1.Awareness of HPV and HPV vaccine and willingness to be vaccinated among parents of children aged 9-14
Bing-han WANG ; Shi-yu YAN ; Sun-yi WANG ; Shi-yi WU ; Qing-qing TAO ; Hui-hui GAO ; Qiu-xiang SHEN ; Hui LI ; Chang-zheng YUAN ; Xi ZHANG ; Li-ying SUN
Journal of Public Health and Preventive Medicine 2023;34(1):39-43
Objective To investigate the HPV vaccination status of children aged 9-14 years, parents’ vaccine-related cognition, willingness to vaccinate children and their influencing factors. Methods From January to April 2021, the convenience sampling method was used to collect data based on the online platform and the Department of Pediatrics and Adolescent Gynecology of the Children's Hospital of Zhejiang University School of Medicine. The data were analyzed by descriptive analysis, Chi-square test, and logistic regression. Results A total of 864 questionnaires were collected, and 846 valid questionnaires were obtained after screening, with an effective rate of 97.9%. 13.57% of mothers and 3.09% of girls were vaccinated, and the vaccine awareness rate was 68.43%. 87.22% of parents were willing to bring their children for vaccination. Risk perception (OR=4.79, 95% CI: 2.22-10.35), willingness to vaccinate themselves (OR =29.01, 95% CI: 12.62-66.69), awareness of sex education (OR =3.73, 95% CI: 1.08-12.83) and whether the vaccines were free (P<0.001) were related to whether parents were willing to vaccinate their children. Conclusion Parents of children aged 9-14 have high awareness of HPV and HPV vaccine and are willing to vaccinate their children with HPV vaccine , but the vaccination rate in children is low. Disease perception, willingness to vaccinate, awareness of sex education, and whether vaccines are free are all the factors influencing parents' willingness to vaccinate children.
2.HbA1c comparison and diagnostic efficacy analysis of multi center different glycosylated hemoglobin detection systems.
Ping LI ; Ying WU ; Yan XIE ; Feng CHEN ; Shao qiang CHEN ; Yun Hao LI ; Qing Qing LU ; Jing LI ; Yong Wei LI ; Dong Xu PEI ; Ya Jun CHEN ; Hui CHEN ; Yan LI ; Wei WANG ; Hai WANG ; He Tao YU ; Zhu BA ; De CHENG ; Le Ping NING ; Chang Liang LUO ; Xiao Song QIN ; Jin ZHANG ; Ning WU ; Hui Jun XIE ; Jina Hua PAN ; Jian SHUI ; Jian WANG ; Jun Ping YANG ; Xing Hui LIU ; Feng Xia XU ; Lei YANG ; Li Yi HU ; Qun ZHANG ; Biao LI ; Qing Lin LIU ; Man ZHANG ; Shou Jun SHEN ; Min Min JIANG ; Yong WU ; Jin Wei HU ; Shuang Quan LIU ; Da Yong GU ; Xiao Bing XIE
Chinese Journal of Preventive Medicine 2023;57(7):1047-1058
Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R2 of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy
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Child
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Humans
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Female
;
Glycated Hemoglobin
;
Cohort Studies
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Diabetes Mellitus/diagnosis*
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Sensitivity and Specificity
;
ROC Curve
3.A novel biodegradable polymer-coated sirolimus-eluting stent: 1-year results of the HELIOS registry.
Bo ZHENG ; Yi LIU ; Ruining ZHANG ; Wangwei YANG ; Fangju SU ; Rutao WANG ; Dapeng CHEN ; Guidong SHEN ; Yumin QIU ; Lianmin WANG ; Chang CHEN ; Zhongwei WU ; Fei LI ; Jiayi LI ; Chengxiang LI ; Chao GAO ; Ling TAO
Chinese Medical Journal 2023;136(15):1848-1854
BACKGROUND:
The HELIOS stent is a sirolimus-eluting stent with a biodegradable polymer and titanium oxide film as the tie-layer. The study aimed to evaluate the safety and efficacy of HELIOS stent in a real-world setting.
