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.

Etiology of anterior choroidal artery infarction:a systematic review

Objective:To systematically review the etiology of anterior choroidal artery(AChA)infarction.Methods:A systematic literature search up to May 11,2024,for AChA infarction with its etiology.Epidemiologic and clinical data of patients,anatomic distribution of the lesions,and etiologic classification of AChA infarction were extracted.Results:A total of 1007 individual patient data was included(967 from retrospective clinical studies and 40 from case reports).Among the clinical research,patients’mean age was 64.7.There were 62.24%of male and 37.76%of female patients.Hypertension(66.04%)was the most common risk factor for patients with AChA infarction.Dyslipidemia(32.92%),diabetes mellitus(30.93%),and smoking(26.54%)were also common risk factors.Moreover,the posterior limb of the internal capsule was the most frequently affected structure.Undetermined etiology(n=173,38.02%),according to the trial of org 10172 in acute stroke treatment(TOAST)etiological classification,was the most common etiology,followed by small vessel disease(n=117,25.71%),large artery atherosclerosis(n=84,18.46%),and cardioembolism(n=63,13.85%).Furthermore,eighteen strokes were caused by other determined etiologies(3.96%).Conclusions:Undetermined etiology was the most common etiology of AChA infarction.Hypertension,dyslipidemia,diabetes mellitus,and smoking were common risk factors for patients with AChA infarction.It is necessary to prevent the risk factors.

Changes in the etiology of liver cirrhosis and the corresponding management strategies

We read with interest the article by Xing Wang,which was published in the recent issue of the World Journal of Hepatology 2023;15:1294-1306.This article focuses particularly on the prevalence and trends in the etiology of liver cirrhosis(LC),prognosis for patients suffering from cirrhosis-related complications and hepatocellular carcinoma(HCC),and management strategies.The etiology of cirrhosis varies according to geographical,economic,and population factors.Viral hepatitis is the dominant cause in China.Vaccination and effective treatment have reduced the number of people with viral hepatitis,but the overall number is still large.Patients with viral hepatitis who progress over time to LC and HCC remain an important population to manage.The increased incidence of metabolic syndrome and alcohol consumption is likely to lead to a potential exponential increase in metabolic dysfunction-associated steatotic liver disease(MASLD)-associated LC and alcoholic liver disease in the future.Investigating the evolution of the etiology of LC is important for guiding the direction of future research and policy development.These changing trends indicate a need for greater emphasis on tackling obesity and diabetes,and implementing more effective measures to regulate alcohol consumption in order to reduce the occurrence of MASLD.In an effort to help cope with these changing trends,the authors further proposed countermeasures for healthcare authorities doctors,and patients.

Etiology and pathogenesis of corona virus disease 2019 on the view of Chinese medicine

Traditional Chinese Medicine has played an important role in the prevention and treatment of the Corona Virus Disease 2019 epidemic.But in views of different TCM scholars there are different opinions about disease name,characteristic of etiology,law of pathogenesis about this epidemic.Based on related literatures,this article overviews of the characteristics of TCM etiology,law of pathogenesis and methods of syndrome differentiation,hoping to find research method that fit in with TCM clinical practice.Prerequisite of treatment is identifying the cause.The clinical manifestations of patients are important to TCM,and the etiological attributes can be inferred from the clinical manifestations.SARS-CoV-2 belongs to exogenous etiological factors,but there are different opinions about its characteristics of six pathogenic factors.Cold,Dampness,Warm,Dry,Toxin,Summer-heat,Wind,are all involved.Thus,different understanding of the pathogenesis and the law of transmission is caused.Such as cold and dampness hurt Yang,furthermore,consumed of Qi;dampness and toxin infected from external environment,turbid dampness produced inside the body;dryness affecting lungs and consume of Yin;warm-heat-turbid-toxin affected lungs,stomach and intestine;and then produced phlegm stagnation or blood stasis,furthermore consumed Qi and Yin.Based on those differences,methods of syndrome differentiation in treatment of COVID-19 are diverse,which contain pattern differentiation of zang-fu organs,pattern differentiation of Wei-defence,Qi,Ying nutrients and blood;pattern differentiation by the eight principles,and pattern differentiation of six meridians.Because of SARS-CoV-2 can spread to the whole country or even the whole world in a short period of time,its pathogenic nature should be roughly the same.So studying the treatment of COVID-19 based on clinical cases,refining the similarities and differences in the clinical presentation of patients with different subtypes during the epidemic,clarification of the etiologic attribution and evolutionary patterns of disease mechanisms,developing a comprehensive understanding of COVID-19 in Chinese medicine is needed.Furthermore,getting a full understanding of COVID-19,and providing reference for the prevention and treatment of unknown infectious diseases.

