therapies targeting aberrant genes and pathways and predict the future trend of precision oncology for PDAC.

There lacks an ideal model for accurately predicting clinically relevant postoperative pancreatic fistula (CR-POPF) after pancreatoduodenectomy (PD). This study aimed at developing a nomogram with high accuracy in predicting CR-POPF after PD. A total of 1182 patients undergoing PD in the First Affiliated Hospital of Sun Yat-sen University (FAHSYSU, n = 762) and Fudan University Shanghai Cancer Center (FUSCC, n = 420) between January 2010 and May 2018 were enrolled. The patients from FAHSYSU were assigned as testing cohort, and those from FUSCC were used as external validation cohort. Univariate and multivariate logistic regression analyses were performed to determine the predictive factors for CR-POPF. Nomogram was developed on the basis of significant predictors. The performance of nomogram was evaluated by area under receiver operating characteristic (ROC) curve (AUC), calibration curve, and decision curve analysis. In testing cohort, 87 out of 762 patients developed CR-POPF. Three predictors were significantly associated with CR-POPF, including body mass index ≥24.0 kg/m2, pancreatic duct diameter

Yitao Gong,1– 4,* Zhiyao Fan,1– 4,* Guopei Luo,1– 4,* Qiuyi Huang,1– 4 Yunzhen Qian,1– 4 He Cheng,1– 4 Kaizhou Jin,1– 4 Quanxing Ni,1– 4 Xianjun Yu,1– 4 Chen Liu1– 4 1Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai 200032, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China; 3Shanghai Pancreatic Cancer Institute, Shanghai 200032, People’s Republic of China; 4Pancreatic Cancer Institute, Fudan University, Shanghai 200032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xianjun Yu; Chen LiuDepartment of Pancreatic Surgery, Fudan University Shanghai Cancer Center, No. 270 DongAn Road, Shanghai 200032, People’s Republic of ChinaTel + 86 21-64175590 ext 1307Fax + 86 21-64031446Email yuxianjun@fudanpci.org; liuchen@fudanpci.orgPurpose: Pancreatic neuroendocrine tumours (panNETs) are rare tumours of pancreas. Lymphocyte subsets in the peripheral blood are reported to reflect tumour prognosis and progression. The objective of the study is to investigate the hypotheses that the levels of peripheral lymphocytes may reflect tumour progression and may predict the prognosis of pancreatic neuroendocrine tumours (panNETs).Patients and Methods: A retrospective cohort study consisting of 73 patients diagnosed with panNETs was conducted. Kaplan–Meier methods and Log rank tests were used to compare the survival rates, and a Cox regression model was used to perform multivariate analyses.Results: panNET patients with distant metastasis were associated with lower peripheral total T cell (p = 0.039) and CD4+ T cell (p = 0.006) counts. Lower peripheral B cells (p = 0.007) and higher peripheral NK cell (p = 0.001) counts indicated worse progression-free survival (PFS) in Log rank tests. In multivariate analyses, low B cell count (hazard ratio (HR): 6.769, 95% confidence interval (CI): 2.158 to 21.228, p = 0.001) and high NK cell count (HR: 3.715, 95% CI: 1.164 to 11.855, p = 0.027) were independent risk factors for progression. NK cells and B cells were also significantly associated with PFS following radical surgical resection.Conclusion: Peripheral total T cell and CD4+ T cell counts may reflect the distant metastasis status in panNET patients. The absolute count of peripheral B cells and NK cells may independently predict the progression of panNET patients, making them promising prognostic indicators and potential targets for treatment of panNETs.Keywords: pancreatic neuroendocrine tumours, panNETs, lymphocyte subsets, progression-free survival, B cells

Mounting evidence has suggested that acute pancreatitis (AP) is a risk factor for pancreatic ductal adenocarcinoma (PDAC), but its role in survival in PDAC patients was rarely investigated. The objective was to investigate the association of a history of AP with survival among PDAC patients who underwent surgical resection.A retrospective cohort study comprising 632 patients who were diagnosed with resectable PDAC was conducted. Survival was evaluated by history of AP prior to a diagnosis of PDAC using Kaplan-Meier methods and log-rank tests. Multivariate analyses for mortality were estimated using the Cox proportional hazards model. Propensity score matching methods were used to balance the difference of clinical characteristics between patients with and without AP history.The log-rank tests showed that patients with a history of AP had a worse overall survival than those without a history of AP (p = 0.006). The multivariable-adjusted hazard ratio (HR) for mortality comparing participants with AP to those without AP was 1.808 (95% CI: 1.241-2.632, p = 0.002). Patients with a recent history of AP (2 years), rather than patients with a remote history of AP (≥2 years), were found to have significantly worse survival (p = 0.014) than those without a history of AP. After adjusted for PSM, history of AP remained an independent survival predictor of PDAC following surgical resection.Our findings indicate that a history of AP, especially a recent history of AP, is associated with poor survival among patients with resectable pancreatic ductal adenocarcinoma.

Diabetic neuropathic pain is one of the most common complications of diabetes. Mechanisms underlying the central modulation are still unclear. Here, we investigated the role of the neuron-restricted silencing factor (NRSF/REST) in diabetic-related neuropathic pain. Mechanical allodynia and thermal hyperalgesia were assessed to evaluate painful behaviors. Our results found that in the anterior cingulate cortex (ACC) of db/db mice, NRSF/REST levels increased significantly. Reduction of NRSF/REST improved the painful sensation. Meanwhile, in vitro study found that high glucose and high palmitic acid treatment induced elevation of NRSF/REST and its cofactors (mSin3A, CoREST and HDAC1), whereas downregulation of GluR2 and NMDAR2B. Knockdown of NRSF/REST could attenuate the LDH release and partially reversed the expression changes of HDAC1 and NMDAR2B. Our results suggested that the elevation of NRSF/REST in the ACC area of db/db mice is one of the key mediators of diabetic neuropathic pain.

