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management of borderline and locally advanced pancreatic cancer:Where do we stand?

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World Journal of Gastroenterology 2014年第9期20卷 2255-2266页

作者： Jin He Andrew J Page matthew Weiss Christopher L Wolfgang joseph m herman Timothy m Pawlik Department of Surgery Johns Hopkins Hospital Baltimore MD 21287 United States Department of Radiation Oncology Johns Hopkins Hospital Baltimore MD 21287 United States

many patients with pancreas cancer present with locally advanced pancreatic cancer(LAPC).The principle tools used for diagnosis and staging of LAPC include endoscopic ultrasound,axial imaging with computed tomography and magnetic resonance imaging,and diagnostic *** definition of resectability has historically been vague,as there is considerable debate and controversy as to the definition of *** the patient with LAPC,there is some level of involvement of the surrounding vascular structures,which include the superior mesenteric artery,celiac axis,hepatic artery,superior mesenteric vein,or portal *** feasible,most surgeons would recommend possible surgical resection for patients with borderline LAPC,with the goal of an R0 *** initially unresectable LAPC,neoadjuvant should be strongly ***,these patients should be offered neoadjuvant therapy,and the tumor should be assessed for possible response and eventual *** efficacy of neoadjuvant therapy with this approach as a bridge to potential curative resection is broad,ranging from 3%-79%.The different modalities of neoadjuvant therapy include sin-gle or multi-agent chemotherapy combined with radiation,chemotherapy alone,and chemotherapy followed by chemotherapy with *** review focuses on patients with LAPC and addresses recent advances and controversies in the field.

关键词： Pancreas Locally advanced Chemotherapy Radiation Irreversible electroporation Pancreatic cancer

Strategies to tackle the challenges of external beam radiotherapy for liver tumors

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World Journal of Hepatology 2017年第14期9卷 645-656页

作者： michael I Lock Jonathan Klein Hans T Chung joseph m herman Edward Y Kim William Small Nina A mayr Simon S Lo Department of Radiation Oncology London Regional Cancer ProgramUniversity of Western Ontario Department of Radiation Oncology Odette Cancer CentreSunnybrook Health Sciences Centre Department of Radiation Oncology the University of Texas Department of Radiation Oncology University of Washington School of Medicine Department of Radiation Oncology Loyola University Medical Center

Primary and metastatic liver cancer is an increasingly common and difficult to control disease *** offers a non-invasive treatment alternative for these patients who often have few options and a poor ***,the anatomy and aggressiveness of liver cancer poses significant challenges such as accurate localization at simulation and treatment,management of motion and appropriate selection of dose *** article aims to review the options available and provide information for the practical implementation and/or improvement of liver cancer radiation programs within the context of stereotactic body radiotherapy and image-guided radiotherapy *** patient inclusion and exclusion criteria are presented given the significant toxicity found in certain sub-populations treated with ***,certain sub-populations,such as those with tumor thrombosis or those with larger lesions treated with transarterial chemoembolization,have been shown to have significant improvements in outcome with the addition of radiation and merit special *** a liver radiation programrequires three primary challenges to be addressed:(1) immobilization and motion management;(2) localization;and(3) dose regimen and constraint *** to deal with motion include simple internal target volume(ITV) expansions,non-gated ITV reduction strategies,breath hold methods,and surrogate marker methods to enable gating or *** of the tumor and organs-at-risk are addressed using contrast infusion techniques to take advantage of different normal liver and cancer vascular anatomy,imaging modalities,and margin ***,a dose response has been demonstrated and dose regimens appear to be converging.A more uniform approach to treatment in terms of technique,dose selection and patient selection will allow us to study liver radiation in larger and,hopefully,multicenter randomized studies.

关键词： Hepatocellular carcinoma Liver metastases 4DCT Image-guided radiotherapy Stereotactic body radiation therapy

monogenic diabetes in children:An underdiagnosed and poorly managed clinical dilemma

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World Journal of Diabetes 2024年第6期15卷 1051-1059页

作者： Saptarshi Bhattacharya joseph m Pappachan Department of Endocrinology Indraprastha Apollo HospitalsDelhi 110076India Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom

monogenic diabetes,constituting 1%-2%of global diabetes cases,arises from single gene defects with distinctive inheritance *** over 50 associated genetic disorders,accurate diagnoses and management of monogenic diabetes remain inadequate,underscoring insufficient clinician *** disease spectrum encompasses maturity-onset diabetes of the young(mODY),characterized by distinct genetic mutations affecting insulin secretion,and neonatal diabetes mellitus(NDm)-a heterogeneous group of severe hyperglycemic disorders in *** diabetes,autoimmune monogenic diabetes,genetic insulin resistance and lipodystrophy syndromes further diversify the monogenic diabetes landscape.A tailored approach based on phenotypic and biochemical factors to identify candidates for genetic screening is recommended for suspected cases of *** diagnosis warrants immediate molecular genetic testing for infants under six *** these genetic defects presents a unique opportunity for precision *** research aimed to develop cost-effective genetic testing methods and gene-based therapy can facilitate appropriate identification and optimize clinical *** and study of new genes offer a valuable opportunity to gain deeper insights into pancreatic cell biology and the pathogenic mechanisms underlying common forms of *** clinical review published in the recent issue of World Journal of Diabetes is such an attempt to fill-in our knowledge gap about this enigmatic disease.

