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Incidence and mortality of acute and chronic pancreatitis in the Netherlands:A nationwide record-linked cohort study for the years 1995-2005

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World Journal of Gastroenterology 2013年第20期19卷 3018-3026页

作者： BW Marcel Spanier Marco J Bruno Marcel GW Dijkgraaf Department of Gastroenterology and Hepatology Rijnstate Hospital6800 TA ArnhemThe Netherlands Department of Gastroenterology and Hepatology Erasmus Medical Center3015 CE RotterdamThe Netherlands Clinical Research Unit Academic Medical Center1105 AZ AmsterdamThe Netherlands

aiM:To analyze trends in incidence and mortality of acute pancreatitis(AP) and chronic pancreatitis(CP) in the Netherlands and for international standard ***:A nationwide cohort is identified through record linkage of hospital data for AP and CP,accumulated from three nationwide Dutch registries:the hospital discharge register,the population register,and the death certificate ***-and age-group specific incidence rates of AP and CP are defined for the period 2000-2005 and mortality rates of AP and CP for the period ***,incidence and mortality rates over time are reported for Dutch and international(European and World Health Organization) standard ***:Incidence of AP per 100000 persons per year increased between 2000 and 2005 from 13.2(95%CI:12.6-13.8) to 14.7(95%CI:14.1-15.3).Incidence of AP for males increased from 13.8(95%CI:12.9-14.7) to 15.2(95%CI:14.3-16.1),for females from 12.7(95%CI:11.9-13.5) to 14.2(95%CI:13.4-15.1).Irregular patterns over time emerged for *** mean incidence per 100000 persons per year was 1.77,for males 2.16,and for females *** for AP fluctuated during 1995-2005 between 6.9 and 11.7 per million persons per year and was almost similar for males and *** CP,mortality for males fluctuated between 1.1(95%CI:0.6-2.3) and 4.0(95%CI:2.8-5.8),for females between 0.7(95%CI:0.3-1.6) and 2.0(95%CI:1.2-3.2).Incidence and mortality of AP and CP increased markedly with *** rates were lowest for World Health Organization standard ***:Incidence of AP steadily increased while incidence of CP *** for both AP and CP remained fairly *** burden and health care costs probably will increase because of an ageing Dutch population.

关键词： Acute pancreatitis Chronic pancreatitis Epidemiology Incidence Mortality

Treatment and Maintenance of Interstitial Cystitis/Bladder Pain Syndrome in Female Patients with Cetirizine-Famotidine: A Case Series

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Case Reports in Clinical Medicine 2023年第2期12卷 61-71页

作者： Reed B. Hogan II Paul H. Moore III Doug Paul Thomas P. Dooley GI Associates Flowood MS USA Division of Urogynecology Department of Obstetrics and Gynecology University of Mississippi Medical Center Jackson MS USA Department of pharmacy Administration School of Pharmacy University of Mississippi Oxford MS USA Trends in pharma Development LLC Pinson AL USA

Purpose: Interstitial cystitis/Bladder pain syndrome is an inflammatory disorder of the bladder, for which histamine has been implicated in the pathogenesis of the disease. The condition is often refractory to standard-of-care medical treatments, including the antihistamines hydroxyzine or cimetidine, and procedures. Herein we report a physician-sponsored proof-of-principle case series of four adult female patients with chronic painful bladder and frequent urination, who were treated once daily with a low dose H1 + H2 histamine receptor antagonist combination. Materials and Methods: Four adult females with Interstitial cystitis/Bladder pain syndrome were treated once daily with a compounded oral dosage form containing the H1 receptor antagonist-cetirizine 8 mg in combination with the H2 receptor antagonist-famotidine 22 mg. The case series consists of a retrospective review of the symptom severity prior to versus following H1 + H2 treatment. Results and Conclusions: The once daily dual histamine receptor antagonist therapy substantially reduced the pain and urination frequency, and prophylactically maintained all four patients long-term with substantially reduced disease severity. The reduction in symptom severity was achieved at amounts that do not exceed the US FDA approved and exceptionally safe daily doses for the two over-the-counter monotherapies. This case series provides proof-of-principle evidence that a dual antihistamine combination of cetirizine plus famotidine effectively treated and maintained female patients, who were previously refractory to standard-of-care medications and/or procedures.

