1. A network pharmacology-based approach to explore mechanism of kaempferol-7 -O -neohesperidoside against prostate cancer
Qiu-Ping ZHANG ; Zhi-Ping CHENG ; Wei XUE ; Qiao-Feng LI ; Hong-Wei GUO ; Qiu-Ping ZHANG ; Jie-Jun FU ; Hong-Wei GUO
Chinese Pharmacological Bulletin 2024;40(1):146-154
Aim To explore the effect of kaempferol-7- 0-neohesperidoside (K70N) against prostate cancer (PCa) and the underlying mechanism. Methods The effect of K70N on the proliferation of PCa cell lines PC3, DU145, C4-2 and LNCaP was detected using CCK8 assay. The effect of K70N on migration ability of DU145 cells was determined by wound healing assay. The targets of K70N and PCa were screened from SuperPred and other databases. The common targets both related to K70N and PCa were obtained from the Venny online platform, a protein-protein interaction network (PPI) was constructed by the String and Cyto- scape. Meanwhile, the GO and KEGG functional enrichment were analyzed by David database. Then, a "drug-target-disease-pathway" network model was constructed. Cell cycle of PCa cells treated with K70N was analyzed by flow cytometry. The expressions of cycle-associated proteins including Skp2, p27 and p21 protein were detected by Western blot. Molecular docking between Skp2 and K70N was conducted by Sybyl X2. 0. Results K70N significantly inhibited the proliferation and migration of PCa cells. A total number of 34 drug-disease intersection targets were screened. The String results showed that Skp2 and p27, among the common targets, were the key targets of K70N for PCa treatment. Furthermore, GO and KEGG functional en-richment indicated that the mechanism was mainly related to the cell cycle. Flow cytometry showed that K70N treatment induced cell cycle arrest at the S phase. Compared with the control group, the protein expression level of Skp2 was significantly down-regulated, while the protein expression levels of p27 and p21 were up-regulated. The network molecular docking indicated that the ligand K70N had a good binding ability with the receptor Skp2. Conclusions K70N could inhibit the proliferation and migration of PCa cells, block the cell cycle in the S phase, which may be related to the regulation of cell cycle through the Skp2- p27/p21 signaling pathway.
2.Pathological characteristics of false-positive lesions of prostate cancer on 68Ga-PSMA-11 PET/CT
Renjie LI ; Yao FU ; Shan PENG ; Fengjiao YANG ; Feng WANG ; Hongqian GUO ; Xuefeng QIU
Journal of Modern Urology 2024;29(11):988-992
[Objective] To investigate the pathological characteristics of false-positive lesions of prostate cancer on 68Ga-PSMA-11 PET/CT based on the pathology of whole mount specimens, in order to more accurately assess the degree of malignancy within the prostate tissue and avoid overdiagnosis and unnecessary treatment. [Methods] A total of 77 patients who underwent 68Ga-PSMA-11 PET/CT before radical prostatectomy in Nanjing Drum Tower Hospital during Jan.2018 and Dec.2022 were retrospectively analyzed.The pathology of whole mount specimens was detected.Two nuclear physicians examined all imaging plates without knowing the pathological results.Two pathological physicians completed all pathological diagnosis without knowing the imaging results.The pathological characteristics of false-positive lesions were determined by matching 68Ga-PSMA-11 PET/CT and pathological specimens.To analyze the pathological features of false-positive lesions, true-negative lesions were randomly delineated and defined.The pathological features of false-positive and true-negative lesions were analyzed and compared using Fisher exact test. [Results] After the imaging and pathological sections were matched, 21(16.3%) false-positive lesions were identified.The pathological characteristics of the 21 false-positive lesions were as follows: 16 (76.2%) simple atrophy with cyst formation, 3(14.3%) prostatic nodular hyperplasia, and 2(9.5%) inflammation.The pathological characteristics of 21 true-negative lesions were: 13(61.9%) normal glands, 5(23.8%) prostatic nodular hyperplasia and 3(14.3%) simple atrophy with cyst formation.Fisher exact test showed that the proportion of simple atrophy with cyst formation in the pathological features of false-positive lesions and true-negative lesions was statistically significant (76.2% vs.14.3%, P<0.001). [Conclusion] Simple atrophy with cyst formation may be a characteristic pathological type of the false-positive lesions of prostate cancer on 68Ga-PSMA-11 PET/CT.
