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Objective:To understand the prevalence of arboviruses in mosquito samples in Xichang City, Sichuan Province, and enrich the data of arbovirus activity and genetic characteristics in southwestern Sichuan Province.Methods:In June 2018, the nucleic acid was extracted from Culex tritaeniorhynchus mosquitoes collected from different pigsties in three villages and suburbs of Xichang City. The specific primers of Yunnan orbivirus, Banna virus, Tibet orbivirus (S7, S10), Flavivirus and alphavirus were used for quantitative polymerase chain reaction examination, and the positive product was cloned for sequencing analysis. Results:A total of 9 012 mosquitoes were collected, of which Cx. tritaeniorhynchus was the dominant species. A number of 88 batches of these mosquitoes were amplified, and 2 strains of Japanese encephalitis virus (JEV), 7 strains of Banna virus (BAV), 7 strains of Tibet orbivirus (TIBOV) and 1 strain of Yunnan orbivirus virus (YOUV) were detected, respectively. By the results of cluster analysis and evolutionary tree analysis, the 17 newly found virus strains were close to the Yunnan isolates, and 2 JEV strains were located in the GI-b clade. The other 7 strains of BAV were A2 evolutionary clades. Of the 7 TIBOV plants, 6 were located in the same clade. One TOUV was in the same clade as the Yunnan strain. Conclusions:Culex tritaeniorhynchus mosquitoes in Xichang city might carry JEV, BAV, YOUV and TIBOV, among them JEV was GI-b type and BAV was A2 type. The results provide data supporting the detection and analysis of arboviruses in Xichang city.
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Objective:To explore the effect of α7 nicotinic acetylcholine receptor (α7nAchR) and changes of inflammatory factors during vagus nerve electrical stimulation in ischemic stroke model mice.Methods:Ninety SPF grade mice were randomly divided into sham operation+ vagus nerve electrical stimulation group (sham+ VNS group), model group (permanent middle cerebral artery occlusion group, pMCAO group), model+ vagus nerve electrical stimulation (pMCAO+ VNS group) and model group+ α7nAchR agonist group (pMCAO+ P group), model + vagus nerve electrical stimulation+ α7nAchR antagonist (pMCAO+ VNS+ A group), model+ vagus nerve electrical stimulation+ α7nAchR antagonist placebo group (pMCAO+ VNS+ AC group), with 15 mice in each group. The changes of vital signs of mice in each group were monitored during modeling.At 7, 14 and 21 days after successful modeling, neurological severity score (NSS) and adhesive removal test were used to evaluate the neurological deficit of mice.Immunofluorescence and Western blot were used to detect the expression of α7nAchR and its neural cell localization. ELISA was used to detect the level of TNF-α and IL-6. Prism 8.0 software was used for statistical analysis, and one-way ANOVA was used to analyze the physiological parameters during modeling.Repeated measurement ANOVA was used to compare the neurobehavioral score results, and t-test was used to compare the protein level and fluorescence intensity. Results:(1)The results of repeated measurement ANOVA showed that the interaction between group and time in NSS score was not significant ( F=0.91, P>0.05), and the group main effect ( F=46.68, P<0.05) and time main effect ( F=25.56, P<0.05) were significant. The results of Tukey's test showed that the NSS scores of pMCAO+ VNS group and pMCAO+ P group were significantly lower than those of pMCAO group (both P<0.05). There was no significant difference between pMCAO+ P group and pMCAO+ VNS group ( P>0.05). The NSS scores in pMCAO+ VNS+ A group were higher than that in pMCAO+ VNS group ( P<0.05), and significantly lower than that in pMCAO+ VNS+ AC group ( P<0.05). In the adhesive removal test, the interaction between group and time in the adhesive tape contact time and tear off time of mice was not significant ( F=0.67, 0.71, all P>0.05), and the group main effect ( F=30.12, 42.46, all P<0.05) and time main effect ( F=52.18, 47.34, all P<0.05) of mice in each group were significant.Tukey's