Regulator of G protein signaling 6 mediates exercise-induced recovery of hippocampal neurogenesis,learning,and memory in a mouse model of Alzheimer’s disease

Hippocampal neuronal loss causes cognitive dysfunction in Alzheimer’s disease.Adult hippocampal neurogenesis is reduced in patients with Alzheimer’s disease.Exercise stimulates adult hippocampal neurogenesis in rodents and improves memory and slows cognitive decline in patients with Alzheimer’s disease.However,the molecular pathways for exercise-induced adult hippocampal neurogenesis and improved cognition in Alzheimer’s disease are poorly understood.Recently,regulator of G protein signaling 6(RGS6)was identified as the mediator of voluntary running-induced adult hippocampal neurogenesis in mice.Here,we generated novel RGS6fl/fl;APP_(SWE) mice and used retroviral approaches to examine the impact of RGS6 deletion from dentate gyrus neuronal progenitor cells on voluntary running-induced adult hippocampal neurogenesis and cognition in an amyloid-based Alzheimer’s disease mouse model.We found that voluntary running in APP_(SWE) mice restored their hippocampal cognitive impairments to that of control mice.This cognitive rescue was abolished by RGS6 deletion in dentate gyrus neuronal progenitor cells,which also abolished running-mediated increases in adult hippocampal neurogenesis.Adult hippocampal neurogenesis was reduced in sedentary APP_(SWE) mice versus control mice,with basal adult hippocampal neurogenesis reduced by RGS6 deletion in dentate gyrus neural precursor cells.RGS6 was expressed in neurons within the dentate gyrus of patients with Alzheimer’s disease with significant loss of these RGS6-expressing neurons.Thus,RGS6 mediated voluntary running-induced rescue of impaired cognition and adult hippocampal neurogenesis in APP_(SWE) mice,identifying RGS6 in dentate gyrus neural precursor cells as a possible therapeutic target in Alzheimer’s disease.

The role of exosomes in adult neurogenesis:implications for neurodegenerative diseases

Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells.As an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous system.Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits.In the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus.An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches.In recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease models.Here,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases.We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults.In addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.

Use of exclusive enteral nutrition in adults with Crohn's disease: A review

Exclusive enteral nutrition(EEN)is well-established as a first line therapy instead of corticosteroid(CS)therapy to treat active Crohn’s disease(CD)in children.It also has been shown to have benefits over and above induction of disease remission in paediatric populations.However,other than in Japanese populations,this intervention is not routinely utilised in adults.To investigate potential reasons for variation in response between adult studies of EEN and CS therapy.The Ovid database was searched over a 6-mo period.Articles directly comparing EEN and CS therapy in adults were included.Eleven articles were identified.EEN therapy remission rates varied considerably.Poor compliance with EEN therapy due to unpalatable formula was an issue in half of the studies.Remission rates of studies that only included patients with previously untreated/new CD were higher than studies including patients with both existing and new disease.There was limited evidence to determine if disease location,duration of disease or age of diagnosis affected EEN therapy outcomes.There is some evidence to support the use of EEN as a treatment option for a select group of adults,namely those motivated to adhere to an EEN regimen and possibly those newly diagnosed with CD.In addition,the use of more palatable formulas could improve treatment compliance.

Adult hippocampal neurogenesis and its impairment in Alzheimer's disease

Adult neurogenesis is the creation of new neurons which integrate into the existing neural circuit of the adult brain.Recent evidence suggests that adult hippocampal neurogenesis(AHN)persists throughout life in mammals,including humans.These newborn neurons have been implicated to have a crucial role in brain functions such as learning and memory.Importantly,studies have also found that hippocampal neurogenesis is impaired in neurodegenerative and neuropsychiatric diseases.Alzheimer’s disease(AD)is one of the most common forms of dementia affecting millions of people.Cognitive dysfunction is a common symptom of AD patients and progressive memory loss has been attributed to the degeneration of the hippocampus.Therefore,there has been growing interest in identifying how hippocampal neurogenesis is affected in AD.However,the link between cognitive decline and changes in hippocampal neurogenesis in AD is poorly understood.In this review,we summarized the recent literature on AHN and its impairments in AD.