关键词： monogenic diabetes maturity-onset diabetes of the young Neonatal diabetes mitochondrial diabetes Insulin resistance syndromes Genetic testing Next generation sequencing

A complete reference genome for the soybean ***

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Plant Communications 2024年第2期5卷 19-22页

作者： Yicheng Huang Dal-Hoe Koo Yizhou mao Eliot m.herman Jianwei Zhang monica A.Schmidt National Key Laboratory of Crop Genetic Improvement Hubei Hongshan LaboratoryHuazhong Agricultural UniversityWuhan 430070China Wheat Genetics Resource Center Department of Plant PathologyKansas State UniversityManhattanKS 66506USA BIO5 Institute School of Plant SciencesUniversity of ArizonaTucsonAZ 85721USA

Dear Editors,Soybeans are a global commodity for their edible protein and vegetable *** global population is predicted to be 9.7 billion by 2050(UN,2022),with a concomitant drastic increase in protein *** already 2.4 billion people suffering from food insecurity(FAO et al.,2023),there is an urgent need to meet future production demands for plant-based proteins.

关键词： commodity soybean urgent

Periodontitis:An often-neglected complication of diabetes

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World Journal of Diabetes 2024年第3期15卷 318-325页

作者： marina G Kudiyirickal joseph m Pappachan Primary Care Dental Practice The Smile ClinicPreston PR16PZUnited Kingdom Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom

The bidirectional association between type 2 diabetes mellitus(T2Dm)and periodontitis is now well established,resulting in periodontal disease being considered as the 6th major complication of diabetes mellitus(Dm)after cardiovascular disease,eye disease,neuropathy,nephropathy,and peripheral vascular *** can worsen the virulence and invasiveness of pathogenic oral microbial flora aggravating the local inflammation and infection in those with periodontal *** the other hand,the chemical and immunological mediators released into the circulation as part of periodontal inflammation worsen the systemic insulin resistance with worsening of *** if undiagnosed or left untreated can also result in eventual tooth loss.A study by Xu et al in the World Journal of Diabetes examined the predictive factors associated with periodontitis in Chinese patients with *** prevalence of periodontitis was found to be 75.7%in this *** on logistic regression analysis,the predictive factors for higher risk were low tooth brushing frequency[odds ratio(OR)=4.3],high triglycerides(TG;OR=3.31),high total cholesterol(TC;OR=2.87),higher glycated hemoglobin(HbA1c;OR=2.55),and higher age(OR=1.05)while higher education level was protective(OR=0.53).However,the most influential variables were HbA1c followed by age,TC,TG,low education level,brushing frequency,and sex on the random forest model(this model showed higher sensitivity for predicting the risk).A good understanding of the predictors for periodontitis in T2Dm patients is important in prevention,early detection of susceptible patients,and intervention to improve periodontal health and enable long-term glycaemic control as observed by Xu et al.

关键词： Diabetes mellitus Periodontitis Predictive factors Cardiovascular disease Glycaemic control

Elucidating the Degradation Pathways of Human Insulin in the Solid State

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Journal of Analysis and Testing 2024年第3期8卷 288-299页

作者： Andrew Fagan Lorraine m.Bateman joseph P.O'Shea Abina m.Crean SSPC the SFI Centre for Pharmaceutical Research School of Pharmacy University College Cork School of Pharmacy University College Cork Analytical and Biological Chemistry Research Facility (ABCRF) University College Cork School of Chemistry University College Cork

While there have been significant advances in the development of peptide oral dosage forms in recent years, highlighted by the clinical and commercial success of approved peptides such as Rybelsus?, there remain several barriers in the way of broad range applicability of this approach to peptide delivery. One such barrier includes the poor physical and chemical stability inherent to their structures, which persists in the solid state although degradation typically occurs at different rates and via different pathways in comparison to the solution state. Using insulin as a model peptide, this work sought to contribute to the development of analytical techniques for investigating common insulin degradation pathways. Chemically denatured,deamidated and aggregated samples were prepared and used to benchmark circular dichroism spectroscopy, reverse phase HPLC and size exclusion chromatography methods for the investigation of unfolding, chemical modifications and covalent aggregation of the insulin molecule respectively. Solid state degraded samples were prepared by heating insulin powder at 60 °C and 75% relative humidity for 1, 3, 5 and 7 d, and the degradation profiles of the samples were evaluated and compared with those observed in solution. While no unfolding was observed to occur, significant deamidation and covalent aggregation were detected. Reductive disulfide bond cleavage using dithiothreitol allowed for separation of the insulin A-and B-chains,offering a facile yet novel means of assessing the mechanisms of deamidation and covalent aggregation occurring in the solid state.