test showed that the adhesive removal test on the 21st day, the adhesive tape contact time and tear off time of pMCAO+ VNS group were significantly shorter than those of pMCAO group (both P<0.05), and there was no significant difference between pMCAO+ P group and pMCAO+ VNS group (both P>0.05). (2)Western blot showed that compared with pMCAO group (0.36±0.01), the expression of α7nAchR in pMCAO+ VNS group (0.83±0.03) and pMCAO+ P group (0.67±0.02) increased ( t=13.53, 16.08, both P<0.01). The expression of α7nAchR in PCAO+ VNS+ A group (0.37±0.01) was significantly lower than that in PCAO+ VNS group ( t=12.88, P<0.01). Immunofluorescence results also showed that compared with pMCAO group (3.75±0.19), the expression of α7nAchR in pMCAO+ VNS group (8.96±0.48) and pMCAO+ P group increased (8.17±0.64) ( t=10.04, 6.67, both P<0.05). Immunofluorescence results also showed that compared with the pMCAO group (3.75±0.19), the expression of α7nAchR protein in the brain tissue of mice in the pMCAO+ VNS group and pMCAO+ P group increased ((8.96±0.48), (8.17±0.64), t=10.04, 6.67, all P<0.05). (3)The results of ELISA showed that compared with pMCAO group, the levels of TNF-a and IL-6 in serum and tissue supernatant of pMCAO+ VNS group and pMCAO+ P group were significantly lower than those of pMCAO group ( t=23.28, 15.30, 12.26, 11.08; all P<0.05). TNF in serum and tissue supernatant of mice in pMCAO+ VNS+ A group The levels of IL-6 in serum and tissue supernatant were significantly higher than those in pMCAO+ VNS group ( t=12.70, 11.01, 11.69, 17.37; all P<0.05) and pMCAO+ VNS+ AC group ( t=12.29, 11.07, 14.61, 29.27; all P<0.05). Conclusion:VNS may reduce inflammation by increasing the expression of α7nAchR protein in brain tissue, thereby playing a certain neuroprotective effect on ischemic stroke.
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Objective:To summarize the computed tomography (CT) and magnetic resonance imaging (MRI) features of acinar cell carcinoma of the pancreas (ACCP).Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 21 patients with ACCP who were admitted to the Affiliated Hospital of Inner Mongolia Medical University from January 2015 to December 2019 were collected. There were 5 males and 16 females, aged (57±9)years, with a range from 41 to 74 years. Patients underwent CT and MRI examinations. Observation indicators: (1) imaging examination; (2) imaging features on CT; (3) imaging features on MRI; (4) pathological examination and immunohistochemistry staining; (5) treatment and follow-up. Follow-up using outpatient examination and telephone interview was conducted at 1, 3, 6 months after discharge and once every 6 months thereafter to detect survival of patients up to December 2019. Measurement data with normal distribution were represented as Mean± SD. Count data were described as absolute numbers. Results:(1) Imaging examination. Of the 21 patients, 7 underwent single CT examination, 11 underwent MRI examination, and 3 underwent both CT and MRI examinations. ① Tumor shape: all the 21 patients had single tumor, including 17 showing round or quasi-round shape, and 4 showing irregular clumps. ② Tumor location: of the 21 patients, 6 had tumor located at pancreatic head, 2 had tumor located at pancreatic head and body, 2 had tumor located at pancreatic body, 4 had tumor located at pancreatic body and tail, 4 had tumor located at pancreatic tail, and 3 had had tumor located at ampulla. ③ The maximum tumor diameter was (43±29)mm, with a range from 11 to 129 mm. ④ Adjacent organ invasion: 10 of the 21 patients had invasion of adjacent organ, including 2 with invasion of stomach, spleen and left adrenal gland invasion, 4 with invasion of duodenum, 3 with invasion of duodenum and common bile duct, 1 with invasion of spleen. ⑤ Vascular invasion: 12 patients had invasion of splenic artery or splenic vein, including 1 combined with invasion of both common hepatic artery and superior mesenteric vein, 1 combined with invasion of celiac root. ⑥ Pancreatic and bile duct invasion: 8 patients had pancreatic and bile duct dilation, including 