A new age in understanding adult hippocampal neurogenesis in Alzheimer’s disease

Several lines of evidence have established that proliferation and differentiation of neural stem cells into neurons within the sub-granular zone of the dentate gyrus,a process named adult hippocampal neurogenesis,contribute to maintaining healthy cognitive functions throughout life.The rate of adult hippocampal neurogenesis decreases with aging and a premature impairment of adult hippocampal neurogenesis has been observed both in animal models of Alzheimer’s disease and human post-mortem tissues.The causal relationship between adult hippocampal neurogenesis and the development of Alzheimer’s disease pathology has,however,not been established.This is partly due to the limitation of recapitulating the development of Alzheimer’s disease pathology in rodent models and the lack of translatable biomarkers to identify tractable targets in humans.While it is tempting to postulate that adult hippocampal neurogenesis could be leveraged to improve cognitive deficits in Alzheimer’s disease,consensual results have yet to be reached to fully explore this hypothesis.In this review,we discuss how the recent progress in identifying molecular pathways in adult hippocampal neurogenesis provides a good framework to initiate strategies for drug-based intervention in neurodegenerative diseases,especially in Alzheimer’s disease.We outline how discrepancies in pre-clinical disease models and experimental methodology have resulted in contradictory findings and propose a shift towards using more translatable approaches to model neurogenesis in Alzheimer’s disease.In particular,we review how exploring novel experimental paradigms including the use of human induced pluripotent stem cells and more complex cell culture systems,as well as standardizing protocols used to investigate evidence of neurogenesis in human tissues,could deliver deeper mechanistic insights that would kick-start innovative drug discovery efforts to promote healthy aging and cellular rejuvenation.

Reoperation in an adult female with "right-sided" Hirschsprung's disease complicated by refractory hypertension and cough

Hirschsprung's disease(HD) is an intestinal malformation caused by the innate absence of ganglion cells in the neural plexus of the colorectal wall, and is most common in male infants. It is rare in adult, and is usually left-sided. Herein we reported based on the CARE guidelines a case of a 47-year-old adult female suffering from "right-sided" HD complicated by refractory hypertension and cough. The patient with a history of cesarean section and with digestive unfitness(abdominal pain, distention, and constipation) only since 20 years old had recurrence of HD after initial surgery due to the incomplete removal of the HD-affected bowel based on a diagnosis of "chronic ileus", leading to the relapse of the digestive symptoms and the emergence of some intractable circulatory and respiratory complications which could be hardly controlled by conservative treatment. During the long interval before coming to our department for help, she had been re-hospitalized for several times with various misdiagnoses and supplied merely with symptomatic treatment which could only achieve temporary symptomatic relief. At her admission to our department, the imaging examinations strongly indicated recurrent HD which was further supportedb y p a t h o l o g i c a l e x a m i n a t i o n s, a n d r i g h t h e m i-colectomy was performed to remove the remnant aganglionic intestinal segment. Intraoperative and postoperative pathology supported the completeness of the definitive resection. Post-operation, the patient's bowel motility significantly improved, and interestingly, the complications disappeared. For adult patients with long-term constipation combined with cough and hypertension, rare diseases like HD which requires definite surgery and which could be "right-sided" should not be overlooked. It is vital to diagnose and cure HD patients in childhood. Through the comparison of the two surgeries, it is noteworthy that for diagnosed HD, sufficient removal of the non-functional intestine confirmed by intraoperative pathology is essential.

Novel case of Trevor's disease:Adult onset and later recurrence

Dysplasia epiphysealis hemimelica(DEH),or Trevor’s disease,is an osteocartilaginous epiphyseal overgrowth typically occurring in children.The literature reports6 adult cases and none describe recurrence requiring additional procedures.We present a new-onset proximal tibial DEH in an adult recurring approximately 3 years after open excision.A 39-year-old female presented with a history of right knee pain,swelling,and instability.Physical examination revealed a firm proximal tibial mass.Computed tomography(CT)imaging showed an exophytic,lobulated,sclerotic mass involving the anterolateral margin of the lateral tibial plateau.Magnetic resonance imaging was suggestive of an osteochondroma.The patient underwent curettage of the lesion due to its periarticular location.Histology revealed benign and reactive bone and cartilage consistent with periosteal chondroma.Two and a half years later,the patient presented with a firm,palpable mass larger than the initial lesion.CT revealed a lateral tibial plateau sclerotic mass consistent with recurrent intraarticular DEH.A complete excision was performed and histology showed sclerotic bone with overlying cartilage consistent with exostosis.DEH is a rare epiphyseal osteocartilaginous outgrowth frequently occurring in the long bones of children less than 8 years old.DEH resembles an osteochondroma due to its pediatric presentation and similar histologic appearance.Adultonset cases comprise less than 1%of reported cases.Recurrence rate after surgical intervention is unknown.Only 1 such case,occurring in a child,has been described.Clinicians contemplating operative treatment for DEH should note the potential for recurrence and consider complete excision.A follow-up period of several years may be warranted to identify recurrent lesions.

