Pathophysiology of severe gallstone pancreatitis:A new paradigm

Severe gallstone pancreatitis(GSP)refractory to maximum conservative therapy has wide clinical variations,and its pathophysiology remains controversial.This Editorial aimed to investigate the pathophysiology of severe disease based on Opie’s theories of obstruction,the common channel,and duodenal reflux and describe its types.Severe GSP might be a hybrid disease with pathology polarized between acute cholangitis with mild pancreatitis(biliary type)and necrotizing pancreatitis uncomplicated with biliary tract disease(pancreatic type),in which hepatobiliary and pancreatic lesion severity is inversely related to the presence or absence of impacted ampullary stones.Severe GSP is caused by stones that are persistently impacted at the ampulla with biliopancreatic obstruction(biliary type),and probably,stones that are either temporarily lodged at the duodenal orifice or passed into the duodenum,thereby permitting reflux of bile or possible duodenal contents into the pancreas(pancreas type).When the status of the stones and the presence or absence of impacted ampullary stones with biliopancreatic obstruction are determined,the clinical course and outcome can be predicted.Gallstones represent the main cause of acute pancreatitis globally,and clinicians are expected to encounter GSP more often.Awareness of the etiology and pathogenesis of severe disease is mandatory.

Mpox and related poxviruses:A literature review of evolution,pathophysiology,and clinical manifestations

The recently re-emerged mpox(monkeypox)virus that causes mpox disease is a member of genus Orthopoxvirus and has unprecedentedly spread worldwide.Numerous studies have contributed to our understanding of its evolution,pathophysiology,and clinical manifestations.The current outbreak of the mpox virus depicts its novel route of transmission as a new variant.However,the exact reason for its transition from an epidemic to a pandemic remains unclear.Furthermore,other poxviruses such as vaccinia virus,variola virus,and cowpox virus,also belong to the same genus,Orthopoxvirus.In the present review,our objective was to summarize the evidence on evolution,pathophysiology,and clinical manifestations of mpox virus and its related poxviruses.The present review would aid in a better understanding of the current circulating mpox virus and its differences from other poxviruses.In addition,the shared genetic factors contributing to virulence in these Orthopoxvirus highlight their evolutionary connections and genetic similarities.While they exhibit differences in virulence,studying these genetic relationships is crucial for understanding their biology,pathogenicity,and the development of effective vaccines and antiviral therapeutics to curb mpox disease.

Recent Advances for Global Perspectives on Etiology, Pathophysiology, Clinical Presentations, and Management of Moyamoya Disease

Moyamoya disease (MMD) is a condition characterized by the gradual narrowing and blockage of blood vessels in the brain, specifically those in the circle of Willis and the arteries that supply it. This results in reduced blood flow and oxygen to the brain, leading to progressive symptoms and potential complications. The underlying pathophysiological mechanism remains elucidated. However, recent studies have highlighted numerous etiologic factors: abnormal immune complex responses, susceptibility genes, branched-chain amino acids, antibodies, heritable diseases, and acquired diseases, which may be the great potential triggers for the development of moyamoya disease. Its clinical presentation has varying degrees from transient asymptomatic events to significant neurological deficits. Moyamoya disease (MMD) shows different patterns in children and adults. Children with MMD are more susceptible to ischemic events due to decreased blood flow to the brain. Conversely, adults with MMD are more prone to hemorrhagic events involving brain bleeding. Children with MMD may experience a range of symptoms including motor impairments, sensory issues, seizures, headaches, dizziness, cognitive delays, or ongoing neurological problems. Although adults may present with similar clinical symptoms as children, they are more prone to experiencing sudden onset intraventricular, subarachnoid, or intracerebral hemorrhages. One of the challenges in moyamoya disease is the potential for misdiagnosis or delayed diagnosis, particularly when physicians fail to consider MMD as a possible cause in stroke patients. This review aims to provide a comprehensive overview of recent global studies on the pathophysiology of MMD, along with advancements in its management. Additionally, the review will delve into various surgical treatment options for MMD, as well as its rare occurrence alongside atrioventricular malformations. Exciting prospects include the use of autologous bone marrow transplant and the potential role of Connexin 43 protein treatment in the development of moyamoya disease.