Genetic regulation of cell type-specific chromatin accessibility shapes brain disease etiology

Nucleotide variants in cell type-specific gene regulatory elements in the human brain are risk factors for human disease.We measured chromatin accessibility in 1932 aliquots of sorted neurons and non-neurons from 616 human postmortem brains and identified 34,539 open chromatin regions with chromatin accessibility quantitative trait loci(caQTLs).Only 10.4%of caQTLs are shared between neurons and non-neurons,which supports cell type-specific genetic regulation of the brain regulome.Incorporating allele-specific chromatin accessibility improves statistical fine-mapping and refines molecular mechanisms that underlie disease risk.Using massively parallel reporter assays in induced excitatory neurons,we screened 19,893 brain QTLs and identified the functional impact of 476 regulatory variants.Combined,this comprehensive resource captures variation in the human brain regulome and provides insights into disease etiology.

Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic targets

Liver fibrosis is a reversible wound-healing process aimed at maintaining organ integrity, and presents as the critical pre-stage of liver cirrhosis, which will eventually progress to hepatocellular carcinoma in the absence of liver transplantation. Fibrosis generally results from chronic hepatic injury caused by various factors, mainly viral infection, schistosomiasis, and alcoholism; however, the exact pathological mechanisms are still unknown. Although numerous drugs have been shown to have antifibrotic activity in vitro and in animal models, none of these drugs have been shown to be efficacious in the clinic. Importantly, hepatic stellate cells(HSCs) play a key role in the initiation, progression, and regression of liver fibrosis by secreting fibrogenic factors that encourage portal fibrocytes, fibroblasts, and bone marrow-derived myofibroblasts to produce collagen and thereby propagate fibrosis. These cells are subject to intricate cross-talk with adjacent cells, resulting in scarring and subsequent liver damage. Thus, an understanding of the molecular mechanisms of liver fibrosis and their relationships with HSCs is essential for the discovery of new therapeutic targets. This comprehensive review outlines the role of HSCs in liver fibrosis and details novel strategies to suppress HSC activity, thereby providing new insights into potential treatments for liver fibrosis.

Epidemiology,etiology,and prevention of esophageal squamous cell carcinoma in China

Esophageal cancer is one of the most fatal diseases worldwide mainly because of its rapid progression and poor prognosis.Although the incidence of esophageal adenocarcinoma has markedly risen in North America and Europe in the past several decades, esophageal squamous cell carcinoma is still the predominant subtype of esophageal cancer, especially in China. It accounts for more than 90% of all esophageal squamous cell carcinoma cases in China. Geographical differentiation is one of the most distinctive characteristics of esophageal cancer. The progression, risk factors, and prognosis of these two subtypes of esophageal cancer differ. This study reviews the epidemiology, etiology, and prevention of esophageal squamous cell carcinoma in China, thereby providing systematic references for policy-makers who will decide on issues of esophageal cancer prevention and control.

