1.Analysis of prostate transcriptome landscape characteristics in benign prostate hyperplasia patients taking finasteride
Lang ZHOU ; Ke LIU ; Min LU ; Hai BI ; Xiao HUO ; Lulin MA ; Cheng LIU
Journal of Modern Urology 2024;29(2):101-107
【Objective】 To explore the effects of finasteride on the gene expression in patients with benign prostatic hyperplasia (BPH) through transcriptome analysis. 【Methods】 Postoperative prostate tissues from patients who underwent prostatectomy at Peking University Third Hospital during Oct.2020 and Oct.2021 were collected.The patients were divided into medication group and non-medication group based on whether they had taken finasteride for a long time before surgery, with 8 patients in either groups.Transcriptome sequencing analysis was performed and the results were validated with qPCR and immunohistochemistry analysis. 【Results】 Compared with the non-medication group, 857 up-regulated and 806 down-regulated genes were screened in the medication group.Pathway enrichment analysis showed that finasteride induced down-regulation of vascular endothelial growth factor D (VEGFD) expression in the focal adhesion pathway.Inter group network analysis suggested that the calcium signaling pathway was key in the entire process.GSEA enrichment analysis further revealed the up regulation of CD38 gene expression in the calcium signaling pathway.The qPCR and immunohistochemistry analysis supported the transcriptome results mentioned above, and found that androgen receptor (AR) expression was also increased. 【Conclusion】 Finasteride reduces prostate microvascular formation by downregulating the expression of VEGFD in the focal adhesion pathway, thereby reducing the risk of bleeding during prostate hyperplasia surgery. Long-term use of finasteride leads to the up regulation of CD38 expression in the calcium signaling pathway, which may lead to the development of finasteride resistance.
2.Bioequivalence study of glipizide tablets in Chinese healthy subjects
Fei-Lang ZHENG ; Lin-Zhong CHENG ; Hai-Ju LI ; Lu YANG ; Ze-Yuan LIU ; Su-Ling WANG
The Chinese Journal of Clinical Pharmacology 2024;40(11):1628-1632
Objective To study the bioequivalence of two glipizide tablets in healthy Chinese subjects.Methods Randomized,open,single-administration,two-period,self-cross-over trial design was used in the study.There were 28 Chinese healthy subjects in the fasted state and 28 in the fed state,complete repeat cross single dose oral glipizide tablets test preparation or reference preparation 5 mg.The plasma concentration of glipizide was determined by liquid chromatography/tandem mass spectrometry at different time points after administration.The non-compartmental model was used to calculate the pharmacokinetic parameters and evaluate the bioequivalence of the two formulations.Results The main pharmacokinetic parameters of glipizide in the fasted state were as follows:Cmax were(551.60±91.26)and(518.10±105.10)ng·mL-1;AUC0-t were(3 074.33±861.91)and(3 026.77±934.25)h·ng·mL-1;AUC0-∞ were(3 204.85±990.78)and(3 166.35±1 107.36)h ng·mL-1.The parameters of glipizide in the fed state were as follows:Cmax were(517.30±98.97)and(472.80±114.48)ng·mL-1;AUC0-t were(3 001.12±830.87)and(2 932.79±736.35)h·ng·mL-1;AUC0-∞ were(3 067.00±918.84)and(2 997.44±819.14)h·ng·mL-1.The 90%confidence interval of the Cmax,AUC0-t and AUC0-∞ of the test formulation and the reference formulation were from 80.00%to 125.00%.The incidence of adverse events in fasted group and fed group was no serious adverse events.Conclusion The two glipizide tablets were bioequivalent under fasted and fed conditions,and good security.