关键词： Biopharmaceutical analysis Covalent aggregation Deamidation Disulfide cleavage Insulin Solid state Stability

Acute worsening of microvascular complications of diabetes mellitus during rapid glycemic control:The pathobiology and therapeutic implications

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World Journal of Diabetes 2024年第3期15卷 311-317页

作者： Dania Blaibel Cornelius James Fernandez joseph m Pappachan Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Department of Endocrinology and metabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom

While chronic hyperglycaemia resulting from poorly controlled diabetes mellitus(Dm)is a well-known precursor to complications such as diabetic retinopathy,neuropathy(including autonomic neuropathy),and nephropathy,a paradoxical intensification of these complications can rarely occur with aggressive glycemic management resulting in a rapid reduction of glycated ***,acute onset or worsening of retinopathy and treatment induced neuropathy of diabetes are more common among these complications,rarely other problems such as albuminuria,diabetic kidney disease,Charcot’s neuroarthropathy,gastroparesis,and urinary bladder dysfunction are also *** World Journal of Diabetes recently published a rare case of all these complications,occurring in a young type 1 diabetic female intensely managed during pregnancy,as a case report by Huret et *** is essential to have a comprehensive understanding of the pathobiology,prevalence,predisposing factors,and management strategies for acute onset,or worsening of microvascular complications when rapid glycemic control is achieved,which serves to alleviate patient morbidity,enhance disease management compliance,and possibly to avoid medico-legal issues around this rare clinical *** editorial delves into the dynamics surrounding the acute exacerbation of microvascular complications in poorly controlled Dm during rapid glycaemic control.

关键词： Diabetes mellitus microvascular complications Diabetic retinopathy Treatment induced neuropathy of diabetes Diabetic nephropathy Charcot’s neuropathy

Non-pharmacological interventions for diabetic peripheral neuropathy:Are we winning the battle?

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World Journal of Diabetes 2024年第4期15卷 579-585页

作者： Dania Blaibel Cornelius James Fernandez joseph m Pappachan Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Department of Endocrinology&metabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine&HealthThe University of ManchesterManchester M139PLUnited Kingdom

Despite the advent of relatively reliable modalities of diagnosing diabetic peripheral neuropathy(DPN),such as nerve conduction studies,there is still a knowledge gap about the pathophysiology,and thus limited available in-terventions for symptom control and curtailing disease *** pharma-cologic aspect of management is mainly centred on pain control,however,there are several important aspects of DPN such as loss of vibration sense,pressure sense,and proprioception which are associated with risks to lower limb health,which pharmacotherapy does not ***,published evidence suggests non-pharmacologic interventions such as glycaemic control through dietary modification and exercise need to be combined with other measures such as psychotherapy,to reach a desired,however modest *** is emerging as an important treatment modality for several chronic medical conditions including neuropathic and other pain *** their study published in the World Journal of Diabetes on the potential of acupuncture to reduce DPN symptoms and enhance nerve conduction parameters,Hoerder et al have been able to demonstrate that acupuncture improves sensory function and that this effect is likely sustained two months after treatment *** previous studies also support these findings,larger multi-center randomized control trials including a sham-controlled arm accounting for a placebo effect are ***,given the satisfactory safety profile and the positive results found in these studies,it is likely that acupuncture may become an important aspect of the repertoire of effective DPN management.

关键词： Diabetic peripheral neuropathy Diabetes mellitus Pharmacotherapy Acupuncture Neuropathic pain Nonpharmacological intervention

Diabetic cardiomyopathy:Emerging therapeutic options

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World Journal of Diabetes 2024年第8期15卷 1677-1682页

作者： Cornelius James Fernandez Sahana Shetty joseph m Pappachan Department of Endocrinology&metabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom Department of Endocrinology Kasturba Medical CollegeManipal Academy of Higher EducationManipal 576104KarnatakaIndia Department of Endocrinology and metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom

Diabetic cardiomyopathy(DbCm)is a common but underrecognized complication of patients with diabetes mellitus(Dm).Although the pathobiology of other cardiac complications of diabetes such as ischemic heart disease and cardiac autonomic neuropathy are mostly known with reasonable therapeutic options,the mechanisms and management options for DbCm are still not fully *** its early stages,DbCm presents with diastolic dysfunction followed by heart failure(HF)with preserved ejection fraction that can progress to systolic dysfunction and HF with reduced ejection fraction in its advanced stages unless appropriately *** from prompt control of Dm with lifestyle changes and antidiabetic medications,disease-modifying therapy for DbCm includes prompt control of hypertension and dyslipidemia inherent to patients with Dm as in other forms of heart diseases and the use of treatments with proven efficacy in HF.A basic study by Zhang et al,in a recent issue of the World Journal of Diabetes elaborates the potential pathophysiological alterations and the therapeutic role of teneligliptin in diabetic mouse models with *** this preliminary basic study might help to improve our understanding of DbCm and offer a potential new management option for patients with the disease,the positive results from such animal models might not always translate to clinical practice as the pathobiology of DbCm in humans could be ***,such experimental studies can encourage more scientific efforts to find a better solution to treat patients with this enigmatic disease.

关键词： Diabetic cardiomyopathy Diabetic cardiomyopathy Heart failure Pathobiology Teneligliptin