4 with bile duct and upper pancreatic duct dilation, and 4 with pancreatic duct dilation. ⑦ Lymph node metastasis: 2 patients had perineoplastic lymph node enlargement. ⑧ Other conditions: 7 patients had tumor center with cystic necrosis. Four patients had atrophy pancreatic parenchyma. Two patients had splenic vein tumor thrombosis. Two patients had cysts. One patient had multiple liver metastases. (2) Imaging features on CT. ① The solid part was dominant in the main body of the 10 patients undergoing CT examination, demostrating equal density, of which 3 cases had clear boundaries, 2 cases had pseudocapsule around the lesion, and 5 cases had low-density necrotic area in the center of lesion. ② In arterial phase of CT examination, the solid part of tumor had a lower enhancement compared with the normal pancreatic tissues in 7 patients, while the solid part of tumor had a high enhancement compared with the normal pancreatic tissues in 3 patients. ③ In delayed phase of CT examination, the tumor density was slightly lower than or equal to density of normal pancreatic parenchyma in 7 patients, showing slightly progressive enhancement, while the tumor density was slightly higher than or equal to density of normal pancreatic parenchyma in 3 patients. (3) Imaging features on MRI. ① MRI plain scan of 14 patients showed that 8 patients demostrated slightly longer T2 and slightly longer T1 signals in lesions, while 6 patients demostrated mixed signals dominated by long T2 and equal T1 signals. The area of cystic necrosis was observed in lesions of 4 patients and was not observed in 10 patients. No antiphase signal reduction was observed in the 14 patients. ② MRI dynamic enhanced scan of 12 patients showed that 11 patients presented mild progressive enhancement in lesions and 1 patient presented obvious confounding enhancement and clearance in the delayed phase. Compared with adjacent normal pancreatic parenchyma, diffused weighted imaging showed high signals in 6 cases, slightly high signals in 6 cases, and high signal halo in 2 cases. The apparent diffusion coefficient in 14 lesions was (1.22±0.14)×10 -3 mm 2/s. (4) Pathological examination and immunohistochemistry staining. Results of pathological examination in the 21 patients: acinic cell carcinoma, mixed ductal-acinic cell carcinoma, acinar-endocrine carcinoma, and atypical hyperplasia inacinus were detected in 14, 5, 1, and 1 patients, respectively. Of the 21 patients, 10 had invasion of adjacent organ, 3 had invasion of bile duct, 2 had invasion of lymph node. Results of immunohistochemistry staining in 17 patients: 17 patients had proliferation index of Ki-67 as 1%-80%; 10 out of 16 patients were positive for synaptophysin; 6 out of 16 patients were positive for CD56 protein; 2 out of 14 patients were positive for Chromogranin A; 12 out of 13 patients were positive for α-antitrypsin; 9 out of 11 patients were positive for cytokeratin; 8 patients were positive for β-catenin; 2 patients were positive for B lymphoma-10 protein. (5) Treatment and follow-up. Of the 21 patients, 10 cases underwent pancreatico-duodenectomy, 6 cases underwent pancreatic body and tail pancreatectomy combined with splenectomy, 2 cases underwent pancreatic body and tail pancreatectomy, 1 case underwent pancreatic tail tumor enucleation, 1 case underwent liver metastasis resection, and 1 case underwent ultrasound-guided pancreatic lesion puncture biopsy. All the 21 patients were followed up for (30±16)years, with a range from 2 to 52 months. There were 13 patient surviving and 8 cases of death. They had survived for (19±13)months, with a range from 2 to 35 months. Conclusions:The CT and MRI enhanced scan of ACCP showed slightly progressive enhancement, with cystic necrosis seen in the center and high signals in diffused weighted imaging. Dilation of bile duct and pancreatic duct is common in patients with pancreatic head tumors, and invasion of splenic artery and vein is common in pancreatic body and tail tumors. Calcification and cyst are rare and lesions of pancreatic head and body cause atrophy in pancreatic tail.
