AIM: To investigate the pharmacokinetic properties and bioequivalence of nifedipine sustained-release tablets after multiple doses administration in healthy volunteers. METHODS: Twenty two male healthy volunteers were enrolled in a randomized two-way crossover design with multiple doses (20 mg·d-1×7 d) study. Nitrendipine was used as the internal standard and the concentrations of nifedipine in plasma were determined by HPLC-APCI-MS. The pharmacokinetic parameters were calculated and the bioequivalence were compared by DAS (ver 1.0) program. RESULTS: The pharmacokinetic parameters of test and reference preparations were as follows: Cmax (52.5±27.4) and (54.0±31.2) ng·ml-1;Cmin (5.4±4.1) and (6.2±5.9) ng·ml-1;Cav (16.8±9.2) and (19.3±12.4) ng·ml-1;Tmax (3.7±0.9) and (4.1±1.1) h;t1/2 (8.9±4.9) and (8.5±3.1) h;AUC0-τ (403.4±221.0) and (461.9±296.6) μg·h·L-1, AUC0-36h (444.4±256.1) and (503.1±330.9) ng·h·ml-1;AUC0-∞ (482.1±268.9) and (542.3±348.4) ng·h·ml-1;DF (299.8±117.7)% and (279.2±97.5)%, respectively. There were no significant differences (P>0.05) in Tmax, Cmax, Cmin, Cav, DF, AUC0-τ, AUC0-36h, AUC0-∞ and t1/2 between the two preparations. The relative bioavailability of test tablets was (100.6±38.6)%. CONCLUSION:The test and reference preparations were bioequivalence.

Objective To investigate the effect of employing achievement management in nursing management of urology department.Method The results of assessments were linked to the achievements by regulating achievement-oriented distribution and assessment methods.Results The degree in patients' satisfaction with nursing service and the score on nursing quality assessment were both significantly improved compared to pre-performance of achievement-oriented distribution and assessment(P<0.01). Conclusion The achievement-oriented management may be effective in mobilizing nurses' working enthusiasm and increase quality of care,which guarantees fundamental nursing care.

Objective To investigate the actuality and risk factors of mild cognitive impairment among the elderly in Xi'an. Methods The elderly from 10 urban communities in Xi'an were selected using random cluster sample method. Mini-Mental Status Examination and cognitive function questionnaire self-designed were assessed. Results and Conclusion There were 396 (25.02%) elder people with cognitive impairment in 1583 cases. The morbidity of mild cognitive impairment was inverse to the educational level, and was related to age, gender, job category, marriage and social support (P<0.05).

Objective To evaluate the prevalence of hepatic steatosis in patients with chronic hepatitis B (CHB) and the impact of hepatic steatosis on the progress of fibrosis. Methods Five hundred and sixty two untreated CHB patients (405 males and 157 females) with an average age of 31.3 underwent liver biopsy from January to August 2007. On the day of liver biopsy, a questionnaire was completed and a blood sample was obtained for laboratory analysis. The degree of liver steatosis, necroinflammation and fibrosis was assessed; demographic information and clinical data including age, gender, body mass index (BMI), history of diabetes mellitus, hypertension, dyslipidemia, and HBeAg status, HBV DNA viral load were documented. Results In 562 patients, 102 (18. 2% ) had steatosis. Multivariate analysis demonstrated that liver steatosis was associated with the levels of TG, APO-B, UA, FSG, and higher BMI; and the progress of fibrosis was associated with high degree of hepatic steatosis and necroinflammation, age over 35 years, HBV DNA > 103 copies/L, high BMI and GGT. Conclusions The results show that obesity and dyslipidemia in CHB patients are associated with the hepatic steatosis, and the latter seems to be an important determinant for fibrosis.