Anti-CD-20 Therapy in Refractory Adult Still’s Disease

Adult Still’s disease is a relatively rare form of rheumatoid arthritis with systemic inflammatory features. The prevalence is around 1.5 cases per 100,000 - 1000,000. In the current case we display a 30-year-old male patient with refractory adult still’s disease who suffered recurrent attacks of fever 39.5°C, arthritis in proximal interphalangeal joints (PIPs), wrists, tempromandibular joints (TMJs), knees and ankles, stitching chest pain, dyspnea, erythematous rash over the trunk, sore throat, weight loss (15 Kilograms in 4 months). The patients’ disease remained uncontrolled despite of synthetic disease modifying anti-rheumatic drugs and repeated intramuscular corticosteroid injections. Laboratory workup revealed erythrocyte sedimentation rate (ESR) of 95, C-reactive protein (CRP) of 100 mg/L, hemoglobin 10.5 gm%, leukocytosis 12,000/microlitre, mild elevation of liver function tests and dyslipidemia. Serology revealed negative rheumatoid factor, anti-nuclear antibody titre of 1:80, elevated serum ferritin 4000 micrograms/litre. The patient was started on rituximab (375 mg/m2), prednisolone 20 mg/day and selective Cox-2 inhibitor. Follow up for over three months following the completion of his pulse therapy, revealed no relapse of fever or fatigue, with morning stiffness of 5 - 10 minutes, VAS of 3, DAS28 of 3.8, HAQDI of 0.62, ESR 23, CRP 4.9, Hb 12.5 gm%, leucocytic count 9000/microlitre, the dose of prednisolone was successfully reduced to a dose of 5 mg/day orally. Conclusion: Anti-CD20 therapy successfully controlled systemic and articular refractory disease with sustained efficacy over a follow up period of up to 24 weeks.

Adult Onset Still’s Disease

The adult onset Still’s disease is a rare affection characterised by occurrence of fever, arthralgia or arthritis and evanescent cutaneous eruption. Multiple other systemic lesions make the diagnosis more difficult. Several diagnostic criteria were formulated to confirm this disease. The physiopathology of the adult onset Still’s disease is not well elucidated. However, several studies based on new facts in physiopathology, improved the therapy of refractory forms for which the biotherapy was an interesting alternative. The TNF alpha receptor antagonists are efficient on systemic and articular manifestations of this disease and allow a corticosteroid’s saving. Tocilizumab (interleukin 6 receptor antagonist), and Anakinra (interleukin 1 receptor antagonist) are also new promising treatments for resistant forms.

Adult Onset Still’s Disease: Articular Manifestations in Twenty Cases

The adult onset Still’s disease is a rare inflammatory pathology of unknown pathogeny. The clinical features are variable. The diagnosis is difficult since exclusion of infectious, systemic and tumoral pathologies should be done. The articular complications are frequent and can be revelatory of this pathology. The articular prognosis depends on the diagnosis delay and the treatment efficiency. Our study aims to analyze different aspects of articular manifestations complicating adult onset Still’s disease to define epidemiological, clinical and evolving characteristics of these complications. It was a cross-sectional study concerning 20 cases of adult onset Still’s disease diagnosed from 1990 to 2015 in the internal medicine A department of Charles Nicolle Hospital in Tunis, meeting Yamaguchi criteria. We identified clinical, radiological, evolving and therapeutic profile of the articular manifestations occurred in these patients. There were 13 women and 7 men. The average age was 25 years. The arthralgias were reported in all cases;while, the arthritis interested fifteen patients. A hand deformation was found in four patients. A wrist ankylosis was noted in one case and a flexion elbow in one patient. The standard articular radiographs were normal in twelve cases. The treatment associated essentially non-steroidal anti-inflammatory and/or corticosteroids and/or methotrexate. Concerning the evolving profile, the monocyclic form was present in 25% of the cases, the intermittent form in 45% and the chronic articular form in 30% of our patients. The adult onset Still’s disease is rare and heterogeneous. The articular disturbances are frequent and have various outcomes.

