Objective To explore the dynamic changes in cerebral hemodynamics in patients with unilateral middle cerebral artery(MCA)occlusion after superficial temporal artery(STA)-MCA bypass surgery.Methods One hundred and nine patients diagnosed with unilateral MCA occlusion by DSA who underwent STA-MCA bypass surgery were retrospectively included in the Department of Neurosurgery of the First Affiliated Hospital of Soochow University.Clinical data of patients were collected within 24 hours after admission,including age,sex,body mass index,stroke risk factors including hypertension,hyperlipidemia,diabetes,smoking,drinking history and atrial fibrillation,clinical manifestations(within the last 6 months;nonspecific symptoms[dizziness,memory loss,unresponsiveness,etc.],transient ischemic attack,and stroke),blood biochemical markers(low density lipoprotein cholesterol,high density lipoprotein cholesterol,triglyceride,total cholesterol,fasting blood glucose,and hypersensitive C-reactive protein),and National Institutes of Health stroke scale(NIHSS)score at admission.Color Doppler ultrasound(CDU)and transcranial color coded Doppler(TCCD)ultrasound were used to evaluate the hemodynamic parameters of STA before and at different periods after surgery(4-7 days and 1,3,6,12 months after surgery)to analyze the patency of bypass arteries and intracranial hemodynamic changes,and to check the consistency of the results of the bridge artery patency at 12 months postoperatively by CDU and DSA,consistency test was performed.According to the results of the DSA examination 12months after surgery,the patients were divided into the bypass artery patency group and the non-patency group(stenosis or occlusion).The hemodynamic parameters at the trunk of STA,namely the extracranial segment,transcranial,and intracranial part of the bypass arteries,were compared between the two groups.It included inner diameter(D),peak systolic velocity(PSV),end-diastolic velocity(EDV),resistance index(RI),pulsation index(PI),time-averaged mean velocity(TAMV),time-averaged peak velocity(TAPV),and calculated flow of the STA trunk including TAMV flow and TAPV flow.Head CT,CT angiography(CTA)above the aortic arch,and CT perfusion(CTP)of the whole brain were performed 1 to 3 days before surgery and 12 and 18 months after surgery to observe the changes in cerebral perfusion.Head CT was performed 1 to 2 days after the operation to observe whether there were new hemorrhagic and ischemic lesions in the operative area.the CTP parameters of the two groups were compared including 12 and 18 months after the operation with 1 to 3 days before the surgery,and the differences in CTP parameters between the two groups were compared.The modified Rankin scale(mRS)was used to evaluate the neurological function prognosis of the patients at 12 and 18 months after surgery.The mRS score 2 was divided into a good prognosis and mRS score≥3 was a poor prognosis.NIHSS score of the patients was recorded 7 days,12,and 18 months after surgery.Results(1)Consistency analysis of CDU and DSA:the consistency of the assessment of bypass artery patency was excellent at 12 months after surgery,and the Kappa value was 0.94(95％CI 0.81-1.00,P＜0.01).According to DSA,101 cases(92.7％)were in bypass artery patency group,while 8 cases(7.3％)in the non-patency group(no case of occluded bridge vessel was found),and the sites of stenosis in the bypass arteries were all located in the transcranial segment.(2)Hemodynamic parameters:compared with the preoperative results,the D of the extracranial segment increased on 4-7 days and 1,3,6,and 12 months after the operation(Wald x2=30.438).Hemodynamic parameters included increased blood velocity such as PSV,EDV,TAMV,and TAPV(Waldx2 was 12.117,29.310,31.075 and 17.525,respectively)and blood flow including TAMV flow and TAPV flow(Wald x2 was 54.503 and 34.986,respectively)increased,while RI and PI values were decreased(Waldx2 was 112.568 and 103.629,respectively),and the differences were statistically significant(all P＜0.05).However,there was no significant difference in hemodynamic parameters in the non-patency group at 12 months after operation(all P＞0.05).Compared with 4-7 days after surgery,PSV(252.0[206.8,315.3]cm/s vs.102.5[84.0,119.0]cm/s)and EDV(119.5[106.3,159.8]cm/s vs.43.5[36.8,52.0]cm/s)in the non-patency group were significantly higher at the cranial entrance 12 months after surgery(both P＜0.05),but there was no significant difference in RI and PI values(both P＞0.05).Compared with 4-7 days after surgery,the blood flow parameters of STA intracranial segment,including PSV(29.4[24.8,41.4]cm/s vs.111.5[63.3,120.0]cm/s),EDV(19.7[15.2,22.2]cm/s vs.58.5[28.3,70.0]cm/s)and PI(0.55[0.42,0.63]vs.0.83[0.61,0.90])values in the non-patency group at 12 months after surgery were significantly decreased(all P＜0.05).