Mechanism of chain propagation for the synthesis of polyoxymethylene dimethyl ethers

Polyoxymethylene dimethyl ethers(PODE)were synthesized from the reaction of paraformaldehyde with dimethoxymethane(DMM)over different acid catalysts at different conditions.Products were found to follow the Schulz-Flory distribution law.The chain propagation proceeds through the insertion of an individual segment of CH2O one by one,while the simultaneous insertion of a few CH2O segments or their assembly is unlikely.Due to the restriction of this law,it is difficult to increase the selectivity to the desired products(e.g.,PODE3 4).

Pancreatic head cancer: Open or minimally invasive pancreaticoduodenectomy?

Pancreatic head cancer still represents an insurmountable barrier for patients and pancreatic surgeons.Pancreaticoduodenectomy(PD)continues to be the operative standard of care and potentially curative procedure for pancreatic head cancer.Despite the rapid development of minimally invasive techniques,whether the efficacy of minimally invasive pancreaticoduodenectomy(MIPD)is noninferior or superior to open pancreaticoduodenectomy(OPD)remains unclear.In this review,we summarized the history of OPD and MIPD and the latest staging and classification information for pancreatic head cancer as well as the proposed recommendations for MIPD indications for patients with pancreatic head cancer.By reviewing the MIPD-vs.OPD-related literature,we found that MIPD shows noninferiority or superiority to OPD in terms of safety,feasibility,enhanced recovery after surgery(ERAS)and several short-term and long-term outcomes.In addition,we analyzed and summarized the different MIPD outcomes in the USA,Europe and China.Certain debates over MIPD have continued,however,selection bias,the large number of low-volume centers,the steep MIPD learning curve,high conversion rate and administration of neoadjuvant therapy may limit the application of MIPD for pancreatic head cancer.

Novel technologies in cfDNA analysis and potential utility in clinic

The profiling of plasma cell-free DNA(cfDNA)is becoming a valuable tool rapidly for tumor diagnosis,monitoring and prognosis.Diverse plasma cfDNA technologies have been in routine or emerging use,including analyses of mutations,copy number alterations,gene fusions and DNA methylation.Recently,new technologies in cfDNA analysis have been developed in laboratories,and potentially reflect the status of epigenetic modification,the immune microenvironment and the microbiome in tumor tissues.In this review,the authors discuss the principles,methods and effects of the current cfDNA assays and provide an overview of studies that may inform clinical applications in the near future.

Analysis of clinical characteristics and treatment of pancreatic cystic tumors

Objective： To summarize experience in the diagnosis and treatment of pancreatic cystic neoplasms.Methods： This is a retrospective study of 207 patients who were diagnosed with pancreatic cystic tumors at Peking Union Medical College Hospital between Jan 2009 and Mar 2014. Clinical data, such as clinical manifestations, radiologieal and pathological images and surgical recordings, were collected. Results： Of the 207 included patients, females accounted for 76.81%, and the mean patient age was 52.04 years. Malignancy was more common in older patients who presented with marasmus and jaundice. Other risk factors included solid components in the tumor, a large tumor size, and elevated levels of tumor markers. Surgical treatment was required when a malignant tumor was suspected. The operation approach was selected based on the location, size and characteristics of the tumor. The position of the tumor relative to the pancreatic duct also played a significant role.

Sulfonated carbon materials with hydrophilic and lipophilic properties

Two acidic carbon materials （H-PRC and HS-C） were used as catalysts for the condensation reaction of methanol with formaldehyde to produce dimethoxymethane （DMM） in aqueous solution （hydrophilic system） and for the etherification of isopentene with methanol to produce tert amyl methyl ether （TAME） in toluene solution （lipophilic system）. Microcalorimetric adsorptions of water and benzene showed that the HS-C was highly hydrophilic without the lipophilicity, while the H-PRC exhibited both the hydrophilicity and lipophilicity. Thus, the HS-C was well dispersed in aqueous solution and difficult to separate from it. On the other hand, the H-PRC was highly active, more active than the acidic resin （D008） and sulfuric acid, for the synthesis of DMM in aqueous solution. The H-PRC was also highly active, more active than the HS-C, for the etherification of isopentene with methanol to produce TAME in toluene solution, probably owing to its amphiphilic surface property as well as its strong surface acidity as measured by the microcalorirnetric adsorption of NH3.

Surgical treatment of pancreatic head cancer: concept revolutions and arguments

As we have a deeper and more thorough understanding of the biological behavior of pancreatic head cancer, surgical treatment concepts of this lethal disease are changing all the time. Meanwhile, numerous arguments emerge. Thus, we will probe into the focuses and arguments in the surgical treatment of pancreatic head cancer in this article, including the scope of lymphadenectomy, total mesopancreas excision（TMp E）, vascular resection, minimally invasive pancreaticoduodenectomy（PD）, palliative resection, surgery for recurrent disease and surgery for primary pancreatic cancer and liver metastasis.

