Exploration in the medication law and core TCM prescriptions of Jia Yuejin in the treatment of coronary heart disease complicated with depression based on the "target-component-Chinese materia medica" and clinical data / 国际中医中药杂志

Objective:To explore the medication law and core TCM prescriptions of Jia Yuejin in the treatment of coronary heart disease (CHD) complicated with depressive disorder (DD) by analyzing target-based network and mining clinical data.Methods:The targets of CHD complicated with DD were obtained by GeneCards, OMIM, TTD and other databases, and then the protein-protein interaction network of the two disease targets was constructed and then screened out the core targets. The Metascape platform was used to perform GO and KEGG pathway enrichment analysis on the intersection targets respectively to analyze the mechanism of action of CHD complicated with DD. Then TCMSP was used to query the active components acting on the targets and the Chinese materia medica containing these active components, and the data were imported into Cytoscape 3.9.0 to construct the core target-active component-Chinese materia medica network for network topology analysis. The outpatient clinical data of Jia Yuejin from January 1, 2015 to January 1, 2021 were collected, and data mining was conducted by using the Ancient and Modern Medical Case Cloud Platform (V2.3.5) to obtain his commonly used prescriptions. The results were fitted with the core TCM prescriptions obtained by target network analysis, and the drugs in the core prescriptions were analyzed.Results:Totally 1 501 intersection targets were obtained by protein interaction network analysis of CHD complicated with DD, which could be divided into 4 core target clusters, including inflammation cause, subclass tumor cause, subclass lipid metabolism factor, and fibrosis factor; a total of 480 active components were obtained by TCMSP, which belonged to 181 types of Chinese materia medica, including 8 core components: quercetin, kaempferol, luteolin, carotene, beta-carotene, acacetin, formononetin and ellagic acid. GO enrichment analysis yielded 61 results, mainly including positive regulation of protein phosphorylation, signal receptor agonist activity, side of membrane , etc.; KEGG pathway enrichment analysis yielded a total of 20 results, mainly including cancer pathways, lipid and atherosclerosis, JAK-STAT signaling pathway, etc. Clinical data mining included 120 cases and 148 prescriptions, including 135 types of Chinese materia medica; the properties were mainly mild, warm, slightly cold and cold; the tastes were mainly sweet, bitter and light, and the medicine mainly belongs to the lung, spleen, liver, heart, stomach, kidney and other meridians; drug association analysis, cluster analysis and complex network analysis were used to synthesize common prescriptions. The core TCM prescriptions obtained from common prescription and target network analysis were fitted: Pinelliae Rhizoma, Glycyrrhizae Radixet Rhizoma, Bupleuri Radix, Cyperi Rhizoma, Salviea Miltiorrhizae Radix et Rhizoma, Corydalis Rhizoma, Codonopsis Radix, Astragali Radix, Acori Tatarinowii Rhizoma. Conclusion:The medication law of Jia Yuejin in the treatment of CHD complicated with DD is in accordance with core TCM prescriptions. This study can provide guidance for clinical treatment and further research of CHD complicated with DD.

Analysis of risk factors for recurrence of differentiated thyroid carcinoma after surgical resection combined with iodine-131 and TSH suppression therapy / 临床耳鼻咽喉头颈外科杂志

Objective:To investigate the risk factors of recurrence after surgical resection of differentiated thyroid carcinoma combined with iodine-131 and TSH（Thyroid stimulating hormone） inhibition therapy. Methods:From January 2015 to April 2020, the clinical data of patients with structural recurrence and without recurrence were retrospectively collected after surgical treatment combined with iodine-131 and TSH inhibition therapy in the First Medical Center of PLA General Hospital. The general conditions of the two groups of patients were analyzed and the measurement data in line with the normal distribution was used for comparison between groups. For measurement data with non-normal distribution, the rank sum test was used for inter-group comparison. The Chi-square test was used for comparison between the counting data groups. Univariate and multivariate regression analyses were used to determine the risk factors associated with relapse. Results:The median follow-up period was 43 months（range 18-81 months） and 100 patients（10.5%） relapsed among the 955 patients. Univariate analysis showed that tumor size, tumor multiple, the number of lymph node metastases>5 in the central region of the neck, and the number of lymph node metastases>5 in the lateral region were significantly correlated with post-treatment recurrence（P<0.001, P=0.018, P<0.001, P<0.001）. Multivariate analysis showed that tumor size（adjusted odds ratio OR: 1.496, 95%CI: 1.226-1.826, P<0.001）, tumor frequency（adjusted odds ratio OR: 1.927, 95%CI: 1.003-3.701, P=0.049）, the number of lymph node metastases in the central neck region>5（adjusted odds ratio OR: 2.630, 95%CI: 1.509-4.584, P=0.001） and the number of lymph node metastases in the lateral neck region>5（adjusted odds ratio OR: 3.074, 95%CI: 1.649-5.730, P=0.001） was associated with tumor recurrence. Conclusion:The study showed that tumor size, tumor multiple, the number of lymph node metastases in the central region of the neck>5 and the number of lymph node metastases in the side of the neck >5 are independent risk factors for recurrence of differentiated thyroid cancer after surgical resection combined with iodine-131 and TSH inhibition therapy.