(3)CTP parameters:the relative cerebral blood flow(rCBF)of the patency group increased at 12 and 18 months after surgery compared to preoperative levels,while relative cerebral blood volume(rCBV),relative peak time(rTTP)and relative mean transit time(rMTT)decreased,with statistical significance(all P＜0.05).At 12 and 18 months after operation,rCBF increased,while rMTT decreased in the non-patency group(both P＜0.05),but there was no significant difference as for rCBV and rTTP.The rTTP of the patency group at 12 and 1 8 months was lower than that of the non-patency group(12 months after surgery:1.14[1.06,1.15]vs.1.20[1.14,1.28],P=0.024;1 8 months after surgery:1.14[1.06,1.15]vs.1.20[1.14,1.28],P=0.023),but there was no statistical significance for other parameters between the two groups(all P＞0.05).(4)NIHSS score and prognosis:clinical follow-up results 18 months after the operation showed that no new stroke occurred during the follow-up period.The NIHSS scores in the patency group and the non-patency group were remarkably lower at 7 days,12,and 18 months after surgery than at admission(patency group:2[0,4],1[0,2],0[0,2]vs.3[0,6],respectively;the non-patency group:3[1,5],3[1,6],2[1,6]vs.4[1,7],respectively),with significant differences(all P＜0.05);However,the NIHSS scores in the patency group were significantly lower than that in the non-patency group at 12 and 18 months after surgery,and the proportion of patients with good prognosis in the patency group was substantially higher than that in the non-patency group(12months:87.1％[88/101]vs.4/8,P=0.039;18 months:90.1％[91/101]vs.4/8,P=0.025).Conclusion CDU can quantitatively evaluate the hemodynamic changes of bypass arteries after the STA-MCA bypass procedure,which can be applied to the long-term dynamic follow-up after the surgery.

Objective To investigate the effect of hypoxia-induced factor 1α and 2α(HIF-1α and HIF-2α)on ethanol-in-duced intestinal epithelium cellular barrier dysfunction of colorectal adenocarcinoma cell(Caco-2)monolayers and its mechanism.Methods Intestinal epithelium monolayer cellular barrier model was obtained by Caco-2 in vitro and induced by ethanol with different concentrations.The cell viability was measured by MTT method.Caco-2 cells were treated with or without ethanol according to the opti-mum concentration and time.The secretions of interleukin 1 β(IL-1 β)and interleukin 6(IL-6)were detected by ELISA.The expres-sions of HIF-lα,HIF-2α,and Neu3 were analyzed by Western blot and RT-PCR.The permeability of Caco-2 cell monolayers was evaluated by transepithelial electrical resistance(TEER).Next,Caco-2 cells were transfected with small interfering RNA(siRNA)to knock down the expression of HIF-1α and HIF-2α.The cell viability,the levels of IL-1 β and IL-6,and the expression of Neu3 and TEER in each group were detected,respectively.Then,the expression of Neu3 was inhibited with siRNA to assess the permeability of Ca-co-2 cell monolayers by TEER.Results The inhibitory effect of ethanol on Caco-2 cells was dose-dependent when the concentration of ethanol was higher than 5％.When Caco-2 cells were treated with ethanol with a concentration of 5％for one hour,the levels of proinflammatory cytokines IL-1 β and IL-6 were promoted.Compared to the control group,ethanol also induced the expression of HIF-1α,HIF-2α,Neu3 and reduced TEER values(P＜0.05).After HIF-1α or HIF-2α siRNA interference in ethanol-induced Caco-2 cells,the cell viability was inhibited,the secretions of IL-1 β and IL-6 were significantly elevated and the values of TEER were decreased(P＜0.05).Interestingly,the expression of Neu3 was inhibited when HIF-2α was deleted but not HIF-1α(P＜0.05).Furthermore,TEER analysis showed an increased cellular permeability when the expression of Neu3 was inhibited(P＜0.05).Conclusion The HIF-1α or HIF-2α signal pathway may be involved regulation process of ethanol-induced increased permeability of the intestinal epithelium cellular barrier.In this process,Neu3 may be mediated by HIF-2α but not HIF-1α,contributing to intestinal epithelium cellular barrier dysfunction in ethanol-induced Caco-2.