Chronic liver disease questionnaire:Translation and validation in Thais

AIM:Quality of life (QOL) is a concept that incorporates many aspects of life beyond“health”.The chronic liver disease questionnaire (CLDQ) was developed to evaluate the impact of chronic liver diseases (CLD) on QOL.The objectives of this study were to translate and validate a liver specific questionnaire,the CLDQ. METHODS:The CLDQ was formally translated from the original version to Thai language with permission.The translation process included forward translation,back translation,cross-cultural adaptation and a pretest.Reliability and validity of the translated version was examined in CLD patients.Enrolled subjects included CLD and normal subjects with age- and sex-matched.Collected data were demography, physical findings and biochemical tests.All subjects were asked to complete the translated versions of CLDQ and SF- 36,which was previously validated.Cronbach's alpha and test-retest were performed for reliability analysis.One-way Anova or non-parametric method was used to determine discriminant validity.Speerman's rank correlation was used to assess convergent validity.P-value<0.05 was considered statistically significant. RESULTS:A total of 200 subjects were recruited into the study,with 150 CLD and 50 normal subjects.Mean ages (SD) were 47.3(11.7) and 49.1(8.5) years,respectively.The number of chronic hepatitis:cirrhosis was 76:74,and the ratio of cirrhotic patients classified as Child A:B:C was 37 (50%):26(35%):11(15%).Cronbach's alpha of the overall CLDQ scores was 0.96 and of all domains were higher than 0.93.Item-total correlation was>0.45.Test-retest reliability done at 1 to 4 wk apart was 0.88 for the average CLDQ score and from 0.68 to 0.90 for domain scores.The CLDQ was found to have discriminant validity.The highest scores of CLDQ domains were in the normal group,scores were lower in the compensated group and lowest in the decompensated group.The significant correlation between domains of the CLDQ and SF-36 was found.The average CLDQ score was strongly correlated with the general health domain of SF-36.(P=0.69:P=0.01). CONCLUSION:The translated CLDQ is valid and applicable in Thais with CLD.CLDQ reveals that QOL in these patients is lower than that in normal population.QOL is more impaired in advanced stage of CLD.

Induced pluripotent stem cells from Huntington's disease patients:a promising approach to define and correct disease-related alterations

Adult somatic cells such as skin or blood cells from either health donors or patients can be reprogrammed into induced pluripotent stem cells(iPSCs).Given their unlimited self-renewal and differentiation capacities,iPSCs are an invaluable resource to generate terminally differentiated cells.Thus,iPSCs can facilitate the study of human diseases and drug screening,holding great promise for regenerative medicine.Another significant advantage of iPSC disease-modeling is that normal and mutant proteins are expressed at endogenous levels.In addition,subtle phenotypes and the effects of genetic background variations can be assessed by comparison between iPSC lines obtained from different patients and healthy donors as well as isogenic lines,in which disease-related mutations are corrected.

Epidemiological and histopathological study of relevance of Guizhou Maotai liquor and liver diseases