Indian perspective on childhood malnutrition:Prevalence,pathophysiology,risk factors,and prevention

BACKGROUND Childhood malnutrition contributes over half of the childhood mortality around the world,predominantly in South-Asian and sub-Saharan countries.AIM To summarize the childhood malnutrition epidemiology along with the comorbid factors associated with it and its management within the community.METHODS The data collection process involved conducting a comprehensive search using specific keywords such as child nutrition disorders and India with Boolean operators.The search was conducted in the Scopus and PubMed electronic databases.RESULTS Inadequate energy consumption initiates pathological alterations in the form of growth retardation,fat,visceral,and muscle loss,a reduction in basal metabolic rate,and a significant reduction in total energy expenditure.It has become evident that malnutrition shows an increased prevalence and incidence rate,despite available guidelines for the management of malnutrition.CONCLUSION Malnutrition can be a major player in the establishment of severe infections that result in significant post discharge mortalities in children.Future trials are required to fill the prime gaps in knowledge regarding the identification of other contributory factors in the pathogenesis of malnutrition and postdischarge infection.New biomarkers for early detection of malnutrition should be the priority of the scientific community for the early management of malnutrition.

Research and Exploration of Ideological and Political Education in the Course of Pathophysiology

Course based ideological and political education (CIPE) is an important way to improve the quality of ideological and political work and talent cultivation. This study explores for the first time the implementation of ideological and political education in the teaching of pathophysiology courses, and also analyzes the evaluation of student psychological status and the importance of mental health education in the implementation of IPE courses. A survey was conducted on 211 students at Yangtze University to understand their motivation and behavior towards learning ideological, political, and pathophysiological courses. In addition, a questionnaire survey was used to explore the relationship between pathophysiology and ideological and political courses, as well as the importance of their satisfaction with the implementation of ideological and political courses in pathophysiology and mental health education. The research results indicate that factors such as educational background and gender differences affect the learning of CIPE. Graduate students are more interested in ideological and political courses, while female students find it difficult to study pathophysiology;In addition, the results of one-way ANOVA indicate that the implementation effect of IPE in pathophysiology courses depends on the level of interest in IPE and pathophysiology courses, the level of consideration for the importance of professional courses, the professional gains after studying pathophysiology, and the level of understanding of the relationship between IPE and CIPE. 81.04% of students believe that in the CIPE process, telling stories by teachers themselves is the most popular way of communication and education. This reflects the importance of mental health education from the perspective of CIPE. In addition, this study also indicates that PBL and flipped classroom teaching models are popular teaching models in CIPE. This study is beneficial for promoting the improvement and implementation of CIPE and mental health education in higher education curricula, thus providing valuable insights for educational decision-makers.

Irritable bowel syndrome:Epidemiology,overlap disorders,pathophysiology and treatment

Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disease with a significant impact on patients’ quality of life and a high socioeconomic burden. And the understanding of IBS has changed since the release of the Rome Ⅳ diagnosis in 2016. With the upcoming Rome Ⅴ revision, it is necessary to review the results of IBS research in recent years. In this review of IBS, we can highlight future concerns by reviewing the results of IBS research on epidemiology, overlap disorders, pathophysiology, and treatment over the past decade and summarizing the latest research.

Recent advances in pathophysiology,diagnosis and management of hepatorenal syndrome:A review

Hepatorenal syndrome with acute kidney injury(HRS-AKI)is a form of rapidly progressive kidney dysfunction in patients with decompensated cirrhosis and/or acute severe liver injury such as acute liver failure.Current data suggest that HRS-AKI occurs secondary to circulatory dysfunction characterized by marked splanchnic vasodilation,leading to reduction of effective arterial blood volume and glomerular filtration rate.Thus,volume expansion and splanchnic vasoconstriction constitute the mainstay of medical therapy.However,a significant proportion of patients do not respond to medical management.These patients often require renal replacement therapy and may be eligible for liver or combined liver-kidney transplantation.Although there have been advances in the management of patients with HRS-AKI including novel biomarkers and medications,better-calibrated studies,more widely available biomarkers,and improved prognostic models are sorely needed to further improve diagnosis and treatment of HRS-AKI.