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Objective:To investigate the efficacy of endovascular embolization in the treatment of traumatic carotid cavernous fistula (TCCF) and the influencing factors of outcomes.Methods:Patients with Barrow A type TCCF underwent intravascular embolization in the Department of Neurosurgery, General Hospital of Ningxia Medical University from January 2009 to November 2019 were enrolled. They were treated with detachable balloons or Onyx-18 combined with coils via transarterial approach, and clinical and imaging follow-up were performed after operation. Recurrence was defined as a lesion that was completely embolized immediately, but the original fistula was redeveloped during imaging follow-up. The clinical recovery was defined as the disappearance of intracranial vascular murmur, pulsatile exophthalmos, conjunctival hyperemia and edema, the movement of eyeball without disorder and the restoration of vision loss. Multivariate logistic regression analysis was used to determine the independent risk factors for affecting imaging recurrence and clinical recovery. Results:A total of 54 patients with Barrow A type TCCF were enrolled. Their age was 42.5±10.6 years (range, 28-70 years); 36 were male (66.7%). Clinical manifestations: 40 patients (74.1%) had ocular symptoms (exophthalmos, conjunctival congestion, etc.), 35 (64.8%) had intracranial vascular murmur, 36 (66.7%) had visual impairment (decreased vision, visual field defect), 32 (59.3%) had headache, 15 (28.3%) had abducens nerve palsy, and 4 (9.1%) had epistaxis. Fourty-seven patients (87.0%) had superior ophthalmic vein drainage, 19 (35.2%) had superior and inferior petrosal sinus drainage, and 9 (16.7%) had cortical vein drainage. Twenty-eight patients (51.9%) were treated with Onyx-18 combined with coils, and 26 (48.1%) were treated with detachable balloons. After operation, 47 patients (87.0%) were immediately totally embobilized, 4 of them were totally embolized with Onyx-18 and coils after the failure of balloon embolization; 7 patients (13.0%) achieved subtotal embolization. Forty-seven patients (87.0%) recovered after surgery, and the symptoms of 4 patients were better than before admission but the vision did not fully recover (among them, 3 had the symptoms of abducens nerve palsy), 2 had mild hemiplegia, and no patients died after surgery. At postoperative follow-up, 5 (9.3%) recurred, and then they achieved total embolization with Onyx-18 combined with coils. Multivariate logistic regression analysis showed that subtotal embolization was an independent risk factor for postoperative imaging recurrence (odds ratio 16.63, 95% confidence interval 1.74-159.33; P=0.015), and the presence of cortical venous drainage was an independent risk factor for affecting postoperative clinical recovery (odds ratio 19.08, 95% confidence interval 1.61-226.58; P=0.020). Conclusion:Both of Onyx-18 combined with coils and detachable balloons are safe and effective for the treatment of TCCF. Subtotal embolization is associated with imaging recurrence, and the presence of cortical venous drainage is an independent influencing factor of clinical recovery.