Effects of hierarchical management based on medical alliances on patency of arteriovenous graft in hemodialysis patients / 中华肾脏病杂志

Objective:To investigate the impacts of hierarchical management based on medical alliance on the patency of arteriovenous graft (AVG),and provide a basis for further exploration of optimal AVG management.Methods:In this retrospective cohort study, clinical and follow-up data of patients with AVG established in the First Affiliated Hospital of Zhengzhou University from January 1, 2018 to December 31, 2021 were analyzed. Patients were divided into medical alliance group and non-medical alliance group according to whether they were under hierarchical management model, and the patency rate of AVGs and the incidence of clinical events were compared between the two groups.Results:A total of 328 AVGs were included in this study, which were from 151 hemodialysis centers, including 189 AVGs (57.6%) from 72 centers in medical alliance group, and 139 AVGs (42.4%) from 79 centers in non-medical alliance group. The age of the patients was (55.57±11.80) years, among whom 130 (39.6%) were males and 126 (38.4%) were diabetic. The follow-up time of AVGs in this cohort was 15.5 (9.5, 26.2) months, with 15.4 (9.8, 25.2) months in medical alliance group and 15.5 (9.2, 27.3) months in non-medical alliance group. The incidence of thrombosis or occlusion (0.328 times/patient-year), graft dissection (0.007 times/patient-year), graft infection (0.030 times/patient-year), and catheter utilization (0.043 times/patient-year) in the medical alliance group were lower than those in the non-medical alliance group (0.589 times/patient-year, 0.040 times/patient-year, 0.054 times/patient-year and 0.147 times/patient-year, respectively), and there was no significant difference in clinic follow-up rates between the two group (1.91 times/patient-year vs. 1.94 times/patient-year). The median primary patency time was 17.4 (95% CI 11.3-23.5) months, the median primary assisted patency time was 32.6 (95% CI 25.0-40.2) months, and the median secondary patency time was 47.9 (95% CI 40.0-55.8) months in the medical alliance group, compared with 12.3 (95% CI 9.4-15.2) months, 19.4 (95% CI 14.3-24.5) months, and 34.6 (95% CI 29.3-39.9) months in the non-medical alliance group, respectively. Primary patency were significantly higher in the medical alliance group (77.4%, 62.2%, 39.9%, and 26.6%) than those in the non-medical alliance group (71.1%, 50.1%, 30.6%, and 13.4%) at 6, 12, 24, and 36 months (Log-rank test, χ2=4.504, P=0.034). Primary assisted patency were significantly higher in the medical alliance group (90.9%, 84.3%, 67.1%, and 46.1%) than those in the non-medical alliance group (89.2%, 75.7%, 42.0%, and 16.6%) at 6, 12, 24, and 36 months (Log-rank test, χ2=10.655, P=0.001). Secondary patency were significantly higher in the medical alliance group (96.8%, 91.8%, 84.2%, and 74.0%) than those in the non-medical alliance group (89.9%, 85.8%, 69.3%, and 47.5%) at 6, 12, 24, and 36 months (Log-rank test, χ2=11.634, P=0.001). Multivariate Cox regression analysis showed that it was a protective factor for primary patency ( HR=0.708, 95% CI 0.512-0.980, P=0.037), primary assisted patency ( HR=0.506, 95% CI 0.342-0.749, P=0.001) and secondary patency ( HR=0.432, 95% CI 0.261-0.716, P=0.001) under the medical alliance model. Conclusion:The hierarchical management based on medical alliances can improve the patency of AVGs and reduce the incidence of clinical events.

Value of 18F-PSMA-3Q PET/CT in prostate cancer patients with low prostate specific antigen level after radical prostatectomy / 中华核医学与分子影像杂志

Objective:To evaluate the value of 18F-prostate specific membrane antigen (PSMA)-3Q PET/CT imaging in prostate cancer patients with serum prostate specific antigen (PSA) less than 1.00 μg/L after radical prostatectomy. Methods:From May 2021 to August 2022, 18F-PSMA-3Q PET/CT images and clinical data of 58 patients with prostate cancer (age 52-82 years) after radical prostatectomy with PSA less than 1.00 μg/L in Chinese PLA General Hospital were analyzed retrospectively. According to the level of PSA, patients were divided into three groups (0-0.19 μg/L group, 0.20-0.49 μg/L group, and 0.50-0.99 μg/L group). 18F-PSMA-3Q PET/CT images were analyzed according to the standardized evaluation criteria of molecular imaging, and lesions with the scores of molecular imaging PSMA (miPSMA)≥1 were defined as recurrent or metastatic lesions. The detection rates of 18F-PSMA-3Q PET/CT for patients in different PSA level groups were compared ( χ2 test). The PSA levels of patients with positive and negative scans were compared by using independent-sample t test. Results:Of the 58 patients, 36(62.1%, 36/58) patients and 85 lesions were found by 18F-PSMA-3Q PET/CT. There was 91.7%(33/36) with oligofocal lesions (1≤number of foci≤3) and 8.3%(3/36) with multiple lesions (number of foci>3). According to the location, 5.2%(3/58) of the recurrent lesions were found in the prostatic bed, 39.7%(23/58) in the bone lesions, 37.9%(22/58) in the pelvic lymph nodes, 12.0%(7/58) in the retroperitoneal lymph nodes and 5.2%(3/58) in the left clavicular lymph node metastases. There were 15 cases in 0-0.19 μg/L group, 22 cases in 0.20-0.49 μg/L group, and 21 cases in 0.50-0.99 μg/L group. The detection rates of 18F-PSMA-3Q PET/CT in the above groups were 5/15, 59.1%(13/22) and 85.7%(18/21), respectively ( χ2=10.33, P=0.006). There was significant difference in PSA level between patients with positive ( n=36) and negative ( n=22) 18F-PSMA-3Q PET/CT scans ((0.48±0.28) vs (0.28±0.25) μg/L; t=2.67, P=0.010). Conclusions:18F-PSMA-3Q PET/CT can be used to detect the recurrence or metastasis in prostate cancer patients with PSA level lower than 1.00 μg/L after radical prostatectomy. In this kind of patients, the common sites of lesions are bone, pelvic lymph nodes, retroperitoneal lymph nodes, left clavicular lymph nodes and prostatic bed, and oligofocal patients are more common.