关键词： Histamine Antihistamine Bladder Treatment Prophylaxis

Phase I trial of icotinib, a novel epidermal growth factor receptor tyrosine kinase inhibitor, in Chinese patients with non-small cell lung cancer

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Chinese Medical Journal 2011年第13期124卷 1933-1938页

作者： WANG Hart-ping ZHANG Li WANG Yin-xiang TAN Fen-lai XIA Ying REN Guan-jun HU Pei JIANG Ji WANG Meng-zhao XIAO Yi Department of Respiratory Medicine Peking Union Medical College HospitalPeking Union Medical College & Chinese Academy of MedicalSciences Beijing 100730 China center of Clinical pharmacology Peking Union Medical College HospitalPeking Union Medical College & Chinese Academy of MedicalSciences Beijing 100730 China Zhejiang Beta pharma Inc. Hangzhou Zhejiang 100176 China

Background The preclinical experiments and studies of congener drugs show icotinib, a new epidermal growth factor receptor （EGFR） tyrosine kinase inhibitor, can specifically bind to the tyrosine kinase domain of the EGFR, block the EGFR related signal, thereby inhibit the growth of tumor cell. The objective of this study was to investigate the safety, tolerability and dose-related biologic effects of icotinib in patients with non-small cell lung cancer （NSCLC） in a Chinese patient population. Methods This was an open-label, phase I, dose escalation, safety/tolerability trial of oral icotinib （100 to 400 mg）, administered twice per day for 28-continuous-day cycles until disease progression or undue toxicity. Results Forty patients with stage IIIB （15%） or IV （85%） NSCLC were included in the study. They had mainly adenocarcinoma （85%）, with a performance status （PS） of 0 （45%） or 1 （55%） and less than half the patients （45%） had histories of smoking and all were pretreated by at least one regimen of chemotherapy. Patients were assigned to three dose levels of 150 mg b.i.d, 200 mg b.i.d, or 125 mg t.i.d. The follow-up periods ranged from 5 to 80 weeks. Adverse events were found in 35% patients, most of which were mild and reversible. The adverse events mainly occurred in the first 4 weeks and included rash （25%）, diarrhea, nausea and abdominal distention. One definite interstitial lung disease （ILD） was found in a patient in the dose of 200 mg b.i.d. According to an 8-week assessment, one （2.5%） patient receiving 150 mg gained complete response （CR） that persisted for 44 weeks, seven （17.50%） patients had partial remission （PR）, and 18 （45%） patients had stable disease （SD）. The objective response including CR＋PR was 20%. The median time of progression-free survival for the 40 patients was 20 weeks （range： 12 to 32 weeks）. The response was not affected by pathological type, history of smoking, or numbers of previous therapeutic regimens. No relationship between dose, r

关键词： icotinib epidermal growth factor receptor tyrosine kinase inhibitor tolerability safety

OxyContin and the McDonaldization of chronic pain therapy in the USA

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Family Medicine and Community Health 2019年第1期7卷 33-35页

作者： Jordan Hughes Neelima Kale Philip Day University of Texas Southwestern Medical center DallasTexasUSA Department of Family and Community Medicine University of Texas Southwestern Medical CenterDallasTexasUSA

Principles and practices gleaned from successful business enterprises have been used to transform the practice of medicine for *** is the process in which principles which govern fast-food businesses,are applied to the practice of *** left unchecked,the application of these principles can have devastating consequences,as in the treatment of chronic,non-malignant pain with *** a time when there was growing concern about the under treatment of pain,Purdue pharma introduced OxyContin,providing an efficient,predictable way of treating chronic *** liberal prescription of this drug contributed,and continues to contribute,to the opioid epidemic we see ***,in confronting this epidemic,we must first understand the process of McDonaldization that has brought us here and then provide safe and effective chronic pain therapies even if they are expensive,time-consuming to deliver,difficult to measure,and unpredictable in their outcomes-all things we’ve grown to detest in our McDonaldized healthcare system.

关键词： pain consequences checked

GPCR activation:protonation and membrane potential

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Protein & Cell 2013年第10期4卷 747-760页

作者： Xuejun C.Zhang Kening Sun Laixing Zhang Xuemei Li Can Cao National Laboratory of Macromolecules National Center for Protein Science-BeijingInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China

GPCR proteins represent the largest family of signaling membrane proteins in eukaryotic *** importance to basic cell biology,human diseases,and pharma-ceutical interventions is well *** crystal structures of GPCR proteins have been reported in both active and inactive *** data indicate that agonist binding alone is not suffi cient to trigger the conformational change of GPCRs necessary for binding of downstream G-proteins,yet other essential factors re-main *** on analysis of available GPCR crystal structures,we identifi ed a potential conformational switch around the conserved Asp2.50,which consistently shows distinct conformations between inactive and active *** the structural information with the current literature,we propose an energy-coupling mechanism,in which the interaction between a charge change of the GPCR protein and the membrane potential of the living cell plays a key role for GPCR activation.