Progress of gastric cancer etiology:N-nitrosamides in the 1990s

Stomach carcinoma is still the leading cause of cancer death in China and the second one in the world. Its possible causes include: A) chemical factors such as intragastric formation of N-nitroso compounds (NOC) and high salt intake; B ) biological factors such as infection of Helicobacter pylori and biotoxins intake; and C ) nutritional factors such as deficiency of vitamin C, selenium, and other antioxidants. Nitrogenous precursors of NOC, e.g., alkylamines, alkylureas, alkylguanidines, and alkylamides, occur widely in nature and potential nitrosating agents, e.g., nitrite (NO2-) and NOx (the gaseous oxides of nitrogen ) are similarly widespread. Relationship between exposure to NOC and causes of human cancer was investigated extensively ten years ago. Results indicated that the exposures of NOC might contribute to the occurrences of malignancy in the upper digestive tracts including stomachs. It was also observed that both high salt intake and deficiency of some micronutrients enhanced NOC-induced carcinogenicity. Recent studies show that infection of H. pylori can lead to atrophic gastritis and achlorhydria, and promote endogenous formation of NOC indirectly[1] . Much attention has been paid to stomach cancer and NOC regarding the characterization of natural N-nitrosamides in human environment in the 1990s.

Study on environmental etiology of high incidence areas of liver cancer in China

INTRODUCTIONChina is a country with a high incidence of liver cancer insome areas.Liver cancer has a wide distribution andthreatens human health seriously.A rough estimationshows that out of a population of 1.2×10~8 in liver

Viral and Bacterial Etiology of Acute Febrile Respiratory Syndrome among Patients in Qinghai, China

Objective This study was conducted to investigate the viral and bacterial etiology and epidemiology of patients with acute febrile respiratory syndrome(AFRS) in Qinghai using a commercial routine multiplex-ligation-nucleic acid amplification test(NAT)-based assay. Methods A total of 445 nasopharyngeal swabs specimens from patients with AFRS were analyzed using the RespiFinderSmart22 kit(PathoFinder BV, Netherlands) and the LightCycler 480 real-time PCR system. Results Among the 225(225/445, 51%) positive specimens, 329 positive pathogens were detected, including 298(90.58%) viruses and 31(9%) bacteria. The most commonly detected pathogens were influenza virus(IFV;37.39%;123/329), adenovirus(AdV;17.02%;56/329), human coronaviruses(HCoVs;10.94%;36/329), rhinovirus/enterovirus(RV/EV;10.03%;33/329), parainfluenza viruses(PIVs;8.51%;28/329), and Mycoplasma pneumoniae(M. pneu;8.51%;28/329), respectively. Among the co-infected cases(17.53%;78/445), IFV/AdV and IFV/M. pneu were the most common co-infections. Most of the respiratory viruses were detected in summer and fall. Conclusion In our study, IFV-A was the most common respiratory pathogen among 22 detected pathogens, followed by AdV, HCoV, RV/EV, PIV, and M. pneu. Bacteria appeared less frequently than viruses, and co-infection was the most common phenomenon among viral pathogens. Pathogens were distributed among different age groups and respiratory viruses were generally active in July, September, and November. Enhanced surveillance and early detection can be useful in the diagnosis, treatment, and prevention of AFRS, as well as for guiding the development of appropriate public health strategies.

Budd-Chiari syndrome:Etiology,pathogenesis and diagnosis

Budd-Chiari syndrome is a congestive hepatopathy caused by blockage of hepatic veins. This syndrome occurs in 1/100 000 in the general population. Hypercoagulable state could be identified in 75% of the patients; more than one etiologic factor may play a role in 25% of the patients. Primary myeloproliferative diseases are the leading cause of the disease. Two of the hepatic veins must be blocked for clinically evident disease. Liver congestion and hypoxic damage of hepatocytes eventually result in predominantly centrilobular fibrosis. Doppler ultrasonography of the liver should be the initial diagnostic procedure. Hepatic venography is the reference procedure if required. Additionally liver biopsy may be helpful for differential diagnosis. The prognosis of the chronic form is acceptable compared to other chronic liver diseases.