Exploration of medication rules and mechanisms of traditional Chinese medical doctor Jia Yuejin for treating depressive disorder based on bio-informatic method / 国际中医中药杂志

Objective:To explore the medication rules and mechanisms of traditional Chinese medical doctor Jia Yuejin for treating depressive disorder based on data mining and network pharmacology. Methods:The medication rules and core prescription were analyzed with the statistics of frequency, properties and analysis of correlation, clustering, and complex network of prescriptions for the treatment of depressive disorder from the outpatient service of Professor Jia in the past five years, from 1st Jan. 2016 to 1st Jul. 2020, with the help of the Ancient and Modern Medical Records Cloud Platform (V 2.2.3). Then we obtained the targets of effective ingredients of each drug of the core prescription and disease targets and took the intersection by virtue of TCMSP, GEO and other databases. We used Cytoscape V 3.8.0 to construct disease-drug-ingredient-target and protein-protein interaction networks, and performed GO and KEGG pathway enrichment analysis, and finally selected the key effective ingredients and key targets to apply software of Vina to molecularly dock. Results:A total of 120 medical records, 148 prescriptions and 138 drugs were obtained. The most common drug properties were gentle, warm, cold. The main tastes were sweet, pungent and bitter, and the meridians were concentrated in two spleen and liver meridians. The core prescription of 8 drugs was obtained through analysis of drug correlation, clustering and complex network. A total of 80 effective ingredients, 772 related targets, 542 intersectional genes of the core prescription were obtained, the key ingredients included dehydroeburicoic acid, α-Amyrin, and the key targets included AKT1, ESR1. The GO enrichment analysis showed metabolic process, immune system process, signaling process, and the KEGG pathway enrichment analysis showed neuroactive ligand-receptor interaction, NF-κB signaling pathway. The results of molecular docking of key ingredients and key targets showed them stable binding.Conclusion:The rules of Chinese Medicines of Professor Jia for depressive disorders show the related multi-ingredient, multi-target, multi-pathway mechanisms, which can provide references for clinical use and further research.

Patency rates and risk factors of arteriovenous graft / 中华肾脏病杂志

Objective:To investigate the patency rates and risk factors of arteriovenous graft (AVG), and provide a clinical guidance for further optimization of vascular access selection and improvement of dialysis quality.Methods:This was a retrospective study. The clinical and follow-up data of patients who received AVG in the Blood Purification Center, First Affiliated Hospital of Zhengzhou University from January 1, 2017 to December 31, 2021 were selected. Kaplan-Meier curve and Cox regression model were used to analyze the patency rates and risk factors of AVG.Results:A total of 381 cases with AVG were included, with 154 cases (40.4%) of males, age of (55.5±11.8) years old, and 140 cases (36.7%) of diabetes. The median time of primary patency was 377.00(95% CI 314.26-439.74) days, and the primary patency rates at 1, 2, and 3 years were 51.0%, 30.7%, and 15.4%, respectively. The median time of primary assisted patency was 839.00(95% CI 668.89-1 009.11) days, and the primary assisted patency rates at 1, 2, and 3 years were 78.3%, 56.4%, and 39.1%, respectively. The secondary patency rates at 1, 2, and 3 years were 96.7%, 90.1%, and 78.5%, respectively. Multivariate Cox regression analysis results showed that anastomotic vein types of basilic vein and cephalic vein (median cubital vein as a reference, HR=1.869, 95% CI 1.124-3.107, P=0.016; HR=2.110, 95% CI 1.176-3.786, P=0.012) and the diameter of anastomotic vein<3.5 mm ( HR=1.411, 95% CI 1.020-1.952, P=0.037) were the independent influencing factors for abnormal primary patency of AVG. Males ( HR=1.680, 95% CI 1.127-2.503, P=0.011), mean arterial pressure<70 mmHg ( HR=3.228, 95% CI 1.109-9.394, P=0.032), Acuseal graft type (Intering as a reference, HR=1.884, 95% CI 1.185-2.994, P=0.007), anastomotic vein type of cephalic vein (median cubital vein as a reference, HR=2.817, 95% CI 1.328-5.977, P=0.007), the diameter of anastomotic vein<3.5 mm ( HR=1.555, 95% CI 1.048-2.306, P=0.028), serum phosphorus ≤1.78 mmol/L (1.13-1.78 mmol/L />1.78 mmol/L, HR=1.737, 95% CI 1.111-2.716, P=0.015;<1.13 mmol/L />1.78 mmol/L, HR=2.162, 95% CI 1.072- 4.362, P=0.031), and ferritin<200 μg/L ( HR=1.850, 95% CI 1.231-2.780, P=0.003) were the independent influencing factors for abnormal primary assisted patency of AVG. Serum albumin<40 g/L ( HR=2.165, 95% CI 1.096-4.275, P=0.026) was an independent influencing factor for abnormal secondary patency of AVG. Conclusions:The primary patency rates of AVG at 1, 2, and 3 years were 51.0%, 30.7%, and 15.4%, respectively. The secondary patency rates of AVG at 1, 2, and 3 years were 96.7%, 90.1%, and 78.5%, respectively. Anastomotic vein types of cephalic vein and basilic vein, and internal diameter<3.5 mm are the independent risk factors for abnormal primary patency of AVG. Anastomotic vein type of cephalic vein and internal diameter<3.5 mm are the independent risk factors for abnormal assisted primary patency of AVG. Serum albumin<40 g/L is an independent risk factor for abnormal secondary patency of AVG. It is suggested that systematic preoperative evaluation and good nutritional status of patients are important to maintain long-term patency of the AVG.