OBJECTIVES: Idiopathic intracranial hypertension (IIH) is a syndrome that excludes secondary causes such as intracranial space-occupying lesion, hydrocephalus, cerebrovascular disease, and hypoxic ischemic encephalopathy. If not be treated promptly and effectively, IIH can cause severe, permanent vision disability and intractable, disabling headache. This study aims to explore the clinical and image features for IIH, to help clinicians to understand this disease, increase the diagnose rate, and improve the outcomes of patients. METHODS: We retrospectively analyzed 15 cases of IIH that were admitted to Xiangya Hospital, Central South University, during January 2015 to September 2020. The diagnosis of IIH was based on the updated modified Dandy criteria. We analyzed clinical data of patients and did statistical analysis, including age, gender, height, weight, medical history, physical examination, auxiliary examination, treatment and outcome. RESULTS: There were 10 females and 5 males. Female patients were 22 to 42 years old with median age of 39.5. Male patients were 27 to 52 years old with the median age of 44.0. The BMI was 24.14-34.17 (28.71±2.97) kg/m CONCLUSIONS IIH primarily affects women of childbearing age who are overweight. The major hazard of IIH is the severe and permanent visual loss. Typical image signs have high specificity in IIH diagnosis. Prompt diagnosis and effective treatment are significantly important to improve the outcomes of patients.
Adult ; Anemia, Iron-Deficiency ; Female ; Humans ; Intracranial Hypertension ; Male ; Middle Aged ; Pseudotumor Cerebri/diagnostic imaging* ; Retrospective Studies ; Ventriculoperitoneal Shunt ; Young Adult

Exosomes are spherical microvesicles(30-100 nm)secreted by a variety of cells and contain a variety of proteins, lipids, mRNAs, and microRNAs.These molecules into exosomes can be transferred to adjacent cells and distant tissues or cells by exosomes to develop full effects.Exosomes-released microRNAs are involved in the pathogenesis of Alzheimer's disease(AD)by regulating the abnormal expression of amyloid β-protein(Aβ)and p-Tau protein, initiating the inflammatory response by interacting with toll-like receptors.In addition, exosomal microRNAs can be used as a potential therapeutic target for AD.Exosomes as good carriers have great research values.This review summarized the literatures related to the role of exosomal microRNAs in the development of AD and the potential therapeutic effect on AD.A large amount of evidence indicates that expression disorder of exosomal microRNA plays an important role in the pathogenesis of AD and can be used as a new potential biomarker and therapeutic target for the diagnosis and treatment of AD.