METHODS:
The HELIOS registry is a prospective, multicenter, cohort study conducted at 38 centers across China between November 2018 and December 2019. A total of 3060 consecutive patients were enrolled after application of minimal inclusion and exclusion criteria. The primary endpoint was target lesion failure (TLF), defined as a composite of cardiac death, non-fatal target vessel myocardial infarction (MI), and clinically indicated target lesion revascularization (TLR) at 1-year follow-up. Kaplan-Meier methods were used to estimate the cumulative incidence of clinical events and construct survival curves.
RESULTS:
A total of 2998 (98.0%) patients completed the 1-year follow-up. The 1-year incidence of TLF was 3.10% (94/2998, 95% closed interval: 2.54-3.78%). The rates of cardiac death, non-fatal target vessel MI and clinically indicated TLR were 2.33% (70/2998), 0.20% (6/2998), and 0.70% (21/2998), respectively. The rate of stent thrombosis was 0.33% (10/2998). Age ≥60 years, diabetes mellitus, family history of coronary artery disease, acute myocardial infarction at admission, and device success were independent predictors of TLF at 1 year.
CONCLUSION:
The 1-year incidence rates of TLF and stent thrombosis were 3.10% and 0.33%, respectively, in patients treated with HELIOS stents. Our results provide clinical evidence for interventional cardiologists and policymakers to evaluate HELIOS stent.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, NCT03916432.
Humans
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Middle Aged
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Sirolimus/therapeutic use*
;
Drug-Eluting Stents/adverse effects*
;
Prospective Studies
;
Cohort Studies
;
Treatment Outcome
;
Risk Factors
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Time Factors
;
Percutaneous Coronary Intervention/adverse effects*
;
Cardiovascular Agents/therapeutic use*
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Coronary Artery Disease/therapy*
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Myocardial Infarction/etiology*
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Thrombosis/complications*
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Polymers
;
Registries
4.Contamination status and exposure risk of mycotoxins in Coicis Semen.
Hong-Xia ZHANG ; Wei-Ke JIANG ; Chang-Gui YANG ; Qing-Song YUAN ; Lan-Ping GUO ; Yuan-Wen SHEN ; Ni-Ting WEN ; Jin-Qiang ZHANG ; Tao ZHOU
China Journal of Chinese Materia Medica 2023;48(6):1491-1497
By investigating the contamination status and predicting the exposure risk of mycotoxin in Coicis Semen, we aim to provide guidance for the safety supervision of Chinese medicinal materials and the formulation(revision) of mycotoxin limit standards. The content of 14 mycotoxins in the 100 Coicis Semen samples collected from five major markets of Chinese medicinal materials in China was determined by UPLC-MS/MS. The probability evaluation model based on Monte Carlo simulation method was established after Chi-square test and One-way ANOVA of the sample contamination data. Health risk assessment was performed on the basis of margin of exposure(MOE) and margin of safety(MOS). The results showed that zearalenone(ZEN), aflatoxin B_1(AFB_1), deoxynivalenol(DON), sterigmatocystin(ST), and aflatoxin B_2(AFB_2) in the Coicis Semen samples had the detection rates of 84%, 75%, 36%, 19%, and 18%, and the mean contamination levels of 117.42, 4.78, 61.16, 6.61, and 2.13 μg·kg~(-1), respectively. According to the limit standards in the Chinese Pharmacopoeia(2020 edition), AFB_1, AFs and ZEN exceeded the standards to certain extents, with the over-standard rates of 12.0%, 9.0%, and 6.0%, respectively. The exposure risks of Coicis Semen to AFB_1, AFB2, ST, DON, and ZEN were low, while 86% of the samples were contaminated with two or more toxins, which needs more attention. It is suggested that the research on the combined toxicity of different mycotoxins should be strengthened to accelerate the cumulative exposure assessment of mixed contaminations and the formulation(revision) of toxin limit standards.