Acute pancreatitis:Etiology and common pathogenesis

Acute pancreatitis is an inflammatory disease of the pancreas.The etiology and pathogenesis of acute pancreatitis have been intensively investigated for centuries worldwide.Many causes of acute pancreatitis have been discovered,but the pathogenetic theories are controversial.The most common cause of acute pancreatitis is gallstone impacting the distal common bile-pancreatic duct.The majority ofinvestigators accept that the main factors for acute billiary pancreatitis are pancreatic hyperstimulation and bile-pancreatic duct obstruction which increase pancreatic duct pressure and active trypsin reflux.Acute pancreatitis occurs when intracellular protective mechanisms to prevent trypsinogen activation or reduce trypsin activity are overwhelmed.However,little is known about the other acute pancreatitis.We hypothesize that acute biliary pancreatitis and other causes of acute pancreatitis possess a common pathogenesis.Pancreatic hyperstimulation and pancreatic duct obstruction increase pancreatic duct pressure,active trypsin reflux,and subsequent unregulated activation of trypsin within pancreatic acinar cells.Enzyme activation within the pancreas leads to auto-digestion of the gland and local inflammation.Once the hypothesis is confirmed,traditional therapeutic strategies against acute pancreatitis may be improved.Decompression of pancreatic duct pressure should be advocated in the treatment of acute pancreatitits which may greatly improve its outcome.

Microscopic colitis: A review of etiology, treatment and refractory disease

Microscopic colitis is a common cause of chronic,nonbloody diarrhea. Microscopic colitis is more common in women than men and usually affects patients in their sixth and seventh decade. This article reviews the etiology and medical management of microscopic colitis. The etiology of microscopic colitis is unknown, but it is associated with autoimmune disorders, such as celiac disease, polyarthritis, and thyroid disorders. Smoking has been identified as a risk factor of mi-croscopic colitis. Exposure to medications, such as non-steroidal anti-inflammatory drugs, proton pump inhibitors, and selective serotonin reuptake inhibitors, is suspected to play a role in microscopic colitis, although their direct causal relationship has not been proven. Multiple medications, including corticosteroids, anti-diarrheals, cholestyramine, bismuth, 5-aminosalicylates, and immunomodulators, have been used to treat microscopic colitis with variable response rates. Budesonide is effective in inducing and maintaining clinical remission but relapse rate is as high as 82% when budesonide is discontinued. There is limited data on management of steroid-dependent microscopic colitis or refractory microscopic colitis. Immunomodulators seem to have low response rate 0%-56% for patients with refractory microscopic colitis. Response rate 66%-100% was observed for use of anti-tumor necrosis factor(TNF) therapy for refractory microscopic colitis. Anti-TNF and diverting ileostomy may be an option in severe or refractory microscopic colitis.

Fatty liver disease,an emerging etiology of hepatocellular carcinoma in Argentina