Diabetes mellitus and atrial fibrillation-from pathophysiology to treatment

Type 2 diabetes mellitus(T2DM)is a leading risk factor for cardiovascular complications around the globe and one of the most common medical conditions.Atrial fibrillation(AF)is the most common supraventricular arrhythmia,with a rapidly increasing prevalence.T2DM has been closely associated with the risk of AF development,identified as an independent risk factor.Regarding cardiovascular complications,both AF and T2DM have been linked with high mortality.The underlying pathophysiology has not been fully determined yet;however,it is multifactorial,including structural,electrical,and autonomic pathways.Novel therapies include pharmaceutical agents in sodium-glucose cotransporter-2 inhibitors,as well as antiarrhythmic strategies,such as cardioversion and ablation.Of interest,glucose-lowering therapies may affect the prevalence of AF.This review presents the current evidence regarding the connection between the two entities,the pathophysiological pathways that link them,and the therapeutic options that exist.

Irritable bowel syndrome:Emerging paradigm in pathophysiology

Irritable bowel syndrome(IBS)is one of the most common gastrointestinal disorders,characterized by abdominal pain,bloating,and changes in bowel habits.These symptoms cannot be explained by structural abnormalities and there is no specific laboratory test or biomarker for IBS.Therefore,IBS is classified as a functional disorder with diagnosis dependent on the history taking about manifested symptoms and careful physical examination.Although a great deal of research has been carried out in this area,the pathophysiology of IBS is complex and not completely understood.Multiple factors are thought to contribute to the symptoms in IBS patients;altered gastrointestinal motility,visceral hypersensitivity,and the brain-gut interaction are important classical concepts in IBS pathophysiology.New areas of research in this arena include inflammation,postinfectious low-grade inflammation,genetic and immunologic factors,an altered microbiota,dietary factors,and enteroendocrine cells.These emerging studies have not shown consistent results,provoking controversy in the IBS field.However,certain lines of evidence suggest that these mechanisms are important at least a subset of IBS patients,confirming that IBS symptoms cannot be explained by a single etiological mechanism.Therefore,it is important to keep in mind that IBS requires a more holistic approach to determining effective treatment and understanding the underlying mechanisms.

Gastroesophageal reflux disease:From pathophysiology to treatment

This review focuses on the pathophysiology of gastroesophageal reflux disease (GERD) and its implications for treatment. The role of the natural anti-reflux mechanism (lower esophageal sphincter, esophageal peristalsis, diaphragm, and trans-diaphragmatic pressure gradient), mucosal damage, type of refluxate, presence and size of hiatal hernia, Helicobacter pylori infection, and Barrett’s esophagus are reviewed. The conclusions drawn from this review are: (1) the pathophysiology of GERD is multifactorial; (2) because of the pathophysiology of the disease, surgical therapy for GERD is the most appropriate treatment; and (3) the genesis of esophageal adenocarcinoma is associated with GERD.

Toll-like receptors in pathophysiology of liver diseases

Toll-like receptors(TLRs) are pattern recognition receptors that participate in host defense by recognizing pathogen-associated molecular patterns alongside inflammatory processes by recognizing damage associated molecular patterns. Given constant exposure to pathogens from gut, strict control of TLR-associated signaling pathways is essential in the liver, which otherwise may lead to inappropriate production of pro-inflammatory cytokines and interferons and may generate a predisposition to several autoimmune and chronic inflammatory diseases. The liver is considered to be a site of tolerance induction rather than immunity induction, with specificity in hepatic cell functions and distribution of TLR. Recent data emphasize significant contribution of TLR signaling in chronic liver diseases via complex immune responses mediating hepatocyte(i.e., hepatocellular injury and regeneration) or hepatic stellate cell(i.e., fibrosis and cirrhosis) inflammatory or immune pathologies. Herein, we review the available data on TLR signaling, hepatic expression of TLRs and associated ligands, as well as the contribution of TLRs to the pathophysiology of hepatic diseases.