Objective:To investigate the miRNA-1246 expression in photoaged human fibroblasts (HSFs) induced by ultraviolet A (UVA) , and to evaluate the effect of upregulating miRNA-1246 expression on its target gene MAPK14 and cell aging.Methods:HSFs were isolated from foreskins of healthy children after circumcision in Children′s Hospital of Soochow University, and irradiated with 10 J/cm 2 UVA once a day for 14 consecutive days. Real-time quantitative PCR was performed to determine the expression of miR-1246 immediately after the first irradiation and on days 3, 7 and 14 after the start of irradiation. Some HSFs were divided into 4 groups: blank control group receiving no treatment, UVA group irradiated with 10 J/cm 2 UVA for 14 days, miR-1246 group transfected with a lentiviral vector carrying miR-1246, and UVA + miR-1246 group transfected with a lentiviral vector carrying miR-1246 followed by irradiation with UVA. After treatment, the HSFs were collected, methyl thiazolyl tetrazolium (MTT) assay was performed to assess cellular proliferativy activity, β-galactosidase staining to detect senescent cells, RT-PCR and Western blot analysis were conducted to measure the mRNA and protein expression of MAPK14 and matrix metalloproteinase 1 (MMP-1) . One-way analysis of variance was used for comparison of means among multiple groups, and least significant difference (LSD) - t test was used for multiple comparisons. Results:On days 7 and 14, the relative expression of miR-1246 in HSFs was significantly lower in the UVA group (4.69 ± 0.85, 3.59 ± 0.45, respectively) than in the blank control group (8.42 ± 0.75, 7.61 ± 0.49, t = 29.84, 31.93, respectively, both P < 0.01) . After upregulation of miR-1246 and irradiation with UVA, MTT assay showed that the cellular proliferative activity significantly differed among the blank control group, UVA group, miR-1246 group, UVA + miR-1246 group (0.82 ± 0.03, 0.23 ± 0.02, 0.81 ± 0.02, 0.61 ± 0.02, respectively; F = 34.90, P < 0.05) , significantly lower in the UVA group than in the blank control group ( t = 28.14, P < 0.01) , lower in the UVA + miR-1246 group than in the miR-1246 group ( t = 10.61, P < 0.01) , but significantly higher in the UVA + miR-1246 group than in the UVA group ( t = 20.30, P < 0.01) . β-Galactosidase staining showed that the proportion of senescent cells significantly differed among the above 4 groups (3.93% ± 1.11%, 81.29% ± 2.53%, 5.50% ± 1.15%, 54.13% ± 2.09%, respectively; F = 16.14, P < 0.05) , significantly higher in the UVA group than in the blank control group ( t = 48.46, P < 0.01) , higher in the UVA + miR-1246 group than in the miR-1246 group ( t = 35.31, P < 0.01) , but significantly lower in the UVA + miR-1246 group than in the UVA group ( t = 14.32, P < 0.01) . Both RT-PCR and Western blot analysis showed that the mRNA and protein expression of MAPK14 and MMP-1 significantly differed among the above 4 groups (both P < 0.05) , significantly higher in the UVA group than in the blank control group ( P < 0.05) , higher in the UVA + miR-1246 group than in the miR-1246 group ( P < 0.05) , but significantly lower in the UVA + miR-1246 group than in the UVA group ( P < 0.05) . Conclusions:In the senescent HSFs induced by UVA, the expression of miR-1246 is suppressed. Upregulating the expression of miR-1246 can exert anti-photoaging effect by inhibiting the expression of its target gene MAPK14 and aging-related protein MMP-1.