Application of multiparametric diagnostic model based on the 18F-FDG PET/MR in the differential diagnosis of benign and malignant pancreatic tumors / 中华核医学与分子影像杂志

Objective:To investigate the value of multiple parameters and the combined model based on 18F-fluorodeoxyglucose (FDG) PET/MR in the differential diagnosis of benign and malignant pancreatic tumors. Methods:A total of 76 patients (50 males, 26 females, age (45.2±18.0) years) with clinically suspected pancreatic tumor who underwent PET/MR between December 2012 and September 2020 in First Medical Center of Chinese PLA General Hospital were retrospectively selected. All patients had definitive diagnoses. PET/MR sequences included T 1 weighted imaging (WI; convention and contrast enhancement), T 2WI, diffusion weighted imaging (DWI) and 18F-FDG PET sequences. Morphological characteristics and scores of lesions in MRI were evaluated. Parameters including parameters of PET and DWI, as well as parameters derived from histogram analysis of apparent diffusion coefficient (ADC) and standardized uptake value (SUV) (maximum (max), minimum (min), mean, median, standard deviation (SD), skewness, kurtosis, entropy) were measured. Independent-sample t test or Mann-Whitney U test were used for data analysis. PET/MR combined model was measured based on logistic regression analysis. Receiver operating characteristic (ROC) curve analysis was used to calculate the differential diagnosis efficacy of PET/MR multiparameters and combined model for benign and malignant lesions. Results:Among 76 patients, 55 were malignant and 21 were benign. (1) Visual evaluation. The main manifestations of pancreatic cancer were unclear margin, abnormal internal MR signal and enhancement, decreased ADC signal and increased radioactive uptake. The main manifestations of benign tumor lesions of pancreas were clear margin, even signal and enhancement, no reduction of ADC, decreased radioactive uptake. (2) Diagnostic efficacy. Multiparameter model established based on logistic regression analysis included SUV max, SUV SD, ADC entropy and ADC skewness. The efficiency of differential diagnosis for benign and malignant pancreatic tumors were shown as follows: multiparametric diagnostic model>ADC entropy>MR score>SUV max>SUV SD>ADC skewness. The multiparametric diagnostic model had the best diagnosis efficiency with the area under curve (AUC) of 0.86, the sensitivity of 69.1%(38/55), and the specificity of 100%(21/21) ( z=-8.73, P<0.001). Conclusions:MR score and multiple quantitative parameters obtained from 18F-FDG PET/MR can be used to differentiate benign and malignant pancreatic tumors. Compared with independent parameter of PET/MR, multiparametric model can further improve the diagnostic efficiency.

Relationships between tau and brain atrophy in Alzheimer′s disease based on 18F-THK5317 PET/MR / 中华核医学与分子影像杂志

Objective:To investigate the neuroimaging relationship between tau protein deposition and brain atrophy, and assess their relationships with cognitive decline in Alzheimer′s disease (AD) patients.Methods:From April 2017 to October 2019, 26 AD patients (12 males, 14 females, age (70.7±12.2) years) and 19 cognitively normal controls (CN; 9 males, 10 females, age (65.6±8.1) years) in Chinese PLA General Hospital were retrospectively enrolled. All subjects received (S)-6-[(3- 18F-fluoro-2-hydroxy)propoxy]-2-(4-methylaminophenyl)quinoline ( 18F-THK5317) PET/MR and the standardized uptake value ratio (SUVR) and gray matter volume (GMV) were measured. General linear model (GLM) was used to evaluate the differences of SUVR and GMV between two groups. Pearson correlation analysis was used to assess the relationships between SUVR and GMV, and relationships of SUVR and GMV with Mini-Mental State Examination (MMSE) scores in AD patients. Results:Compared with CN, the AD patients showed significantly increased 18F-THK5317 retention in lateral temporal, frontal, posterior cingulated/precuneus and occipital cortex with significant differences of SUVR between two groups (2.18±0.54 vs 1.78±0.09, 2.13±0.50 vs 1.82±0.06, 2.03±0.45 vs 1.69±0.08, 2.18±0.57 vs 1.76±0.10, t values: 2.58-6.57, all P<0.001). The AD patients also showed decreased GMV in medial temporal, posterior cingulated/precuneus and orbitofrontal cortex ( t values: 3.67-8.85, all P<0.001). In AD patients, SUVR was negatively associated with GMV in bilateral lateral temporal cortex, pre-frontal cortex and orbital frontal cortex ( r values: from -0.52 to -0.43, all P<0.05). Both SUVR ( r=-0.599, P=0.001) and GMV ( r=0.443, P=0.023) were significantly correlated with MMSE scores in AD patients. Conclusion:AD patients have neocortical 18F-THK5317 abnormal uptake and GMV reduction, which are significantly correlated with cognitive decline.