Pathophysiology of colorectal peritoneal carcinomatosis: Role of the peritoneum

Colorectal cancer(CRC) is the third most common cancer and the fourth most common cause of cancerrelated death worldwide. Besides the lymphatic and haematogenous routes of dissemination,CRC frequently gives rise to transcoelomic spread of tumor cells in the peritoneal cavity,which ultimately leads to peritoneal carcinomatosis(PC). PC is associated with a poor prognosis and bad quality of life for these patients in their terminal stages of disease. A loco-regional treatment modality for PC combining cytoreductive surgery and hyperthermic intraperitoneal peroperative chemotherapy has resulted in promising clinical results. However,this novel approach is associated with significant morbidity and mortality. A comprehensive understanding of the molecular events involved in peritoneal disease spread is paramount in avoiding unnecessary toxicity. The emergence of PC is the result of a molecular crosstalk between cancer cells and host elements,involving several well-defined steps,together known as the peritoneal metastatic cascade. Individual or clumps of tumor cells detach from the primary tumor,gain access to the peritoneal cavity and become susceptible to the regular peritoneal transport. They attach to the distant peritoneum,subsequently invade the subperitoneal space,where angiogenesis sustains proliferation and enables further metastatic growth. These molecular events are not isolated events but rather a continuous and interdependent process. In this manuscript,we review current data regarding the molecular mechanisms underlying the development of colorectal PC,with a special focus on the peritoneum and the role of the surgeon in peritoneal disease spread.

Nervous and Neuroendocrine regulation of the pathophysiology of cholestasis and of biliary carcinogenesis

Cholangiocytes, the epithelial cells lining the biliary ducts, are the target cells in several liver diseases. Cholangiopathies and cholangiocarcinoma generate interest in many scientists since the genesis. The developing mechanisms, and the therapeutic tools of these diseases are still undefined. Several studies demonstrate that many hormones, neuropeptides and neurotransmitters regulate malignant and non-malignant cholangiocyte pathophysiology in the course of chronic biliary diseases. The aim of this review is to present the findings of several studies published in the recent years that contributed to clarifying the role of nervous and neuroendocrine regulation of the pathophysiologic events associated with cholestasis and cholangiocarcinoma development. This manuscript is organized into two parts. The first part offers an overview of the innervation of the liver and the origin of neuroendocrine hormones, neurotransmitters and neuropeptides affecting cholangiocyte function and metabolism. The first section also reviews the effects played by several neuroendocrine hormones and nervous system on cholangiocyte growth, survival and functional activity in the course of cholestasis. In the second section, we summarize the results of some studies describing the role of nervous system and neuroendocrine hormones in the regulation of malignant cholangiocyte growth.

Pathophysiology of chronic pancreatitis induced by dibutyltin dichloride joint ethanol in mice

AIM: To search for a new chronic pancreatitis model in mice suitable for investigating the pathophysiological processes leading to pancreatic fibrosis.METHODS: The mice were randomly divided into 2 groups(n = 50), control group and model group. The mice in model group were given ethanol(10%) in drinking water after injection of dibutyltin dichloride(DBTC)(8 mg/kg BW) in tail vein. The mice in control group were injected with only solvent into tail vein( 60 % ethanol, 20% glycerine and 20% normal saline) and drank common water. At days 1, 7, 14, 28, and 56 after application of DBTC or solvent, 10 mice in one group were killed at each time point respectively. Blood was obtained by inferior vena cava puncture. The activity of amylase, concentration of bilirubin and hyaluronic acid in serum were assayed. The pancreas was taken to observe the pancreatic morphology by HE staining, and to characterize the pancreatic fibrosis by Masson staining. The expression of F4/80, CD3 and fibronectin(FN) were assayed by immuno-histochemistry or Immunofluorescence technique. Collagen typeⅠ(COL1A1) in pancreas were detected by Western blot. The expression of matrix metalloproteinase-1(MMP-1) and tissue inhibitor of metalloproteinases-1(TIMP-1) m RNA in the pancreas was assessed by real time PCR.RESULTS: DBTC induced an acute edematous pancreatitis within 1 d. The dilated acini, scattered acinar cell necrosis, and inflammatory cells were found at day 7. Extensive infiltration with inflammatory cells following deposition of connective tissue was observed at day 14. At day 28, level of pancreatic fibrosis was aggravated. The pancreatic tissue was replaced by an extended interstitial fibrosis at the end of 2 mo. There was significant difference in the level of amylase, bilirubin and hyaluronic acid in serum between control group and model group(P < 0.05). The level of COL1A1 and FN in pancreas increased. The expression of MMP-1 m RNA in pancreas decreased, but TIMP-1 m RNA increased at model group.CONCLUSION: DBTC joint Ethanol drinking can induce chronic pancreatitis in accordance with the pathophysiological modification of human. DBTC joint Ethanol-induced pancreatitis in mice is an effective and handy experimental method. The model is suitable to study the mechanism of pancreatic fibrosis in chronic pancreatitis.