AIM: To explore the relevance of Maotai liquor and liver diseases. METHODS: Epidemiological study was conducted on groups of subjects, each consisting of 3 subjects from the Maotai liquor group consisting of 99 individuals and one from the non-alcoholic control group consisting of 33 individuals. Liver biopsy was performed on 23 volunteers from Guizhou Maotai Distillery who had a constant and long history of drinking Maotai liquor. Experimental histopathological study was conducted as follows: sixty male Wistar rats were divided into 3 groups randomly and fed with Maotai liquor, ordinary white wine, and physiological saline respectively for a period of 8 and 12 weeks. The rats were sacrificed in batches, then serum ALT, AST, TBil, and AKP were measured. Rat livers were harvested to measure the liver indexes, GSH, and MDA. Histopathological examinations were also performed. Another eighty mice were randomly divided into 4 groups and fed with Maotai (at different dosages of 10 ml.kg(-1) and 20 ml.kg(-1)), ethanol, and physiological saline. The animals were sacrificed after 4 weeks and serum ALT was determined. Then the livers were harvested and liver indexes and MDA were measured. RESULTS: The incidence rate of hepatic symptoms, splenomegaly, liver function impairment, reversal of Albumin/Globulin and increased diameter of portal veins in the Maotai liquor group were 1.0% 1/99 , 1.0% 1/99 , 1.0% 1/99 , 1.0% 1/99 , 0 0/99 and 0 0/99 , 0 0/99 ,0 0/99 , 0 0/99 , 0 0/99 , respectively. There was no significant difference between the Maotai group and the non-alcoholic control group P】0.05 . Various degree of fatty infiltration of hepatocytes was found in the 23 volunteers receiving liver biopsy, but there was no obvious hepatic fibrosis or cirrhosis. A comparison was made between the Maotai liquor group and the ordinary white wine group. It was found that hepatic MDA in rats and mice were 0.33+/-0.10 and 0.49+/-0.23 respectively in Maotai group and 0.61+/-0.22 and 0.66+/-0.32 in the ordinary white wine group; MDA had an obvious decrease in the Maotai liquor group (P【0.05); hepatic GSH were 0.12 mg.g(-1)+/-0.06 mg.g(-1) in rats of the Maotai liquor group and (0.08+/-0.02)mg.g(-1) in white wine group, it was obviously increased in the Maotai liquor group (P【0.05). After the 20 rats had been fed with ordinary white wine for 8 weeks consecutively, disarranged hepatocyte cords, fatty infiltration of hepatocytes, and fibrous septa of varying widths due to hepatic connective tissues proliferation were observed; after 12 weeks, the fibrous tissue proliferation continued and early cirrhosis appeared. Compared with the ordinary white wine group, fatty infiltration was observed in the 8-week and 12-week groups, but no necrosis or fibrosis or cirrhosis was found in the Maotai liquor group (P【0.05). CONCLUSION: Maotai liquor may cause fatty liver but not hepatic fibrosis or cirrhosis, and it can strengthen lipid peroxidation in the liver.

Peripheral blood lymphocytes DNA in patients with chronic liver diseases

BACKGROUND: Viral replication in blood cells with nucleases may lead to the damage of lymphocytes genetic apparatus and the beginning of immunopathological reactions. AIM: Of this investigation is to reveal the damage to peripheral blood lymphocytes (PBL) DNA in the patients with chronic liver diseases. MATERIALS AND METHODS: Sixteen-nine patients with chronic liver diseases (37 patients with chronic viral hepatitis, 2 patients with liver cirrhosis of mixed etiology (alcohol+virus G), 30 women with primary biliary cirrhosis-PBC) were examined. The condition of DNA structure of PBL was measured by the fluorescence analysis of DNA unwinding (FADU) technique with modification. Changes of fluorescence (in %) reflected the DNA distractions degree (the presence of DNA single-stranded breaks and alkalinelabile sights). RESULTS AND CONCLUSION: The quantity of DNA single-stranded breaks and alkalinelabile sights in DNA in all patients with chronic viral hepatitis didn't differ from the control group, excluding the patients with chronic hepatitis (CH) C+G. Patients with HGV and TTV monoinfection had demonstrated the increase of the DNA single-stranded breaks PBL quantity. This fact may be connected with hypothesis about the viruses replication in white blood cells discussed in the literature. Tendency to increase quantity of DNA PBL damages in the patients with primary biliary cirrhosis (PBC) accordingly to the alkaline phosphatase activity increase was revealed. Significant decrease of the DNA single-stranded breaks and alkalinelabile sights in the PBC patients that were treated with prednisone was demonstrated. Probably, the tendency to increase the quantity of DNA single stranded breaks and alkalinelabile sights in lymphocytes of the PBC patients was depended on the surplus of the blood bile acid content.