International consensus guidelines on robotic pancreatic surgery in 2023

Background:With the rapid development of robotic surgery,especially for the abdominal surgery,robotic pancreatic surgery(RPS)has been applied increasingly around the world.However,evidence-based guidelines regarding its application,safety,and efficacy are still lacking.To harvest robust evidence and comprehensive clinical practice,this study aims to develop international guidelines on the use of RPS.Methods:World Health Organization(WHO)Handbook for Guideline Development,GRADE Grid method,Delphi vote,and the AGREE-II instrument were used to establish the Guideline Steering Group,Guideline Development Group,and Guideline Secretary Group,formulate 19 clinical questions,develop the recommendations,and draft the guidelines.Three online meetings were held on 04/12/2020,30/11/2021,and 25/01/2022 to vote on the recommendations and get advice and suggestions from all involved experts.All the experts focusing on minimally invasive surgery from America,Europe and Oceania made great contributions to this consensus guideline.Results:After a systematic literature review 176 studies were included,19 questions were addressed and 14 recommendations were developed through the expert assessment and comprehensive judgment of the quality and credibility of the evidence.Conclusions:The international RPS guidelines can guide current practice for surgeons,patients,medical societies,hospital administrators,and related social communities.Further randomized trials are required to determine the added value of RPS as compared to open and laparoscopic surgery.

Comprehensive multi-omics profiling identifies novel molecular subtypes of pancreatic ductal adenocarcinoma

Pancreatic cancer,a highly fatal malignancy,is predicted to rank as the second leading cause of cancer-related death in the next decade.This highlights the urgent need for new insights into personalized diagnosis and treatment.Although molecular subtypes of pancreatic cancer were well established in genomics and transcriptomics,few known molec-ular classifications are translated to guide clinical strategies and require a paradigm shift.Notably,chronically developing and continuously improving high-throughput technologies and systems serve as an important driving force to further portray the molecular landscape of pancreatic cancer in terms of epigenomics,proteomics,metabonomics,and metagenomics.Therefore,a more comprehensive understanding of molecular classifications at multiple levels using an integrated multi-omics approach holds great promise to exploit more potential ther-apeutic options.In this review,we recapitulated the molecular spectrum from different omics levels,discussed various subtypes on multi-omics means to move one step forward towards bench-to-beside translation of pancreatic cancer with clinical impact,and proposed some methodological andscientific challengesinstore.

Uncovering chromatin accessibility and cancer diagnostic potential via cell-free DNA utilization

Gene expression patterns of tumor cells can be inferred from features of circulating cell-free DNA(cfDNA),such as histone modifications and fragmentation patterns at promoters.However,the direct relationship between cfDNA patterns and tumor-specific chromatin accessibility has not yet been experimentally established,limiting its current application to cancer diagnosis alone.

Immune-related signature identifies IL1R2 as an immunological and prognostic biomarker in pancreatic cancer

Objective:Pancreatic cancer is one of the most aggressive malignancies,a robust prognostic signature and novel biomarkers are urgently needed for accurate stratification of the patients and optimization of clinical decision-making.Methods:A list of bioinformatic analysis were applied in public dataset to construct an immune-related signature.Furthermore,the most pivotal gene in the signature was identified.The potential mechanism of the core gene function was revealed through GSEA,CIBERSORT,ESTIMATE,immunophenoscore(IPS)algorithm,single-cell analysis,and functional experiment.Results:An immune-related prognostic signature and associated nomogram were constructed and validated.Among the genes constituting the signature,interleukin 1 receptor type II(IL1R2)was identified as the gene occupying the most paramount position in the risk signature.Meanwhile,knockdown of IL1R2 significantly inhibited the proliferation,invasion,and migration ability of pancreatic cancer cells.Additionally,high IL1R2 expression was associated with reduced CD8+T cell infiltration in pancreatic cancer microenvironment,which may be due to high programmed cell death-ligand-1(PD-L1)expression in cancer cells.Finally,the IPS algorithm proved that patients with high IL1R2 expression possessed a higher tumor mutation burden and a higher probability of benefiting from immunotherapy.Conclusion:In conclusion,our study constructed an efficient immune-related prognostic signature and identified the key role of IL1R2 in the development of pancreatic cancer,as well as its potential to serve as a biomarker for immunotherapy efficacy prediction for pancreatic cancer.

