1.The inhibitory effect of artesunate on hepatocellular carcinoma cells by regulating expression of GADD45A and NACC1
Guan-Tong SHEN ; Jin-Yao DONG ; Jing FENG ; Nan QIN ; Gen-Lai DU ; Fei ZHU ; Ke LIAN ; Xin-Yu LIU ; Qing-Liang LI ; Xun-Wei ZHANG ; Ru-Yi SHI
Chinese Pharmacological Bulletin 2024;40(6):1089-1097
Aim To explore the effect and mechanism of the artesunate(ART)on hepatocellular carcinoma(HCC).Methods The cell lines MHCC-97H and HCC-LM3 were used to be detected.MTT and clone formation were used to determine the cell proliferation;Wound healing was used to detect the cell migration;Transwell was used to test the cell invasion.Flow-cy-tometry was used to detect cell apoptosis and cell cy-cle.RNA-seq and qRT-PCR was used to detect the genes expression.Results The proliferation,migra-tion and invasion of treated cells were obviously inhibi-ted(P<0.01).Moreover,the apoptosis rate in-creased significantly,so did the proportion of G2/M cells.Transcriptomic analysis identified GADD45A as a potential target of ART through RNA-sequencing da-ta,and suggested that ART might induce apoptosis and cell cycle arrest through regulating the expression of GADD45A.In addition,the results of mechanism studies and signaling analysis suggested that GADD45A had interaction with its upstream gene NACC1(nucle-us accumbens associated 1).Moreover,after ART treatment,the expressions of GADD45A and NACC1 were changed significantly.Conclusion ART may be a potential drug to resist HCC by affecting the expres-sion of GADD45A and its upstream gene NACC1,which provides a new drug,a new direction and a new method for the clinical treatment of HCC.
2. Research progress on experimental animal models of hyperuricemia
Yi-Song YUE ; Xue-Mei QIN ; Yi-Song YUE ; Wen ZHANG ; Yi-Fei XIE ; Guan-Hua DU
Chinese Pharmacological Bulletin 2023;39(2):201-206
Hyperuricemia is a chronic metabolic disease caused by purine metabolism disorder or uric acid excretion disorder. The experimental animal model of hyperuricemia is the basis for studying the pathological mechanism and drug treatment of hyperuricemia. This paper reviews the experimental animal models of hyperuricemia commonly used in drug research, and introduces the modeling principle, preparation methods, species selection and related detection techniques of the models, so as to provide reference for the application of such models in research.
3. The reversal effect of albiflorin on multidrug resistance of human ovarian cancer and its mechanism
Li HAN ; Xiao-Juan GUO ; Rui-Juan DU ; Yi CHEN ; Qing-Lin FEI ; Ke-Lei GUO ; Hua BIAN ; Li HAN ; Rui-Juan DU ; Ke-Lei GUO ; Hua BIAN
Chinese Pharmacological Bulletin 2023;39(2):268-274
Aim To study the reversal effect of albiflorin(AL)on multidrug resistance of human ovarian cancer and the potential mechanism. Methods The drug resistance reversal effect of AL on SKOV3/DDP cells was detected by CCK-8 kit,and the effect of AL on P-glycoprotein(P-gp)function was detected by flow cytometry. The effects of AL on MYC,WWP1 and ABCB1 in SKOV3/DDP cells were detected by RT-qPCR and Western blot. The MYC-knockdown SKOV3/DDP cell line was constructed by RNA interference technology,and its drug resistance,P-gp function and related gene and protein expression changes were investigated. Results AL had a drug resistance reversal effect on SKOV3/DDP cells and a concentration-dependent inhibitory effect on P-gp function. The inhibitory effects of AL 25,50 and 100 μmol·L-1 on ABCB1/P-gp,MYC and WWP1 were gradually enhanced. The inhibitory effect of MYCi975,a MYC inhibitor,on ABCB1/P-gp,MYC and WWP1 was stronger than or equivalent to that of AL 100 μmol·L-1 group. After knockdown of MYC in SKOV3/DDP cells,cell drug resistance,P-gp function,and related gene and protein expression were inhibited. Conclusions The drug resistance reversal effect of AL on SKOV3/DDP cells may be related to the inhibition of P-gp function and the expression of ABCB1/P-gp,MYC and WWP1,which provides an experiment base for the development of AL as a drug resistance reversal agent for the clinical treatment of ovarian cancer.