3.A clinical prediction model based on 68Ga-PSMA-11 PET/CT and mpMRI parameters to determine the diagnostic accuracy of targeted biopsy alone in prostate cancer population
Chaoli AN ; Xuefeng QIU ; Feng WANG ; Yao FU ; Xiaozhi ZHAO ; Hongqian GUO
Journal of Modern Urology 2024;29(3):212-218
【Objective】 To develop a clinical prediction model based on 68Ga-prostate-specific membrane antigen-11 (68Ga-PSMA-11), positron emission tomography/computed tomography (PET/CT) and multiparametric magnetic resonance imaging (mpMRI) parameters to stratify prostate cancer patients undergoing targeted biopsy, so as to avoid unnecessary systematic biopsy. 【Methods】 A total of 96 clinically significant prostate cancer (csPCa) patients who underwent 68Ga-PSMA-11 PET/CT and mpMRI prior to prostate targeted biopsy with systematic biopsy during Jan.2020 and Feb.2023 in Nanjing Drum Tower Hospital were retrospectively analyzed.By univariate and multivariate logistic regression analyses, maximum standard uptake value (SUVmax) in 68Ga-PSMA-11 PET/CT and minimum apparent diffusion coefficien (ADCmin) in mpMRI, as well as clinical parameters were evaluated to identify the independent predictors correlative with the effective diagnosis of targeted biopsy, and a clinical prediction model was constructed. 【Results】 Multivariate logistic regression analysis showed that SUVmax (OR=0.878, 95%CI: 0.804-0.959, P=0.004) and ADCmin (OR=1.005, 95%CI:1.001-1.010, P=0.027) were independent predictors of the effective diagnosis of targeted biopsy alone.The sensitivity, specificity, accuracy and area under the receiver operator characteristic curve (AUC) of the model were 0.80, 0.80, 0.83 and 0.84, respectively. 【Conclusion】 The clinical prediction model based on 68Ga-PSMA-11 PET/CT and mpMRI parameters is helpful to improve the effective diagnosis of targeted biopsy alone, and has practical value to stratify patients with csPCa so as to safely avoid systematic biopsy and effectively balance the benefits and risks.
4.DRG weight algorithm optimization in Beijing from the perspective of hospital performance evaluation
Yelong QIU ; Moning GUO ; Yin CHEN ; Jianxiong MA ; Airan DONG ; Tinghui FU
Chinese Journal of Hospital Administration 2024;40(7):563-567
Objective:To optimize the diagnosis-related groups (DRG) weight calculation method based on the perspective of hospital performance evaluation and the high-quality development orientation of public hospitals.Methods:Using the first page data of 3 256 701 inpatient medical records from secondary and tertiary hospitals in Beijing from January to December 2021, three algorithms including payment DRG weight, five-category DRG weight, and optimized DRG weight were used to calculate the weights of each DRG, and the differences between different algorithms were analyzed. The case-mix index (CMI) of the entire hospital and the clinical specialties to which the key DRG belongs in secondary and tertiary hospitals was calculated by using the three DRG weight algorithms, to reflect the performance evaluation results of different algorithms.Results:The results of one-way ANOVA showed that there was a significant difference ( P=0.019) among the three DRG weight algorithms. Comparing the optimized DRG weight with the payment DRG weight, the weight of BD29 (neural stimulator implantation or removal surgery) in the key DRG decreased from 7.77 to 4.61, and the weight of LA19 (renal tumor surgery) increased from 2.06 to 2.58; Compared with the five-category DRG weight, the weight of ES31 (respiratory infection/inflammation with severe complications or comorbidities) decreased from 2.36 to 1.72, and the weight of CB39 (crystalloid surgery) increased from 0.22 to 0.30. Comparing the use of optimized DRG weights and five-category DRG weights to calculate CMI, all types of hospitals and clinical specialties showed varying degrees of improvement in CMI. The CMI of tertiary hospitals increased from 1.02 to 1.20, and the CMI of secondary hospitals increased from 0.88 to 0.95. The difference in CMI between secondary and tertiary hospitals was even more pronounced. Conclusions:Optimized DRG weights could better reflect the value of medical technology compared with the payment DRG weights. Compared to five-category DRG weights, optimized DRG weights could better reflect the differences in CMI of different levels of hospitals.