Comparative analysis of the accuracy of visual qualitative assessment and semi-quantitative analysis in 18F-florbetaben β-amyloid imaging / 中华核医学与分子影像杂志

Objective:To compare the accuracy of visual qualitative assessment and semi-quantitative analysis for 18F-florbetaben ( 18F-FBB) β-amyloid (Aβ) imaging in the diagnosis of Alzheimer′s disease (AD) and to explore their clinical application value. Methods:From January 2019 to October 2019, 17 patients (8 males, 9 females, age (74.1±8.5) years) with mild/moderate-stage clinically probable AD and 17 cognitive normal control (NC; 9 males, 8 females, age (64.5±6.3) years) were prospectively enrolled in this study. All patients underwent dynamic 18F-FBB PET/CT brain imaging in the Chinese PLA General Hospital. Visual qualitative assessment and semi-quantitative analysis methods were used to analyze PET brain imaging results. The difference of standardized uptake value ratio (SUVR) between the two methods was analyzed by using independent sample t test. The consistency of the two methods and clinical results was analyzed by Kappa test. The cut-off value of SUVR for the diagnosis of AD was determined by receiver operating characteristic (ROC) curve. Results:The sensitivity, specificity and accuracy of visual qualitative assessment to diagnose AD were 14/17, 16/17 and 88.2% (30/34). The global SUVR of NC and AD group were 1.09±0.85 and 1.75±0.25 ( t=-10.263, P<0.001), and the composite SUVR were 1.16±0.57 and 1.89±0.15 ( t=-10.789, P<0.001), respectively. The cut-off value of SUVR for the diagnosis of AD was 1.47, with the sensitivity of 15/17, the specificity of 16/17 and the accuracy of 91.2%(31/34). The visual qualitative assessment and semi-quantitative analysis had good consistency with clinical diagnosis results with Kappa value of 0.765 and 0.824 respectively (both P<0.001). Conclusion:The visual qualitative assessment and semi-quantitative analysis methods used in 18F-FBB Aβ imaging to diagnose AD patients show high accuracy and can provide effective value for clinical diagnosis, but the visual qualitative assessment method is concise and easy to grasp, which is worth further promotion and use in clinical.

Association of CYP2C19 and CYP3A5 gene polymorphisms with myocardial infarction / 中华医学遗传学杂志

OBJECTIVE@#To assess the association of CYP2C19 and CYP3A5 gene polymorphisms with the risk of myocardial infarction.@*METHODS@#Five hundred patients with myocardial infarction and 500 healthy controls were randomly selected. Fluorescent PCR and Sanger sequencing were used to detect the CYP2C19 and CYP3A5 gene polymorphisms. Logistic regression was used to analyze the correlation between the polymorphisms and myocardial infarction. Quanto software was used to evaluate the statistical power.@*RESULTS@#The two groups had significant difference in the frequency of AG, GG genotypes and A allele of the CYP2C19 gene rs4986893 locus and the AA, AG, GG genotypes and G allele of the CYP3A5 gene rs776746 locus ( P<0.05), but not in the frequency of genotypes and alleles of CYP2C19 gene rs4244285 and rs12248560 loci, and the AA genotype of the rs4986893 locus. After correction for age, gender, and body mass index, Logistic regression indicated that the AG genotype and A allele of the CYP2C19 gene rs4986893 locus, and the GG genotype and G allele of CYP3A5 gene rs776746 locus are associated with susceptibility of myocardial infarction, while rs4986893 GG genotype and AA and AG genotypes of rs776746 may confer a protective effect. Based on the sample size and allele frequency, analysis with Quanto software suggested that the result of this study has a statistical power of 99%.@*CONCLUSION@#CYP2C19 and CYP3A5 gene polymorphisms may increase the risk for myocardial infarction.

Constitutive androstane receptor induced-hepatomegaly and liver regeneration is partially

The constitutive androstane receptor (CAR, NR3I1) belongs to nuclear receptor superfamily. It was reported that CAR agonist TCPOBOP induces hepatomegaly but the underlying mechanism remains largely unknown. Yes-associated protein (YAP) is a potent regulator of organ size. The aim of this study is to explore the role of YAP in CAR activation-induced hepatomegaly and liver regeneration. TCPOBOP-induced CAR activation on hepatomegaly and liver regeneration was evaluated in wild-type (WT) mice, liver-specific YAP-deficient mice, and partial hepatectomy (PHx) mice. The results demonstrate that TCPOBOP can increase the liver-to-body weight ratio in wild-type mice and PHx mice. Hepatocytes enlargement around central vein (CV) area was observed, meanwhile hepatocytes proliferation was promoted as evidenced by the increased number of KI67

