1.Analysis of HPV infection and genotype distribution among 1 658 male reproductive health outpatients
Nazhakaiti ABUDUKELIMU ; Jian-Hui LI ; Tian-Cheng ZHANG ; Xin WANG ; Zhi-Ming XU ; Qian-Xi ZHU
Fudan University Journal of Medical Sciences 2024;51(1):69-75
Objective To investigate the human papillomavirus(HPV)infection and genotype distribution characteristics among male reproductive health outpatients,and to compare the differences among different age groups of outpatients.Methods A total of 1 658 males,visited in the Affiliated Hospital of Shanghai Institute of Planned Parenthood Research from 2018 to 2022,were selected and 23 HPV genotypes were detected by PCR-reverse dot hybridization.Results Among the 1 658 subjects,the overall HPV infection rate was 22.50%.Single infection accounted for 66.76%,which was the main infection type.HPV infection among different age groups were statistically significant(P<0.001),with HPV infection of 16.83%,22.87%,34.63%,and 29.35%for 18-30,31-40,41-50,and≥51 years,respectively.The top 5 high risk HPV genotypes were HPV52(3.56%),HPV16(3.26%),HPV39(2.41%),HPV51(2.17%),HPV58(2.17%),and the top 1 low risk HPV genotype was HPV81(2.90%).The proportions of infected individuals in this study that could be completely covered by bivalent,quadrivalent,and nine-valent HPV vaccines were 7.77%,12.33%,and 26.27%,respectively.Conclusion The predominant infection type among male reproductive health outpatients was single infection type.HPV 52,16,39,51 and 58 were the most common high risk genotypes,while HPV 81 was the most common low risk genotype.Individuals aged 41-50 years had the highest HPV infection rate.
2.Effects of emodin modulation of the HIF-1α/VEGF pathway on vascular endothelial cells damage in diabetic macroangiopathy rats
Qiu-Xiao ZHU ; Hui-Yao HAO ; Zi-Bo LIU ; Ming GAO ; Fang ZHANG ; Jing ZHOU ; Zhi-Hua HAO ; Li-Hui ZHANG ; Yong-Mei HAO
The Chinese Journal of Clinical Pharmacology 2024;40(6):859-863
Objective To investigate the impact of emodin(EM)on vascular endothelial cell injury in rats with diabetes macroangiopathy by regulating hypoxia inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway.Methods SD rats were divided into blank group and modeling group,the rats in the modeling group were fed with high fat and high sugar combined with N-nitro-L-arginine methyl ester to build the diabetes macroangiopathy model,and the blank group was fed with ordinary diet.The vascular endothelial cells successfully isolated from the thoracic aorta of rats in blank group and modeling group were named control group and model group,respectively.The vascular endothelial cells in the modeling group were divided into model group,dimethyloxallyl glycine(DMOG)group(10 μmol·L-1DMOG),combined group(80 mg·L-1EM+10 μmol·L-1 DMOG)and experimental-L,-M,-H groups(20,40,80 mg·L-1 EM).The apoptosis of rat vascular endothelial cells was detected by flow cytometry;Western blot was applied to detect the expression of HIF-1αand VEGF proteins in rat vascular endothelial cells.Results The apoptosis rates of vascular endothelial cells in experimental-M,-H groups,DMOG group,combined group,model group and control group were(10.18±0.36)%,(6.28±0.20)%,(24.96±1.18)%,(12.36±0.49)%,(18.76±0.68)%and(4.59±0.26)%;HIF-1α protein levels were 0.96±0.07,0.78±0.06,2.03±0.12,1.05±0.13,1.58±0.12 and 0.69±0.05;VEGF protein levels were 0.59±0.05,0.23±0.02,0.98±0.06,0.63±0.04,0.86±0.07 and 0.11±0.01.The above indexes in the model group were compared with the control,DMOG,experimental-M and experimental-H groups,and the above indexes in the combined group were compared with the experimental-H group,and the differences were statistically significant(all P<0.05).Conclusion EM may inhibit HIF-1α/VEGF pathway to improve vascular endothelial cell injury in rats with diabetes macroangiopathy.