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Objective To establish the method for isolation and culture of urine-derived stem cells (USCs) from female patients with interstitial cystitis/bladder pain syndrome (IC/BPS).Methods The USCs were collected from fresh midstream urine samples from 6 female IC/BPS patients admitted to our hospital from June 2018 to December 2018.The 6 patients were 33-55 years old (average 41.5 years old),and their course of illness was 2-18 years (average 8 years).The USCs were isolated from the urine through times of centrifugation and cultured in specific medium.Growth curve and cell cycle of USCs were observed.The expression of surface markers of USCs was analyzed by flow cytometry and immunofluorescence,the smooth muscle and epithelial differentiation potential of USCs were detected by immunofluorescence staining of surface markers of smooth muscle cells and epithelial cells.Results USCs were successfully extracted from 3 of 6 female patients,and the success rate reached 50％ by once extraction.USCs showed a "rice-grain" spindle appearance and showed logarithmic growth.USCs expressed surface markers associated with mesenchymal stem cells (e.g.CD44,CD73,CD105,CD133) and embryonic stem cells [e.g.stage-specific embryonic antigen 4 (SSEA4)] and pericytes[e.g.CD146,platelet derived growth factor beta receptor (PDGFRB) and NG2],but didn't express hematopoietic stem cell surface markers(e.g.CD31,CD34 and CD45).When induced to smooth muscle cells or epithelial cells,the cells expressed the surface markers of smooth muscle cells [e.g.desmin,myosin,alpha-smooth muscle actin(otSMA) and vimentin] and epithelial cells(e.g.uroplakin 1A,uroplakin 3B,AE1/AE3 and cytokeratin 13).Conclusions The method of isolation and culture of USCs from female IC/BPS patients was successfully established,and it provides a preliminary technical method for exploring the application of USCs in the clinical study of IC/BPS patients with autologous treatment.
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Objective@#To investigate the different functions of humanized and murinized CD19 chimeric antigen receptor (CAR)-T cells against Raji cell line in vitro and in vivo.@*Methods@#Peripheral blood samples were collected from eight patients with lymphoma who were going to receive CD19 CAR-T cell therapy and used for the preparation of peripheral blood mononuclear cells (PBMC) as well as humanized and murinized CAR-T cells. Cell proliferation and cytotoxicity were detected with CCK-8 and LDH assays, respectively. A tumor-bearing mouse model was established by injecting BALB/c female nude mice with fluorescent Raji cells. Changes in tumor volume in these mice were observed by in vivo imaging technology. The transfection efficiency and amount of CAR-T cells in the mice were detected with flow cytometry.@*Results@#No statistical difference in transfection efficiency was found between humanized and murinized CAR-T cells, nor in cell proliferation at 24 h of culture in vitro(P=0.104). The proliferation of humanized CAR-T cells showed a significant increase compared with that of murinized CAR-T cells at 48 h of culture (P=0.009). Similarly, the cytotoxicity of the two types of CAR-T cells against Raji cells showed no significant difference at 24 h at any effector/target (E/T) ratio (1∶1 or 4∶1), and that of humanized CAR-T cells was higher than that of murinized CAR-T cells at both E/T ratios at 48 h (E/T ratio=1∶1, P=0.005; E/T ratio=4∶1, P=0.008). Moreover, the cytotoxicity of CAR-T cells was higher than that of PBMC in any case. Tumor volumes in mice were reduced 14 d after humanized or murinized CAR-T cell therapy, while the mice in the PBMC control group suffered tumor progression. Tumor volume began to increase in mice 21 d after murinized CAR-T cell therapy, while no significant change was observed in the mice treated with humanized CAR-T cells. All of the mice died 25 d after murinized CAR-T cell therapy, while the deaths among those under humanized CAR-T cell therapy occurred on 31 d. The proportion of CAR-T cells in mice reached the peak 7 d after receiving humanized or murinized CAR-T cell therapy, while that in the humanized group was significantly higher than that in the murinized group at any time point (P4 d=0.001, P7 d=0.000, P14 d=0.003). Murinized CAR-T cells became undetectable on 21 d, while humanized CAR-T cells on 35 d. The maximum survival time for mice in the PBMC and murinized and humanized CAR-T cell groups was 20 d, 25 d and 53 d, respectively.@*Conclusions@#Compared with murinized CD19 CAR-T cells, humanized CD19 CAR-T cells showed stronger proliferation potential and cytotoxicity and remained in vivo detectable for a longer period of time. This study indicated that humanized CD19 CAR-T cells were superior to murinized CD19 CAR-T cells for the treatment of B cell lymphoma.