Objective:To conduct clinical and genetic analysis in two cases of cholestatic liver disease to determine the specific etiology of cholestasis.Methods:Clinical data and the medical histories in family members of two cases were collected. The gene variation was detected by whole-exome sequencing technology. Sanger sequencing validation and bioinformatics analysis were performed on patients and their parents with suspected pathogenic mutations.Results:Whole-exome sequencing showed that the ABCB4 gene of case 1 (a male, 16 years old) had compound heterozygous mutations of c.646C > T from the father and c.927T > A from the mother, while the ABCB4 gene of case 2 (a female, 17 years old) had a compound heterozygous mutation of c.2784-1G > A from the father and c.646C > T from the mother. New mutation sites that had not been previously reported were c.646C > T, c.927T > A, and c.2784-1G > A.Conclusion:In this study, both cases had progressive familial intrahepatic cholestasis type 3 (PFIC-3) caused by ABCB4 gene mutations, and it also enriched the ABCB4 pathogenic variant spectrum. Whole-exome sequencing technology provides a reliable diagnostic tool for etiological analysis.

Objective To explore the features of peripheral blood immune cells in long-term survival recipients after liver transplantation.Methods The expression of T subsets (Th1,Th2,Th17,Th22,Tregs),NK cells,NKt cells,Bregs,MDSC in long-term survival recipients (postoperative follow-up time ≥5 years,30 cases),short-term survival recipients(postoperative follow-up time ≤1 year,15 cases) and healthy control (15 cases) were determined by flowcytometry.Results Th17 cells were significantly higher in the long-term group compared with short-term group and healthy control group(P ＜0.01).Tregs in long-term group compared with short-term group were significantly higher (P ＜ 0.01),but the difference was not statistically significant compared with healthy control group (P ＞ 0.05).NK cells were significantly higher in long-term group compared with short-term group and healthy control group (P ＜ 0.01).MDSC were significantly higher in long-term group compared with short-term group and healthy control group (P ＜0.01).Conclusions Th17,Tregs,NK cells and MDSC were significantly higher in long-term survival of liver recipients,which may be related to immune tolerance.

ObjectiveTo investigate the occurrence, development, treatments and prognosis of ischemic type biliary lesions (ITBL) complicated with portal hypertension after liver transplantation (LT). MethodsClinical data of 32 ITBL patients with portal hypertension after LT in Liver Transplantation Center, the Third Affiliated Hospital of Sun Yat-sen University from January 2003 to April 2009 were analyzed retrospectively. The informed consents of all patients were obtained and the ethical committee approval was received. There were 28 males and 4 females with a mean age of (46±14) years old. The patients were followed up regularly and the occurrence, development, treatments and prognosis of portal hypertension were observed.ResultsWhen ITBL was diagnosed, mild splenomegaly was found in 11 cases, moderate splenomegaly in 14 cases and severe splenomegaly in 4 cases. Three cases were observed without splenomegaly. During the follow-up period, 5 cases were observed in stable states with mild splenomegaly or splenomegaly improving from moderate to mild. While for the other 27 cases, portal hypertension symptoms like splenomegalyetc. were observed becoming worse as ITBL developed including 11 cases with severe splenomegaly. Esophageal and gastric fundus varices were found in 53% (17/32) of the patients including 2 cases of lower esophagus mild varices, 8 cases of lower esophagus and gastric fundus mild to moderate varices, and 7 cases of moderate to severe varices. All the patients received intervention treatments via endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC). Liver retransplantation was performed in 11 cases, choledochojejunostomy in 4 cases and choledocholithiasis + biliary tract exploration in 1 case. Eighteen cases survived and 14 cases died. Four cases died of aggravating jaundice and liver failure, 4 liver cancer recurrence, 3 massive hemorrhage in upper gastrointestinal tract, and 1 severe infection, 1 multiple organ failure, 1 renal failure after liver retransplantation.ConclusionsMost of ITBL patients with portal hypertension after LT gradually deteriorates with the progression of ITBL. The treatments mainly include intervention treatments, liver retransplantation, and choledochojejunostomy. The prognosis is very poor.