3.Study on long-term toxicity of Tripterygium glycosides tablets based on type Ⅱ collagen-induced arthritis model rats
Tian-Xiang YE ; Ming-Zhu SHI ; Wei-Dong YANG ; Yan-Ming WEI ; Hui-Fang LI ; Sheng-Hui CHENG
The Chinese Journal of Clinical Pharmacology 2024;40(9):1296-1300
Objective To observe the multi-system toxicity of Tripterygium glycosides tablets in rats with type Ⅱ collagen-induced arthritis(CIA).Methods Healthy SD rats were randomly divided into normal group,model group and experimental group,with 10 rats in each group.In addition to the normal group,the other groups were established collagen-induced arthritis model.After the first immunization,the normal group and the model group were given an equal volume of 0.3%sodium carboxymethyl cellulose solution,and the experimental group was given 72 mg·kg-1·d-1 Tripterygium glycosides solution,once a day for 6 weeks.On the 42 nd day,the blood routine of each group was detected and the organ index was calculated.The levels of liver,kidney function and sex hormones in rats were detected by enzyme-linked immunosorbent assay.The histopathological changes of liver,kidney,ovary and testis were observed by hematoxylin-eosin(HE)staining.Results The testicular indexes of the normal group,the model group and the experimental group were(0.81±0.05)%,(0.97±0.06)%and(0.81±0.12)%;the estradiol contents were(63.90±16.19),(55.42±7.23)and(40.04±5.97)pg·mL-1;the testosterone contents were(1 290.96±257.94),(1 198.43±190.77)and(912.62±61.72)pg·mL-1,respectively.There were statistically significant differences in the above indexes between the model group and the experimental group(P<0.01,P<0.05).HE pathological results showed that Tripterygium glycosides tablets could cause abnormal histopathological changes of ovary and testis in CIA model rats.Conclusion Continuous administration of 8-fold clinical equivalent dose of Tripterygium glycosides tablets for 6 weeks can cause damage to the reproductive system of CIA rats.
4.Effects of hesperidin in promoting acute skin wound healing
Yi-Ming HUANG ; Fei-Fei CHEN ; Rong-Rong ZHANG ; Guang-Hui ZHU
The Chinese Journal of Clinical Pharmacology 2024;40(14):2093-2097
Objective To study the effects of hesperidin on the migration ability of human keratinocytes(HaCaT)and human skin fibroblasts(HSF).Additionally,this research aims to preliminary investigate the influence and underlying mechanism of Hesperidin in facilitating the healing process of acute skin wounds in mice.Methods HaCaT and HSF were divided into blank group(without any treatment),control group(added 0.1%dimethyl sulfoxide)and experimental group(added 5.0 μg·mL-1 hesperidin)for 48 h.The healing ability of cells in vitro was detected by scratch test.The migration of cells was detected by Transwell migration test.C57 mice were randomly divided into model group,experimental-L,-H groups.The acute full-thickness skin defect wound model was established by surgical clipping of the full-thickness skin of the back of mice.The model group was given 0.5%dimethyl sulfoxide,and the experimental-L,-H groups were given 10,50 mg·kg-1 hesperidin solution,respectively.The protein expressions levels of β-catenin,proliferating cell nuclear antigen(PCNA),keratin 14 and collagen Ⅰ were detected by Western blot.Results The scratch healing rates of HaCaT-blank group,HaCaT-control group and HaCaT-experimental group were(21.05±1.10)%,(22.33±1.72)%and(41.61±2.90)%;the cell migration numbers were 57.00±11.36,60.38±10.11 and 287.75±20.21,respectively.The scratch healing rates of HSF-blank group,HSF-control group and HSF-experimental group were(17.82±1.62)%,(19.81±3.87)%and(64.22±1.94)%,the cell migration numbers were 43.25±7.98,40.75±6.70 and 140.88±14.35,respectively.The HaCaT-experimental group was compared with HaCaT-blank group and HaCaT-control group,and the HSF-experimental group was compared with HSF-blank group and HSF-control group,the differences were statistically significant(all P<0.05).The protein expression levels of β-catenin in the model group,experimental-L,-H groups were 0.53±0.06,0.74±0.17 and 1.44±0.11;the protein expression levels of keratin 14 were 0.33±0.06,0.54±0.07 and 1.26±0.16;the protein expression levels of PCNA were 0.46±0.05,0.72±0.09 and 1.14±0.11;the protein levels of collagen Ⅰ were 0.52±0.03,0.77±0.05 and 1.28±0.13,respectively.There were significant differences in the above indexes between the experimental-L,-H groups and the model group(P<0.05,P<0.01).Conclusion Hesperidin may promote the healing of acute skin wounds in mice by activating the Wnt/β-catenin signaling pathway and increasing the migration of HaCaT and HSF.