Patients with distal (body/tail) pancreatic cancer have been found to present worse outcome than patients with head cancer, which is generally attributed to the great proportion of advanced stages for body/tail cancers upon detection. However, differences in prognosis between head and body/tail pancreatic cancers controlled by stage have not been analyzed in-depth. In this study, differences in prognosis between head and body/tail pancreatic cancers were examined using the Surveillance, Epidemiology, and End Results Program (SEER) (1973-2014 registry, 85,715 cases). We found that patients with body/tail pancreatic cancer had worse prognosis than patients with head cancer for all combined stages [adjusted hazard ratio (HR), 1.03, 95% confidence interval (CI), 1.00-1.05, P=0.025]. Compared with patients with head cancer, patients with body/tail cancer had lower mortality for stage I cancers (HR, 0.85, 95% CI, 0.76-0.94, P=0.001), no difference in mortality for stages II or III (stage II, HR, 1.00, 95% CI, 0.95-1.06, P=0.965; stage III, 0.97, 95% CI, 0.91-1.04, P=0.398), and higher mortality for stage IV (HR, 1.07, 95% CI, 1.04-1.10, P

Purpose Kras mutation and abnormal immune status are associated with pancreatic cancer development and progression. In this study, we evaluated the Kras mutation status in circulating tumor DNA and circulating T cell subsets in a cohort of advanced pancreatic cancer patients. Methods Samples were retrospectively obtained from a series of 210 pathological advanced pancreatic cancer patients between 2012 and 2014. The Kras mutation status was detected in cell‐free circulating tumor DNA (ctDNA) by ddPCR and circulating T cell subsets were analyzed by flow cytometry. Results Univariate analysis found that tumor node metastasis (TNM) stage, chemotherapy, circulating regulatory T cells, CA19‐9 levels, CA125 levels, and KrasG12D and KrasG12V mutations were significantly related to overall survival in advanced pancreatic cancer patients. Multivariate analysis identified that TNM stage (P = .03, HR:1.422), Tregs (P = .004, HR:1.522), CA19‐9 levels (P = .009, HR:1.488), KrasG12D mutation (P = .044, HR:1.353), and KrasG12V mutation (P = .001, HR:1.667) were independent prognostic markers. Furthermore, we found that KrasG12V mutation in ctDNA was correlated with high circulating proportion of Tregs, and patients with both KrasG12V mutation and high levels of Tregs were associated with extremely poor survival in advanced pancreatic cancer. Conclusion KrasG12V mutation was associated with high circulating regulatory T cell levels, and both of them predicted worse prognosis in advanced pancreatic cancer patients., KrasG12V mutation in ctDNA was correlated with high circulating proportion of Tregs. Patients with both KrasG12V mutation and high levels of Tregs were associated with extremely poor survival in advanced pancreatic cancer.

Background and Purpose Cerebral organoids (COs) have been used for studying brain development, neural disorders, and species‐specific drug pharmacology and toxicology, but the potential of COs transplantation therapy for brain injury remains to be answered. Methods With preparation of traumatic brain injury (TBI) model of motor dysfunction, COs at 55 and 85 days (55 and 85 d‐CO) were transplanted into damaged motor cortex separately to identify better transplantation donor for brain injury. Further, the feasibility, effectiveness, and underlying mechanism of COs transplantation therapy for brain injury were explored. Results 55 d‐CO was demonstrated as better transplantation donor than 85 d‐CO, evidenced by more neurogenesis and higher cell survival rate without aggravating apoptosis and inflammation after transplantation into damaged motor cortex. Cells from transplanted COs had the potential of multilinage differentiation to mimic in‐vivo brain cortical development, support region‐specific reconstruction of damaged motor cortex, form neurotransmitter‐related neurons, and migrate into different brain regions along corpus callosum. Moreover, COs transplantation upregulated hippocampal neural connection proteins and neurotrophic factors. Notably, COs transplantation improved neurological motor function and reduced brain damage. Conclusions This study revealed 55 d‐CO as better transplantation donor and demonstrated the feasibility and efficacy of COs transplantation in TBI, hoping to provide first‐hand preclinical evidence of COs transplantation for brain injury.

Chest wall tumors are a relatively uncommon disease in clinical practice. Most of the published studies about chest wall tumors are usually single-center retrospective studies, involving few patients. Therefore, evidences regarding clinical conclusions about chest wall tumors are lacking, and some controversial issues have still to be agreed upon. In January 2019, 73 experts in thoracic surgery, plastic surgery, science, and engineering jointly released the Chinese Expert Consensus on Chest Wall Tumor Resection and Chest Wall Reconstruction (2018 edition). After that, numerous experts put forward new perspectives on some academic issues in this version of the consensus, pointing out the necessity to further discuss the points of contention. Thus, we conducted a survey through the administration of a questionnaire among 85 experts in the world. Consensus has been reached on some major points as follows. (I) Wide excision should be performed for desmoid tumor (DT) of chest wall. After excluding the distant metastasis by multi-disciplinary team, solitary sternal plasmacytoma can be treated with extensive resection and adjuvant radiotherapy. (II) Wide excision with above 2 cm margin distance should be attempted to obtain R0 resection margin for chest wall tumor unless the tumor involves vital organs or structures, including the great vessels, heart, trachea, joints, and spine. (III) For patients with chest wall tumors undergoing unplanned excision (UE) for the first time, it is necessary to carry out wide excision as soon as possible within 1-3 months following the previous surgery. (IV) Current Tumor Node Metastasis staging criteria (American Joint Committee on Cancer) of bone tumor and soft tissue sarcoma are not suitable for chest wall sarcomas. (V) It is necessary to use rigid implants for chest wall reconstruction once the maximum diameter of the chest wall defect exceeds 5 cm in adults and adolescents. (VI) For non-small cell lung cancer (NSCLC) invading the chest wall, wide excision with neoadjuvant and/or adjuvant therapy are recommended for patients with stage T3-4N0-1M0. As clear guidelines are lacking, these consensus statements on controversial issues on chest wall tumors and resection could possibly serve as further guidance in clinical practice during the upcoming years. ispartof: TRANSLATIONAL LUNG CANCER RESEARCH vol:10 issue:11 pages:4057-4083 ispartof: location:China status: published

Stroke is the second leading cause of death and main cause of disability worldwide, but with few effective therapies. Although stem cell-based therapy has been proposed as an exciting regenerative medicine strategy for brain injury, there are limitations. The developed cerebral organoids (COs) represent a promising transplantation source for stroke that remains to be answered. Here, we transplanted COs at 55 days and explored the feasibility in the rat middle cerebral artery occlusion (MCAO) model of stroke. COs transplantation at 6 h or even 24 h after MCAO significantly reduces brain infarct volume and improves neurological motor function. Transplanted COs show the potential of multilineage differentiation to mimic in vivo cortical development, support motor cortex region-specific reconstruction, form neurotransmitter-related neurons, and achieve synaptic connection with host brain via in situ differentiation and cell replacement in stroke. Cells from transplanted COs show extensive migration into different brain regions along corpus callosum. The mechanisms underlying COs transplantation therapy are also associated with enhanced neurogenesis, synaptic reconstruction, axonal regeneration and angiogenesis, and decreased neural apoptosis with more survival neurons after stroke. Moreover, COs transplantation promotes predominantly exogenous neurogenesis in the transplantation periphery of ipsilateral cortex and predominantly endogenous neurogenesis in the hippocampus and subventricular zone. Together, we demonstrate the efficacy and underlying mechanisms of COs transplantation in stroke. This preliminary but promising study provides first-hand preclinical evidence for COs transplantation as a potential and effective intervention for stroke treatment. Electronic supplementary material The online version of this article (10.1007/s12975-019-00773-0) contains supplementary material, which is available to authorized users.

