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Autoimmune pancreatitis:Cornerstones and future perspectives

World Journal of Gastroenterology 2024年第8期30卷 817-832页

作者： Camilla Gallo Giulia Dispinzieri Nicola Zucchini Pietro Invernizzi Sara Massironi Division of Gastroenterology and Center for Autoimmune Liver Diseases Department of Medicine and SurgeryFondazione IRCCS San Gerardo dei TintoriUniversity of Milano-BicoccaMonza 20900Italy Department of Pathology Fondazione IRCCS San Gerardo dei TintoriMonza 20900Italy

Autoimmune pancreatitis(AIP)is an autoimmune subtype of chronic pancreatitis resulting from the aberrant immune response against the pancreas,leading to inflammation and fibrosis.Although AIP is rare,its incidence is increasing and is often misdiagnosed as other pancreatic diseases.AIP is commonly classified into two types.Type 1 AIP(AIP-1)is typically associated with elevated serum immunoglobulin G4(IgG4)levels and systemic manifestations,while type 2 AIP is typically a more localized form of the disease,and may coexist with other autoimmune disorders,especially inflammatory bowel diseases.Additionally,there is emerging recognition of a third type(type 3 AIP),which refers to immunotherapy-triggered AIP,although this classification is still gaining acceptance in medical literature.The clinical manifestations of AIP mainly include painless jaundice and weight loss.Elevated serum IgG4 levels are particularly characteristic of AIP-1.Diagnosis relies on a combination of clinical,laboratory,radiological,and histological findings,given the similarity of AIP symptoms to other pancreatic disorders.The mainstay of treatment for AIP is steroid therapy,which is effective in most cases.Severe cases might require additional imm-unosuppressive agents.This review aims to summarize the current knowledge of AIP,encompassing its epidemiology,etiology,clinical presentation,diagnosis,and treatment options.We also address the challenges and controversies in diagnosing and treating AIP,such as distinguishing it from pancreatic cancer and managing long-term treatment,highlighting the need for increased awareness and knowledge of this complex disease.

关键词： Autoimmunity Pancreatitis Autoimmune pancreatitis Immunoglobulin G4 steroids Relapse

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Does the use of double hormone replacement therapy for trauma patient organ donors improve organ recovery for transplant

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World Journal of Transplantation 2024年第2期14卷 119-125页

作者： Eden M Gallegos Tanner Reed Paige Deville Blake Platt Claudia Leonardi Lillian Bellfi Jessica Dufrene Saad Chaudhary John Hunt Lance Stuke Patrick Greiffenstein Jonathan Schoen Alan Marr Anil Paramesh Alison A Smith Department of Physiology Louisiana State University Health Sciences Center New OrleansNew OrleansLA 70124United States Department of Medicine Louisiana State University Health Sciences Center New OrleansNew OrleansLA 70112United States Department of Surgery Louisiana State University Health Sciences Center New OrleansNew OrleansLA 70112United States Department of Trauma Surgery Tacoma General HospitalTacoma 98405United States Department of Public Health Louisiana State University Health Sciences Center New OrleansNew OrleansLA 70112United States Department of Donation Services Louisiana Organ Procurement AgencyCovingtonLA 70433United States Department of Surgery Tulane Transplant InstituteTulane University School of MedicineNew OrleansLA 70112United States

BACKGROUND With an ongoing demand for transplantable organs,optimization of donor management protocols,specifically in trauma populations,is important for obta-ining a high yield of viable organs per patient.Endocrine management of brain-dead potential organ donors(BPODs)is controversial,leading to heterogeneous clinical management approaches.Previous studies have shown that when levo-thyroxine was combined with other treatments,including steroids,vasopressin,and insulin,BPODs had better organ recovery and survival outcomes were increased for transplant recipients.AIM To determine if levothyroxine use in combination with steroids in BPODs increased the number of organs donated in trauma patients.METHODS A retrospective review of adult BPODs from a single level 1 trauma center over ten years was performed.Exclusion criteria included patients who were not solid organ donors,patients who were not declared brain dead(donation after circulatory death),and patients who did not receive steroids in their hospital course.Levothyroxine and steroid administration,the number of organs donated,the types of organs donated,and demographic information were recorded.Univariate analyses were performed with Psteroids(ST/LT group)vs 19(22%)receiving steroids without levothyroxine(ST group).No differences were observed between the groups for gender,race,pertinent injury factors,age,or other hormone therapies used(P>0.05).In the ST/LT group,68.1%(n=47)donated a high yield(3-5)of organ types per donor compared to 42.1%(n=8)in the ST group(P=0.038).There was no difference in the total number of organ types donated between the groups(P=0.068).CONCLUSION This study suggests that combining levothyroxine and steroid administration increases high-yield organ donation per donor in BPODs in the trauma patient population.Limitations to this study include the retrospective design and the relatively smal