Consensus on the clinical diagnosis and treatment of grade 3 pancreatic neuroendocrine tumors

The World Health Organization(WHO)2017 classifications for neuroendocrine neoplasms(NENs)subdivided grade 3 pancreatic neuroendocrine neoplasms(pNENs)into G3 well-differentiated pancreatic neuroendocrine tumors(G3 pNETs)and poorly differentiated pancreatic neuroendocrine carcinomas(pNECs),according to the mitotic count,Ki-67 index,and cell differentiation.As a new category,G3 pNETs remain a challenging group of tumors to manage by lacking large randomized trials and consensus to support its clinical practice.Therefore,the Chinese Pancreatic Surgery Association,Chinese Society of Surgery,Chinese Medical Association gathered experts in this field to formulate this consensus for the diagnosis and treatment of G3 pNETs.

Introducing Covalent Metal-Phosphorus Bonds into Intermetallic Platinum-Based Catalysts for High-Performance Fuel Cells

The inadequate performance of oxygen reduction reaction(ORR)catalysts hampers the development of proton exchange membrane fuel cells(PEMFCs).Herein,we proposed an approach to tackle this problem by modulating the chemical bond type of intermetallic Pt-based catalysts,using phosphorus(P)doped L1_(0)-PtFeGa_(0.1)/C(P-L1_(0)-PtFeGa_(0.1)/C)as a proof of concept.X-ray absorption spectroscopy(XAS)demonstrated that the doped P transferred electrons to Pt,and thus,modified the electronic structure of Pt,weakening the adsorption strength with oxygen-containing species.Therefore P-L1_(0)-PtFeGa_(0.1)/C showed 13 times mass activity(MA)compared with commercial Pt/C,with a decay of only 28%after 100,000 potential cycles.When equipped in the membrane electrode assembly,the P-L1_(0)-PtFeGa_(0.1)/C catalyst also exhibited a remarkable activity(MA=0.84 A mgPt^(−1)at 0.9 V)and stability(MA retention=72%and voltage loss=9 mVat 0.8 A cm^(−2)after 30,000 cycles),making it one of the best performers among recorded Pt-based catalysts.Theoretical studies demonstrated that the doping of P optimized the adsorption energy between Pt and oxygen intermediates through sp-d orbital interactions and prevented metal dissolution by forming stronger Pt-P covalent bonds compared with Pt–Pt bonds.

Metformin inhibits pancreatic cancer metastasis caused by SMAD4 deficiency and consequent HNF4G upregulation

Pancreatic ductal adenocarcinoma(PDAC)has poor prognosis due to limited therapeutic options.This study examines the roles of genome-wide association study identified PDAC-associated genes as therapeutic targets.We have identified HNF4G gene whose silencing most effectively repressed PDAC cell invasiveness.HNF4G overexpression is induced by the deficiency of transcriptional factor and tumor suppressor SMAD4.Increased HNF4G are correlated with SMAD4 deficiency in PDAC tumor samples and associated with metastasis and poor survival time in xenograft animal model and in patients with PDAC(log-rank P=0.036;HR=1.60,95%CI=1.03–2.47).We have found that Metformin suppresses HNF4G activity via AMPK-mediated phosphorylation-coupled ubiquitination degradation and inhibits in vitro invasion and in vivo metastasis of PDAC cells with SMAD4 deficiency.Furthermore,Metformin treatment significantly improve clinical outcomes and survival in patients with SMAD4-deficient PDAC(log-rank P=0.022;HR=0.31,95%CI=0.14–0.68)but not in patients with SMAD4-normal PDAC.Pathway analysis shows that HNF4G may act in PDAC through the cell-cell junction pathway.These results indicate that SMAD4 deficiency-induced overexpression of HNF4G plays a critical oncogenic role in PDAC progression and metastasis but may form a druggable target for Metformin treatment.