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Objective To investigate the different functions of humanized and murinized CD19 chimeric antigen receptor ( CAR)-T cells against Raji cell line in vitro and in vivo. Methods Peripheral blood samples were collected from eight patients with lymphoma who were going to receive CD19 CAR-T cell therapy and used for the preparation of peripheral blood mononuclear cells ( PBMC) as well as humanized and murinized CAR-T cells. Cell proliferation and cytotoxicity were detected with CCK-8 and LDH assays, respectively. A tumor-bearing mouse model was established by injecting BALB/c female nude mice with flu-orescent Raji cells. Changes in tumor volume in these mice were observed by in vivo imaging technology. The transfection efficiency and amount of CAR-T cells in the mice were detected with flow cytometry. Re-sults No statistical difference in transfection efficiency was found between humanized and murinized CAR-T cells, nor in cell proliferation at 24 h of culture in vitro(P=0. 104). The proliferation of humanized CAR-T cells showed a significant increase compared with that of murinized CAR-T cells at 48 h of culture ( P=0. 009). Similarly, the cytotoxicity of the two types of CAR-T cells against Raji cells showed no significant difference at 24 h at any effector/target (E/T) ratio (1 : 1 or 4 : 1), and that of humanized CAR-T cells was higher than that of murinized CAR-T cells at both E/T ratios at 48 h (E/T ratio=1 : 1, P=0. 005;E/T ratio=4 : 1, P=0. 008). Moreover, the cytotoxicity of CAR-T cells was higher than that of PBMC in any case. Tumor volumes in mice were reduced 14 d after humanized or murinized CAR-T cell therapy, while the mice in the PBMC control group suffered tumor progression. Tumor volume began to increase in mice 21 d after murinized CAR-T cell therapy, while no significant change was observed in the mice treated with hu-manized CAR-T cells. All of the mice died 25 d after murinized CAR-T cell therapy, while the deaths among those under humanized CAR-T cell therapy occurred on 31 d. The proportion of CAR-T cells in mice reached the peak 7 d after receiving humanized or murinized CAR-T cell therapy, while that in the humanized group was significantly higher than that in the murinized group at any time point (P4 d=0. 001, P7 d=0. 000, P14 d=0. 003). Murinized CAR-T cells became undetectable on 21 d, while humanized CAR-T cells on 35 d. The maximum survival time for mice in the PBMC and murinized and humanized CAR-T cell groups was 20 d, 25 d and 53 d, respectively. Conclusions Compared with murinized CD19 CAR-T cells, humanized CD19 CAR-T cells showed stronger proliferation potential and cytotoxicity and remained in vivo detectable for a longer period of time. This study indicated that humanized CD19 CAR-T cells were superior to murinized CD19 CAR-T cells for the treatment of B cell lymphoma.
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Objective To investigate the relationship between spina bifida occulta in lumbasacral portion and functional defe-cation abnormality among middle-aged and elderly people.Methods The cross-sectional and cluster random sampling survey meth-od was adopted to select the residents aged 45-90 years old in 7 communities of Zhengzhou City as the respondents.All respond-ents underwent the physical examination and lumbosacral digital radiography(DR)examination in the physical examination center of the First Affiliated Hospital of Zhengzhou University,and filled the related questionnaire about defecation abnormality.The rela-tionship between SBO and functional defecation abnormality among middle-aged and elderly people was studied by diagnosing and analyzing the functional constipation(FC)and functional incontinence(FC).Results The effective sample amounts were 1 057 ca-ses,including 497 males and 560 females,167 cases of SBO(86 males and 81 females).The morbidity rate of functional defecation abnormality was 26.02%(275/1 057),23.34%(116/497)in males and 28.39%(159/560)in females.Among 275 cases of functional defecation abnormality,there were 72 cases of complicating SBO.The Logistic regression analysis results showed that age,SOB,physical activity status,diet and living habits,education level and psychological factors were the risk factors for functional defecation abnormality (P<0.05),while there was no relationship between between past-history of stroke and functional defecation abnormality(P>0.05).Con-clusion SBO may be one of risk factors for functional defecation abnormality among middle-aged and elderly people.