4. Treatment advice of small molecule antiviral drugs for elderly COVID-19
Min PAN ; Shuang CHANG ; Xiao-Xia FENG ; Guang-He FEI ; Jia-Bin LI ; Hua WANG ; Du-Juan XU ; Chang-Hui WANG ; Yan SUN ; Xiao-Yun FAN ; Tian-Jing ZHANG ; Wei WEI ; Ling-Ling ZHANG ; Jim LI ; Fei-Hu CHEN ; Xiao-Ming MENG ; Hong-Mei ZHAO ; Min DAI ; Yi XIANG ; Meng-Shu CAO ; Xiao-Yang CHEN ; Xian-Wei YE ; Xiao-Wen HU ; Ling JIANG ; Yong-Zhong WANG ; Hao LIU ; Hai-Tang XIE ; Ping FANG ; Zhen-Dong QIAN ; Chao TANG ; Gang YANG ; Xiao-Bao TENG ; Chao-Xia QIAN ; Guo-Zheng DING
Chinese Pharmacological Bulletin 2023;39(3):425-430
COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.
5.Diagnosis and treatment of four cases of asymptomatic and non-hydrous ureteral calculi.
Cai Peng QIN ; Fei WANG ; Yi Qing DU ; Xiao Wei ZHANG ; Qing LI ; Shi Jun LIU ; Tao XU
Journal of Peking University(Health Sciences) 2023;55(5):939-942
This paper analyzed the clinical data, diagnosis and treatment of 4 asymptomatic patients with ureteral calculi without hydrops in our hospital from October 2018 to January 2019, and comprehensively discussed the previous literature. The 4 patients in this group had no obvious clinical symptoms, no positive stones were found in the B-ultrasound of the urinary system, and no hydroureter and hydroureter of the affected side was found. Urinary CT scan confirmed ureteral stones. They were all located in the lower ureter, and the stones obstructed the lumen. The stones were round and smooth, and there was no obvious hyperplasia and edema in the surrounding mucosa. The lithotripsy was completed in the first-stage operation, and the DJ catheter was left behind for one month after the operation. Based on the clinical diagnosis and treatment process of the 4 cases of asymptomatic calculi in this group and the analysis of previous studies, these patients were mostly detected by imaging examinations or other systematic imaging examinations during the regular review of urinary calculi. Ureteral stones with obstruction did not necessarily have stone-related symptoms. The onset of renal colic involved an increase in intraluminal pressure, related stimulation of nerve endings, smooth muscle spasms caused by stretching of the ureteral wall, and systemic changes in cytokines and related hormones. Cascade reactions, etc., were associated with the movement of stones down. Ureteral stones without hydrops were mostly located in the lower ureter, which had a certain buffering effect on obstructive pressure. Asymptomatic ureteral calculi could also induce irreversible damage to renal function, and the proportion of damage increased with the diameter of the stone. Patients with a history of urinary calculi, especially those with asymptomatic stones for the first time, should be paid attention to during clinical follow-up. At present, there are few research reports on asymptomatic and non-accumulating ureteral calculi. We analyze the clinical diagnosis and treatment process and characteristics of this group of patients combined with previous literature to provide a reference for the diagnosis and treatment of such patients.
Humans
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Ureteral Calculi/therapy*
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Urinary Calculi/therapy*
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Ureter
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Lithotripsy/methods*
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Edema/therapy*
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Kidney Calculi/therapy*
6.Research progress of optical coherence tomography angiography in detecting retinal and choroidal thickness and blood flow in patients with high myopia
Yi-Fei ZHANG ; Wan-Hong DU ; Mei-Sheng ZHAO ; Chao ZHU
International Eye Science 2023;23(4):597-601
High myopia is a state of refractive error with myopia over -6.00D. High myopia is typically accompanied by multiple fundus lesions, thus making patients with high myopia suffer from varying degrees of impairment in visual function. As an emerging auxiliary way in ophthalmology, optical coherence tomography angiography(OCTA)can efficiently and non-invasively obtain microvascular stratified images of the retina and choroid and quantitatively analyze blood flow signals. Since the advent of OCTA, there have been numerous studies observing fundus changes in those with high myopia through OCTA. In this paper, some studies in which OCTA is applied to obtain retinal and choroidal thickness from patients with high myopia are reviewed, with a view to revealing the correlation between high myopia and the parameters such as retinal thickness, choroidal thickness, vessel density and the area of the foveal avascular zone and providing novel ideas to deeply investigate the mechanism of high myopia and delay the occurrence and development of high myopia.