Diagnosis of brain tumor with multi-modality imaging of 11C-MET PET combined with functional MRI / 中华核医学与分子影像杂志

Objective To evaluate the diagnostic efficiency of the parameters obtained from PET/MR in brain tumors.Methods In this prospective study,28 patients (21 males,7 females,age range: 6-82 years) with clinical suspicion of brain tumor from November 2012 to September 2015 underwent PET/MR multi-modality imaging.The examination of PET/MR included 11C-MET PET and multiple MR sequences.The qualities of images were estimated firstly.The ROC curve and the accuracy of SUVmax,ADCmean,rCBF and NAA/(Cho+Cre) ratio were calculated.The pathology or final clinical diagnosis was taken as the standard.The diagnostic efficiency of the multi-modality imaging was determined based on the cutoff values of the four parameters.Two-sample t test was used to analyze the differences of parameters between glioma group and inflammatory group.Results SUVmax,ADCmean,rCBF and NAA/(Cho+Cre) ratio were validated to be effective parameters in diagnosing brain tumors with the diagnostic accuracy of 89.3％(25/28),82.1％(23/28),78.6％(22/28) and 75.0％(21/28),respectively.The SUVmax exhibited the highest diagnostic accuracy,while the diagnostic efficiency of the combination of four parameters was superior to the separate parameter.The values of SUVmax,rCBF and NAA/(Cho+Cre) ratio were significantly different between glioma group(n=10) and inflammatory group(n=11;t values:-2.31,-3.11,-2.77,all P<0.05).Conclusions PET/MR can provide a one-stop examination with multi-modality imaging of brain.The obtained parameters SUVmax,ADCmean,rCBF and NAA/(Cho+Cre) ratio,especially their combination,have effective diagnostic values on brain tumor.

Multiple modalities PET/CT neuroimaging for the diagnosis of Parkinson's disease and multiple system atrophy: statistical parametric mapping analysis / 中华神经科杂志

Objective To investigate the topographic distributions of dopamine transporter (DAT),dopamine D2 receptor and glucose in Parkinson's disease (PD) and multiple system atrophy (MSA) using positron emission tomography/computed tomography (PET/CT) scanning and statistical parametric mapping (SPM) analysis.Methods Seventy subjects (39 PD patients,15 MSA patients and 16 normal controls) who came from People's Liberation Army General Hospital from September 2013 to November 2015 underwent DAT,D2 receptor and glucose brain PET/CT scans using 11 C-methyl-N-2-β-carbomethoxy-3-β-(4-fluorophenyl) tropane (11C-β-CFT),11C-raclopride and 18F-fluorodeoxyglucose (18 F-FDG) as radiotracers,respectively.The uptake patterns were analyzed using SPM software.Results Striatal DAT binding decreased in the putamen in PD patients compared with controls (Z =5.21-5.77,P =0.002-0.016).D2 receptor showed no significant differences.However,glucose uptake decreased in cingulate gyrus(Z =4.51-4.67,P =0.010-0.017).For MSA patients,both DAT and D2 receptor binding decreased in the putamen(Z =2.13-3.42,P =0.000-0.016).Glucose uptake decreased in the bilateral putamen,cerebellum and part of frontal temporal lobes (Z =1.86-3.75,P =0.000-0.032).Conclusion Multiple modalities PET/CT scans using the ligands 11 C-β-CFT,11C-raclopride,and 18F-FDG are valuable in diagnosis of MSA and differential diagnosis of MSA from PD.

Keap1-tat peptide attenuates oxidative stress damage in hippocampal CA1 region and learning and memory deficits following global cerebral ischemia / 北京大学学报(医学版)

Objective:To design Keap1-tat peptide and explore its neuroprotective role on hipocampal CA1 neuron,as well as the effect on spacial learning and memory function following global cerebral ische-mia.Methods:Adult male Sprague Dawley (SD)rats were subjected to global cerebral ischemia (GCI) by four-vessel occlusion for 1 5 min and randomly divided into five groups:sham,sham+Keap1-tat,is-chemia/reperfusion (I/R),Keap1-tat peptide-and vehicle-administrated groups.For Keap1-tat or vehi-cle groups,the rats were treated with Keap1-tat (30,50,1 00 μg in 5 μL 0.9%saline)or the same vo-lume vehicle by intracerebroventricular injection (icv)30 min prior to ischemia.Cresyl violet staining was used to observe the surviving neurons and 4-hydroxy-2-noneal (4-HNE ) and 8-hydroxy-2′-deox-yguanosine (8-OHdG)immunostaining were used to detect the change of markers response to oxidative stress in hippocampal CA1 region.The spatial learning and memory function of the rats was evaluated using Morris water maze.Results:Compared with sham group,the number of surviving neurons in ische-mia-reperfusion and vehicle groups significantly decreased in the hippocampal CA1 region (P<0.05 ), while administration of Keap1-tat significantly decreased the damage following GCI (P<0.05),and the dose of 50 μg existed the most effective neuroprotective role.Furthermore,immunostaining intensity of 4-HNE and 8-OHdG,markers of oxidative stress damage attenuated by Keap1-tat peptide as compared with vehicle group in CA1 region.Of significant interest,the time of finding underwater platform in Keap1-tat group animals was significantly short,and after removing the platform,the probe time of Keap1-tat group animals in the original quadrant where the platform was significantly increased compared with that of vehi-cle and I/R group animals (P<0.05).Conclusion:Keap1-tat peptide can effectively attenuate neuro-nal damage in hippocampal CA1 region and improve learning and memory function,which might bedue to the attenuation of oxidative stress caused by GCI.