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Objective To analyze the epidemiological characteristics of fatty liver complicating gallbladder diseases among the people undergoing healthy physical examination and to investigate its onset risk factors.Methods A total of 7 364 subjects undergoing abdominal color Doppler ultrasonography in the physical examination center of this hospital from June 2011 to June 2015 were selected as the study subjects and divided into 4 groups according to the examination results,fatty liver complicating gallbladder disease group,simple fatty liver group,simple gallbladder diseases group and non-fatty liver and non-gallbladder disease group.The Logistic regression model was used to analyze the influence of related factors on the patients with fatty liver complicating gallbladder diseases.Results The prevalence rate of gallbladder diseases in the patients with fatty liver ia significantly higher than that in the patients without fatty liver(P＜0.05).The multivariate Logistic regression model statistical analysis results showed that often skip breakfast,greasy food,eating more meat,eating much sweet food,dirking more tea,gender(female),age and LDL-C were the independent risk factors for fatty liver complicating gallbladder diseases(P＜0.05).Conclusion The unhealthy living habits were the independent risk factors for fatty liver complicating gallbladder diseases.
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Insulin autoimmune syndrome ( IAS) is a rare type of hypoglycemia. Chinese herbal extract may induce IAS, which seems to be associated with some Chinese herb medicine ingredients of paste which contains sulfhydryl group. In order to attract the attention of the clinicians, we should raise awareness of the disease, and avoid unnecessary operation or serious adverse consequences. This paper reviewed domestic reports in lately 30 years of diagnosis and treatment of IAS, evaluated traditional Chinese medicine and traditional Chinese medicine compound preparations which contain sulfhydlyl group.
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Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are confirmed to be expressed in bladder interstitial Cajal-like cells (ICC-LCs), but little is known about their possible role in cystitis-associated bladder dysfunction. The present study aimed to determine the functional role of HCN channels in regulating bladder function under inflammatory conditions. Sixty female wild-type C57BL/6J mice and sixty female HCN1-knockout mice were randomly assigned to experimental and control groups, respectively. Cyclophosphamide (CYP)-induced cystitis models were successfully established in these mice. CYP treatment significantly enhanced HCN channel protein expression and I(h) density and significantly altered bladder HCN1 channel regulatory proteins. Carbachol (CCH) and forskolin (FSK) exerted significant effects on bladder ICC-LC [Ca²⁺]i in CYP-treated wild-type (WT) mice, and HCN1 channel ablation significantly decreased the effects of CCH and FSK on bladder ICC-LC [Ca²⁺]i in both naive and CYP-treated mice. CYP treatment significantly potentiated the spontaneous contractions and CCH (0.001-10 µM)-induced phasic contractions of detrusor strips, and HCN1 channel deletion significantly abated such effects. Finally, we demonstrated that the development of CYP-induced bladder overactivity was reversed in HCN1 -/- mice. Taken together, our results suggest that CYP-induced enhancements of HCN1 channel expression and function in bladder ICC-LCs are essential for cystitis-associated bladder hyperactivity development, indicating that the HCN1 channel may be a novel therapeutic target for managing bladder hyperactivity.