5.Clinical characteristics and drug resistance analysis of Pantoea agglomerans infection
Ming-Ming XIN ; Xu-Zhu MA ; Xiao-Hui WANG ; Ming-Gui LIN
The Chinese Journal of Clinical Pharmacology 2024;40(19):2763-2765
Objective To analyze the clinical characteristics of patients infected with Pantoea agglomerans and the drug resistance of the strains,providing corresponding reference for the rational use of antibiotics in clinical practice.Methods The clinical characteristics,treatment outcomes of patients infected with Pantoea agglomerans,and the drug resistance of Pantoea agglomerans were analyzed.Results Among the 22 patients infected with Pantoea agglomerans,16 were male(72.7%),and 6 were female(27.3%).Patients over 60 years old were the main infected population(72.7%),and 11 patients had underlying diseases that caused low immune function(50.0%).Lung,urinary system,and blood were the most common sites of infection,and 59.1%were nosocomial infections.Pantoea agglomerans showed good sensitivity to commonly used clinical antibiotics.The sensitivity rates of piperacillin/tazobactam,ertapenem,amikacin,and cefoperazone/sulbactam were 100.0%,and the sensitivity rate of levofloxacin was 94.4%,and the sensitivity rate of ceftriaxone was 81.3%.Conclusion Infections caused by Pantoea agglomerans are mostly nosocomial infections,and the main infected population is the elderly.Although most Pantoea agglomerans are sensitive to commonly used clinical antibiotics,some strains have shown multiple drug resistance.
6.Combining 18F-PSMA PET/CT and biparametric MRI predicts pathological upgrading after radical prostatectomy for prostate cancer
Wen LIU ; Miao WANG ; Guilan HU ; Jiangyu MA ; Chunmei LI ; Wei ZHANG ; Hui ZHU ; Min CHEN ; Li HUO ; Ming LIU
Chinese Journal of Urology 2024;45(3):180-186
Objective:To investigate the application value of the maximum standardized uptake value (SUVmax) of 18F prostate-specific membrane antigen (PSMA) PET/CT combined with the minimum apparent diffusion coefficient (ADCmin) of biparametric magnetic resonance imaging (bpMRI) in predicting pathological upgrading after radical prostatectomy (RP) for prostate cancer. Methods:The data of 89 patients with localized prostate cancer treated at Beijing Hospital from April 2019 to October 2023 were retrospectively analysed. The average age of patients was (68.4±7.0) years old, with prostate-specific antigen (PSA) level of 7.7 (5.4, 12.9) ng/ml, prostate volume of 34.6 (26.9, 47.1) ml, tumor diameter of 1.3 (1.0, 1.8) cm, prostate imaging reporting and data system(PI-RADS) score of 5 in 29 cases (32.6%), clinical stage ≥T 3 in 13 cases (14.6%). There were 31 cases (34.8%) in group 1 of targeted biopsy International Society of Urological Pathology (ISUP)grading groups, 36 cases (40.4%) in group 2, 11 cases (12.4%) in group 3, and 11 cases (12.4%) in group 4. All patients underwent 18F-PSMA PET/CT and bpMRI examinations before RP. The index lesion, identified as the highest Gleason score in pathological whole-mount sections, were outlined. SUVmax and ADCmin values were calculated from the images' region of interest. Pathological upgrading was defined as the post-RP grade group higher than the targeted-biopsy grade group. Clinical data of patients with and without pathological upgrading were compared. Spearman correlation coefficient analysis was used to assess the correlation between SUVmax and ADCmin. Multivariate logistic regression analysis was conducted to evaluate the factors influencing pathological upgrading. Receiver operating characteristic (ROC) curve analysis was employed to assess the predictive value of each indicator for pathological upgrading. Results:Among the 89 cases, 31 cases (34.8%) experienced pathological upgrading. Compared with the patients without pathological upgrading, the SUVmax [11.3 (8.1, 16.4) vs. 6.7 (4.6, 9.2)], SUVmax/ADCmin ratio [3.1 (2.0, 4.6) vs. 1.4 (0.9, 2.1)], PSA [9.8 (6.3, 15.6) ng/ml vs. 7.1 (5.1, 10.5) ng/ml], PSA density [0.3 (0.2, 0.5) ng/ml 2 vs. 0.2 (0.1, 0.3) ng/ml 2], and post-RP ISUP grade group [≥3 group 17 cases (54.8%) vs. 13 cases(22.4%) ]were higher in patients with pathological upgrading, while ADCmin [3.8 (3.0, 5.3) ×10 -4 mm 2/s vs. 5.2 (3.6, 6.1)×10 -4 mm 2/s] and targeted biopsy ISUP grade group [≤2 group 27 cases(87.1%) vs. 40 cases(69.0%) ] were lower (all P<0.05). Spearman analysis showed a negative correlation between SUVmax and ADCmin ( R = -0.227, P = 0.032). Multivariate logistic regression analysis revealed that SUVmax ( OR = 1.108, 95% CI 1.020-1.238), ADCmin ( OR=0.607, 95% CI 0.390-0.874), and SUVmax/ADCmin ratio ( OR = 1.815, 95% CI 1.282-2.949) independently predicted pathological upgrading. The AUC of the SUVmax/ADCmin ratio for predicting pathological upgrading (AUC = 0.817) was higher than that of SUVmax (AUC = 0.774) and ADCmin (AUC=0.686), indicating a higher predictive efficiency. Conclusions:SUVmax, ADCmin, and SUVmax/ADCmin ratio can independently predict pathological upgrading in targeted biopsy of prostate cancer. The SUVmax/ADCmin ratio has a stronger predictive value for pathological upgrading.