Probable Sporadic Creutzfeldt-Jakob Disease:A Study of Glucose Metabolism byStatistical Parameter Mapping / 中国医学影像学杂志

PurposeTo analyze fluorodeoxyglucose (FDG) PET/CT images in patients with probable sporadic Creutzfeldt-Jakob disease (sCJD) and the affected encephalic regions by statistical parameter mapping (SPM) so that image information can be provided for early clinical diagnosis.Materials and MethodsSeven patients with probable sCJD diagnosed according to the WHO criteria and 2009 clinical diagnosis criteria and 7 controls at the matched age were enrolled in the study. Both groups underwent FDG PET/CT scan and the images were analyzed visually and by SPM.ResultsThe visual analysis showed that the patients with probable sCJD had a hypometabolism in the wide pallium and basal ganglia region and that a portion of patients mainly had a lateral decrease. The SPM analysis exhibited that patients in sCJD group had a pattern of hypometabolism that affected bilateral parietal, frontal, occipital cortices and head of caudate (P<0.05) and indicated that the patients with lateral hypometabolism existed crossed cerebella diaschisis (P<0.05).ConclusionFDG PET/CT image features of sCJD patients present a hypometabolism in the wide pallium and basal ganglia region, which may be helpful in the diagnosis of sCJD in certain clinical situations.

An improved fixation method of the indwelling needle inserted in the rat tail vein / 中国比较医学杂志

Objective To improve the fixation method of indwelling needle inserted in the tail vein in rats to keep the inserted needle for a longer indwelling time .Methods One hundred healthy Wistar rats ( age 5~6 months, male:female=1:1) were randomly divided into two groups: the experimental group and the control group .Rats in both groups received the same tail vein indwelling needle puncture and cannulation .The control group got the traditional fixation , namely fixed by sticking with 3M transparent dressing paste .The experimental group received in addition to the traditional fixation, a 0.1 mm-thick aluminum tube placed outside the needle fixation site .The indwelling time in the rats were recorded and analyzed .Results The indwelling time was (166.86 ±9.03) h and (20.24 ±5.04) h in the experimental and control groups, respectively (t =68.546, P<0.01).Conclusions Our improved method is safe and reliable.It can prolong the indwelling time of the punctured intravenous indwelling needle , and provides a useful rat model in studies on the complications of intravenous indwelling needle kept for a longer time .

Estrogen decreases vascular damage induced by chronic hypoperfusion through upregulating VEGF expression / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the effect of physiological dose 17-β-estrodiol (E2) replacement therapy on vascular dementia caused by cerebral chronic hypoperfusion.</p><p><b>METHODS</b>The rats with bilateral common carotid artery occlusion (BCCAO) received E2 treatment starting from 3 days or 3 months after the operation. IgG leakage into the brain parenchyma and the changes of microvascular ultrastructure following BCCAO were examined using immunohistochemistry and electron microscopy, respectively; Western blotting was used to detect the expression of vascular endothelial growth factor (VEGF) protein.</p><p><b>RESULTS</b>Compared with the sham-operated groups, the rats at 3 days and 3 months after BCCAO showed extensive vascular damages surrounded by IgG immunoreactivity in both the cortical and hippocampal CA1 regions. Stronger IgG immunoreactivity in the hippocampal CA1 region was observed at 3 days after BCCAO than at 3 months, but no significant IgG leakage was found in rats with continuous E2 treatment. Electron microscopy revealed severe edema around the blood vessels, mild vascular dilation, and endothelial cell damages at both 3 days and 3 months after BCCAO. E2 treatment markedly reduced the microvascular ultrastructural damages. Western blot analysis showed a significant increase in VEGF expression in the CA1 region at 6 h and 1 day after BCCAO followed by an obvious reduction till reaching the lowest level at 3 days; VEGF expression remained low even at 3 months after BCCAO and was significantly increased by E2 treatment.</p><p><b>CONCLUSIONS</b>Vascular structural damage occurs early after BCCAO and can last for 3 months. E2 replacement therapy at physiological doses can reduce the incidence of BCCAO-induced vascular dementia by up-regulating VEGF expression.</p>

Brain imaging of 18 F-Fallypride in healthy volunteers / 中华核医学与分子影像杂志

Objective To evaluate dopamine D2/D3 receptors status in striatal and extra?striatal re?gions with 18 F?Fallypride PET/CT. Methods A total of 11 healthy volunteers ( 4 males, 7 females, age (43.5±13.7) years) underwent PET/CT at 1 h after 18F?Fallypride injection. Imaging data was analyzed u?sing visual and ROI methods. The SUV ratios of different brain regions to cerebellar lobe were calculated. In?formed consent was obtained from all volunteers. The study was approved by the Ethics Committee of the PLA General Hospital. Results 18 F?Fallypride was widely distributed in striatal and extra?striatal brain re?gions. Distribution of 18 F?Fallypride was consistent in all healthy subjects and the rank order of receptor con?centration(brain region SUV/cerebellum SUV) was putamen(15.72±3.69)>pituitary(10.24±6.55)>cau?date(8.38±1.26)>amygdala(6.92±1.32)>thalamus(4.87±1.50)>colliculi(3.91±1.08)>substantia nigra (3.20±0.95)>cortex(temporal cortex: 2.11±1.34, parietal cortex: 1.51±0.57, occipital cortex: 1.31± 0?11, frontal cortex:1?30±0.25). Conclusion 18F?Fallypride PET/CT is suitable to study D2/D3 recep?tors status in striatal and extra?striatal brain regions.