Pathophysiology and biology of peritoneal carcinomatosis

Peritoneal carcinomatosis represents a devastating form of cancer progression with a very poor prognosis.Its complex pathogenesis is represented by a dynamic process comprising several steps.To the best of our knowledge pathogenesis can be partly explained by 3 major molecular pathways: (1) dissemination from the primary tumor;(2) primary tumor of peritoneum;and (3) independent origins of the primary tumor and peritoneal implants.These are not mutually exclusive and combinations of different mechanisms could occur inside a single case.There are still several aspects which need explanation by future studies.A comprehensive understanding of molecular events involved in peritoneal carcinomatosis is of paramount importance and should be systematically pursued not only to identify novel strategies for the prevention of the condition,but also to obtain therapeutic advances,through the identification of surrogate markers of prognosis and development of future molecular targeted therapies.

Efficacy of prone position in acute respiratory distress syndrome patients: A pathophysiology-based review

Acute respiratory distress syndrome(ARDS) is a syndrome with heterogeneous underlying pathological processes. It represents a common clinical problem in intensive care unit patients and it is characterized by high mortality. The mainstay of treatment for ARDS is lung protective ventilation with low tidal volumes and positive end-expiratory pressure sufficient for alveolar recruitment. Prone positioning is a supplementary strategy available in managing patients with ARDS. It was first described 40 years ago and it proves to be in alignment with two major ARDS pathophysiological lung models; the "sponge lung"- and the "shape matching"-model. Current evidence strongly supports that prone positioning has beneficial effects on gas exchange, respiratory mechanics, lung protection and hemodynamics as it redistributes transpulmonary pressure, stress and strain throughout the lung and unloads the right ventricle. The factors that individually influence the time course of alveolar recruitment and the improvement in oxygenation during prone positioning have not been well characterized. Although patients' response to prone positioning is quite variable and hard to predict, large randomized trials and recent meta-analyses show that prone position in conjunction with a lung-protective strategy, when performed early and in sufficient duration, may improve survival in patients with ARDS. This pathophysiology-based review and recent clinical evidence strongly support the use of prone positioning in the early management of severe ARDS systematically and not as a rescue maneuver or a last-ditch effort.

Solitary rectal ulcer syndrome:Clinical features,pathophysiology,diagnosis and treatment strategies

Solitary rectal ulcer syndrome (SRUS) is an uncommon benign disease, characterized by a combination of symptoms, clinical findings and histological abnormalities. Ulcers are only found in 40% of the patients; 20% of the patients have a solitary ulcer, and the rest of the lesions vary in shape and size, from hyperemic mucosa to broad-based polypoid. Men and women are affected equally, with a small predominance in women. SRUS has also been described in children and in the geriatric population. Clinical features include rectal bleeding, copious mucus discharge, prolonged excessive straining, perineal and abdominal pain, feeling of incomplete defecation, constipation, and rarely, rectal prolapse. This disease has well-described histopathological features such as obliteration of the lamina propria by fibrosis and smooth muscle fibers extending from a thickened muscularis mucosa to the lumen. Diffuse collage deposition in the lamina propria and abnormal smooth muscle fiber extensions are sensitive markers for differ-entiating SRUS from other conditions. However, the etiology remains obscure, and the condition is frequently associated with pelvic floor disorders. SRUS is difficult to treat, and various treatment strategies have been advocated, ranging from conservative management to a variety of surgical procedures. The aim of the present review is to summarize the clinical features, pathophysiology, diagnostic methods and treatment strategies associated with SRUS. (C) 2014 Baishideng Publishing Group Co., Limited. All rights reserved.