7.The diagnostic value of 18F-PSMA PET/CT PRIMARY score combined with mpMRI PI-RADS sore in clinically significant prostate cancer
Hui ZHU ; Wenrui XU ; Yue GUO ; Longteng LIU ; Miao WANG ; Huimin HOU ; Chunmei LI ; Wei ZHANG ; Fugeng LIU ; Ming LIU
Chinese Journal of Urology 2024;45(6):439-444
Objective:To explore the diagnostic value of 18F-prostate specific membrane antigen (PSMA) PET/CT PRIMAY score combined with multiparameter MRI (mpMRI) PI-RADS score for clinically significant prostate cancer (CsPCa). Methods:The data of 63 patients with prostate cancer who underwent radical prostatectomy at Beijing Hospital from January 2019 to December 2023 were retrospectively analyzed. The median age was 70 (64, 75) years old with prostate-specific antigen (PSA) level of 8.46 (5.40, 14.80) ng/ml. All patients underwent 18F-PSMA PET/CT and mpMRI examination before surgery, and pathological large sections of prostate specimens were made after surgery. The prostate lesions were diagnosed and located by two radiologists and one pathologist respectively. Lesions with Gleason scores (GS)≥3+ 4 from the surgical pathology were diagnosed with CsPCa, and lesions with negative or GS=6 were diagnosed with non-CsPCa. The PSMA PET/CT images were evaluated using the PRIMARY study criteria (5-level PRlMARY score): no pattern (score of 1), diffuse transition zone or central zone(not focal) (score of 2), focal transition zone(score of 3), focal peripheral zone(score of 4), or an SUV max of at least 12 (score of 5). The degree of uptake of imaging agent in prostate lesions was semi-quantitatively evaluated using lesion-to-background ratios (LBR) of SUV max. MpMRI was evaluated according to the Prostate Imaging Reporting and Data System (PI-RADS) version 2.1. The patients were divided into CsPCa group and non-CsPCa group based on patients and lesions. Mann-Whitney U test and chi-square test were used to compare the differences between groups. Multivariate logistic regression analysis was performed to determine the independent predictive factors of CsPCa. Receiver operator characteristic (ROC) curve was used to determine the optimal diagnostic threshold for each independent predictor. Predictive models were constructed for PRIMARY score, PI-RADS score, and their combined application, and the diagnostic performance of each model for CsPCa was compared. Results:Of all 63 patients, there were 54 cases in CsPCa group (85.7%) and 9 cases in non-CsPCa group (14.3%).There was significant difference between CsPCa group and non-CsPCa group in the serum PSA level [9.64 (6.1, 15.3) ng/ml vs. 5.6 (4.6, 7.6) ng/ml]( P<0.05). There was no statistically significant difference in age [71 (64, 75) years vs. 65 (63, 69) years], and number of lesions [2 (1, 2) vs. 2 (1, 3)] (all P>0.05). Of all 109 lesions, there were 81 lesions in CsPCa group(including 49 lesions with Gleason score = 3+ 4, 16 lesions with Gleason score=4+ 3, 14 lesions with Gleason score = 8, and 2 lesions with Gleason score>8) and 28 lesions in non-CsPCa group(including 14 lesions with Gleason score = 3+ 3 and 14 with benign prostate lesions). There was significant difference between CsPCa group and non-CsPCa group in PRIMARY score [4 (3, 5) vs. 2 (1, 4)], LBR [2.69 (2.08, 4.48) vs. 1.89 (1.45, 2.48)], PI-RADS score [4 (3, 5) vs. 2 (2, 3)] (all P<0.05). There was no statistically significant difference in the lesion distribution including the number of lesions located in the transition zone [15(18.5%) vs. 8(28.6%)] and in the peripheral zone[66(81.5%) vs. 20(71.4%)]( P>0.05). Multivariate logistic regression analysis indicated that PRIMARY score ( OR=2.134, 95% CI 1.429-3.187) and PI-RADS score ( OR=2.689, 95% CI 1.618-4.469) were independent predictors of CsPCa (both P<0.01). ROC curves analysis revealed that the cut-off value for diagnosing CsPCa was