Purpose The aim of this work was to evaluate the prognostic value of tumor length and diameter for patients with esophageal squamous cell cancer (ESCC) treated with definitive (chemo)radiotherapy to identify potential indicators for separate nonsurgical T staging, which are needed in clinical practice. Materials and Methods A total of 682 patients with ESCC who underwent definitive (chemo)radiotherapy between 2009 and 2015 were reviewed. Esophageal tumor length and diameter were determined by barium esophagography and computed tomography before treatment. Univariate and multivariate analyses were used to assess the impact of tumor length and diameter on long‐term overall survival (OS) and progression‐free survival (PFS). Propensity score matching (PSM) analysis was also used to control intergroup heterogeneity. Results The median OS and PFS were 22.2 months and 15.4 months, respectively, in the tumor length ≤ 6 cm group, which were significantly longer than those in the tumor length > 6 cm group (13.4 and 8.5 months, respectively). The median OS and PFS were 23.3 months and 15.9 months, respectively, in the tumor diameter ≤ 3.5 cm group, which were also significantly longer than those in the tumor diameter > 3.5 cm group (13.3 and 8.8 months, respectively). Similar results were found after PSM. Univariate and multivariate analyses showed that tumor length and diameter were both independent predictors of long‐term survival. Conclusion Tumor length and diameter are both independent prognostic factors for ESCC patients treated with definitive (chemo)radiotherapy. These two imaging parameters have the potential for development and use in nonsurgical T staging., Tumor length and diameter are both independent prognostic factors for esophageal squamous cell cancer patients treated with definitive (chemo)radiotherapy. These two imaging parameters have the potential to develop nonsurgical T staging.

Bursts of 16 femtosecond laser pulses are generated in a fourfold Michelson interferometer with a tunable delay and envelope. Solutions are given to solve the “forward problem” (bursts from a given parameter set) and “inverse problem” (obtain parameter set from a given burst). Three types of bursts are generated experimentally with envelopes suitable for applications in laser materials processing and the generation of terahertz radiation.

Purpose The CRP/albumin (Alb) ratio, a recently reported predictor, has shown value for prognosis in various human cancers. This study aimed to determine the prognostic value of baseline CRP/Alb and to explore the relevance between postchemotherapy CRP/Alb and the efficacy of chemotherapy in advanced pancreatic cancer patients. Patients and methods Five hundred and ninety-five patients diagnosed with locally advanced or metastatic adenocarcinoma of the pancreas were enrolled. Cut-off Finder was used to calculate the best cut‑off value for baseline CRP/Alb. The primary endpoint was overall survival, which was analyzed by Kaplan-Meier survival curves with 95% confidence intervals. The log rank test and Cox proportional hazard model were used to evaluate the univariate and multivariate analyses. Results The optimal cut-off value for baseline CRP/Alb was determined to be 0.18. Both the baseline CRP/Alb (CRP/Alb≥0.18 vs. CRP/Alb

Adjuvant chemotherapy (AC) has been proven to yield an approximately 5% improvement in 5-year survival for patients with early-stage non-small-cell lung cancer. With such small gains in survival, the optimal treatment regimen remains to be established. Traditional Chinese medicine (TCM) treatment in combination with AC is frequently used in China. The efficacy and safety of this integrated approach should be scientifically evaluated. We present the rationale and study design of the Combined Adjuvant Chemotherapy and Traditional Chinese Medicine (ACTCM) trial (ChiCTR-IPR-16009062). The ACTCM trial, a prospective multicenter double-blind randomized placebo-controlled study, will recruit 312 patients overall from 5 clinical research centers in China. Within 6 weeks of the thoracic surgery, eligible participants with stages IB-IIIA non-small-cell lung cancer will be randomly assigned in a 1:1 ratio to either the treatment or control group. Patients in the treatment group will receive AC combined with TCM herbal treatment for 4 cycles, then TCM herbal plus injection treatment for 4 cycles. Patients in the control group will receive AC combined with TCM placebo for 4 cycles and then TCM placebo for 4 cycles. Treatment will be discontinued if disease progression or unacceptable toxicity occurs. The primary end point is 2-year disease-free survival. Secondary end points include disease-free survival and quality of life. Other end points are TCM symptoms, performance status, and safety of the regimens. Recruitment started in October 2016 and is ongoing.

Background Both the 7th and 8th editions of the American Joint Committee on Cancer (AJCC) staging systems have been introduced for pancreatic adenocarcinoma. However, the applicability of these classifications for invasive intraductal papillary mucinous neoplasms (IPMN) has not been systematically examined. Methods Patients with invasive IPMN were retrieved from a cohort of 18 geographical sites (1973–2014 varying) in the Surveillance, Epidemiology, and End Results (SEER) cancer registry. The 7th and 8th editions of the AJCC staging were compared. Survival rates and multivariate analyses were computed. Results In total, 1216 patients with resected invasive IPMN were included. A major difference between the 7th and 8th systems is the definition of stage IIA (7th, beyond the pancreas without involvement of major arteries; 8th, maximum tumor diameter > 4 cm). The hazard ratio (HR) of stage IIA disease (versus stage IA, HR = 2.33, P 2 cm (size > 4 cm versus > 2 ≤ 4 cm, HR = 0.91, P = 0.420). Conclusions The AJCC 7th edition staging classification is more applicable than the 8th edition classification for invasive IPMN.

Background The impact of sex on prognosis of patients with esophageal squamous cell cancer (ESCC) who underwent definitive radiotherapy remained unclear. The present study aimed to determine the impact of sex on the prognosis of patients with ESCC underwent definitive radiotherapy. Methods Between January 2009 and December 2015, patients with ESCC underwent definitive radiotherapy in Shantou Central Hospital were included in this study. The Progression-free survival (PFS) and overall survival (OS) rates were estimated using the Kaplan-Meier method. The PFS and OS were compared between female and male patients. The Cox regression model was used to identify prognostic factors. Propensity score-matched analysis was performed to balance baseline characteristics between female and male patients. Results A total of 683 ESCC patients treated with definitive radiotherapy were included, with 497 male and 186 female patients. In the whole cohort, female patients had a significantly longer median PFS (14.0 months vs 10.6 months, P = 0.0001, HR = 0.688, 95% CI, 0.567–0.836) and OS (20.8 months vs 15.9 months, P = 0.0005, HR = 0.702, 95% CI, 0.575–0.857). In the matched cohort, female patients still had a significantly longer median PFS (13.5 months vs 11.6 months) and OS (19.6 months vs 16.1 months). Multivariate analysis showed that sex was an independent prognostic factor for PFS (HR = 0.746, 95% CI, 0.611–0.910, P = 0.004) and OS (HR = 0.755, 95% CI, 0.615–0.926, P = 0.007). Conclusions This present study indicated that sex was an independent prognostic factor in Chinese patients with ESCC underwent definitive radiotherapy, with better survival outcome for women than men. Efforts should be made to investigate the underlying biological mechanism. Electronic supplementary material The online version of this article (10.1186/s13014-019-1278-0) contains supplementary material, which is available to authorized users.