Objective:To investigate the influence of echinoside on the expressions of inducible nitric oxide synthase (iNOS) and transforming growth factor-β1 (TGF-β1) in renal tissues of diabetic nephropathy rats.Methods:A total of 60 male SD rats were randomly divided into the normal group, model group, glibenclamide group and low-, medium-, high-dose echinoside treatment group. the rat model of diabetic nephropathy was established through the streptozocin induction and the glibenclamide treatment was applied as control. After molding, glibenclamide group was given 5 mg/(kg?d) of glibenclamide, and low-, medium-, high-dose echinoside treatment group was given 50, 100 and 200 mg/(kg?d) of echinacoside solution. The normal group and model group were intragastrically given equal volume of normal saline. After 4 weeks, the change rate of body weight, kidney weight/body weight, blood glucose, serum TC, TG, BUN, SCR and 24 h urinary protein levels were measured, and the NO release concentration in renal tissue cell culture medium was measured, the renal pathology was observed by HE staining, the expression of iNOS and TGF-β1 proteins in renal tissues was detected by Western blotting.Results:Compared with the model group, the body weight of rats in the medium-dose group significantly increased ( P<0.05); the weight change rate and kidney weight/body weight of rat in the medium-, high-dose group significantly decreased ( P<0.05), and the NO release concentration in the medium-, high-dose group decreased ( P<0.05); the level of blood glucose, TC, TG, BUN, SCr, and 24-hour urinary protein in the low-, medium- and high-dose groups significantly decreased ( P<0.05), and iNOS in renal tissue of rats in the low-, medium- and high-dose groups was significantly lower ( P<0.05). Compared with the model group, the relative expression levels of TGF-β1 (1.35 ± 0.06, 1.15 ± 0.05, 0.91 ± 0.04 vs. 4.58 ± 0.09) and TGF-β1 (1.24 ± 0.04, 1.41 ± 0.05, 0.89 ± 0.04 vs. 3.04 ± 0.05) in the low-, medium- and high-dose groups significantly decreased ( P<0.05). Conclusions:The echinoside can prevent weight loss, reduce blood glucose and triglyceride, inhibit the production of NO in renal tissues, reduce the expression of iNOS and TGF-β1 among diabetic nephropathy rats. It has been proved to play a protective role in diabetic nephropathy pathological tissues.

Enterovirus D68 (EV-D68) was first isolated in 1962, and then reported infrequently. As its genetic diversity increased rapidly, the detection rate of EV-D68 has been rising worldwide in recent decade. Since EV-D68 caused the most widespread outbreak in the United States, Canada and Europe in 2014, an increasing number of studies had reported that EV-D68 was associated with severe respiratory diseases and neurological complications, even death. However, the pathogenesis of EV-D68 remains unclear. Moreover, no vaccines or specific antiviral agents are available for prevention and treatment for EV-D68 infection at present. Therefore, continued surveillance and rapid diagnosis of EV-D68 infection will be beneficial to prevent and manage the potential outbreak. This article gives an overview of the biological characteristics, clinical features, and epidemiology of EV-D68.

Five patients with myopathy associated with anti-signal recognition peptide antibodies, admitted to our hospital from December 2015 to June 2018, were chosen in our study, and their clinical and pathological manifestations and treatments were retrospectively analyzed. Five patients showed subacute or chronic onset and proximal limb muscle weakness. Serum creatine kinase level was significantly elevated. Immunoblotting assay confirmed the positive anti-signal recognition particle antibody. EMG prompted myogenic damage. Pathological features included muscle degeneration, necrosis with regeneration, visible atrophy and hypertrophic of muscle fiber, connective tissue hyperplasia and a small amount of inflammatory cell infiltration. Immunohistochemical staining showed necrotizing muscle fiber infiltrated with CD4-positive and CD8-positive lymphocytes and CD68-positive macrophages, and no CD20-positive lymphocytes and CD303-positive dendritic cells were observed. Two patients had expressed a bit of c5b-9 positive capillary. Anti-sarcoglycans staining, anti-dysferlin staining and dystrophin staining showed continuous strong positive expression. Follow-up study found that all patients were response to glucocorticoid, and a combination therapy of immunoglobulin and immunosuppression were necessary for some patients.
Autoantibodies ; Follow-Up Studies ; Humans ; Muscular Diseases ; Protein Sorting Signals ; Retrospective Studies

To analyze the clinical and image features for 12 patients of cerebral autosomal dominant arteriopathy with subcortical infarct and leucoencephalopathy (CADASIL).
 Methods: A total of 12 CADASIL patients were collected in Xiangya Hospital of Central South University from January 2013 to December 2018. The clinical manifestation, risk factors, MRI imaging data and NOTCH3 mutations were analyzed retrospectively.