International expert consensus on laparoscopic pancreaticoduodenectomy

Importance:While laparoscopic pancreaticoduodenectomy(LPD)is being adopted with increasing enthusiasm worldwide,it is still challenging for both technical and anatomical reasons.Currently,there is no consensus on the technical standards for LPD.Objective:The aim of this consensus statement is to guide the continued safe progression and adoption of LPD.Evidence Review:An international panel of experts was selected based on their clinical and scientific expertise in laparoscopic and open pancreaticoduodenectomy.Statements were produced upon reviewing the literature and assessed by the members of the expert panel.The literature search and its critical appraisal were limited to articles published in English during the period from 1994 to 2019.The Web of Science,Medline,and Cochrane Library and Clinical Trials databases were searched,The search strategy included,but was not limited to,the terms'laparoscopic','pancreaticoduodenectomy,'pancreatoduodenectomy','Whipple's operation',and'minimally invasive surgery'.Reference lists from the included articles were manually checked for any additional studies,which were included when appropriate.Delphi method was used to establish expert consensus and the AGREE II-GRS Instrument was applied to assess the methodological quality and externally validate the final statements.The statements were further discussed during a one-day face-to-face meeting at the 1st Summit on Minimally Invasive Pancreatico-Biliary Surgery in Wuhan,China.Findings:Twenty-eight international experts from 8 countries constructed the expert panel.Sixteen statements were produced by the members of the expert panel.At least 80%of responders agreed with the majority(80%)of statements.Other than three randomized controlled trials published to date,most evidences were based on level 3 or 4 studies according to the AGREE II-GRS Instrument.Conclusions and Relevance:The Wuhan international expert consensus meeting on LPD has produced a set of clinical practice statements for the safe development and progression of LPD.LPD is currently in its development and exploration stages,as defined by the international IDEAL framework for surgical innovation.More robust randomized controlled trial and registry study are essential to proceed with the assessment of LPD.

Real-world study of surgical treatment of pancreatic cancer in China: annual report of China Pancreas Data Center (2016-2020)

Objective: In 2015, the Chinese Pancreatic Association of the Chinese Society of Surgery of the Chinese Medical Association launched a national multicenter online system for registration of surgical treatment of pancreatic cancer in China, called China Pancreas Data Center (CPDC). With continued effort, the CPDC has developed over time. Herein, we report the general results of the CPDC from January 2016 to January 2020 to present the real-world situation of surgical treatment of pancreatic cancer in China.Methods: The data of the CPDC from January 2016 to January 2020 were retrieved and analyzed in this real-world study, including the data on patient demographics, comorbidities, diagnostic modalities, neoadjuvant treatment, surgical procedures, postoperative complications and treatment, pathological examinations, postoperative adjuvant treatment, survival, and risk factors.Results: A total of 13,595 cases from 70 centers in 28 provinces were retrieved for analysis. This study reported the largest cohort of patients who underwent surgical treatment for pancreatic cancer in China to date. More cases were derived from the Eastern regions, among which Shanghai, Beijing, and Zhejiang ranked in the top three. The peak age of the patients ranged from 60 to 69 years. The ratio of males to females was 1.5:1. Overall, 64.3% of the tumors were located in the head and neck of the pancreas, and 35.7% in the body and tail of the pancreas. Of the patients, 23.0% underwent positron-emission tomography-computed tomography, 21.6% underwent endoscopic ultrasound, and 4.8% underwent preoperative biopsy. Two percent of the patients underwent neoadjuvant treatment, while 68.9% underwent R0 surgical resection (margin free of tumor cells). Of the latter, 78.6% of the operations were open procedures, 12.6% were laparoscopic procedures, 2.9% were robotic procedures, and 3.7% were converted to open procedures. The in-hospital mortality rate after surgery was 0.4%. The incidence of grade 2 and grade 3 postoperative pancreatic fistulas was 25.5% and 2.5%, respectively. The incidence of complications based on the Clavien-Dindo classification was 17.9% of grade II, 4.3% of grade IIIa, 1% of grade IIIb, and 0.6% of grade IV. Of the patients, 28.9% underwent postoperative adjuvant chemotherapy. The 1-year, 2-year, and 3-year overall survival of these patients were 77%, 51%, and 38%, respectively. In the 8542 patients who underwent R0 resection, the 1-year, 2-year, and 3-year overall survival and disease-free survival were 77% , 54%, and 43%, and 68%, 49%, and 41%, respectively. The factors related to the prognosis of these patients were also identified after uni-and multi-variate analyses.Conclusion: The surgical quality, safety, and long-term survival of the patients in CPDC are similar to those of international high-volume pancreatic centers. However, neoadjuvant and postoperative adjuvant chemotherapy should be improved.

Mechanisms of obesity-and diabetes mellitus-related pancreatic carcinogenesis:a comprehensive and systematic