COVID-19 pandemic:Pathophysiology and manifestations from the gastrointestinal tract

The pandemic of coronavirus disease 2019(COVID-19),caused by a newly identifiedβ-coronavirus(SARS-CoV-2)has emerged as a dire health problem,causing a massive crisis for global health.Primary method of transmission was firstly thought to be animal to human transmission.However,it has been observed that the virus is transmitted from human to human via respiratory droplets.Interestingly,SARS-CoV-2 ribonucleic acid(RNA)has been isolated from patient stools,suggesting a possible gastrointestinal(GI)involvement.Most commonly reported clinical manifestations are fever,fatigue and dry cough.Interestingly,a small percentage of patients experience GI symptoms with the most common being anorexia,diarrhea,nausea and vomiting.The presence of viral RNA in stools is also common and fecal tests can be positive even after negative respiratory samples.The exact incidence of digestive symptoms is a matter of debate.The distribution of Angiotensin converting enzyme type 2 receptors in multiple organs in the body provides a possible explanation for the digestive symptoms’mechanism.Cases with solely GI symptoms have been reported in both adults and children.Viral RNA has also been detected in stool and blood samples,indicating the possibility of liver damage,which has been reported in COVID-19 patients.The presence of chronic liver disease appears to be a risk factor for severe complications and a poorer prognosis,however data from these cases is lacking.The aim of this review is firstly,to briefly update what is known about the origin and the transmission of SARS-CoV-2,but mainly to focus on the manifestations of the GI tract and their pathophysiological background,so that physicians on the one hand,not to underestimate or disregard digestive symptoms due to the small number of patients exhibiting exclusively this symptomatology and on the other,to have SARS-CoV-2 on their mind when the“gastroenteritis”type symptoms predominate.

Hemorrhoids:From basic pathophysiology to clinical management

This review discusses the pathophysiology,epidemiology,risk factors,classification,clinical evaluation,and current non-operative and operative treatment of hemorrhoids.Hemorrhoids are defined as the symptomatic enlargement and distal displacement of the normal anal cushions.The most common symptom of hemorrhoids is rectal bleeding associated with bowel movement.The abnormal dilatation and distortion of the vascular channel,together with destructive changes in the supporting connective tissue within the anal cushion,is a paramount finding of hemorrhoids.It appears that the dysregulation of the vascular tone and vascular hyperplasia might play an important role in hemorrhoidal development,and could be a potential target for medical treatment.In most instances,hemorrhoids are treated conservatively,using many methods such as lifestyle modification,fiber supplement,suppositorydelivered anti-inflammatory drugs,and administration of venotonic drugs.Non-operative approaches include sclerotherapy and,preferably,rubber band ligation.An operation is indicated when non-operative approaches have failed or complications have occurred.Several surgical approaches for treating hemorrhoids have been introduced including hemorrhoidectomy and stapled hemorrhoidopexy,but postoperative pain is invariable.Some of the surgical treatments potentially cause appreciable morbidity such as anal stricture and incontinence.The applications and outcomes of each treatment are thoroughly discussed.

New insights into the pathophysiology of achalasia and implications for future treatment

Idiopathic achalasia is an archetype esophageal motor disorder, causing significant impairment of eating ability and reducing quality of life. The pathophysiological underpinnings of this condition are loss of esophageal peristalsis and insufficient relaxation of the lower esophageal sphincter(LES). The clinical manifestations include dysphagia for both solids and liquids, regurgitation of esophageal contents, retrosternal chest pain, cough, aspiration, weight loss and heartburn. Even though idiopathic achalasia was first described more than 300 years ago, researchers are only now beginning to unravel its complex etiology and molecular pathology. The most recent findings indicate an autoimmune component, as suggested by the presence of circulating anti-myenteric plexus autoantibodies, and a genetic predisposition, as suggested by observed correlations with other well-defined genetic syndromes such as Allgrove syndrome and multiple endocrine neoplasia type 2 B syndrome. Viral agents(herpes, varicella zoster) have also been proposed as causative and promoting factors. Unfortunately, the therapeutic approaches available today do not resolve the causes of the disease, and only target the consequential changes to the involved tissues, such as destruction of the LES, rather than restoring or modifying the underlying pathology. New therapies should aim to stop the disease at early stages, thereby preventing the consequential changes from developing and inhibiting permanent damage. This review focuses on the known characteristics of idiopathic achalasia that will help promote understanding its pathogenesis and improve therapeutic management to positively impact the patient's quality of life.