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OBJECTIVE Alzheimer's disease(AD)and vascular dementia(VD)are the primary causes of dementia in elderly individuals,and therapeutic options for both conditions are limited.Overactivation of N-methyl-D-aspartate(NMDA)receptors,decreased cerebral blood flow,and subsequent pathological events,play signifi-cant roles in the progression of AD and VD.METHODS In this study,we investigated the therapeutic effects and underlying mechanisms of MN-08,a novel memantine nitrate,in mouse models of AD and rats with VD.RESULTS MN-08 was found to inhibit Aβ accumulation,prevent neuronal and dendritic spine loss,and attenuate cognitive deficits in 2-month-old APP/PS1 transgenic mice(following a 6-month preventative course)and in 8-month-old triple-transgenic(3×Tg-AD)mice(following a 4-month therapeutic course),as well as in rat models of VD with preventive and therapeutic treatments.In vitro,MN-08 was shown to bind to and antagonize NMDA receptors,inhibit calcium influx,and reverse dysregula-tions of the ERK and PI3K/Akt/GSK3β pathway,subse-quently preventing glutamate-induced neuronal loss.Additionally,MN-08 exhibited favorable pharmacokinet-ics,blood-brain barrier penetration,and safety profiles in rats and beagle dogs.CONCLUSION These findings suggest that the novel memantine nitrate MN-08 may be a useful therapeutic agent for AD and VD.
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Objective:To evaluate the clinical value of percutaneous transhepatic one-step biliary fistulation(PTOBF)lithotomy plus laparoscopic cholecystectomy(LC) in the treatment of choledocholithiasis combined with cholecystolithiasis.Methods:From Jul 2012 to Jun 2018, 44 patients with cholecystolithiasis and choledocholithiasis were treated by PTOBF + LC ( n=20) vs laparoscopic common bile duct exploration(LCBDE)+ LC( n=24). Results:The success rate of one-step operation in both groups was 100%.The average intra-operative hemorrhage and the average hospital stay after operation were higher in LCBDE+ LC group (all P<0.05). The post-operative complication rate of PTOBF lithotomy + LC group was 10.0% (2/20), recurrence rate of observation period was 10.0% (2/20), while that of LCBDE+ LC group was 8.3% (2/24), and 12.5% (3/24), the difference was not statistically significant (all P>0.05). Conclusion:PTOBF lithotomy combined with LC is a safe, effective and feasible minimally invasive method for the treatment of choledocholithiasis combined with gall stones.
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Objective:To study the use of percutaneous transhepatic one-step biliary fistulation based on three-dimensional visualization technology (3D-PTOBF) in the treatment of complex hepatolithiasis.Methods:A retrospective analysis was conducted on 116 patients with complex hepatolithiasis treated in the First Affiliated Hospital of Guangzhou Medical University from January 2016 to December 2019. There were 56 patients in the 3D-PTOBF group (treated by 3D-PTOBF), and 60 patients in the traditional PTOBF group (received traditional PTOBF approach). The stone clearance rate, postoperative complication rate, intraoperative blood loss, hospitalization time, number of cholangioscopic treatment procedures and stone recurrence rate were compared between the two groups.Results:When compared with the traditional PTOBF group, the 3D-PTOBF group had significantly less procedures (1.43±0.71 vs. 2.07±1.22, P<0.05), and shorter hospital stay (4.6±2.3 d vs. 6.1±2.9 d, P<0.05). There were no significant differences in the immediate stone clearance, final stone clearance, postoperative complications and stone recurrence rates between the two groups (all P>0.05). Conclusion:3D-PTOBF was safe and feasible to treat complex hepatolithiasis. When compared with PTOBF, it had the advantages of shorter operation time and decreased hospital stay.
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Objective To study the efficacy and safety of percutaneous transhepatic one-step biliary fistulation (PTOBF) with rigid cholangioscopic lithotripsy for treatment of complicated hepatolithiasis under the ultrasonic navigation technique.Methods In this retrospective study,PTOBF lithotripsy surgery was performed in 94 patients with hepatolithiasis under general anesthesia with tracheal intubation,and with percutaneous transhepatic puncture of targeted bile duct under ultrasonic navigation in The First Affiliated Hospital of Guangzhou Medical University.Biliary expanders were used along a guidewire to expand the sinus gradually until 14Fr to establish a fistulous channel.Lithotripsy was then performed through the channel by rigid cholangioscopy.The operation-related data were collected and analyzed,including puncture and fistula establishment success ratio,complication rate,intraoperative blood loss,residual and recurrence hepatolithiasis rates.Results 94 patients (total 122 patient-times) underwent PTOBF lithotripsy.There was no perioperative mortality.The overall puncture success rate was 100％,and the fistula/puncture rate was 97.5％ (119/122).In 118 patients success was achieved in 2 time (96.7％).The complication rate was 9.6％ (9/94).The average intraoperation blood loss were (24.9 ± 21.3)ml.The residual calculus rate after therapy was 13.8％ (13/94).All patients were followed-up for a period that ranged between 18 and 30 months.The recurrence rate was 14.9％ (14/94).Conclusions Ultrasonic navigation technique plays an important role in bile duct puncture,sinus expansion and rigid cholangioscopic lithotripsy for treatment of complicated hepatolithiasis.PTOBF lithotripsy is a safe and effective procedure,which provides a new way in mini-invasive treatment for hepatolithiasis.It is worth generalizing.