Ileocolic Intussusception Prolapsing from the Rectum in von Recklinghausen's Disease

Intussusception is a paediatric condition that rarely presents in adults. We report an exceptional case of ileocolic intussusception prolapsing from the rectum in an adult with Von Recklinghausen′s disease. A 31-year-old man with von Recklinghausen′s disease presented to emergency department with a history of severe abdominal pain, vomits and rectal bleeding. Abdominal computed tomography showed intestinal obstruction probably due to a sigmoidorectal intussusception. Ileum, appendix, cecum and ascending colon were found to be intussuscepting through transverse, descending and sigmoid colon and prolapsing from the rectum during an emergent laparotomy. A right hemicolectomy was performed. An anatomical pathology examination revealed a neurofibroma of the appendix as lead point for intussusception. Intussusception in adults requires early surgical resection regardless of the nature of the initial case. Neurofibroma of the appendix is very rare;although it is benign, prompt resection is recommended because of a high risk of appendicitis and malignant transformation.

Acquired segmental colonic hypoganglionosis in an adult Caucasian male:A case report

BACKGROUND Hypoganglionosis is a rare condition that most often presents with abnormal gastrointestinal transit and usually arises in early childhood or adolescence. Two types have been described(Type I and Type II). The adult-onset form(acquired hypoganglionosis) is extremely uncommon and is thought to arise due to cellular remodelling as a result of chronic inflammation. It differs from Hirschprung's disease in that there is a reduction in ganglion cells in the colonic neural plexuses as opposed to being completely absent.CASE SUMMARY A 31 year-old male presented to hospital with recurrent abdominal pain and vomiting over thirteen months. Abdominal computed tomography scans demonstrated thickening and stranding affecting the transverse, descending and sigmoid colon. Endoscopic appearances were non-specific but confirmed a mixed picture of mucosal inflammation and necrosis in various stages of healing.Numerous investigations were performed to elucidate an underlying aetiology but neither an infective nor ischaemic cause could be proven. Biopsy features were not typical of inflammatory bowel disease. Due to persistence of his symptoms and failure of medical management, a segmental colectomy was performed. Histological examination of the specimen revealed an unexpected finding of segmental hypoganglionosis. Complete surgical excision of the diseased segment of colon was curative and since his operation the patient has had no recurrence of symptoms requiring hospitalisation.CONCLUSION Our case serves to raise awareness of acquired hypoganglionosis as a rare condition that can result from chronic colitis.

Nigral dopaminergic neuron replenishment in adult mice through VE-cadherin-expressing neural progenitor cells

The function of dopaminergic neurons in the substantia nigra is of central importance to the coordination of movement by the brain＇s basal ganglia circuitry. This is evidenced by the loss of these neurons, resulting in the cardinal motor deficits associated with Parkinson＇s disease. In order to fully understand the physiology of these key neurons and develop potential therapies for their loss, it is essential to determine if and how dopaminergic neurons are replenished in the adult brain. Recent work has presented evidence for adult neurogenesis of these neurons by Nestin＋/Sox2 neural progenitor cells. We sought to further validate this finding and explore a potential atypical origin for these progenitor cells. Since neural progenitor cells have a proximal association with the vasculature of the brain and subsets of endothelial cells are Nestin＋, we hypothesized that dopaminergic neural progenitors might share a common cell lineage. Therefore, we employed a VE-cadherin promoter-driven CREERT2：TIlox/Tlox transgenic mouse line to ablate the tyrosine hydroxylase gene from endothelial cells in adult animals. After 26 weeks, but not 13 weeks, following the genetic blockade of tyrosine hydroxylase expression in VE-cadherin＋ cells, we observed a significant reduction in tyrosine hydroxylase＋ neurons in the substantia nigra. The results from this genetic lineage tracing study suggest that dopaminergic neurons are replenished in adult mice by a VE-cadherin＋ progenitor cell population potentially arising from an endothelial lineage.