5.Practical research on the training of intensive care medicine talents in Xizang based on cloud teaching rounds
Wei DU ; Guoying LIN ; Xiying GUI ; Li CHENG ; Xin CAI ; Jianlei FU ; Xiwei LI ; Pubu ZHUOMA ; Yang CI ; Danzeng QUZHEN ; Lü JI ; Ciren SANGZHU ; Wa DA ; Juan GUO ; Cheng QIU
Chinese Journal of Medical Education Research 2024;23(8):1065-1068
In view of the problem of slow development of intensive care medicine in Xizang, the research team made full use of the national partner assistance to Xizang, gathered resources across all cities in Xizang, and formed a national academic platform for critical care medicine in plateau areas. Adhering to the academic orientation with hemodynamics as the main topic, critical care ultrasound as the bedside dynamic monitoring and evaluation method, and blood flow-oxygen flow resuscitation as the core connotation, we have achieved the goals of improving the critical care talent echelon throughout Xizang, driving the overall progress of intensive care medicine in Xizang, making a figure in China, and focusing on training of top-notch talents.
6.Epidemiological distribution of genotypes and sub-genotypes of hepatitis B virus in 15 ethnic groups in China.
Xiao Qi GUO ; Shuang ZHANG ; Hui ZHENG ; Feng WANG ; Ning MIAO ; Qiu Dong SU ; Sheng Li BI ; Guo Min ZHANG ; Fu Zhen WANG ; Li Ping SHEN
Chinese Journal of Epidemiology 2023;44(5):759-764
Objective: To understand the distribution of genotypes and sub-genotypes of HBV in different ethnic groups in China. Methods: The HBsAg positive samples were selected by stratified multi-stage cluster sampling from the sample base of national HBV sero-epidemiological survey in 2020 for the amplification of S gene of HBV by nested PCR. A phylogeny tree was constructed to determine the genotypes and sub-genotypes of HBV. The distribution of genotypes and sub-genotypes of HBV were analyzed comprehensively by using laboratory data and demographic data. Results: A total of 1 539 positive samples from 15 ethnic groups were successfully amplified and analyzed, and 5 genotypes (B, C, D, I and C/D) were detected. The proportion of genotype B was higher in ethnic group of Han (74.52%, 623/836), Zhuang (49.28%, 34/69), Yi (53.19%, 25/47), Miao (94.12%, 32/34), Buyi (81.48%, 22/27). The proportions of genotype C were higher in ethnic groups of Yao (70.91%, 39/55). Genotype D was the predominant genotype in Uygur (83.78%, 31/37). Genotype C/D were detected in Tibetan (92.35%,326/353). In this study, 11 cases of genotype I were detected, 8 of which were distributed in Zhuang nationality. Except for Tibetan, sub-genotype B2 accounted for more than 80.00% in genotype B in all ethnic groups. The proportions of sub-genotype C2 were higher in 8 ethnic groups, i.e. Han, Tibetan, Yi, Uygur, Mongolian, Manchu, Hui and Miao. The proportions of sub-genotype C5 were higher in ethnic groups of Zhuang (55.56%, 15/27) and Yao (84.62%, 33/39). For genotype D, sub-genotype D3 was detected in Yi ethnic group and sub-genotype D1 was detected in both Uygur and Kazak. The proportions of sub-genotype C/D1 and C/D2 in Tibetan were 43.06% (152/353) and 49.29% (174/353). For all the 11 cases of genotype I infection, only sub-genotype I1 was detected. Conclusions: Five genotypes and 15 sub-genotypes of HBV were found in 15 ethnic groups. There were significant differences in the distribution of genotypes and sub-genotypes of HBV among different ethnic groups.