Background Carbohydrate antigen 19-9 (CA19-9) is the best-validated biomarker for pancreatic cancer. The National Comprehensive Cancer Network (NCCN) guideline asserts that “CA19-9 will be undetectable in Lewis antigen-negative individuals”. However, reports of CA19-9 secretion and its significance in Lewis (-) patients with pancreatic cancer have been inconsistent. This study was to examine serum CA19-9 levels in patients with pancreatic cancer according to Lewis status. Methods Patients with pancreatic cancer (1482 cases) were retrieved from a prospectively maintained database. Patients with benign pancreatic disease (210 cases) and normal subjects (315 cases) were used as controls. Lewis genotypes were examined by fucosyltransferase 3 (FUT3) sequencing. Results In patients with pancreatic cancer, 8.4% of subjects were Lewis (-), but only 41.9% of Lewis (-) subjects had CA19-9 values ≤ 2 U/mL. CA19-9 was even elevated (>37 U/mL) in 27.4% of Lewis (-) patients. The area under the receiver operating characteristic (ROC) curve for CA19-9 as a diagnostic biomarker was 0.842 in Lewis (-) patients with pancreatic cancer, which is closing to that of CA19-9 applied in all of patients with pancreatic cancer (0.898). Lewis (-) status was an independent prognostic factor for shorter survival in a multivariable analysis (hazard ratio (HR), 1.30, 95% confidence interval (CI), 1.03–1.64; P = 0.028). Conclusions Not all Lewis (-) patients with pancreatic cancer are non-secretors of CA19-9. Contrary to general understanding, CA19-9 can retain its utility as a biomarker in these patients in spite of Lewis (-) genotype.

Background The prognostic value of supra-clavicular lymph node (SCLN) metastases in esophageal cancer (EC) is still not clear. Method From January 2009 to December 2015, a survival analysis was performed to retrospectively identify the prognostic value of SCLN metastasis on survival on 751 patients with EC treated with definitive chemo-radiotherapy (dCRT). Results The median follow-up duration for living patients was 56.6 months. The median overall survival (OS) for all patients was 16.6 months. Patients with SCLN metastasis had a much poorer prognosis for OS (χ 2 = 17.342, P

Nowadays, the hospital layout in China is commonly characterized by a large number of crowds on each floor of the inpatient department, a large mobility of patients in and out of hospital, and a complex patient composition. Because of the special composition of crowd and the general particularity of behavior, patients not only have certain physical defects, but also bear greater psychological pressure than normal people. For example, some patients with cardiovascular disease would be nervous when they encounter sudden accidents, and they would not get help for a long time, which is more likely to lead to their aggravation of disease, or even a sudden death. It is assumed that most people will subconsciously show herd behavior when an accident occurs on the inpatient floor. Due to their physiological and psychological defects, patients are more likely to have herd behavior, especially some patients with poor ability of action are relatively weak in escape. Therefore, more professional medical staff are needed to help patients with dysfunction and need to assist in evacuation. In order to optimize the layout of the inpatient department, make the evacuation more smooth and efficient, reduce the overall evacuation time of the inpatient department, and improve the survival rate of patients, this paper mainly studies the single floor of the oncology department of a TCM hospital, draws up the evacuation stairs and fire elevator as the evacuation exit, and uses the Pathfinder model to construct the layout according to the particularity of the inpatient floor and finally obtains a general optimal layout.

Shengming Deng,1– 4,* Zhiyao Fan,1– 4,* Huanyu Xia,1– 4,* Yitao Gong,1– 4 Yunzhen Qian,1– 4 Qiuyi Huang,1– 4 He Cheng,1– 4 Kaizhou Jin,1– 4 Zhiwen Xiao,1– 4 Guopei Luo,1– 4 Xianjun Yu,1– 4 Chen Liu1– 4 1Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, People’s Republic of China; 3Shanghai Pancreatic Cancer Institute, Shanghai, People’s Republic of China; 4Pancreatic Cancer Institute, Fudan University, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Chen Liu; Xianjun YuShanghai Pancreatic Cancer Institute, 270 Dong an Road, Shanghai 200032, People’s Republic of ChinaTel/Fax +86-21-6403-1446Email liuchen@fudanpci.org; yuxianjun@fudanpci.orgBackground: The fibrinogen/albumin ratio (FAR) has been widely reported to be a possible biomarker for predicting prognosis in several types of tumors, but the prognostic value of the FAR in pancreatic neuroendocrine neoplasms (Pan-NENs) has not been systematically studied.Patients and Methods: In total, 324 patients with Pan-NENs were recruited. The patients were divided into 2 subgroups according to the FAR cutoff value, and clinicopathological characteristics of the 2 subgroups were compared. Overall survival (OS) was the primary endpoint, and progression-free survival (PFS) was the secondary endpoint. The prognostic value of the FAR was analyzed in univariate and multivariate analyses.Results: The optimal cutoff value for the FAR was calculated to be 0.08 for OS. The patients with a FAR ≥ 0.08 had higher proportions of nonfunctioning tumors, Pan-NECs, grade 3 tumors, and stage IV tumors than those with a FAR < 0.08. In the univariate analysis, a FAR ≥ 0.08 was associated with poor OS (hazard ratio (HR) = 2.37, P < 0.001) and PFS (HR = 2.37, P < 0.001). In the multivariate analysis, a FAR ≥ 0.08 was an independent risk factor for poor OS (HR = 4.70, P < 0.001) and PFS (HR = 1.80, P = 0.006).Conclusion: The pretreatment FAR, which includes fibrinogen and albumin, was a feasible and predictive biomarker for prognosis in patients with Pan-NENs. An elevated FAR, based on a cutoff value of 0.08, was an independent risk factor for poor OS and PFS.Keywords: pancreatic neuroendocrine neoplasms, survival, fibrinogen/albumin ratio