3.A nomogram for predicting postoperative pulmonary infec-tion in gastric cancer patients
Yun-Yun WU ; Jian-Hua LANG ; Jian-Zhong WU ; Zheng-Hai QIAN ; Peng-Fei LIU
Chinese Journal of Current Advances in General Surgery 2023;26(12):951-955
Objective:To identifying risk factors of postoperative pulmonary infection(POI)in gastric cancer(GC)patients as well as generating an effective nomogram for the POI.Methods:Pa-tients with gastric cancer after surgery from 1st January 2010 to 31st December 2020 were retro-spectively analysed.Their clinical and pathological data were collected.Multiple logistic regression analysis was conducted to identify risk factors for POI and to generate the nomogram prediction model.Predictive accuracy,discriminatory capability,and clinical usefulness were evaluated by cali-bration curves,concordance index(C-index),and decision curve analysis(DCA).Results:Multivari-ate regression analysis revealed that age,smoking,chronic respiratory diseases,laparoscopic surgery,intraoperative blood loss and lung function exercise compliance were independent prognos-tic factors for POI in GC patients.The nomogram had a Cindex of 0.878(95%CI:0.801~0.956).The calibration curves showed good consistency between actual and nomogram-predicted probabilities.The area under the curve(AUC)was 0.878,while the cutoff value was-2.088 with a sensitivity of 80.6%and a specifificity of 82.9%.DCA showed that the nomogram had better clinical usefulness.Conclusions:The present study provides a nomogram developed with perioperative features to predict the incidence of POI in GC patients.
5. Anti-oxidative stress mechanism of velvet antler polypeptide in Alzheimer's disease model mice
Wei-Ya LANG ; Tong-Hui YI ; Ke-Shuang ZHANG ; Hai-Yan ZHANG ; Chun-Mei ZHANG ; Yu-Di ZHANG ; Zhong-Jin LIU
Acta Anatomica Sinica 2022;53(4):432-439
Objective To study the effect of velvet antler polypeptides (VAP) on antioxidant in Alzheimer' s disease model mice. Methods Eight months old male amyloid precursor protein (APP)/presenilin-l (PS1) double transgenic mice were selected as Alzheimer' s disease (AD) model and divided into the model group and the VAP intervention group, 12 in each group. Besides, normal mice of the same brood (with no transgene) were recruited as a control group (n= 12).After 6 months of intragastric administration, behavior, morphology and oxidative stress related indicators were detected.SH-SY5 cells were used to establish AD model of damaged by Ap2535. The expression levels of APP and p-secreatase-l(BACE1) protein in mouse hippocampus were detected by Western blotting. VAP intervention group SH-SY5Y cells was cultured with VAP (500 g/L) and amyloid P(Ap) 2535(25 ixmol/L) for 24 hours. Control group cells were normally cultured by DMEM medium. Cell apoptosis, membrane potential, reactive oxygen species (ROS) levels and oxidative stress related indexes were detected. Results In animal models, compared with the model group, the escape latency of mice in the VAP intervention group was shortened (P<0. 05). The neuronal cells in the CA1 region of the hippocampus of the model group were reduced and arranged disorderly. The arrangement of the VAP intervention group was relatively regular, and the morphology was significantly improved. Compared with the model group, senile plaques were decreased in the VAP intervention group. Compared with the model group, the malondialdehyde (MDA) content ol the VAP intervention group increased, and the superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) content increased, the difference was statistically significant. Compared with the control group, the APP and BACE1 content in the model group increased. Compared with the model group, the contents of APP and BACE1 in the VAP intervention group decreased, and the difference was statistically significant (P<0. 05). In the cell model, the apoptosis rates of the VAP intervention group decreased. Compared with the model group, the mitochondrial membrane potential of the VAP intervention group increased, the content ol ROS decreased, the content of MDA decreased, and the content of SOD and GSH-Px increased. The difference were statistically significant (P<0. 05). Conclusion VAP has a protective effect on oxidative stress damage caused by Alzheimer' s disease model animals and cells, which may be achieved by reducing ROS production and increasing the activity of antioxidant enzymes to reduce Ap deposition.
6. Effects of velvet antler polypeptide on Rho/ROCK pathway in APP/ PSl double transgenic mice
Zhong-Jin LIU ; Chun-Mei ZHANG ; Yu-Di ZHANG ; Tong-Hui YI ; Wei-Ya LANG ; Hai-Yan ZHANG
Acta Anatomica Sinica 2022;53(2):190-195
Objective To study the effect of velvet antler polypeptides (VAP) on Rho/ROCK pathway in APP/ PSl double transgenic mice. Methods APP/PSl double transgenic mice were randomly divided into model group and velvet antler polypeptide group, 20 mice in each group, and control group consisting of 20 mice of the same litter and the same gender negative. The mice in VAP group were given velvet antler polypeptide 100 mg/kg by intragastric administration once a day for 28 days. After treatment, the water maze experiment was detected and recorded the escape latency and the number of crossing platforms of the mice; the ultrastructures of the synapse were observed by transmission electron microscopy; the expression of Rhs homolog gene family member A(RhoA) and Rho associated coiled-coil forming protein kinase II(ROCKII) in the hippocampal CAI area were observed by immunofluorescence. The expression levels of RhoA and ROCKII protein in the hippocampus were detected by Western blotting. The contents of hippocampus amyloid (3-protein(A(3),
7.Oral Mucosal Diffuse Large B-cell Lymphoma Caused by Long-term Oral Methotrexate:Report of One Case.