Research on obesity-and diabetes mellitus(DM)-related carcinogenesis has expanded exponentially since these two diseases were recognized as important risk factors for cancers.The growing interest in this area is prominently actuated by the increasing obesity and DM prevalence,which is partially responsible for the slight but constant increase in pancreatic cancer(PC)occurrence.PC is a highly lethal malignancy characterized by its insidious symptoms,delayed diagnosis,and devastating prognosis.The intricate process of obesity and DM promoting pancreatic carcinogenesis involves their local impact on the pancreas and concurrent wholebody systemic changes that are suitable for cancer initiation.The main mechanisms involved in this process include the excessive accumulation of various nutrients and metabolites promoting carcinogenesis directly while also aggravating mutagenic and carcinogenic metabolic disorders by affecting multiple pathways.Detrimental alterations in gastrointestinal and sex hormone levels and microbiome dysfunction further compromise immunometabolic regulation and contribute to the establishment of an immunosuppressive tumor microenvironment(TME)for carcinogenesis,which can be exacerbated by several crucial pathophysiological processes and TME components,such as autophagy,endoplasmic reticulum stress,oxidative stress,epithelialmesenchymal transition,and exosome secretion.This review provides a comprehensive and critical analysis of the immunometabolic mechanisms of obesity-and DM-related pancreatic carcinogenesis and dissects how metabolic disorders impair anticancer immunity and influence pathophysiological processes to favor cancer initiation.

The role of histone methylation in the development of digestive cancers:a potential direction for cancer management

Digestive cancers are the leading cause of cancer-related death worldwide and have high risks of morbidity and mortality.Histone methylation,which is mediated mainly by lysine methyltransferases,lysine demethylases,and protein arginine methyltransferases,has emerged as an essential mechanism regulating pathological processes in digestive cancers.Under certain conditions,aberrant expression of these modifiers leads to abnormal histone methylation or demethylation in the corresponding cancer-related genes,which contributes to different processes and phenotypes,such as carcinogenesis,proliferation,metabolic reprogramming,epithelial–mesenchymal transition,invasion,and migration,during digestive cancer development.In this review,we focus on the association between histone methylation regulation and the development of digestive cancers,including gastric cancer,liver cancer,pancreatic cancer,and colorectal cancer,as well as on its clinical application prospects,aiming to provide a new perspective on the management of digestive cancers.

International consensus statement on robotic pancreatic surgery

The robotic surgical system has been applied to various types of pancreatic surgery. However, controversies exist regarding a variety of factors including the safety, feasibility, efficacy, and cost-effectiveness of robotic surgery. This study aimed to evaluate the current status of robotic pancreatic surgery and put forth experts' consensus and recommendations to promote its development. Based on the WHO Handbook for Guideline Development, a Consensus Steering Group* and a Consensus Development Group were established to determine the topics, prepare evidence-based documents, and generate recommendations. The GRADE Grid method and Delphi vote were used to formulate the recommendations. A total of 19 topics were analyzed. The first 16 recommendations were generated by GRADE using an evidence-based method (EBM) and focused on the safety, feasibility, indication, techniques, certification of the robotic surgeon, and cost-effectiveness of robotic pancreatic surgery. The remaining three recommendations were based on literature review and expert panel opinion due to insufficient EBM results. Since the current amount of;evidence was low/meager as evaluated by the GRADE method, further randomized controlled trials (RCTs) are needed in the future to validate these recommendations.

Integrated analysis of gene expression and methylation profiles of novel pancreatic cancer cell lines with highly metastatic activity

Pancreatic cancer is one of the most lethal human malignancies, partly because of its propensity for metastasis. However, highly metastatic human pancreatic cancer cell lines suitable for studies of metastasis are currently lacking. Here we established two highly metastatic human pancreatic cancer cell lines, MIA PaCa-2 In8 and Panc-1 In8, by Matrigel induction assay. The cell lines were further characterized both in vitro and in vivo. MIA PaCa-2 In8 and Panc-1 In8 cells demonstrated increased migration and invasion compared with their respective parental cells. Following injection into nude mice, MIA PaCa-2 In8 and Panc-1 In8 cells resulted in more pulmonary metastases compared with the parental cells. Furthermore, analyses of m RNA, long non-coding RNA, micro RNA, and methylation profiling revealed that these factors were aberrantly regulated in the highly metastatic cells,indicating that they probably affected metastasis. We thus established and characterized two highly metastatic human pancreatic cell lines that could be used as valuable tools for future investigations into the pathogenesis, metastasis, and potential treatment of human pancreatic cancer.

Guidelines for the diagnosis and treatment of acute pancreatitis in China (2021)

Acute pancreatitis(AP)is a common acute abdominal condition of the digestive system.In recent years,treatment concepts,methods,and strategies for the diagnosis of AP have advanced,and this has played an important role in promoting the standardization of AP diagnosis and treatment and improving the treatment quality of AP patients.On the basis of previous guidelines and expert consensus,this guideline adopts an evidence-based,problem-based expression;synthesizes important clinical research data at home and abroad in the most recent 5 years;and forms 29 recommendations through multidisciplinary expert discussion,including diagnosis,treatment,and follow-up.It is expected to provide evidence support for the treatment of AP in the clinical setting in China.