Background: Pancreatic cancer is a highly fatal disease and is becoming an increasingly common cause of cancer mortality. The extent of pancreatoduodenectomy for pancreatic head cancer is still controversial, and more high-level clinical evidence is needed. We compared the outcomes of standard pancreatoduodenectomy (SPD) with those of radical pancreatoduodenectomy (RPD) with retroperitoneal nerve resection in pancreatic head cancer patients in this multicentre randomized controlled trial. Methods: RAPNER was open-label, multicentre randomised trial, patients aged 18–80 years with stage I or II pancreatic head cancer undergoing curative resection were enrolled at 6 centres from China. Patients were allocated (1:1) by use of a computer-based randomisation service to assigned to receive standard pancreatoduodenectomy (PD) or radical PD, with the latter followed by the combined dissection of additional lymph nodes (LNs), nerves and soft tissues 270° on the right side surrounding the superior mesenteric artery and celiac axis. This trial is registered with Chinese Clinical Trial Registry (http://www.chictr.org.cn), ChiCTR-TRC-12002548. Findings: Between October 3, 2012, and February 15, 2017, 468 patients were enrolled; of these, 400 were randomly assigned to the RPD group (n=201) or the SPD group (n=199). The operation time was longer with RPD than with SPD, but the R1 resection rate was slightly higher in the SPD group (12·56%) than in the RPD group (8·46%). Both the total number of retrieved LNs and number of positive LNs were significantly higher in the RPD group (20 (7-63) and 1 (0-29)) than in the SPD group (15 (7-63) and 1 (0-11)). Both the morbidity and inpatient mortality rates were comparable between the two groups. The median overall survival (OS) of the RPD and SPD groups were 23·0 months and 20·2 months (p=0·100), and the disease-free survival (DFS) were 15·6 months and 13·5 months (p=0·060). In the subgroup with a preoperative CA19-9 level less than 200 U/ml, the median OS in the RPD group was 30·8 months, which was significantly longer than that in the SPD group (20·9 months; p=0·009), and the median DFS was significantly longer in the RPD group than in the SPD group (22·3 months vs. 15·0 months, p=0·002). Furthermore, clinical benefit could be found in the RPD group in the subgroup of well & moderate histological differentiation, preoperative CEA level less than 5·00 ng/ml, R0 resection and postoperative adjuvant chemotherapy based on DFS analysis. A multivariate Cox proportional hazards model showed that initial CA19-9≥200 U/ml, N1 stage and poor differentiation suggested poor OS. Radical resection achieved equivalent prognosis regardless of perineural invasion except for aortic nerve plexus invasion. The RPD group exhibited significantly lower locoregional and mesenteric LN recurrence rates but a higher peritoneal seeding frequency. The RPD group also exhibited significantly less back pain intensity 6 months after surgery than the SPD group. Interpretation: This study suggests that in pancreatic head cancer patients, RPD with retroperitoneal nerve resection does not provide a significant survival benefit compared with SPD. RPD can be performed safely, and be considered a treatment option with improving prognosis for patients with a low chance of systemic metastasis in pancreatic head cancer. Trial Registration: ChiCTR-TRC-12002548. Funding Statement: Sun Yat-sen University Clinical Research 5010 Program (Grant No. 2012007), China; National Natural Science Foundation of China (Grant No. 81871945). Declaration of Interests: We declare no competing interests. Ethics Approval Statement: This study was approved and overseen by the clinical ethics committee of each participating hospital.

Background Glutamine-fructose-6-phosphate transaminase 1 (GFPT1) is the first rate-limiting enzyme of the hexosamine biosynthesis pathway (HBP), which plays a pivotal role in the progression of pancreatic ductal adenocarcinoma (PDAC). Therefore, we investigated the prognostic significance of GFPT1 expression in patients with resectable PDAC. Methods We analyzed public datasets to compare GFPT1 expression in tumor tissues and normal/adjacent pancreatic tissues. We measured the relative GFPT1 expression of 134 resected PDAC specimens in our institution, using real-time polymerase chain reaction (PCR). Survival was compared between high and low GFPT1 expression groups using Kaplan-Meier curves and log-rank tests. Multivariate analyses were estimated using Cox regression and logistic regression models. Results GFPT1 is generally upregulated in PDAC tissues, according to the analysis of public datasets. The data from our institution shows that high GFPT1 expression was correlated with a high rate of lymph node (LN) metastasis (p = 0.038) and was an independent risk factor for LN metastasis (odds ratio (OR) = 3.14, 95% confidence interval (CI) = 1.42 to 6.90, P = 0.005). High GFPT1 expression was significantly associated with poor overall survival (OS; P = 0.019) in patients with resected PDAC. The multivariable-adjusted hazard ratio (HR) for mortality when comparing patients with high and low GFPT1 expression was 2.54 (95% CI = 1.35 to 4.79, P = 0.004). Conclusions GFPT1 is generally upregulated in PDAC tissue and is associated with a high risk of LN metastasis and an unfavorable outcome in patients with resectable PDAC, suggesting its crucial role in PDAC progression.

Objective: To investigate the effectiveness of pain coping skills training in pain, function, and psychological outcomes for patients with osteoarthritis, compared to the control group; and to compare the effectiveness of pain coping skills training between the intervention involving and without involving exercise. Data sources: PubMed, Embase, the Cochrane Library, PEDro, Clinical Trials, and the WHO Clinical Trials Registry Platform (to 30 September 2020). Review methods: To calculate the results, we used standardized mean difference, and mean difference for the outcomes of continuous variables, risk difference for the risk of adverse events. Heterogeneity was identified with I2 test, and publication bias was identified with Egger’s test. Results: A total of 1195 patients with osteoarthritis underwent ten trials were included. The intervention group had significant differences in pain (SMD = −0.18; 95% CI −0.29 to −0.06), function (SMD = −0.19; −0.30 to −0.07), coping attempts (SMD = 0.37; 0.24 to 0.49), pain catastrophizing (SMD = −0.16; −0.29 to −0.02), and self-efficacy (SMD = 0.27; 0.07 to 0.46) than the control group. Between-group differences measured by the McMaster Universities Osteoarthritis Index subscales of pain (MD = −0.62; −1.48 to 0.24) or function (MD = −3.01; −6.26 to 0.24) were not statistically significant and did not reach the minimal clinically important differences that have been established. Subgroup analyses revealed no significant subgroup differences. Besides, no specific intervention-related adverse events were identified. Conclusion: Our results supported the effectiveness and safety of pain coping skills training for managing osteoarthritis in pain, function, and psychological aspects. Besides, exercise could not add benefits when combined with pain coping skills training.