Humans
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Mycotoxins/analysis*
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Coix
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Aflatoxin B1/analysis*
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Chromatography, Liquid/methods*
;
Food Contamination/analysis*
;
Tandem Mass Spectrometry/methods*
5.Apoptosis-promoting effect of temozolomide loaded nanoparticles combined with low intensity focused ultrasound on human glioma cells
Ruijiao CHANG ; Hongyu TAO ; Hongyuan SHEN ; Qian ZHANG ; Guangfei YANG
Chinese Journal of Ultrasonography 2023;32(1):86-91
Objective:To prepare liquid-gas phase modified nanoparticles (TMZ/PFP/PLGA NPs) of perfluoropentane (PFP) and temozolomide (TMZ) encapsulated by polylactic-glycolic acid copolymer (PLGA), combined with low intensity focused ultrasound (LIFU) irradiation, and to investigate its ultrasound imaging ability and intervention effect on human glioma cells in vitro.Methods:TMZ/PFP/PLGA NPs were prepared by compound emulsion method. The basic physical and chemical properties and drug loading ability of TMZ/PFP/PLGA NPs were detected. CCK-8 assay was used to detect the cytotoxicity of nanoparticles in vitro and the effect of synergistic intervention with LIFU on the survival rate of glioma cells. The expression levels of apoptosis related proteins Bcl-2, Bax and caspase-3 were detected by Western blot.Results:Under transmission electron microscope, TMZ/PFP/PLGA NPs showed a circular core-shell structure with regular morphology, particle size was (137.9±63.31)nm, encapsulation efficiency of TMZ was (83.01±5.57)%, drug loading was (3.19±0.22)%. The survival rate of U251 cells was still above 70% after 24 hours of co-incubation with nanoparticles. Under the synergistic effect of LIFU irradiation, the apoptosis of U251 cells was accelerated and the survival rate of U251 cells was significantly decreased. The results of Western blot showed that the synergic intervention could significantly down-regulate the expression of apoptosis related protein Bcl-2, and significantly up-regulate the expression of Bax protein and caspase-3 protein (all P<0.05). Conclusions:TMZ/PFP/PLGA NPs have good basic physical and chemical properties. TMZ/PFP/PLGA NPs have low cytotoxicity in vitro while efficiently loading chemotherapeutic drug timozolomide. Synergistic intervention under LIFU irradiation can significantly accelerate the apoptosis of U251 glioma cells, which has a good application prospect.
6.Clinical treatment guideline for pulmonary blast injury (version 2023)
Zhiming SONG ; Junhua GUO ; Jianming CHEN ; Jing ZHONG ; Yan DOU ; Jiarong MENG ; Guomin ZHANG ; Guodong LIU ; Huaping LIANG ; Hezhong CHEN ; Shuogui XU ; Yufeng ZHANG ; Zhinong WANG ; Daixing ZHONG ; Tao JIANG ; Zhiqiang XUE ; Feihu ZHOU ; Zhixin LIANG ; Yang LIU ; Xu WU ; Kaican CAI ; Yi SHEN ; Yong SONG ; Xiaoli YUAN ; Enwu XU ; Yifeng ZHENG ; Shumin WANG ; Erping XI ; Shengsheng YANG ; Wenke CAI ; Yu CHEN ; Qingxin LI ; Zhiqiang ZOU ; Chang SU ; Hongwei SHANG ; Jiangxing XU ; Yongjing LIU ; Qianjin WANG ; Xiaodong WEI ; Guoan XU ; Gaofeng LIU ; Junhui LUO ; Qinghua LI ; Bin SONG ; Ming GUO ; Chen HUANG ; Xunyu XU ; Yuanrong TU ; Liling ZHENG ; Mingke DUAN ; Renping WAN ; Tengbo YU ; Hai YU ; Yanmei ZHAO ; Yuping WEI ; Jin ZHANG ; Hua GUO ; Jianxin JIANG ; Lianyang ZHANG ; Yunfeng YI