both 3 for PRIMARY score and PI-RADS score. The accuracy for PRIMARY score, PI-RADS score, and their combined complication in diagnosing CsPCa was 72%, 67%, and 83%, respectively. The sensitivity was 72%, 63%, and 91%, and the specificity was 75%, 79%, and 57%, respectively. The positive predictive value was 89%, 89%, and 86%, and the negative predictive value was 48%, 42%, and 70%, respectively. The area under the curve of the PRIMARY score, PI-RADS score, and their combined complication of the ROC curve for CsPCa were 0.733 (95% CI 0.624-0.842), 0.708 (95% CI 0.599-0.817), and 0.743 (95% CI 0.623-0.862), respectively. The diagnostic efficacy of their combined complication was higher than PRIMARY score or PI-RADS score alone (both P<0.01). Conclusions:Both the 18F-PSMA PET/CT PRIMAY score and the mpMRI PI-RADS score have good diagnostic value for CsPCa. The combined application of the two imaging parameters can improve the accuracy, sensitivity, and negative predictive value, which have a higher diagnostic efficiency of CsPCa.
8.Establishment and evaluation methods of a novel animal model of liver depression transforming into fire syndrome-related depression
Dan SU ; Jian LI ; Gen-hua ZHU ; Ming YANG ; Liang-liang LIAO ; Zhi-fu AI ; Hui-zhen LI ; Ya-li LIU ; Yong-gui SONG
Acta Pharmaceutica Sinica 2024;59(6):1680-1690
Through a compound induction method, combined with neurobehavioral, macroscopic characterization and objective pathological evaluation indicators, a murine depression model of liver depression transforming into fire syndrome was constructed and confirmed. The model was constructed using a combination of sleep deprivation, light exposure, and alternate-day food deprivation. Evaluation was conducted at three levels: face validity, constructs validity, and predictive validity. The establishment of the liver depression transforming into fire syndrome depression model was further validated through the counterproof of traditional Chinese medicine formulas. In terms of face validity, compared to the control group, mice in the model group exhibited typical depressive symptoms in neurobehavioral assessments; the general observation of the model group mice reveals disheveled and lackluster fur, along with delayed and easily agitated responses. Additionally, there is a substantial increase in water consumption. In the sleep phase detection of mouse, the model group showed a significant increase in the proportion of time spent in the wake phase during sleep, accompanied by a significant decrease in the proportions of time spent in both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep phases. There are significant differences in physiological indicators such as average blood flow velocity, blood flow rate, tongue, urine, and claw color (r values) in the internal carotid artery. Structural validity demonstrated that levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and
9.A novel chalcone derivative C13 inhibits the growth of human gastric cancer cells through suppressing ErbB4/PI3K/AKT signaling pathway
Peng TAN ; Yun-feng ZHANG ; Long-yan WANG ; Hui-ming HUANG ; Fei WANG ; Xue-jiao WEI ; Zhu-guo WANG ; Jun LI ; Zhong-dong HU
Acta Pharmaceutica Sinica 2024;59(4):957-964
3ʹ-Hydroxy-4ʹ-methoxy-2-hydroxy-5-bromochalcone (hereinafter referred to as C13) is a novel chalcone derivative obtained in the process of structural modification of DHMMF, the antitumor active compound of
10.Cloning and interacted protein identification of AGL12 gene from Lonicera macranthoides
Li-jun LONG ; Hui-jie ZENG ; Zhong-quan QIAO ; Xiao-ming WANG ; Chang-zhu LI ; Si-si LIU ; Ying-zi MA
Acta Pharmaceutica Sinica 2024;59(5):1458-1466
MADS-box protein family are important transcriptional regulatory factors in plant growth and development. The

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