Helical structures exhibit novel optical and mechanical properties and are commonly used in different fields such as metamaterials and microfluidics. A few methods exist for fabricating helical microstructures, but none of them has the throughput or flexibility required for patterning a large surface area with tunable pitch. In this paper, we report a method for fabricating helical structures with adjustable forms over large areas based on multiphoton polymerization (MPP) using single-exposure, three dimensionally structured, self-accelerating, axially tunable light fields. The light fields are generated as a superposition of high-order Bessel modes and have a closed-form expression relating the design of the phase mask to the rotation rate of the beam. The method is used to fabricate helices with different pitches and handedness in the material SU-8. Compared to point-by-point scanning, the method reported here can be used to reduce fabrication time by two orders of magnitude, paving the way for adopting MPP in many industrial applications.

Mucinous cystic neoplasms (MCNs) of the pancreas have malignant potential. Carbohydrate antigen 125 (CA125) is a common widely used biomarker for cancers. However, the role of CA125 in predicting the malignant change of MCNs is currently unidentified. Patients with resected and pathologically confirmed MCN were identified from a prospectively maintained database. The predictive role of serum CA125 in assessing malignant change of MCNs was analyzed and compared with serum carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA). This study included 164 patients with MCN (low/moderate grade, 153 cases; high grade and invasive, 11 cases). The serum levels of CA125 in the high grade and invasive group (45.1±42.1 U/ml) was significantly higher than those in the low/moderate grade group (21.0±46.2 U/ml, P=0.006). The area under the receiver operating characteristic (ROC) curve of CA125 (0.75) for predicting malignancy of MCNs was higher than that of CA19-9 (0.68) or CEA (0.72). The prediction value of CA125 was improved when combined with CEA (CA125 alone, sensitivity 36.4%, specificity 90.6%, accuracy 86.6%; combined with CEA, sensitivity 45.5%, specificity 88.2%, accuracy 85.0%). It was concluded that serum CA125 shows value in predicting the malignant change of MCNs, especially when combined with serum CEA.

We propose and theoretically demonstrate a highly sensitive optofluidic refractive index (RI) sensor based on a spectral filter formed by a segment of liquid-filled seven-hole Teflon-cladding fiber sandwiched by two standard single mode fibers (SMFs). When liquid flows through the air hole channels of the seven-hole Teflon-cladding fiber, it forms a seven-liquid-core fiber (SLCF) and the lightwaves are well guided by the liquid cores owing to total inner reflection. When the input SMF is aligned to the central core of the SLCF, the light excited in the central core will couple to outer cores periodically along the length of the SCLF. At the detection port, the output SMF is also aligned to the central core of the SLCF. Since the coupling coefficient depends on wavelength, the coupling efficiency is also wavelength dependent, leading to a filter spectrum for a given length of the SLCF. The spectral response of the filter to the change in RI of the liquid cores is numerically simulated based on the coupled-mode theory through finite-element method. The dependence of the RI sensitivity on the diameter and pitch of air holes of the SLCF are studied, respectively. Finally, a very high sensitivity of 25,300 nm/RIU for RI around 1.333 is achieved.

Introduction: Increasing evidence suggests that borderline and exercise pulmonary hypertension (PH), bPH and ePH respectively, are associated with increased mortality. bPH and ePH may represent early stages of PH. Micro-RNAs (miRNAs) have been shown to play a key role in the pathophysiology of PH. We sought to identify miRNA signatures for early detection of PH, bPH and ePH. Methods: 245 plasma samples were collected at rest from PH (mPAP >25 mmHg, n=75), bPH (mPAP 21-24 mmHg, n=27), ePH (mPAP 30mmHg with exercise, n=39) and non-PH dyspnea patients (DC, n=104)) and assayed for N-terminal pro b-type natriuretic peptide (NTproBNP) and 600 miRNAs. Samples were randomly partitioned into training and validation sets. MiRNA signatures were generated with or without NTproBNP from the training set for distinguishing DC from PH, bPH, “bPH+ePH”, and “PH+bPH+ePH” and tested on a naive (split-sample) validation set. Results: The average Area Under the Curve (AUC) for miRNA vs. NTproBNP was 0.71 vs. 0.59, 0.60 vs. 0.56, 0.75 vs. 0.70, and 0.74 vs. 0.81 for distinguishing “DC” from “bPH+ePH”, “bPH”, “PH+bPH+ePH”, and “PH”, respectively. Conclusion: miRNA signatures can discriminate early stage disease (bPH and ePH) from DC better than NTproBNP, suggesting that miRNA signatures are capable of identifying the pulmonary vascular disease phenotype before disease progression to PH with significant RV dysfunction.

Objectives Type 2 diabetes mellitus (T2DM) has been associated with several types of cancers, but the role of T2DM in pancreatic neuroendocrine tumors (pNETs) has not been systematically studied. Methods In this study, 299 patients with pNETs were recruited, and the clinicopathologic characteristics and prognosis of the diabetic and nondiabetic patients were compared. The association between metformin use and survival was assessed to examine whether metformin impacts the prognosis of pNETs patients. Results The prevalence of T2DM in the cohort was 20.7% (n = 62). The proportions of grade 3 tumors, distant metastases, and nerve invasion in pNET patients with T2DM were higher than those in patients without T2DM, and as a result, the survival was worse in patients with T2DM. After adjusting for the tumor stage, diabetic status was not associated with poor survival in the univariate analysis. The results of logistic regression showed that pNET patients with T2DM were at high risk for tumor metastasis (odds ratio [OR], 2.81; P = 0.001), nerve invasion (OR, 2.43; P = 0.029), and grade 3 tumors (OR, 4.97; P = 0.010). Conclusions Type 2 diabetes mellitus is associated with pNET metastasis and not an independent risk factor for poor prognosis in pNETs.

Carbohydrate antigen 19-9 (CA19-9) is the best validated biomarker and an indicator of aberrant glycosylation in pancreatic cancer. CA19-9 functions as a biomarker, predictor, and promoter in pancreatic cancer. As a biomarker, the sensitivity is approximately 80%, and the major challenges involve false positives in conditions of inflammation and nonpancreatic cancers and false negatives in Lewis-negative Individuals. Lewis antigen status should be determined when using CA19-9 as a biomarker. CA19-9 has screening potential when combined with symptoms and/or risk factors. As a predictor, CA19-9 could be used to assess stage, prognosis, resectability, recurrence, and therapeutic efficacy. Normal baseline levels of CA19-9 are associated with long-term survival. As a promoter, CA19-9 could be used to evaluate the biology of pancreatic cancer. CA19-9 can accelerate pancreatic cancer progression by glycosylating proteins, binding to E-selectin, strengthening angiogenesis, and mediating the immunological response. CA19-9 is an attractive therapeutic target for cancer, and strategies include therapeutic antibodies and vaccines, CA19-9-guided nanoparticles, and inhibition of CA19-9 biosynthesis.