Yan-Quan LIU ; Xiao-Mei HU ; Yue YIN ; Lang-Hui ZHANG ; Hai-Ying FU ; Ting-Bo LIU ; Jian-Zhen SHEN
Acta Academiae Medicinae Sinicae 2021;43(3):488-493
A case of primary oral mucosal diffuse large B-cell lymphoma(DLBCL)due to long-term use of methotrexate(MTX)for the treatment of rheumatoid arthritis(RA)was admitted to the Department of Hematology,Fujian Medical University Union Hospital.We analyzed and discussed the clinical features,diagnosis and treatment,and prognosis of specific malignant lymphoma induced by MTX in this RA patient.Our purpose is to improve the awareness and knowledge of other iatrogenic immunodeficiency-associated lymphoproliferative disorders of clinicians and pathologists.This study provides a new reference for the clinical diagnosis and treatment of MTX-associated DLBCL.
Arthritis, Rheumatoid/drug therapy*
;
Humans
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Lymphoma, Large B-Cell, Diffuse/drug therapy*
;
Lymphoproliferative Disorders
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Methotrexate/adverse effects*
8.Effects of Blast Wave-induced Biomechanical Changes on Lung Injury in Rats.
Wei LIU ; Jia Ke CHAI ; Bin QIN ; Shao Fang HAN ; Xiao Teng WANG ; Shuai JIANG ; Hai Liang BAI ; Ling Ying LIU ; Yang CHANG ; Xiao Tong YUE ; Yu Shou WU ; Zi Hao ZHANG ; Lang TANG
Biomedical and Environmental Sciences 2020;33(5):338-349
Objective:
To observe the dynamic impacts of shock waves on the severity of lung injury in rats with different injury distances.
Methods:
Simulate open-field shock waves; detect the biomechanical effects of explosion sources at distances of 40, 44, and 48 cm from rats; and examine the changes in the gross anatomy of the lungs, lung wet/dry weight ratio, hemoglobin concentration, blood gas analysis, and pathology.
Results:
Biomechanical parameters such as the overpressure peak and impulse were gradually attenuated with an increase in the injury distance. The lung tissue hemorrhage, edema, oxygenation index, and pathology changed more significantly for the 40 cm group than for the 44 and 48 cm groups. The overpressure peak and impulse were significantly higher for the 40 cm group than for the 44 and 48 cm groups ( < 0.05 or < 0.01). The animal mortality was significantly higher for the 40 cm group than for the other two groups (41.2% . 17.8% and 10.0%, < 0.05). The healing time of injured lung tissues for the 40 cm group was longer than those for the 44 and 48 cm groups.
Conclusions
The effects of simulated open-field shock waves on the severity of lung injuries in rats were correlated with the injury distances, the peak overpressure, and the overpressure impulse.