关键词： GPCR membrane potential protonation ac-tivation

Metabolic pathways as possible therapeutic targets for progressive multiple sclerosis

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Neural Regeneration Research 2017年第8期12卷 1262-1267页

作者： Rebecca M.Heidker Mitchell R.Emerson Steven M.Le Vine Department of Molecular and Integrative Physiology University of Kansas Medical Center Department of pharmaceutical Sciences College of Pharmacy-Glendale Midwestern University

Unlike relapsing remitting multiple sclerosis, there are very few therapeutic options for patients with progressive forms of multiple sclerosis. While immune mechanisms are key participants in the pathogenesis of relapsing remitting multiple sclerosis, the mechanisms underlying the development of progressive multiple sclerosis are less well understood. Putative mechanisms behind progressive multiple sclerosis have been put forth： insufficient energy production via mitochondrial dysfunction, activated microglia, iron accumulation, oxidative stress, activated astrocytes, Wallerian degeneration, apoptosis, etc. Furthermore, repair processes such as remyelination are incomplete. Experimental therapies that strive to improve metabolism within neurons and glia, e.g., oligodendrocytes, could act to counter inadequate energy supplies and/or support remyelination. Most experimental approaches have been examined as standalone interventions; however, it is apparent that the biochemical steps being targeted are part of larger pathways, which are further intertwined with other metabolic pathways. Thus, the potential benefits of a tested intervention, or of an established therapy, e.g., ocrelizumab, could be undermined by constraints on upstream and/or downstream steps. If correct, then this argues for a more comprehensive, multifaceted approach to therapy. Here we review experimental approaches to support neuronal and glial metabolism, and/or promote remyelination, which may have potential to lessen or delay progressive multiple sclerosis.

关键词： acetyl-coenzyme A carboxylase biotin estrogen iron Kynurenine pathway mitochondria thyroidhormone remyelination stem cells vitamin D

Glycemic Index of a Diabetes-Specific Nutritional Powder: An Open-Label Study in Healthy Indian Adults

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Food and Nutrition Sciences 2023年第3期14卷 200-224页

作者： Kirti Patel Vinay Kudrigikar Deepak Bachani Suyog Mehta Sun pharmaceutical Industries Ltd. Mumbai Maharashtra India Sun pharma Laboratories Ltd. Mumbai Maharashtra India

Background: A balanced diet with a low glycemic index (GI) plays an important role in controlling and managing type 2 diabetes mellitus (T2DM). Here, we compared the GI of 2 flavors (vanilla and chocolate) of diabetes-specific nutritional (DSN) supplements to its comparator in healthy Indian adults under fasting conditions. Methods: This study was a 39-day open-label, non-comparative, single-center trial involving healthy adults aged between 18 to 45 years. The subjects received equal doses of 2 DSN powder (Treatments A and B), the comparator product (Treatment C), and dextrose monohydrate as a reference (Treatment R). Doses were administered as per the dosing schedule, after an overnight fast for 10 hours, with 2 intervening non-dosing days. Blood samples were collected on the dosing days to assess changes in capillary blood glucose levels. The primary endpoint of the study was the mean GI of Treatments A, B, and C (Defined as low: GI ≤ 55;medium: 55 GI ≤ 70;High: GI > 70), generated using the incremental area under the curve (AUCi) methodology. Safety was assessed throughout the study. Values of all study parameters were represented in ±SD or standard deviation. Results: Fourteen adult male subjects with a mean age of 29.42 ± 4.46 years, and a body mass index of 22.0 ± 1.95 Kg/m2, were enrolled in the study. The mean AUCi for treatments A, B, and C were 104 ± 10, 111 ± 12, and 87 ± 12 mmol min/L, respectively and for Treatment R it was 276 ± 16, 319 ± 28 and 338 ± 25 mmol min/L for Days 1, 6 and 8, respectively. The mean GI of Treatment A was 33 ± 3, Treatment B was 35 ± 3 and Treatment C was 29 ± 5;all GI means were ≤55. Mild adverse events were reported in 2 (14.3%) subjects. No serious adverse events or deaths were reported in the study. All treatments were well tolerated by the subjects. Conclusion: The glycemic index of both test products and comparator was low (i.e., GI 55) as per ISO 26642:2010 standard.