Hyperglycaemia has been indicated as a pro-tumoural factor; however, the prognostic role of diabetes mellitus (DM) in pancreatic neuroendocrine tumours (panNETs) remains ambiguous, partly due to the effects of anti-diabetic drugs. We hypothesise that the blood sugar level per se affects the outcome of panNETs, and thus, we investigated the prognostic significance of the fasting blood glucose (FBG) level in resected panNET patients with no pre-existing DM. A retrospective cohort study comprising 201 patients with radically resected non-functional panNETs was conducted. A total of 164 patients without pre-existing DM were further studied. An FBG level greater than 5.6 mmol/L was defined as high (otherwise, normal). Survival was evaluated using Kaplan–Meier methods and log-rank tests. Multivariate analyses for survival were performed using the Cox regression model. High FBG levels were significantly associated with poor overall survival (OS; p = 0.019) and recurrence-free survival (RFS; p = 0.011) in resected patients with panNET who had no pre-existing DM. The multivariable-adjusted hazard ratios (HRs) for mortality and recurrence comparing patients with high and normal FBG levels were 12.19 (95% confidence interval (CI) = 1.15–128.78, p = 0.038) and 2.43 (95% CI = 1.03–5.72, p = 0.042), respectively. A pre-operative FBG level greater than 5.6 mmol/L is associated with poor OS and RFS metastasis for patients with panNET who undergo radical surgical resection.

Purpose To explore the clinical significance of perioperative CTCs counts, EMT-CTCs and CTC- white blood cells (WBCs) in renal cancer patients.Materials and Methods A total of 131 patients with renal cancer who underwent operation from the Second Affiliated Hospital of Xi’an Jiaotong University were enrolled. 20 patients with benign renal diseases were used as control. 5 mL Peripheral blood was extracted from 131 patients with renal cancer before operation and about 3 months after operation. Control patients took blood at the corresponding time. CanPatrol CTC detection technique was used to enrich and identify CTCs, EMT-CTCs and CTC-WBCs simultaneously.Results All patients enrolled were T1-3N0M0. 52 renal cancer patients received radical resection, while other 79 patients underwent nephron-sparing surgery. The positive rate of CTC, mesenchymal CTCs (MCTC) and CTC-WBC before surgery were 95.4% (125/131), 61.1% (80/131) and 11.5% (15/131), respectively. Preoperative total CTCs, mesenchymal CTCs or CTC-WBCs were poorly correlated with patients’ parameters. Preoperative CTC, MCTC or CTC-WBC showed little association with progression-free survival (PFS), while post-operation total CTC (≥ 6), positive mesenchymal CTCs and positive CTC-WBC significantly correlated with early recurrence and metastasis, and remained independent indicators for worse PFS. In addition, the elevation of CTC and MCTC after operation were also correlated with unfavourable PFS.Conclusions With the detection of CTCs in peripheral blood, better risk stratification of renal cancer patients might therefore help to identify a subset of patients that might have higher recurrent risk than the overall population of patients.

Highlights • Longitudinal sera were globally analyzed for identification of surgery-associated serum biomarker for the first time. • Autoantibody repertories are stable for a single individual at different time points but highly variable among individuals. • Surgery-associated serum biomarkers are prevalent in lung adenocarcinoma patients., Background Autoantibodies against tumor associated antigens are highly related to cancer progression. Autoantibodies could serve as indicators of tumor burden, and have the potential to monitor the response of treatment and tumor recurrence. However, how the autoantibody repertoire changes in response to cancer treatment are largely unknown. Methods Sera of five lung adenocarcinoma patients before and after surgery, were collected longitudinally. These sera were analyzed on a human proteome microarray of 20,240 recombinant proteins to acquire dynamic autoantibody repertoire in response to surgery, as well as to identify the antigens with decreased antibody response after tumor excision or surgery, named as surgery-associated antigens. The identified candidate antigens were then used to construct focused microarray and validated by longitudinal sera collected from a variety of time points of the same patient and a larger cohort of 45 sera from lung adenocarcinoma patients. Findings The autoantibody profiles are highly variable among patients. Meanwhile, the autoantibody profiles of the sera from the same patient were surprisingly stable for at least 3 months after surgery. Six surgery-associated antigens were identified and validated. All the five patients have at least one surgery-associated antigen, demonstrating this type of biomarkers is prevalent, while specific antigens are poorly shared among individuals. The prevalence of each antigen is 2%–14% according to the test with a larger cohort. Interpretation To our knowledge, this is the first study of dynamically profiling of autoantibody repertoires before/after surgery of cancer patients. The high prevalence of surgery-associated antigens implies the possible broad application for monitoring of tumor recurrence in population, while the low prevalence of specific antigens allows personalized medicine. After the accumulation and analysis of more longitudinal samples, the surgery-associated serum biomarkers, combined as a panel, may be applied to alarm the recurrence of tumor in a personalized manner. Funding Research supported by grants from National Key Research and Development Program of China Grant (No. 2016YFA0500600), National Natural Science Foundation of China (No. 31970130, 31600672, 31670831, and 31370813), Open Foundation of Key Laboratory of Systems Biomedicine (No. KLSB2017QN-01), Science and Technology Commission of Shanghai Municipality Medical Guidance Science &Technology Support Project (16411966100), Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20172005), Shanghai Municipal Commission of Health and Family Planning Outstanding Academic Leaders Training Program (2017BR055) and National Natural Science Foundation of China (81871882).

Cross-regional collaborative innovation is the inevitable choice for the in-depth development of the integration of regional economics. Based on the existing bibliography, this paper provides a systematic and brief review on the studies and progress related to inter-regional collaborative innovation from three aspects, including the multidimensional proximity, knowledge and technology transfer, and innovation clusters. This paper also offers recommendations for future studies, concerning the role of government in the collaborative system, national innovation platform’s construction and operation mechanism, measuring effectiveness of cross-regional collaborative innovation.