7.Jiedu Recipe, a compound Chinese herbal medicine, inhibits cancer stemness in hepatocellular carcinoma via Wnt/β-catenin pathway under hypoxia.
Bing-Jie GUO ; Yi RUAN ; Ya-Jing WANG ; Chu-Lan XIAO ; Zhi-Peng ZHONG ; Bin-Bin CHENG ; Juan DU ; Bai LI ; Wei GU ; Zi-Fei YIN
Journal of Integrative Medicine 2023;21(5):474-486
OBJECTIVE:
Jiedu Recipe (JR), a Chinese herbal remedy, has been shown to prolong overall survival time and decrease recurrence and metastasis rates in patients with hepatocellular carcinoma (HCC). This work investigated the mechanism of JR in HCC treatment.
METHODS:
The chemical constituents of JR were detected using liquid chromatography-mass spectrometry. The potential anti-HCC mechanism of JR was screened using network pharmacology and messenger ribonucleic acid (mRNA) microarray chip assay, followed by experimental validation in human HCC cells (SMMC-7721 and Huh7) in vitro and a nude mouse subcutaneous transplantation model of HCC in vivo. HCC cell characteristics of proliferation, migration and invasion under hypoxic setting were investigated using thiazolyl blue tetrazolium bromide, wound healing and Transwell assays, respectively. Image-iT™ Hypoxia Reagent was added to reveal hypoxic conditions. Stem cell sphere formation assay was used to detect the stemness. Epithelial-mesenchymal transition (EMT) markers like E-cadherin, vimentin and α-smooth muscle actin, and pluripotent transcription factors including nanog homeobox, octamer-binding transcription factor 4, and sex-determining region Y box protein 2 were analyzed using Western blotting and real-time polymerase chain reaction. Western blot was performed to ascertain the anti-HCC effect of JR under hypoxia involving the Wnt/β-catenin pathway.
RESULTS:
According to network pharmacology and mRNA microarray chip analysis, JR may potentially act on hypoxia and inhibit the Wnt/β-catenin pathway. In vitro and in vivo experiments showed that JR significantly decreased hypoxia, and suppressed HCC cell features of proliferation, migration and invasion; furthermore, the hypoxia-induced increases in EMT and stemness marker expression in HCC cells were inhibited by JR. Results based on the co-administration of JR and an agonist (LiCl) or inhibitor (IWR-1-endo) verified that JR suppressed HCC cancer stem-like properties under hypoxia by blocking the Wnt/β-catenin pathway.
CONCLUSION
JR exerts potent anti-HCC effects by inhibiting cancer stemness via abating the Wnt/β-catenin pathway under hypoxic conditions. Please cite this article as: Guo BJ, Ruan Y, Wang YJ, Xiao CL, Zhong ZP, Cheng BB, Du J, Li B, Gu W, Yin ZF. Jiedu Recipe, a compound Chinese herbal medicine, inhibits cancer stemness in hepatocellular carcinoma via Wnt/β-catenin pathway under hypoxia. J Integr Med. 2023; 21(5): 474-486.
Animals
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Mice
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Humans
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Carcinoma, Hepatocellular/genetics*
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beta Catenin/pharmacology*
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Liver Neoplasms/genetics*
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Drugs, Chinese Herbal/therapeutic use*
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RNA, Messenger/therapeutic use*
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Cell Line, Tumor
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Cell Proliferation
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Cell Movement
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Gene Expression Regulation, Neoplastic
8.Efficacy and safety of autologous hematopoietic stem cell transplantation pretreated with Melphalan hydrochloride for injection in the treatment of 125 cases of multiple myeloma.