AIM To investigate any changing trends in the etiologies of hepatocellular carcinoma(HCC) in Argentina during the last years. METHODS A longitudinal cohort study was conducted by 14 regional hospitals starting in 2009 through 2016. All adult patients with newly diagnosed HCC either with pathology or imaging criteria were included. Patients were classified as presenting non-alcoholic fatty liver disease(NAFLD) either by histology or clinically, provided that all other etiologies of liver disease were ruled out, fatty liver was present on abdominal ultrasound and alcohol consumption was excluded. Complete follow-up was assessed in all included subjects since the date of HCC diagnosis until death or last medical visit.RESULTS A total of 708 consecutive adults with HCC were included. Six out of 14 hospitals were liver transplant centers(n = 484). The prevalence of diabetes mellitus was 27.7%. Overall, HCV was the main cause of liver disease related with HCC(37%) including cirrhotic and non-cirrhotic patients, followed by alcoholic liver disease 20.8%, NAFLD 11.4%, cryptogenic 9.6%, HBV 5.4% infection, cholestatic disease and autoimmune hepatitis 2.2%, and other causes 9.9%. A 6-fold increase in the percentage corresponding to NAFLDHCC was detected when the starting year, i.e., 2009 was compared to the last one, i.e., 2015(4.3% vs 25.6%; P < 0.0001). Accordingly, a higher prevalence of diabetes mellitus was present in NAFLD-HCC group 61.7% when compared to other than NAFLD-HCC 23.3%(P < 0.0001). Lower median AFP values at HCC diagnosis were observed between NAFLD-HCC and non-NAFLD groups(6.6 ng/m L vs 26 ng/m L; P = 0.02). Neither NAFLD nor other HCC etiologies were associated with higher mortality.CONCLUSION The growing incidence of NAFLD-HCC documented in the United States and Europe is also observed in Argentina, a confirmation with important Public Health implications.

Severe acute pancreatitis in the elderly: Etiology and clinical characteristics

AIM: To investigate the etiology and clinical characteristics of severe acute pancreatitis (SAP) in elderly patients (≥ 60 years of age). METHODS: We reviewed retrospectively all the SAP cases treated in Xuanwu Hospital in Beijing between 2000 and 2007. RESULTS: In 169 patients with SAP, 94 were elderly and 16 died. Biliary and idiopathic etiologies were the first two causes that accounted for over 90% of SAP in the elderly. Biliary, hyperlipemic and alcoholic etiologies were the first three causes in the young. The proportion of co- morbidity of cholelithiasis, biliary infection, hypertension and coronary heart disease in the aged was significantly higher than that in their young partners. The scores of APACHE Ⅱ and Ranson were also significantly higher in the elderly except the CT score. Organ failures were more common in the elderly, but the local pancreatic complications were not different between the two groups. Mortality of the aged was correlated with the severity of SAP, multiple co-morbidity and incidence of multiple organ dysfunction syndrome (MODS). MODS was the main cause of death. CONCLUSION: The etiology of SAP in the elderly is quite different from that in the young. Biliary and unknown factors are main causes in the aged. The elderly are subject to major organ failures but there is no difference in the occurrence of local pancreatic complications between the elderly and the young. It is crucial to monitor and improve the functions of major organs so as to prevent MODS in the aged with SAP.

Liver diseases in COVID-19:Etiology,treatment and prognosis

In December 2019,a novel coronavirus named severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)was identified in Wuhan,China causing coronavirus disease-2019(COVID-19).Numerous studies have shown varying degrees of liver damage in patients infected with SARS-CoV-2.However,in previous case studies of COVID-19,the exact cause of liver injury has not been clearly elucidated,nor is there clear evidence of the interaction between liver injury and COVID-19.This study will analyze the causes of liver injury in COVID-19 and the influence of liver-related complications on the treatment and prognosis of COVID-19.

Etiology and evaluation of diarrhea in AIDS:a global perspective at the millennium

INTRODUCTIONIt has now been almost 20 years since the initialdescriptions of a heretofore unrecognized disorderafflicting homosexual men and manifesting asPneumocystis carinii pneumonia and Kaposi’ssarcoma.With the identification of the humanimmunodeficiency virus(HIV) as the etiology ofthis syndrome,there has been exponential growth inour understanding of this devastating

Etiology,diagnosis, management and outcomes of epiphora referrals to an oculoplastic practice

AIM： To investigate the etiology, diagnosis, management and outcome of epiphora referrals to an oculoplastic practice.METHODS： Retrospective chart review of patients referred for epiphora to an oculoplastic clinic between 2005 and 2009. Patient demographics, past history, ophthalmic examination, treatment and outcome were analyzed.RESULTS： There were 237 subjects with a primary complaint of epiphora. They included 130 （55%） females and 107 （45%） males with an average age of 55.9±25.9y. The most common cause of epiphora was lacrimal obstruction （46%）; followed by multifactorial epiphora （22%）, reflex tearing （22%） and eyelid malposition （11%）. Differences in prevalence of etiology were noted in terms of age and gender distribution. Of the 182 （77%） patients who returned for follow up, 41 （23%） reported a complete resolution and 102 （56%） reported a significant improvement in their symptoms.CONCLUSION： Epiphora is a common condition with many causes. A thorough history and examination are required to provide the appropriate treatment tailored to the underlying cause.