关键词： Organ donation Trauma Brain death Levothyroxine Hormone replacement therapy steroids Organ donor Retrospective

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Prospects of polyglycolic acid sheets for the treatment of esophageal stricture after esophageal endoscopic submucosal dissection

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World Journal of Gastrointestinal Endoscopy 2024年第1期16卷 1-4页

作者： Qing-Xia Wang Rui-Hua Shi Department of Gastroenterology Southeast University Affiliated Zhongda HospitalMedical SchoolNanjing 210009Jiangsu ProvinceChina

Esophageal cancer is the seventh most common type of cancer and the sixth leading cause of cancer-related mortality worldwide.Endoscopic submucosal dissection(ESD)is widely used for the resection of early esophageal cancer.However,post-ESD esophageal stricture is a common long-term complication,which requires attention.Patients with post-ESD esophageal stricture often experience dysphagia and require multiple dilatations,which greatly affects their quality of life and increases healthcare costs.Therefore,to manage post-ESD esophageal stricture,researchers are actively exploring various strategies,such as pharmaceutical interventions,endoscopic balloon dilation,and esophageal stenting.Although steroids-based therapy has achieved some success,steroids can lead to complications such as osteoporosis and infection.Meanwhile,endoscopic balloon dilatation is effective in the short term,but is prone to recurrence and perforation.Additionally,esophageal stenting can alleviate the stricture,but is associated with discomfort during stenting and the complication of easy displacement also present challenges.Tissue engineering has evolved rapidly in recent years,and hydrogel materials have good biodegradability and biocompatibility.A novel type of polyglycolic acid(PGA)sheets has been found to be effective in preventing esophageal stricture after ESD,with the advantages of a simple operation and low complication rate.PGA membranes act as a biophysical barrier to cover the wound as well as facilitate the delivery of medications to promote wound repair and healing.However,there is still a lack of multicenter,large-sample randomized controlled clinical studies focused on the treatment of post-ESD esophageal strictures with PGA membrane,which will be a promising direction for future advancements in this field.

关键词： Polyglycolic acid Endoscopic submucosal dissection Esophageal stenosis Esophageal cancer steroids

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Human HAND1 inhibits the conversion of cholesterol to steroids in trophoblasts

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Journal of Genetics and Genomics 2022年第4期49卷 350-363页

作者： Haibin Zhu Qianlei Ren Ziyi Yan Shouying Xu Jiahao Luo Ximei Wu Chao Tang National Clinical Research Center for Child Health of the Children’s Hospital Zhejiang University School of MedicineHangzhouZhejiang 310052China Department of Obstetrics and Gynaecology The First Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejiang 310003China Department of Pharmacology School of MedicineZhejiang UniversityHangzhouZhejiang 310058China

Steroidogenesis from cholesterol in placental trophoblasts is fundamentally involved in the establishment and maintenance of pregnancy.The transcription factor gene heart and neural crest derivatives expressed1(Hand1)promotes differentiation of mouse trophoblast giant cells.However,the role of HAND1 in human trophoblasts remains unknown.Here,we report that HAND1 inhibits human trophoblastic progesterone(P4)and estradiol(E2)from cholesterol through downregulation of the expression of steroidogenic enzymes,including aromatase,P450 cholesterol side-chain cleavage enzyme(P450 scc),and 3β-hydroxysteroid dehydrogenase type 1(3β-HSD1).Mechanically,although HAND1 inhibits transcription of aromatase by directly binding to aromatase gene promoter,it restrains transcription of P450 scc by upregulation of the methylation status of P450 scc gene promoter through its binding to ALKBH1,a demethylase.Unlike aromatase and P450 scc,HAND1 decreases 3β-HSD1 m RNA levels by the reduction of its RNA stability through binding to and subsequent destabilizing protein Hu R.Finally,HAND1 suppresses circulating P4 and E2 levels derived from JEG-3 xenograft and attenuates uterine response to P4 and E2.Thus,our results uncover a hitherto uncharacterized role of HAND1 in the regulation of cholesterol metabolism in human trophoblasts,which may help pinpoint the underlying mechanisms involved in supporting the development and physiological function of the human placenta.