Animals
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Biomechanical Phenomena
;
Blast Injuries
;
etiology
;
pathology
;
Disease Models, Animal
;
Explosions
;
Lung Injury
;
etiology
;
pathology
;
Male
;
Random Allocation
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Rats
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Rats, Sprague-Dawley
9. Effect of epigallocatechin gallate on expressions of synaptic plasticity and neural cell adhesion molecules in APP / PS1 double transgenic mice
Wei-Ya LANG ; Hai-Yan ZHANG ; Li-Hui SUN ; Kun-Jie ZHU ; Zhong-Jin LIU
Acta Anatomica Sinica 2020;51(4):495-501
Objective To observe the effect of epigallocatechin gallate (EGCG) on the spatial learning memory deficit in amyloid procursor protein (APP) / presenilin-1 (PS1) double transgenic mice, synaptic ultrastructure and expression of neural cell adhesion molecule in hippocampal CA1 region. Methods Eight weeks old male APP / PS1 double transgenic mice were selected as Alzheimer’s disease (AD) model and divided into the model group, the EGCG group and the donepezil hydrochloride group, 12 in each group.Besides,normal mice of the same brood (with no transgene) were recruited as a normal group (n = 12). Related indices were detected after 6 months continuous gastrogavage. The spatial learning-memory deficit of APP / PS1 double transgenic mice was detected by Morris water maze test. The synaptic ultrastructure of hippocampal CA1 region was observed by transmission electron microscopy. The expression levels of neural cell adhesion molecule (NCAM) and polysialyltranseferase α2,8-polysialic acid (ST8Sia Ⅱ) protein in hippocampal CA1 region of APP / PS1 transgenic mice were detected by immunofluorescence and Western blotting. Results Compared with the normal group, the mean value of escape latency in the model group was extended, and compared with the model group, the mean value of escape latency in the EGCG group and donepezil hydrochloride group were increased (P < 0. 05) . The result of electron microscope showed that the changes of synaptic interface curvature of EGCG group and donepezil hydrochloride group were not obvious. Compared with the model group, the width of the synaptic gap becomes narrower and the thickness of the post-synaptic compact were increases (P < 0. 05) . Immunofluorescence showed that the expression of NCAM and ST8Sia Ⅱ proteins in the hippocampus CA1 region was expressed in the cytoplasm of neurons, the expressions of NCAM and ST8Sia Ⅱ in hippocampal CA1 region were significantly increased in EGCG group and donepezil hydrochloride group (P< 0. 05) . Their contents also showed higher levels of expression in Western blotting (P < 0. 05) . Conclusion EGCG shows improvement on the spatial learning-memory deficit in APP / PS1 double transgenic mice,which may be associated with affecting the synaptic structure of hippocampus and improving the expressions of neural cell adhesion molecule.
10.Predictive Value of Neutrophil Gelatinase-associated Apolipoprotein on Contrast Induced Nephropathy in Patients After Percutaneous Coronary Intervention
Xiao-Jin XU ; Qing ZHANG ; Bing-Jian WANG ; Hai-Lang LIU ; Shu-Ren MA
Chinese Circulation Journal 2018;33(4):327-331
Objectives: To investigate the early diagnostic value of neutrophil gelatinase-associated apolipoprotein (NGAL) on contrast induced nephropathy (CIN) in patients after percutaneous coronary intervention (PCI). Methods: A total of 200 patients received coronary angiography (CAG) and PCI in our hospital from 2016-01 to 2017-02 were enrolled and the research included in 2 groups: CIN group, 23 and Non-NCI group, according to 4:1 ratio, 92 patients without NCI. Serum levels of creatinine, blood and urine levels of NGAL were examined and compared at pre-operation and 4 h, 24 h, 48 h and 72 h after the operation between 2 groups. Results: All patients received CAG and CIN occurred in 23/200 (11.5%) patients. Compared with Non-CIN group, CIN group had more patients with elder age, more smokers and diabetes, P<0.05. Pre-operative blood and urine NGAL were both at normal level and it was similar between 2 groups, P>0.05. In CIN group, urine NGAL was significantly increasing at 4 h after operation and gradually increasing to 72 h after operation; blood NGAL was significantly increasing at 4 h after operation, it began decreasing at 24 h after operation and remained a relatively high level at 72 h after operation; post-operative blood and urine levels of NGAL were different from pre-operative condition at each time points, all P<0.05. In Non-CIN group, post-operative blood and urine levels of NGAL were similar to pre-operative condition, P>0.05. Post-operative blood and urine NGAL were different at the same time point between 2 groups, P<0.01. AUC of ROC for post-operative urine NGAL at 4h, 24h, 48h and 72h were 0.908, 0.926, 0.931 and 0.957 respectively, the sensitivity and specificity for CIN diagnosis were 91.3% and 100% at 4 time points; AUC of ROC for post-operative blood NGAL at 4 h and 24 h were 0.964 and 0.913, the sensitivity and specificity for CIN diagnosis were 87.3% and 100% at both time points. Conclusions: Blood and urine levels of NGAL may reflect renal function changes earlier than serum creatinine in CAG/PCI patients, it had the higher sensitivity and specificity for CIN diagnosis and could be used as the early predictor for CIN occurrence.

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