Chinese Journal of Trauma 2023;39(12):1057-1069
Pulmonary blast injury has become the main type of trauma in modern warfare, characterized by externally mild injuries but internally severe injuries, rapid disease progression, and a high rate of early death. The injury is complicated in clinical practice, often with multiple and compound injuries. Currently, there is a lack of effective protective materials, accurate injury detection instrument and portable monitoring and transportation equipment, standardized clinical treatment guidelines in various medical centers, and evidence-based guidelines at home and abroad, resulting in a high mortality in clinlcal practice. Therefore, the Trauma Branch of Chinese Medical Association and the Editorial Committee of Chinese Journal of Trauma organized military and civilian experts in related fields such as thoracic surgery and traumatic surgery to jointly develop the Clinical treatment guideline for pulmonary blast injury ( version 2023) by combining evidence for effectiveness and clinical first-line treatment experience. This guideline provided 16 recommended opinions surrounding definition, characteristics, pre-hospital diagnosis and treatment, and in-hospital treatment of pulmonary blast injury, hoping to provide a basis for the clinical treatment in hospitals at different levels.
7.Activation of Dopamine D2 Receptors Alleviates Neuronal Hyperexcitability in the Lateral Entorhinal Cortex via Inhibition of HCN Current in a Rat Model of Chronic Inflammatory Pain.
Shi-Hao GAO ; Yong TAO ; Yang ZHU ; Hao HUANG ; Lin-Lin SHEN ; Chang-Yue GAO
Neuroscience Bulletin 2022;38(9):1041-1056
Functional changes in synaptic transmission from the lateral entorhinal cortex to the dentate gyrus (LEC-DG) are considered responsible for the chronification of pain. However, the underlying alterations in fan cells, which are the predominant neurons in the LEC that project to the DG, remain elusive. Here, we investigated possible mechanisms using a rat model of complete Freund's adjuvant (CFA)-induced inflammatory pain. We found a substantial increase in hyperpolarization-activated/cyclic nucleotide-gated currents (Ih), which led to the hyperexcitability of LEC fan cells of CFA slices. This phenomenon was attenuated in CFA slices by activating dopamine D2, but not D1, receptors. Chemogenetic activation of the ventral tegmental area -LEC projection had a D2 receptor-dependent analgesic effect. Intra-LEC microinjection of a D2 receptor agonist also suppressed CFA-induced behavioral hypersensitivity, and this effect was attenuated by pre-activation of the Ih. Our findings suggest that down-regulating the excitability of LEC fan cells through activation of the dopamine D2 receptor may be a strategy for treating chronic inflammatory pain.