关键词： HAND1 Trophoblast Cholesterol steroids

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Bilateral pericapsular end nerve blocks for steroid-induced avascular necrosis following COVID-19 infection requiring bilateral total hip replacement

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World Journal of Anesthesiology 2024年第1期13卷 1-8页

作者： Somita Christopher Sweety Dutta Thota Venkata Sanjeev Gopal Department of Anaesthesiology Care HospitalsHyderabad 500025India

BACKGROUND Osteonecrosis or avascular necrosis(AVN)of the hip was one of the dreaded complications of coronavirus disease 2019(COVID-19),which emerged in patients who received steroid therapy.Corticosteroids have been a mainstay in the treatment protocol of COVID-19 patients.Popular corticosteroid drugs used in patients suffering from COVID-19 were intravenous(IV)or oral dexamethasone,methylprednisolone or hydrocortisone.The use of such high doses of corticost-eroids has shown very positive results and has been lifesaving in many cases.Still,long-term consequences were drug-induced diabetes,osteoporosis,Cushing syndrome,muscle wasting,peripheral fat mobilization,AVN,hirsutism,sleep disturbances and poor wound healing.A significant number of young patients were admitted for bilateral total hip replacements(THR)secondary to AVN following steroid use for COVID-19 treatment.AIM To assess the efficacy of bilateral pericapsular end nerve group(PENG)blocks in patients posted for bilateral THR post-steroid therapy after COVID-19 infection and assess the time taken to first ambulate after surgery.METHODS This prospective observational study was conducted between January 2023 and August 2023 at Care Hospitals,Hyderabad,India.Twenty young patients 30-35 years of age who underwent bilateral THR were studied after due consent over 8 months.All the patients received spinal anaesthesia for surgery and bilateral PENG blocks for postoperative analgesia.RESULTS The duration of surgery was 2.5 h on average.Seventeen out of twenty patients(85%)had a Visual Analog Score(VAS)of less than 2 and did not require any supplementation.One patient was removed from the study,as he required re-exploration.The remaining two patients had a VAS of more than 8 and received IV morphine post-operatively as a rescue analgesic drug.Fifteen out of seventeen patients(88.2%)could be mobilized 12 h after the procedure.CONCLUSION Osteonecrosis or AVN of the hip was one of the dreaded complications of COVID-19,which surfaced in patients who received steroid

关键词： Avascular necrosis Pericapsular end nerve group block Analgesia Hip replacement COVID-19 steroids

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Breakthrough in the challenging P450-catalyzed chemoenzymatic synthesis of C14-functionalized steroids

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中国科学:化学英文版 2023年第9期66卷 2435-2436页

作者： Manfred T.Reetz Frank Hollmann Max-Planck-Institut für Kohlenforschung Kaiser-Wilhelm-Platz 145480 MülheimGermany Tianjin Institute of Industrial Biotechnology Chinese Academy of SciencesTianjin 300308China Department of Biotechnology Delft Universityvan der Maasweg 92629 HZ DelftNetherlands

Intensive past research has demonstrated that cytochrome P450 monooxygenases are involved in the biosynthesis of numerous natural products and in human metabolism of various pharmaceuticals [1]. This inspired synthetic organic and pharmaceutical chemists to test them as catalysts in the oxidative hydroxylation of steroids. Unfortunately, wildtype P450s generally proved to show low levels of regio-and diastereoselectivity as well as suboptimal activity.

关键词： steroids catalyzed synthesis

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Apoptosis in Granulosa cells during follicular atresia: relationship with steroids and insulin-like growth factors

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Cell Research 2004年第4期14卷 341-346页

作者： Yuan Song YU, Hong Shu SUI, Zheng Bin HAN, Wei LI, Ming Jiu LUO, Jing He TAN Laboratory of Animal Reproduction and Embryology College of Animal Sciences and Veterinary Medicine, Shandong Agricultural University, Taian, Shandong 271018, China Present address: College of life science. University of Beijing, Beijing, China. Laboratory of Animal Reproduction and Embryology College of Animal Sciences and Veterinary Medicine Shandong Agricultural University Taian China College of life science University of Beijing Beijing China

It is well known that during mammalian ovarian follicular development, the majority of follicles undergo atresia at various stages of their development. However, the mechanisms controlling this selection process remain unknown. In this study, we investigated apoptosis in granulosa cells during goat follicular atresia by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL). The changes in the levels of steroids, insulin-like growth factors (IGFs) and IGF receptors were studied by radioimmunoassay (RIA) and semi-quantitative reverse transcrip-tion-PCR. We found that the percentage of apoptotic granulosa cells in the atretic (A) follicles was significantly higher than that in the slightly atretic (SA) and healthy (H) follicles. The level of estradiol and the ratio of estradiol to progesterone in H follicles were significantly higher than those in A follicles. On the other hand, the level of progesterone was not significantly different among these follicle types. We also found that t

关键词： apoptosis ovarian follicle steroids IGFs atresia.