Objective:To establish standard spatial brain template and ROIs template of 11C-methyl- N-2β-carbomethoxy-3β-(4-fluorophenyl)tropane (CFT) PET images for automated quantitative analysis of dopamine transporter (DAT) distribution. Methods:From May 2014 to December 2015, 11C-CFT PET and MRI T 1 brain images of 16 healthy volunteers (3 males, 13 females; age (63.3±6.9) years) from Huashan Hospital, Fudan University were co-registered and smoothed using statistical parametric mapping(SPM)5 software based on MATLAB to create a standard spatial brain template. The ROIs template was established by ScAnVp procedures. These templates were clinically verified by using 11C-CFT PET images of 37 healthy volunteers (23 males, 14 females; age (61.7±7.1) years), 32 Parkinson′s disease (PD) patients (20 males, 12 females; age (61.1±5.4) years), 10 multiple system atrophy with predominant parkinsonism (MSA-P) patients (7 males, 3 females; age (60.8±7.1) years) and 10 progressive supranuclear palsy (PSP) patients (5 males, 5 females; age (58.4±6.1) years) from Huashan Hospital, Fudan University between January 2014 and March 2019. One-way analysis of variance was used to analyze data. Results:Based on the 11C-CFT PET images and MRI T 1 images of healthy volunteers, a standard spatial brain template for normalization of 11C-CFT PET images was created. The ROIs template was established including seven regions: bilateral caudate, anterior putamen, posterior putamen (along the long axis) and the occipital cortex. The ROIs template was accurately aligned in each verification group. The normal reference values of semi-quantitative DAT distribution in caudate, anterior putamen and posterior putamen were obtained (1.84±0.13, 2.18±0.16, 1.77±0.11). The semi-quantitative values of 11C-CFT uptake in each ROI in patients were significantly lower than those in healthy volunteers ( F values: 49.79-283.83, all P<0.05). Conclusion:The established brain templates with accurate spatial alignment for 11C-CFT image analysis can provide foundational tools for the application of 11C-CFT PET imaging in clinical practice and scientific research.

Objective Exploring the mechanism of electroacupuncture's anti anxiety effect through methods such as hippocampal metabolomics and 16S rRNA sequencing.Methods Rats were randomly divided into normal group,model group,electroacupuncture group,and diazepam group.A rat model of anxiety disorder was prepared using chronic restraint stress method.During the modeling period of the electroacupuncture group,simultaneous"Zusanli"acupoint electroacupuncture intervention was performed for 30 minutes each time,once a day,for 21 days.The diazepam group received daily gavage of diazepam for a total of 21 days.After the completion of modeling,open field experiments and elevated cross maze experiments were conducted to observe the behavior of rats.Subsequently,pathological staining was performed to observe the pathological changes in the hippocampus and colon of rats.Metabolomics detection of changes in metabolites in the hippocampus of rats.16S rRNA and short chain fatty acid analysis were used to detect changes in gut microbiota and short chain fatty acids in rats.Western blot detection of Occludin in the colon and TLR4,NF-κB P65 and NLRP3 in the hippocampus of rats.Immunofluorescence detection of IBA-1,NLRP3,and IL-1β in the hippocampus Protein expression.Result The results of the open field experiment showed that compared with the normal group,the total activity distance(P<0.001),central area activity distance(P<0.01),and average velocity(P<0.01)of the model group decreased.Compared with the model group,the total activity distance(P<0.05,P<0.001),central area activity distance(P<0.05,P<0.01),and average velocity(P<0.05,P<0.01)of the electroacupuncture group and diazepam group all increased.The results of the elevated cross maze experiment showed that compared with the normal group,the model group had a decrease in OE%(P<0.001)and OT%(P<0.001).Compared with the model group,both the electroacupuncture group and the diazepam group could increase OE%(P<0.05,P<0.001)and OT%(P<0.01,P<0.001).The HE staining results of the hippocampus showed that the CA1 area of the hippocampus in the normal group rats showed clear and hierarchical structures in various regions of the hippocampus.In the hippocampus of the model group,a small amount of neural cell nuclei in the CA1 area were observed to be wrinkled and deeply stained,with unclear cell boundaries and irregular arrangement,and the cytoplasm was vacuolate.The intervention of electroacupuncture and diazepam can alleviate the above pathological phenomena to varying degrees,respectively;The results of hippocampal metabolomics showed that electroacupuncture can improve hippocampal metabolic disorders caused by modeling,mainly involving taurine and low taurine metabolism,cysteine and methionine metabolism,and regulation of glycine,serine,and threonine metabolic pathways;The results of 16S rRNA sequencing and short chain fatty acid detection showed that electroacupuncture can improve the disturbance of intestinal microbiota caused by modeling,and can regulate serum LPS and levels of butyric acid,caproic acid,and valeric acid.HE staining and Western blot results showed that the model group had pathological damage to the intestine,and compared with the normal group,the expression of Occludin in the colon of the model group decreased(P<0.05).However,the intervention of electroacupuncture and diazepam could improve the pathological damage of the colon and upregulate the expression of Occludin(P<0.05,P<0.05).The immunofluorescence results showed that compared with the normal group,the expression levels of IBA-1,NLRP3,and IL-1β in the hippocampus of the model group increased(P<0.05,P<0.01,P<0.01),while compared with the model group,the electroacupuncture group and diazepam group could reduce the expression levels of IBA-1(P<0.05,P<0.05),NLRP3(P<0.05,P<0.05),and IL-1β(P<0.05,P<0.05).Western blot results showed that compared with the normal group,the expression levels of TLR4,NF-κB P65,and NLRP3 proteins in the hippocampus of the model group increased(P<0.05,P<0.001,P<0.05).Compared with the model group,the electroacupuncture group and diazepam group were able to downregulate the expression levels of NF-κB P65(P<0.01,P<0.001)and NLRP3(P<0.05,P<0.05)proteins.Conclusion The anxiolytic of electroacupuncture involves the regulation of the"microbiota-gut-brain"axis.