Etiology and portal vein thrombosis in Budd-Chiari syndrome

AIM: To research the etiology, portal vein thrombosis and other features of Budd-Chiari syndrome (BCS) patients prospectively. METHODS: A total of 75 patients (40 female, 35 male) who were diagnosed between January 2002 and July 2004 as having BCS were studied prospectively. Findings from on physical examination, ultrasonography, duplex ultrasonography and venography were analyzed. Hemogram and blood chemistry were studied at the time of diagnosis and on each hospital visit. Bone marrow examination and immune phenotyping were performed by a hematologist when necessary. Protein C, S, antithrombin Ⅲ, activated protein C resistance, and anticardiolipin antibodies, antinuclear antibodies, and anti ds-DNA were studied twice. The presence of ascite, esophageal varices, and portal thrombosis were evaluated at admission and on every visit. RESULTS: At least one etiological factor was determined in 54 (72%) of the patients. The etiology could not be defined in 21 (28%) patients. One etiological factor was found in 39, 2 factors in 14 and 3 factors in 1 patient. The most common cause was the web (16%), the second was Hydatid disease (11%), the third was Behcet’s disease (9%). Portal vein thrombosis was present in 11 patients and at least one etiology was identified in 9 of them (82%). CONCLUSION: Behcet’s disease and hydatid disease are more prominent etiological factors in Turkey than in other countries. Patients with web have an excellent response to treatment without signs of portal veinthrombosis while patients having thrombofilic factors more than one are prone to develop portal vein thrombosis with worse clinical outcome.

Etiology and functional status of liver cirrhosis by ^(31)P MR spectroscopy

AIM: To assess the functional status and etiology of liver cirrhosis by quantitative 31p magnetic resonance spectroscopy (MRS).METHODS: A total of 80 patients with liver cirrhosis of different etiology and functional status described by Child-Pugh score were examined and compared to 11 healthy volunteers. MR examination was performed on a 1.5 T imager using a 1H/31P surface coil by the 2D chemical shift imaging technique.Absolute concentrations of phosphomonoesters (PME),phosphodiesters (PDE), inorganic phosphate (Pi) and adenosine triphosphate (ATP) were measured.RESULTS: MRS changes reflected the degree of liver dysfunction in all the patients as well as in individual etiological groups. The most important change was a decrease of PDE. It was possible to distinguish alcoholic,viral and cholestatic etiologies based on MR spectra.Alcoholic and viral etiology differed in PDE (alcoholic,viral, controls: 6.5±2.3, 6.5±3.1, 10.8±2.7 mmol/L,P＜0.001) and ATP (alcoholic, viral, controls: 2.9±0.8, 2.8±0.9, 3.7±1.0 mmol/L, P＜0.01) from the control group.Unlike viral etiology, patients with alcoholic etiology also differed in Pi (alcoholic, controls: 1.2±0.4, 1.6±0.6mmol/L, P＜0.05) from controls. No significant changes were found in patients with cholestatic disease and controls; nevertheless, this group differed from both alcoholic and viral groups (cholestatic, alcoholic, viral: 9.4±2.7, 6.5±2.3, 6.5±3.1 mmol/L, P＜0.005) in PDE.CONCLUSION: 31p MRS can significantly help in noninvasive separation of different etiological groups leading to liver cirrhosis. In addition, MRS changes reflect functional liver injury.