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A retrospective study of epidural and intravenous steroids after percutaneous endoscopic lumbar discectomy for large lumbar disc herniation

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Chinese Journal of Traumatology 2017年第1期20卷 34-38页

作者： Yang Zhang Xin-Jian Yang Teng-Hui Zeng Yi-Yan Qiu Yi-Tian Wang Fei-Guo Liang Clinical School of Shenzhen Second People's Hospital Anhui Medical University. Hefei 230032. China Department of Spinal Surzery Shenzhen Second People's Hospital Shenzhen 518035 China

OBJECTIVE:To assess the early curative effect of epidural or intravenous administration of steroids during a percutaneous endoscopic lumbar discectomy (PELD).;METHODS:28 consecutive patients who underwent PELD due to large lumbar disc herniation between November 2014 and January 2016 were followed up for 6 months. These patients were divided into two groups according to the treatment they received after PELD. 14 patients (Group A) were treated by PELD and epidural steroids, while the other 14 patients (Group B) were treated by PELD and intravenous steroids. We evaluated the effectiveness by the preoperative and postoperative visual analogue scale (VAS) scores for back and leg pain, and the postoperative Oswestry disability index (ODI) at 3 weeks after surgery via the clinical charts and telephone interview. Postoperative hospital stay and time return to work were investigated as well.;RESULTS:There is a significant decrease in VAS (back, leg), ODI, and time return to work (p < 0.05). For VAS (back), Group A showed a significant decrease compared with Group B at 1 day and 1 week after surgery (p = 0.011, p = 0.017). As for VAS (leg), Group A showed a significant decrease compared with Group B at 1 day, 1 week, 3 weeks, and 3 months follow-up examinations (p = 0.002, p = 0.006, p < 0.001, p < 0.001). For ODI, Group A showed a notable decrease compared with Group B (p < 0.001). The postoperative hospital stay in two groups was not statistically different (p = 0.636). But the time return to work in Group A was significantly shorter than that in Group B (p = 0.023).;CONCLUSIONS:Patients who underwent PELD with epidural steroid administration for large lumbar disc herniation showed favorable curative effect compared with those who underwent PELD with intravenous steroid administration.

关键词： Endoscopic lumbar discectomy Large lumbar disc herniation steroids

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Four new steroids from the marine soft coral-derived fungus Penicillium sp. SCSIO41201

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Chinese Journal of Natural Medicines 2020年第4期18卷 250-255页

作者： LONG Jie-Yi WANG Jun-Feng LIAO Sheng-Rong LIN Xiu-Ping ZHOU Xue-Feng LI Yun-Qiu YANG Bin LIU Yong-Hong CAS Key Laboratory of Tropical Marine Bio-resources and Ecology/Guangdong Key Laboratory of Marine Materia Medica South China Sea Institute of OceanologyChinese Academy of SciencesGuangzhou 510301China University of Chinese Academy of Sciences Beijing 100049China School of Pharmacy Guilin Medical UniversityGuilin 541004China South China Branch of Innovation Academy for Drug Discovery and Development Chinese Academy of SciencesGuangzhou 510650China

Penicildiones A-D(1-4), four new steroids derivatives together with three known compounds including 16α-methylpregna-17α,19-dihydroxy-(9,11)-epoxy-4-ene-3,18-dione-20-acetoxy(5), stachybotrylactone B(6) and stachybotrin(7) were isolated from the soft coral-derived fungus Penicillium sp. SCSIO41201, cultured in the 1% NaCl PDB substrate. Their structures were determined through spectroscopic methods and X-ray crystallography. Biological evaluation results revealed that 6 exhibited significant cytotoxic activity against HL-60, K562, MOLT-4, ACHN, 786-O, and OS-RC-2 cell lines with IC50 values of 5.23, 4.12, 4.31, 23.55, 7.65 and 10.81 μmol·L-1, respectively, while other compounds showed weak or no cytotoxicity at 50 μmol·L-1.

关键词： Soft corals Marine fungus Penicillium sp. steroids Penicildione

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Structural Modification for Antitumor Nitrogenous steroids

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Chinese Journal of Structural Chemistry 2017年第12期36卷 2007-2019页

作者：谢田鹏杨康张立志陈德胜邹坤黄年玉 Hubei Key Laboratory of Natural Products Research and Development College of Biological and Pharmaceutical Sciences China Three Gorges University

Natural steroids have been showing notable cytotoxic activities, which are quite interesting lead compounds for the development of anticancer drug including estramustine and prednimustine. Considering that these semi-synthetic molecules are nitrogen mustard functionalized steroidal derivatives, the present review is focused on the methodologies of introducing nitrogen atom or nitrogen-containing heterocycles on A^D rings or side chains of steroids, and analysis of the structure-activity relationship（SAR） for these man-made cytotoxic steroids.

关键词： steroids structural modification N-hetercycles antitumor structure-activity relationship

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