Anti-fibrotic role of AcSDKP through inhibition of P38MAPK pathway activity mediated transforming growth beta receptors in rat with silicosis / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the distribution and expression of transforming growth factor beta (TGF-β) receptors I and II, p38 mitogen-activated protein kinase (p38 MAPK), and type I and type III collagen in the lungs of rats with silicosis and cultured pulmonary fibroblasts, and to investigate the relationship of the anti-fibrosis effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) with its inhibition of TGF-β receptor-mediated p38 MAPK pathway activity.</p><p><b>METHODS</b>Rats were randomly divided into control group, silicosis model group, and AcSDKP treatment group (n = 10 for each group). For the model group and AcSDKP treatment group, rats were intratracheally instilled with silica to establish a silicosis model. Cultured pulmonary fibroblasts from neonatal rats were divided into control group, TGF-β1 stimulation group, TGF-β receptor inhibition group, p38 MAPK pathway inhibition group, and AcSDKP treatment group. The protein expression of TGF-β receptors I and II, p38 MAPK, and type I and type III collagen were determined by immunohistochemistry and Western blot. The mRNA expression of TGF-β receptors I and II were determined by real-time PCR. The distribution and nuclear translocation of phospho-p38 MAPK in cultured fibroblasts were determined by laser scanner confocal microscopy.</p><p><b>RESULTS</b>In the AcSDKP treatment group, AcSDKP reduced the expression of TGF-β receptors I and II, phospho-p38 MAPK, and type I and type III collagen to 86.12%, 41.01%, 42.63%, 89.05%, and 52.71%, respectively, of those of the silicosis model group (P < 0.05). In cultured fibroblasts, AcSDKP reduced the mRNA expression of TGF-β receptors I and II to 42.26% and 54.33%, respectively, of those of the TGF-β1 stimulation group; the protein expression of TGF-β receptors I and II, phospho-p38 MAPK, and type 1 and type III collagen was reduced to 58.14%, 51.40%, 45.6%, 58.04%, and 44.74%, respectively, of those of the TGF-β1 stimulation group. The phospho-p38 MAPK translocation from plasma to the nucleus was also inhibited; the nucleus/plasma ratio of p38 MAPK and the protein expression of type I and type III collagen were reduced to 68.60%, 58.04%, and 44.74%, respectively, of those of the TGF-β stimulation group (P < 0.05).</p><p><b>CONCLUSION</b>AcSDKP can inhibit the expression of collagen through inhibition of TGF-β receptor-mediated p38 MAPK pathway activity, and is thus able to exert anti-fibrosis effect in rats with silicosis.</p>

Comparative proteomic analysis on anti-fibrotic effect of N-acetyl-seryl-aspartyl-lysyl-proline in rats with silicosis / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To perform a comparative proteomic analysis for identification of pulmonary proteins related to the progression of silicosis and anti-fibrotic effect of N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP).</p><p><b>METHODS</b>Bronchial instillation of SiO₂powder (for 4 or 8 weeks) was applied in rats to establish a silicosis model. Ac-SDKP treatment was performed before (prevention group) or after (treatment group) SiO₂instillation. The control group was treated by bronchial instillation of sodium chloride solution of the same volume as SiO₂powder for 4 or 8 weeks. Proteins in lung tissue were separated by two-dimensional gel electrophoresis and stained with colloidal Coomassie brilliant blue. The gel images were scanned with the Lab Scan III system and analyzed with Imagemaster 6.0. The protein spots with significant differences between two groups (i.e., P value was less than 0.05 in One-way ANOVA) and with a change in volume over 30% were defined as differential proteins. Comparison was performed between the silicosis group and control group after 4 or 8 weeks, between the Ac-SDKP treatment group and silicosis group after 8 weeks, and between the Ac-SDKP prevention group and silicosis group after 8 weeks. The differentially expressed proteins were subjected to in-gel digestion with trypsin and MALDI-TOF-MS and Mascot search engine analysis to identify these proteins.</p><p><b>RESULTS</b>Thirty-three differential proteins were identified. In comparison with the control group (4 weeks), the silicosis group (4 weeks) had 17 up-regulated proteins and 11 down-regulated proteins. In comparison with the control group (8 weeks), the silicosis group (8 weeks) had 16 up-regulated proteins and 12 down-regulated proteins. In comparison with the silicosis group (8 weeks), the Ac-SDKP treatment group had 5 up-regulated proteins and 6 down-regulated proteins, and the Ac-SDKP prevention group had 8 up-regulated proteins and 10 down-regulated proteins.</p><p><b>CONCLUSION</b>Critical regulatory proteins related to silicotic fibrosis and anti-silicotic effect of Ac-SDKP have been identified. These proteins may play an important role in proliferation, apoptosis, inflammation, epithelial-mesenchymal transition, and signal transduction in silicosis.</p>