Subject(s)
Animals , Female , Humans , Mice , Carbachol , Colforsin , Cyclophosphamide , Cystitis , Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels , Telocytes , Up-Regulation , Urinary BladderABSTRACT
<p><b>OBJECTIVE</b>To assess the association of neural development-related genes LIS1and TSNAX with bipolar disorder in a Chinese Han population.</p><p><b>METHODS</b>Three hundred and eight five patients (including 188 males and 197 females) from Guangzhou Brain Hospital with bipolar disorder meeting the Diagnostic and Statistic Manual of Bipolar Disorder (BDI) (Fourth Edition) criteria and 475 healthy controls from the local community were recruited. Ten single nucleotide polymorphisms (SNPs) of the LIS1 and TSNAX genes were genotyped by GoldenGate genotyping assay on an Illumina Beadstation 500 machine. Association analyses of SNPs and haplotypes were performed with Plink 1.07 software.</p><p><b>RESULTS</b>Analysis of the total sample has failed to find any association of SNP or haplotype of the two genes with BDI (P> 0.05). When patients were divided into subgroups with or without psychotic symptom, no significant association of the two genes was found with psychotic BDI or non-psychotic BDI (P> 0.05). No significant association was found between any SNP and haplotype of two genes and female BDI or male BDI, nor were significant association found between age of onset and LIS1 and TSNAX gene polymorphisms.</p><p><b>CONCLUSION</b>Our results indicated that LIS1 and TSNAX genes are not associated with susceptibility to bipolar I disorder in Chinese Han population.</p>
Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , 1-Alkyl-2-acetylglycerophosphocholine Esterase , Genetics , Asian People , Ethnology , Genetics , Bipolar Disorder , Ethnology , Genetics , Case-Control Studies , DNA-Binding Proteins , Genetics , Genetic Predisposition to Disease , Genotype , Microtubule-Associated Proteins , Genetics , Polymorphism, Single NucleotideABSTRACT
<p><b>OBJECTIVE</b>To explore the association of a functional polymorphism Val158Met of COMT gene and attention and executive function in first-episode treatment-naive patients with schizophrenia and healthy controls.</p><p><b>METHODS</b>Trail making test (TMT) and clinical performances were evaluated in 103 first-episode treatment-naive patients with schizophrenia and 99 healthy controls. Polymorphism of COMT Val158Met was analyzed using polymerase chain reaction-restriction fragment length polymorphism method. A general linear model was used to investigate the effect of genotype subgroups on the attention and executive function.</p><p><b>RESULTS</b>There was a significant difference between control subjects and patients with schizophrenia on the TMT-A and B. However, no significant difference among Val/Val, Val/Met and Met/Met on the TMT-A and B in control subjects and patients with schizophrenia was detected.</p><p><b>CONCLUSION</b>The association among COMT Met variant and trail making testing (attention and executive function) has been replicated. However, no association of COMT Met variant with disruption of dopaminergic influence on neurocognitive function was detected. This may be due to the heterogeneity of population.</p>
Subject(s)
Adolescent , Adult , Female , Humans , Male , Young Adult , Amino Acid Substitution , Attention , Physiology , Catechol O-Methyltransferase , Genetics , Executive Function , Physiology , Gene Frequency , Genotype , Polymerase Chain Reaction , Polymorphism, Genetic , Polymorphism, Restriction Fragment Length , Schizophrenia , Genetics , Schizophrenic Psychology , Trail Making TestABSTRACT
Objective To study the prevalence of common infections with soil-borne intestinal nematodes amongst kindergarten children aged 3 to 6 years in Hangzhou,Zhejiang Province to provide evidence for determination of the priority of disease prevention and control.Methods Totally,1667 preschool children were selected from 14 kindergartens of Classes A,B and C in east,middle and west Hangzhou.Perianal skin Scotch Tape(a short strip of sealing cellophane pressure-sensitive tape)specimens were collected for detection of eggs of Enterobius vermicularis,and stool specimens for eggs of Ascaris lumbricoides,Ancylostoma duodenale and Trichuris trichiura by Kato-Katz method and saturated brine floatation,as well as questionnaire interview,for all the children.Results Two hundred and sixteen of 1667 children examined were found infected with common soil-borne intestinal nematodes,with an overall prevalence of 12.96%,4.44% for Enterobius vermicularis,8.28% for Ascaris lumbricoides,0.54% for Trichuris trichiura and 0.24% for Ancylostoma duodenale.Prevalence of infection of common intestinal nematodes was 7.31% in children of the Class A kindergartens,12.60% of Class B,and 21.47% of Class C,with statistically significant difference(?~2 = 49.95,P