Humans
;
Asian People
;
China/epidemiology*
;
Ethnicity
;
Genotype
;
Gerbillinae
;
Hepatitis B virus/genetics*
;
Hepatitis B/virology*
7.Exosomes Derived from Human Amniotic Mesenchymal Stem Cells Facilitate Diabetic Wound Healing by Angiogenesis and Enrich Multiple lncRNAs
Shangfeng FU ; Hongyan ZHANG ; Xiancai LI ; Qiling ZHANG ; Chunyan GUO ; Keqing QIU ; Junyun FENG ; Xiaoxiao LIU ; Dewu LIU
Tissue Engineering and Regenerative Medicine 2023;20(2):295-308
BACKGROUND:
Diabetic wound healing remains a major challenge due to the impaired functionality of angiogenesis by persistent hyperglycemia. Mesenchymal stem cell exosomes are appropriate candidates for regulating the formation of angiogenesis in tissue repair and regeneration. Here, we explored the effects of exosomes derived from human amniotic mesenchymal stem cell (hAMSC-Exos) on the biological activities of human umbilical vein endothelial cells (HUVECs) treated with high glucose and on diabetic wound healing and investigate lncRNAs related to angiogenesis in hAMSC-Exos.
METHODS:
hAMSCs and hAMSC-Exos were isolated and identified by flow cytometry or western blot. A series of functional assays such as cell counting kit-8, scratching, transwell and tube formation assays were performed to evaluate the potential effect of hAMSC-Exos on high glucose-treated HUVECs. The effect of hAMSC-Exos on diabetic wound healing were tested by measuring wound closure rates and immunohistochemical staining of CD31. Subsequently, the lncRNAs profiles in hAMSC-Exos and hAMSCs were examined to screen the lncRNAs related to angiogenesis.
RESULTS:
The isolated hAMSC-Exos had a size range of 30–150 nm and were positive for CD9, CD63 and CD81. The hAMSC-Exos facilitate the functional properties of high glucose-treated HUVECs including the proliferation, migration and the angiogenic activities as well as wound closure and angiogenesis in diabetic wound. hAMSC-Exos were enriched lncRNAs that related to angiogenesis, including PANTR1, H19, OIP5-AS1 and NR2F1-AS1.
CONCLUSION
Our findings demonstrated hAMSC-Exos facilitate diabetic wound healing by angiogenesis and contain several exosomal lncRNAs related to angiogenesis, which may represent a promising strategy for diabetic wound healing.