Objectives We aimed to evaluate whether carboplatin has a comparable efficacy with cisplatin as part of weekly concurrent chemoradiotherapy for cervical cancer (Car-RT vs. Cis-RT). Methods A literature search was conducted and both prospective and retrospective studies that evaluated the efficacy of Car-RT for cervical cancer were included. The primary endpoints were complete response (CR) rate, progression-free survival (PFS)/disease-free survival (DFS), overall survival (OS), reported as odds ratios (ORs) and 95% confidence intervals (CIs). The estimated CR rate and survival of patients treated with Car-RT were pooled. Acute toxicity was also summarized. Results Twelve studies consisting of 1698 patients were eligible for meta-analysis. A lower CR rate (OR, 0.53; 95% CI, 0.34–0.82, I2 = 0%) and a trend toward poorer 3-year PFS/DFS (OR, 0.71; 95% CI, 0.49–1.02, I2 = 0%) and 3-year OS (OR, 0.70; 95% CI, 0.46–1.05, I2 = 36%) were found in Car-RT compared with Cis-RT. For the Car-RT groups, the pooled overall CR rate was 81% (95% CI 0.74–0.89). The pooled 3-year PFS/DFS rate was 64% (95% CI 0.52–0.78). The pooled 3-year OS rate was 73% (95% CI 0.62–0.87). Acute toxic events ≥ grade 3 were infrequent in the Car-RT groups. Conclusions Car-RT showed a poorer tumor response and a trend toward inferior survival compared with Cis-RT in the treatment of cervical cancer. However, this evidence was limited by the imbalance among studies. Due to the encouraging efficacy and low toxicity, carboplatin is a suitable concurrent agent for patients with contraindications to cisplatin.

Natural killer cells (NK) are often believed to play a positive role in the antitumor immune response. However, this is not the case for patients with advanced pancreatic cancer. This study was performed to determine the unique subtype of “educated” NK cells and their prognostic value in patients with advanced pancreatic cancer. We divided 378 eligible patients into a derivation cohort (September 2010 to December 2014, n = 239) and a validation cohort (January 2015 to April 2016, n = 139). Flow cytometry was performed to analyze NK cells. Enzyme-linked immunosorbent assay was used to detect interleukin-2 (IL-2), interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) production. The Kaplan–Meier method and the Cox proportional hazards model were used. Survival analysis showed that a high density of NK cells accompanied by a high neutrophil-to-lymphocyte ratio was associated with reduced overall survival in both the derivation and validation cohorts. Multivariable analysis also showed that high NK infiltration (HR 1.45, 95% CI 1.17 to 1.79, p = 0.001) was an independent prognostic factor. In these patients, high NK infiltration was associated with reduced levels of IL-2, IFN-γ and TNF-α, although only IFN-γ reached statistical significance, which accounted for this unique phenomenon. Natural killer cells in patients with advanced pancreatic cancer are a unique subtype with anergic features. A high density of NKs predicts poor survival in these patients, possibly because an active inflammatory response and reduced secretion of IL-2, IFN-γ and TNF-α inhibit NK activation.

Many inflammatory markers can be used for the prognostication of pancreatic cancer, but which combination of inflammatory factors may be the best remains unclear. This study focused on the potential feasibility of the newly discovered C-reactive protein (CRP)/lymphocyte ratio (CLR) as a prognostic biomarker for patients with pancreatic cancer. The study enrolled 997 patients with pancreatic cancer. Six combinations of inflammatory markers, namely, the neutrophil/lymphocyte ratio (NLR), the platelet/lymphocyte ratio (PLR), the CRP/albumin ratio (CAR), the neutrophil/albumin ratio (NAR), the platelet/albumin ratio (PAR), and CLR, were examined to determine which combination offers the highest accuracy for predicting poor survival by receiver operating characteristic curve analysis. The prognostic value of the CLR was analyzed by uni- and multivariate analyses. The newly developed CLR was more accurate than the NLR, PLR, CAR, NAR, and PAR in predicting survival. The optimal cutoff value for the CLR was calculated to be 1.8 for survival. A CLR higher than 1.8 was associated with poor survival in both the univariate (hazard ratio [HR] 2.00; P

This paper presents an electrified powertrain including the switched reluctance generator (SRG), the switched reluctance motor (SRM) and the corresponding integrated power converters for series hybrid electric vehicle (HEV). Five driving modes for the series HEV are implemented according to the state-of-charge (SOC) of battery bank and road conditions. The corresponding control strategies are proposed for the electric drive system to achieve different driving modes. The experiments are carried out to verify the effectiveness of proposed integrated powertrain and the control schemes.

Pancreatic cancer is the most lethal tumor. CA125 (gene symbol MUC16) is an important serum marker for pancreatic cancer diagnosis and treatment. High serum CA125 is related to metabolic tumor burden and poor prognosis. The circulating Treg subset is another independent prognostic factor for pancreatic cancer. Our unpublished data indicated that the circulating Treg proportion might be related to the serum CA125 level. However, the potential relationship and underlying mechanism of MUC16 and Treg in pancreatic cancer tissues remain unclear. In this study, we found that pancreatic cancer tissues were positive for both MUC16 C terminal (MUC16c) and Foxp3 expression and that their expression was correlated. MUC16c released into the cytoplasm via EGF induction significantly increased IL-6 expression and secretion. The PI3K/AKT pathway may participate in the regulation of IL-6 expression and secretion. By treating CD4+ T cells with IL-6 or co-culturing the cells with pancreatic cancer cells, tumor-derived IL-6 was identified to promote Foxp3 expression and Treg differentiation, which was significantly inhibited by the JAK2 inhibitor AG-490. In sum, our study demonstrated that the relationship between the MUC16c level and Foxp3 expression in the local tumor environment was consistent with that of the serum CA125 level and circulating Treg proportion in the systemic environment. MUC16c promoted Foxp3 expression and tumor-associated Treg enrichment in tumor tissues through tumor-secreted IL-6 activation of the JAK2/STAT3 pathway. These findings may provide deeper insight into potential pancreatic cancer therapy approaches.

Most patients with pancreatic cancer are not diagnosed until the disease develops to an advanced stage. It is essential to evaluate tumor response because some patients benefit from a particular therapy, while others do not. Evaluating therapeutic response is crucial to achieve the maximum possible benefit. However, the current criteria for evaluating tumor response requires at least two months after the initial treatment, and by that time, some patients have progressed to an untreatable stage. Thus, robust early response biomarkers, or predictive markers, are required to personalize treatment. In this review, we summarize the novel potential biomarkers for the evaluation of therapeutic response in advanced pancreatic cancer. The biomarkers are categorized into seven groups: serum tumor biomarkers, inflammation markers, circulating tumor cells (CTC) and DNA, non-coding RNA, exosomes, DNA methylation, and other markers. These markers may serve as potential criteria to use in the evaluation of treatment response. Advances in the understanding of the molecular events in tumorigenesis and proliferation have identified potential biomarkers that could be used to evaluate therapeutic responses. A major obstacle, however, is integrating these markers into a system, such as a scoring system, which would be more powerful than evaluating with a single biomarker.