 Results: The mean age of 12 patients was (47.25±9.49) years. The clinical manifestation was most common in cognitive impairment (75%) and stroke events (58.3%), and 2 cases showed cerebral hemorrhage. Migraine was only seen in 25% patients. All MRI showed white matter hyperintensity (WMH), lacune and enlarged perivascular space (PVS). WMH mainly occurred in the frontal parietal lobe (100%), temporal lobe (83.3%), external capsule (66.7%), occipital lobe (41.6%), callosum 41.6% and the temporal pole (33.3%), while lacune mainly appeared in frontal lobe (91.6%), parietal lobe(83.3%), temporal lobe(66.7%), basal ganglia (66.7%), brain stem (41.6%), occipital lobe (33.3%), cerebellum (8.3%). Enlarged PVS located in the basal ganglia (100%), partly under the cortex (45.4%). WMH of the patient with intracerebral hemorrhage was mild (Fezakas score 1-2), which was not found in external capsule. 16.7% of the patients had intracranial arterial stenosis. In 12 patients, 8 different Notch3 mutations were detected. The c1013G>c p.(Cys338Ser) located in exon 6, which was a new pathogenic mutation of CADASIL.
 Conclusion: The patients with cerebral hemorrhage have mild WMH and specific genotype, indicating that the clinical characteristics of CADASIL with cerebral hemorrhage may be related to image features and genotype.
Adult ; CADASIL ; Cerebral Infarction ; Humans ; Leukoencephalopathies ; Middle Aged ; Retrospective Studies ; Temporal Lobe

To determine the etiologies and risk factors of intracerebral hemorrhage in young people.
 Methods: A total of 401 young patients with intracerebral hemorrhage were enrolled, and they were assigned into a 20-29 , a 30-39, and a 40-45 age group. The differences of various etiologies and risk factors among the three groups were analyzed.
 Results: There were 273 men and 128 women in the 401 young patients. The etiologies of 294 patients (73.32%) were identified while 107 patients (26.68%) were unknown. Among those with identified etiology, 226 patients (56.36%) suffered from hypertension, 41 patients (10.22%) congenital cerebrovascular malformation (including 25 patients with cerebral arteriovenous malformation, 8 intracranial cavernous hemangioma, and 8 intracranial aneurysm), and 27 other etiologies (including 9 patients with moyamoya disease, 6 cerebral venous sinus thrombosis, 4 drug abuse, 3 hemorrhagic brain tumor, 2 intracranial infection, 1 systemic lupus erythematosus, 1 drug-induced, and 1 eclampsia). Risk factors included hypertension (237 cases, 59.10%), smoking (123 cases, 30.67%), alcohol consumption (74 cases, 18.45%), and others (19 cases, 4.74%; including 8 cases of pregnancy or in the puerperium, 8 family history of intracerebral hemorrhage, and 3 taking anti-platelet aggregation/anticoagulation agents). The rate of hypertension induced hemorrhage significantly increased with age (P<0.01); the rate of vascular malformations in 20-29 age group was obviously higher than other groups (P<0.01); the rate of unknown cause in the 40-45 age group was significantly lower than other groups (P<0.01) and the rate of other etiologies showed no significant difference in the 3 groups. The rate of hypertension was significantly elevated with the age (P<0.01), while smoking, alcohol consumption, and other risk factors showed no significant difference in the 3 groups.
 Conclusion: The rate of intracerebral hemorrhage in young people increases with the increasing of age and hemorrhage affects men more than women; hypertension may be the main cause and congenital cerebrovascular malformation is the second cause, which may be more common in younger patients. Hypertension, smoking, and alcohol consumption may be the major controllable risk factors in intracerebral hemorrhage in young people.
Adult ; Cerebral Hemorrhage ; etiology ; Female ; Humans ; Hypertension ; complications ; Intracranial Aneurysm ; complications ; Intracranial Arteriovenous Malformations ; complications ; Male ; Middle Aged ; Pregnancy ; Risk Factors ; Young Adult