8.Efficacy of surgical treatment for 35 children with nail matrix nevi
Yan LIU ; Lin QIU ; Yuexian FU ; Xiaofei TIAN ; Xingang YUAN ; Jun XIAO ; Tianwu LI ; Xiaobo MAO ; Ailian MEI ; Yongqiang GUO ; Rong ZHOU
Chinese Journal of Dermatology 2022;55(5):430-433
Objective:To explore rational surgical treatment for childhood nail matrix nevi.Methods:A retrospective analysis was conducted on clinical data from 35 children with pathologically confirmed nail matrix nevi, who received surgical treatment in Children′s Hospital of Chongqing Medical University from September 2015 to March 2019. Different surgical approaches were adopted according to the site and width of lesions. For lesions with a width of ≤ 3 mm, the nail bed and nail matrix lesions were directly excised with 1-to-2-mm margins and sutured in 11 cases. For lesions with a width of > 3 mm, one of the following 3 surgical procedures was selected by the children′s parents: (1) shaving of nail bed and nail matrix lesions under a microscope at ×8 magnification (8 cases) ; (2) excision of lesions followed by full-thickness skin grafting on the periosteum of the phalanx (8 cases) ; (3) excision of lesions of the second to fifth fingers followed by transfer of skin flaps from the thenar muscle area and full-thickness skin grafting (5 cases) , or excision of lesions of the thumb followed by abdominal-wall flap transfer (3 cases) . The patients were followed up for 12 months, and clinical efficacy was evaluated.Results:During the follow-up, no recurrence occurred in the 11 cases receiving direct excision and suture, with good appearances and longitudinal linear scars on the nail. Among the 8 cases receiving shaving therapy under a microscope, 4 experienced relapse during the follow-up of 6 - 12 months, and the nail/toenail plates were rough and poor in lustrousness in the other 4 without recurrence. No recurrence was observed in the 8 cases receiving excision of the lesions and full-thickness skin grafting, of whom 1 experienced skin graft necrosis, and skin grafts survived with obvious pigmentation in the other 7 cases. Among cases receiving excision of the lesions combined with transfer of skin flaps from the thenar muscle area or abdominal-wall flap transfer, no recurrence was observed, and all transferred flaps survived; good appearances, nearly normal color and gloss of nails were obtained in the cases after transfer of skin flaps from the thenar muscle area, while the color and gloss of postoperative nails were markedly different from those of normal nails in the cases receiving abdominal-wall flap transfer.Conclusion:For nail matrix nevi with a width of ≤ 3 mm, direct excision and suture with 1-to-2-mm margins are recommended; for those with a width of > 3 mm, excision of lesions combined with full-thickness skin grafting, transfer of skin flaps from the thenar muscle area or abdominal-wall flap transfer is recommended; the shaving procedure under a microscope should be used with caution.
9.Application of limiting antigen avidity enzyme immunoassay for estimating HIV-1 incidence in men who have sex with men.
Xi Jia TANG ; Lei Jing DUAN ; Wen Li LIANG ; Si CHENG ; Ting Li DONG ; Zhen XIE ; Kang Mai LIU ; Fei YU ; Zi Huang CHEN ; Guo Dong MI ; Liang LIANG ; Hong Jing YAN ; Lin CHEN ; Li LIN ; Dian Min KANG ; Xiao Bing FU ; Mao Feng QIU ; Zhen JIANG ; Jie XU ; Zun You WU
Chinese Journal of Epidemiology 2022;43(1):72-77
Objective: To estimate the incidence of HIV-1 infection in men who have sex with men (MSM) in key areas of China through HIV-1 limiting antigen avidity enzyme immunoassay (LAg-Avidity EIA), analyze the deviation from the actual results and identify influencing factors, and provided reference for improving the accuracy of estimation results. Methods: Based on the principle of the cohort randomized study design, 20 cities were selected in China based on population size and the number of HIV-positive MSM. The sample size was estimated to be 700 according to the HIV-1 infection rate in MSM. MSM mobile phone app. was used to establish a detection appointment and questionnaire system, and the baseline cross-sectional survey was conducted from April to November 2019. LAg-Avidity EIA was used to identify the recent infected samples. The incidence of HIV-1 infection was calculated and then adjusted based on the estimation formula designed by WHO. The influencing factors were identified by analyzing the sample collection and detection processes. Results: Among the 10 650 blood samples from the participants, 799 were HIV-positive in initial screening, in which 198 samples (24.78%) missed during confirmation test. Only 621 samples were received by the laboratory. After excluding misreported samples, 520 samples were qualified for testing. A total of 155 samples were eventually determined as recent infection through LAg-Avidity EIA; Based on the estimation formula , the incidence of HIV-1 infection in MSM in 20 cities was 4.06% (95%CI:3.27%-4.85%), it increased to 5.53% (95%CI: 4.45%-6.60%)after the adjusting for sample missing rate. When the sample missing rate and misreporting rate were both adjusted, the incidence of HIV-1 infection in the MSM increased to 5.66% (95%CI:4.67%-6.65%). The actual incidence of HIV-1 infection in MSM in the 20 cities might be between 4.06% and 5.66%. Conclusions: Sample missing and misreporting might cause the deviation of the estimation of HIV-1 infection incidence. It is important to ensure the sample source and the quality of sample collection and detection to reduce the deviation in the estimation of HIV-1 infection incidence.