Purpose To investigate the characteristics of 18F-Florbetaben(18F-FBB)β-amyloid(Aβ)PET imaging in different brain regions of Alzheimer's disease(AD)patients with different degrees of cognitive impairment,and to explore the correlation between Aβ deposition and cognitive dysfunction.Materials and Methods A total of eighteen patients with a clinical diagnosis of probable AD from August 2022 to October 2023 were retrospectively included in Huashan Hospital.All patients had Aβ abnormal deposition in the brain as confirmed by 18F-FBB PET imaging.According to the severity of symptoms,they were divided into the AD-induced mild cognitive impairment(MCI)group(8 cases)and the dementia group(10 cases).In addition,12 healthy controls were included.First,the standardized uptake value ratio of abnormal Aβ deposition in the frontal lobe,lateral parietal lobe,lateral temporal lobe,anterior and posterior cingulate gyrus,and compound cortex was semi-quantitatively calculated and compared among the three groups based on the subjects'brain MRI and automated anatomical labeling template.The correlation between the degree of Aβ deposition in the brains of AD patients and cognitive scale scores(mini-mental state examination,Montreal cognitive assessment)was then further analyzed.Results The standardized uptake value ratio values of Aβabnormal deposition in the frontal lobe,lateral temporal lobe,lateral parietal lobe,anterior and posterior cingulate cortex and compound cortex in the AD-induced MCI and dementia groups were significantly higher than those in the healthy controls(t=7.442-9.151,all P＜0.05).However,there was no significant difference in the standardized uptake value ratio values of Aβ abnormal deposition in the above brain regions between the MCI and dementia groups(t=0.312-0.996,all P＞0.05).In addition,there was no significant correlation between the degree of Aβ deposition in the brain and the cognitive scale scores(mini-mental state examination,Montreal cognitive assessment)in the AD-induced MCI and dementia groups(r=-0.049-0.050,all P＞0.05).Conclusion Aβ deposition in the brains of AD-induced MCI and dementia is significantly higher than in the healthy controls.However,Aβ deposition cannot identify AD patients with different degrees of cognitive impairment,reflecting that Aβ deposition has certain limitations in assessing the severity of clinical symptoms of AD.