Wen Yang HUANG ; Wei LIU ; Hui Min LIU ; Yan XU ; Qi WANG ; Chen Xing DU ; Wen Jie XIONG ; Wei Wei SUI ; Fei TIAN ; Jing WANG ; Shu Hua YI ; Gang AN ; Lu Gui QIU ; De Hui ZOU
Chinese Journal of Hematology 2023;44(2):148-150
9.PD-1 inhibitor plus anlotinib for metastatic castration-resistant prostate cancer: a real-world study.
Xin-Xing DU ; Yan-Hao DONG ; Han-Jing ZHU ; Xiao-Chen FEI ; Yi-Ming GONG ; Bin-Bin XIA ; Fan WU ; Jia-Yi WANG ; Jia-Zhou LIU ; Lian-Cheng FAN ; Yan-Qing WANG ; Liang DONG ; Yin-Jie ZHU ; Jia-Hua PAN ; Bai-Jun DONG ; Wei XUE
Asian Journal of Andrology 2023;25(2):179-183
Management and treatment of terminal metastatic castration-resistant prostate cancer (mCRPC) remains heavily debated. We sought to investigate the efficacy of programmed cell death 1 (PD-1) inhibitor plus anlotinib as a potential solution for terminal mCRPC and further evaluate the association of genomic characteristics with efficacy outcomes. We conducted a retrospective real-world study of 25 mCRPC patients who received PD-1 inhibitor plus anlotinib after the progression to standard treatments. The clinical information was extracted from the electronic medical records and 22 patients had targeted circulating tumor DNA (ctDNA) next-generation sequencing. Statistical analysis showed that 6 (24.0%) patients experienced prostate-specific antigen (PSA) response and 11 (44.0%) patients experienced PSA reduction. The relationship between ctDNA findings and outcomes was also analyzed. DNA-damage repair (DDR) pathways and homologous recombination repair (HRR) pathway defects indicated a comparatively longer PSA-progression-free survival (PSA-PFS; 2.5 months vs 1.2 months, P = 0.027; 3.3 months vs 1.2 months, P = 0.017; respectively). This study introduces the PD-1 inhibitor plus anlotinib as a late-line therapeutic strategy for terminal mCRPC. PD-1 inhibitor plus anlotinib may be a new treatment choice for terminal mCRPC patients with DDR or HRR pathway defects and requires further investigation.
Male
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Humans
;
Prostate-Specific Antigen
;
Treatment Outcome
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Prostatic Neoplasms, Castration-Resistant/drug therapy*
;
Immune Checkpoint Inhibitors/therapeutic use*
;
Retrospective Studies
10.Analysis of the status of occupational disease prevention and control of enterprises in mining and manufacturing industries in China in 2019.
Jin Nan ZHENG ; Yue YU ; Si Yu ZHANG ; Xie Yi DU ; Hong Fei WANG ; Wei Jiang HU
Chinese Journal of Industrial Hygiene and Occupational Diseases 2023;41(5):338-344
Objective: To analyze the status of prevention and treatment of occupational diseases among mining and manufacturing industries in China in 2019, provide the scientific basis for the formulation and revision of policies and standards of prevention and treatment of occupational diseases. Methods: In May 2022, Collecting data of a project named Surveillance of Occupational Hazards in the Workplace in 2019 through the National Surveillance System for Occupational Hazards in the workplace. Compare the status of prevention and treatment of occupational diseases in 63 563 enterprises of mining and manufacturing industries among different dimensions. Results: The training rate of managers was 76.17% and that of occupational health managers was 76.97%. The rate of reporting of occupational diseases hazardous items was 67.58%, the rate of launching of the detection of occupational hazards was 57.16%, and the rate of launching of occupational health examination was 62.42%. Excluding the distribution rate of dust mask, the installation rate of various occupational prevention facilities and the distribution rate of gas mask and hearing protector were less than 80%. The differences in all the indicators among different areas, enterprise scales, economic types were statistically significant (P<0.05) . Conclusion: There are still some enterprises which are relatively weak in the ability of the prevention and treatment of occupational diseases in China. Measures such as special support, guidance and strengthen supervision should be taken towards those enterprises toimprove the awareness of prevention and treatment of occupational diseases and the level of that.
Humans
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Occupational Exposure
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Occupational Diseases/prevention & control*
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Manufacturing Industry
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Workplace
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China/epidemiology*
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Occupational Health

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