关键词： Balanced Diet Dietary Substitute Glycemic Index Healthy Subjects India

NADPH homeostasis in cancer:functions,mechanisms and therapeutic implications

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Signal Transduction and Targeted Therapy 2020年第1期5卷 518-529页

作者： Huai-Qiang Ju Jin-Fei Lin Tian Tian Dan Xie Rui-Hua Xu State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterSun Yat-sen University510060 GuangzhouChina Research Unit of Precision Diagnosis and Treatment for Gastrointestinal Cancer Chinese Academy of Medical Sciences510060 GuangzhouChina

Nicotinamide adenine dinucleotide phosphate(NADPH)is an essential electron donor in all organisms,and provides the reducing power for anabolic reactions and redox *** homeostasis is regulated by varied signaling pathways and several metabolic enzymes that undergo adaptive alteration in cancer *** metabolic reprogramming of NADPH renders cancer cells both highly dependent on this metabolic network for antioxidant capacity and more susceptible to oxidative *** the unique NADPH homeostasis of cancer cells might be an effective strategy to eliminate these *** this review,we summarize the current existing literatures on NADPH homeostasis,including its biological functions,regulatory mechanisms and the corresponding therapeutic interventions in human cancers,providing insights into therapeutic implications of targeting NADPH metabolism and the associated mechanism for cancer therapy.

关键词： homeostasis therapeutic metabolism

A peptide containing the receptor binding site of insulin-like growth factor binding protein-2 enhances bone mass in ovariectomized rats

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Bone Research 2018年第3期6卷 280-288页

作者： Gang Xi Christine Wai Clifford J.Rosen David R.Clemmons Department of Medicine University of North Carolina at Chapel HillChapel HillUSA Maine Medical center Research Institute ScarboroughUSA

Male Igfbp2-/-mice have a significant reduction in bone mass and administration of a peptide that contains the insulin-like growth factor binding protein-2(IGFBP-2) receptor-binding domain stimulates bone formation in these animals. Female Igfbp2-/-mice do not have this phenotype but following ovariectomy(OVX) lose more bone than OVX wild-type mice. This suggests that in the absence of estrogen, IGFBP-2 is required to maintain bone mass. Therefore these studies were undertaken to determine if this peptide could stimulate bone acquisition in OVX rats. OVX rats were divided into seven treatment groups: sham animals, OVX animals, OVX animals receiving a control scrambled peptide, or one of three doses of the active peptide termed PEG-HBD-1(0.7, 2,and 6 mg·kg^(-1)) and an OVX group receiving parathyroid hormone(PTH)(50 μg·kg-1 per day). The peptides were administered for8 weeks. DXA revealed a significant reduction in femoral and tibial areal bone mineral density(aBMD) after OVX, whereas treatment with the high-dose peptide increased aBMD by 6.2% ± 2.4%(P < 0.01) compared to control peptide; similar to the increase noted with PTH(5.6% ± 3.0%, P < 0.01). Similar increases were noted with two lower doses of the peptide(3.8% ± 1.5%, P < 0.05 for low dose; 3.1% ± 1.6%, P = 0.07 for middle dose). Micro CT showed that the OVX control peptide animals had reductions of 41% and64% in femoral trabecular BV/TV and trabecular number, respectively. All three doses of the peptide increased bone volume/total volume(BV/TV) significantly, while the low and middle doses increased trabecular number. Cortical BV/TV and thickness at the midshaft increased significantly with each dose of peptide(18.9% ± 9.8%, P < 0.01 and 14.2% ± 7.9%, P < 0.01 for low dose; 23.7% ±10.7%, P < 0.001 and 15.8% ± 6.1%, P < 0.001 for middle dose; 19.0% ± 6.9%, P < 0.01 and 16.2% ± 9.7%, P < 0.001 for high dose)and with PTH(25.8% ± 9.2%, P < 0.001 and 19.4% ± 8.8%, P < 0.001). Histomorphometry showed that the low

关键词： insulin-like growth factor binding protein-2 OVX wild-type mice