Cross-Sectional Studies
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HIV Infections/epidemiology*
;
HIV-1
;
Homosexuality, Male
;
Humans
;
Immunoenzyme Techniques
;
Incidence
;
Male
;
Sexual and Gender Minorities
10.Analysis of HIV-1 genetic subtype and pretreatment drug resistance among men who have sex with men infected with HIV-1 from 19 cities of 6 provinces in China.
Ran ZHANG ; Ting Li DONG ; Wen Li LIANG ; Zhao Bing CAO ; Zhen XIE ; Kang Mai LIU ; Fei YU ; Geng Feng FU ; Yu Qi ZHANG ; Guo Yong WANG ; Qiao Qin MA ; Shao Bin WU ; Yan LI ; Wei DONG ; Zhen JIANG ; Jie XU ; Zun You WU ; Jun YAO ; Pin Liang PAN ; Mao Feng QIU
Chinese Journal of Epidemiology 2022;43(4):523-527
Objective: To investigate the distribution of HIV-1 genetic subtypes and pretreatment drug resistance (PDR) among men who have sex with men (MSM) from 19 cities of 6 provinces in China. Methods: From April to November 2019, 574 plasma samples of ART-naive HIV-1 infected MSM were collected from 19 cities in Hebei, Shandong, Jiangsu, Zhejiang, Fujian, and Guangdong provinces, total ribonucleic acid (RNA) was extracted and amplified the HIV-1 pol gene region by nested polymerase chain reaction (PCR) after reverse transcription. Then sequences were used to construct a phylogenetic tree to determine genetic subtypes and submitted to the Stanford drug resistance database for drug resistance analysis. Results: A total of 479 samples were successfully amplified by PCR. The HIV-1 genetic subtypes included CRF01_AE, CRF07_BC, B, CRF55_01B, CRF59_01B, CRF65_cpx, CRF103_01B, CRF67_01B, CRF68_01B and unrecognized subtype, which accounted for 43.4%, 36.3%, 6.3%, 5.9%, 0.8%, 0.8%, 0.4%, 0.4%, 0.2% and 5.5%, respectively. The distribution of genetic subtypes among provinces is statistically different (χ2=44.141, P<0.001). The overall PDR rate was 4.6% (22/479), the drug resistance rate of non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, and protease inhibitors were 3.5% (17/479), 0.8% (4/479) and 0.2% (1/479), respectively. The PDR rate of recent infections was significantly higher than that of long-term infections (χ2=4.634, P=0.031). Conclusions: The HIV-1 genetic subtypes among MSM infected with HIV-1 from 19 cities of 6 provinces in China are diverse, and the distribution of subtypes is different among provinces. The overall PDR rate is low, while the PDR rate of recent infections was significantly higher than that of long-term infections, suggesting the surveillance of PDR in recent infections should be strengthened.
China/epidemiology*
;
Cities
;
Drug Resistance
;
Drug Resistance, Viral/genetics*
;
Female
;
Genotype
;
HIV Infections/epidemiology*
;
HIV Seropositivity/drug therapy*
;
HIV-1/genetics*
;
Homosexuality, Male
;
Humans
;
Male
;
Phylogeny
;
Reverse Transcriptase Inhibitors/therapeutic use*
;
Sexual and Gender Minorities

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