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Objective To observe the clinical effect of percutaneous transhepatic one-step biliary fistulation (PTOBF) and percutaneous transhepatic cholangioscopy (PTCS) in the treatment of hepatolithiasis with hepatobiliary surgery history,and to explore the clinical application value of PTOBF.Methods This is retrospective analysis of 68 patients with hepatolithiasis who were admitted to hepatobiliary surgery in the First Affiliated Hospital of Guangzhou Medical University from November 2009 to October 2017.Among these cases,35 patients in the observation group (group PTOBF) were treated with PTOBF,and 33 patients in the control group (group PTCS) received PTCS treatment.The final clearance rate,the postoperative complications rate,the hospitalization time,the operation times within the course of treatment,the recurrence rate and the residual stenosis rate of the two groups were compared.Results Compared with group PTCS,the clearance rate was significantly higher in group PTOBF(82.9％ vs 54.6％,P＜0.05),while the postoperative complications rate between the two groups are similar (14.3 ％ vs 30.3 ％,P＞ 0.05);Besides,the hospitalization time(12.3±5.3 d vs 17.4±7.0 d,P＜0.05),the operation times within the course of treatment (2.2±1.3 vs 2.8±1.0,P＜0.05) and the recurrence rate(17.4％ vs 39.4％,P＜0.05) of group PTOBF were obviously lower.Conclusions PTOBF is a safe and feasible treatment for hepatolithiasis with hepatobiliary surgery history.Compared with PTCS,it has the advantages of short hospitalization time,fewer operations and better recovery.
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Objective To study the correlation between the renin-angiotensin-aldosterone system angiotensinogen (AGT) gene M235T,angiotensin Ⅱ type 1 receptor (AGTR1) gene Al166C,aldosterone synthase (CYP11B2) gene -344C/T polymorphisms and large-artery atherosclerotic (LAA) stroke in a southern Chinese Han population.Methods Polymerase chain reaction and gene sequencing technology were used for the genotyping in patients with LAA and normal controls with AGT gene M235T,AGTR1 gene A1166C,and CYP11B2 gene - 344C/T polymorphisms in a southern Chinese Han population,and to determine the correlation between the 3 gene polymorphisms and LAA by binary logistic regression analysis.Results A total of 107 patients with LAA and 142 healthy controls were included in the study.The frequencies of the AGT gene 253TT genotype (66.36％ vs.50.70％,x2 =6.122,P =0.047) and T allele (79.44％ vs.70.07％ ％,x2 =5.581,P =0.018) in the LAA group were significantly higher than those in the control group.The frequencies of the AGTR1 gene 1166CC genotype (0％ vs.0％,x2 =1.494,P =0.222) and C allele (7.48％ vs.4.93％,x2 =1.399,P =0.237) in the LAA group were no significantly differences with those in the control group.The frequencies of the CYP11B2 gene - 344CC genotype (9.35％ vs.4.23％,x2 =3.603,P =0.165) and C allele (27.10％ vs.26.06％,x2 =0.069,P =0.793) in the LAA group were no significant differences with those in the control group.Binary logistic regression analysis showed that there was no significant correlation between the three gene polymorphisms and the simple LAA diseases.The frequencies of AGT gene 235TT genotype (68.00％ vs.41.90％,x2 =12.446,P =0.002) and T allele (79.33％ vs.64.76％,x2 =8.993,P =0.003) in the LAA patients complicated with hypertension were significantly higher than those in the normotensive control group.Logistic regression analysis showed that the odds ratio (OR) exposed to TT genotype was 2.153 (95％ confidence interval [CI] 0.789-5.872).The OR of T allele was 2.089 (95％ CI 1.285-3.396).Conclusions The AGT gene M235T polymorphism is not associated with the simple LAA in the southern Chinese Han population,but it may be associated with the risk of LAA complicated with hypertension;CYP11B2 gene -344C/T polymorphism and AGTR1 gene A1166C polymorphism are not associated with the onset of LAA in the southern Chinese Han population.