Cow’s milk-induced gastrointestinal disorders:From infancy to adulthood

Milk is related to many gastrointestinal disorders from the cradle to the grave due to the many milk ingredients that can trigger gastrointestinal discomfort and disorders.Cow’s milk protein allergy(CMPA)is the most common food allergy,especially in infancy and childhood,which may persist into adulthood.There are three main types of CMPA;immunoglobulin E(IgE)-mediated CMPA,non-IgEmediated CMPA,and mixed type.CMPA appears before the first birthday in almost all cases.Symptoms may start even during the neonatal period and can be severe enough to simulate neonatal sepsis.CMPA(often non-IgE mediated)can present with symptoms of gastroesophageal reflux,eosinophilic esophagitis,hemorrhagic gastritis,food protein-induced protein-losing enteropathy,and food protein-induced enterocolitis syndrome.Most CMPAs are benign and outgrown during childhood.CMPA is not as common in adults as in children,but when present,it is usually severe with a protracted course.Lactose intolerance is a prevalent condition characterized by the development of many symptoms related to the consumption of foods containing lactose.Lactose intolerance has four typical types:Developmental,congenital,primary,and secondary.Lactose intolerance and CMPA may be the underlying pathophysiologic mechanisms for many functional gastrointestinal disorders in children and adults.They are also common in inflammatory bowel diseases.Milk consumption may have preventive or promoter effects on cancer development.Milk may also become a source of microbial infection in humans,causing a wide array of diseases,and may help increase the prevalence of antimicrobial resistance.This editorial summarizes the common milk-related disorders and their symptoms from childhood to adulthood.

成人Moyamoya病15例临床及DSA影像分析

目的探讨成人Moyamoya病的临床特点及血管造影特征。方法回顾性分析15例经数字减影血管造影(DSA)确诊的成人Moyamoya病患者的临床表现及DSA影像特征。结果本组成人Moyamoya病患者男∶女为1∶1.5,确诊时年龄为21-64岁,平均年龄为42.8±11.28岁。其中脑出血或脑室出血7例(46.7%),脑梗死或短暂性脑缺血发作4例(26.7%),反复头痛、头晕发作3例(20.0%),癫痫发作1例(6.7%)。DSA Suzuki分期:1期1例,2期2例,3期10例,4期2例。基底节穿支动脉代偿性增生扩张14例,软脑膜动脉侧枝代偿14例,眼动脉及筛前、后动脉侧枝代偿7例,硬脑膜动脉颅内代偿6例。结论女性发病占优势。临床表现以出血性卒中为主(46.7%)。DSA Suzuki分期多为3期,对称性动脉狭窄或闭塞多见于前循环,仅见2例大脑后动脉受累,提示该病高度选择性侵犯前循环动脉,前后循环受累差异性的病理生理机制值得探讨。在Willis环动脉慢性闭塞的过程中,除软脑膜动脉及基底节穿支动脉代偿外,硬脑膜动脉及眼动脉也相继参与代偿。对于卒中患者、不明原因的癫痫或反复头痛、头晕患者,建议行颅脑MRA或CTA检查以筛查Willis环动脉有无病变。DSA是Moyamoya病诊断的金标准,可明确脑动脉病变及侧枝代偿途径,为后续药物治疗及血运重建外科治疗提供重要参考。

Suzuki分级及异常代偿血管与成人烟雾病脑出血及缺血的关系

目的进一步探讨成人烟雾病患者脑出血及脑缺血事件的发生机制。方法对86例经全脑血管造影证实的成人烟雾病患者[脑出血52例(104个大脑半球,脑出血组),脑缺血34例(68个大脑半球,脑缺血组)]的临床资料进行回顾性分析,对Suzuki分级、烟雾样血管的丰富程度分期及颅内小动脉扩张不同者的脑出血及脑缺血发生率进行χ2检验及Mann-Whitney U检验。结果①两组Suzuki分级无显著差异,Mann-Whitney U检验Z=0.656、P=0.512;Suzuki分级Ⅲ～Ⅳ级者脑出血率显著高于脑缺血率(P<0.05)。②两组颅底烟雾样异常血管丰富程度分期有显著差异,Mann-Whitney U检验Z=3.909、P=0.000;其中2～4期者脑出血率显著高于脑缺血率(P<0.05)。③两组扩张小动脉无显著差异,Mann-Whitney U检验Z=1.183,P=0.237;同种血管扩张者脑出血率显著高于脑缺血率(P<0.05)。结论成人烟雾病患者脑出血及缺血发生与Suzuki分级无显著相关;烟雾样血管的丰富程度升高及颅内主要小动脉扩张预示脑出血事件发生的可能性大。