Animals
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Chronic Pain
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Entorhinal Cortex/metabolism*
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Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels
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Neurons/metabolism*
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Rats
;
Receptors, Dopamine D1/metabolism*
;
Receptors, Dopamine D2
8.Transcriptome Analysis of Xianlian Jiedu Prescription in Intervention of Colorectal Carcinoma Due to Dampness, Heat, Stasis, and Toxin in Mice
Tong-qing CHEN ; Cheng-tao YU ; Hui-qin XU ; Hai-bo CHENG ; Wei-xing SHEN ; Jia-ni TAN ; Chang-liang XU ; Yue-yang LAI ; Min-min FAN
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(8):63-71
ObjectiveTo analyze the transcriptome characteristics of Xianlian Jiedu prescription (XLJDP) in the intervention of colorectal carcinoma by high-throughput cDNA-sequencing (RNA-seq). MethodNinety male C57BL/6 mice were randomly divided into the control group, colorectal carcinoma due to dampness, heat, stasis, and toxin model group, and XLJDP group, with 30 mice in each group. Mice in the model group and XLJDP group were fed a high-fat diet and provided with azoxymethane and dextran sodium sulfate (AOM/DSS) for inducing colorectal carcinoma. Those in the XLJDP group were further treated with intragastric administration of 12.9 g·kg-1 XLJDP since the day of modeling for 112 days. The colorectal tissues were collected from each group 4 h after the last drug treatment and stained with hematoxylin-eosin (HE) and methylene blue for observing the pathological changes. The total RNA was extracted from colorectal tissues for RNA-Seq-based transcriptome profiling, followed by gene oncology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis and the screening and verification of differentially expressed genes. ResultCompared with the model group, XLJDP significantly relieved the colorectal congestion and edema and decreased tumor number and volume in mouse colorectal tissues. The methylene blue staining results indicated that XLJDP significantly suppressed the development of aberrant crypt foci (ACF,P<0.01). As revealed by HE staining, XLJDP significantly alleviated the injury and dysplasia of colorectal tissues. Transcriptome analysis identified 615 differentially expressed genes (446 up-regulated and 169 down-regulated) between the model group and the blank group and 54 differentially expressed genes (29 up-regulated and 25 down-regulated) between the XLJDP group and model group. XLJDP mainly affected the expression of NIMA-related protein kinase 7 gene (Nek7, P<0.01), Mucin 16 (Muc16, P<0.01), SiahE3 ubiquitin protein ligase family member 3 (Siah3, P<0.01), regenerating islet-derived protein 3-gamma (Reg3g, P<0.01), RNA polymerase Ⅱ elongation factor-associated factor 2 (Eaf2, P<0.01), transforming growth factor‐alfa gene (TGF-α, P<0.05), secretoglobin family 1A member 1 (Scgb1a1, P<0.05), family with sequence similarity 227 member B (Fam227B, P<0.05), cytochrome P450 family 2 subfamily c polypeptide 40 (Cyp2c40, P<0.01), and ankyrin repeat and EF-hand domain containing protein 1 (Ankef1, P<0.05). Enrichment analysis showed that intestinal epithelial cell proliferation, metabolism of xenobiotics by cytochrome P450, and arachidonic acid metabolism signaling pathway were significantly enriched. ConclusionXLJDP is able to interfere with colorectal tumorigenesis and development due to dampness, heat, stasis, and toxin in mice, which has been proved by transcriptome analysis to be related to the regulation of metabolism-related pathways.
9.Effect of Xianlian Jiedu Prescription on Proliferation and Glycolysis of Human Colorectal Cancer HCT-116 Cells and Mechanism
Li-huiping TAO ; Yue-yang LAI ; Hai-bo CHENG ; Wei-xing SHEN ; Jia-ni TAN ; Chang-liang XU ; Cheng-tao YU ; Min-min FAN ; Liu LI ; Zheng-jie SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(8):72-78
ObjectiveTo explore the effect of Xianlian Jiedu prescription (XLJDP) on the proliferation and glycolysis of human colorectal cancer HCT-116 cells and the underlying mechanism. MethodHCT-116 cells were cultured with XLJDP and then the survival rate was examined by methyl thiazolyl tetrazolium (MTT) assay. The effect on the HCT116 cell proliferation was detected by colony formation assay and 5-ethynyl-2′-deoxyuridine (EDU) incorporation assay. The amount of glucose consumed by HCT-116 cells was measured by glucose test kit, and the amount of produced lactic acid was determined by lactic acid test kit 48 h after the treatment with XLJDP. The expression of glycolysis-related proteins mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), glucose transporter 1 (GLUT1), and lactate dehydrogenase (LDHA) was detected by Western blot. ResultThe half-maximal inhibitory concentration (IC50) of XLJDP against HCT-116 cells was 6.82 g·L-1. Compared with the blank group, XLJDP (1.625, 3.25, 6.50 g·L-1) inhibited the proliferation of HCT-116 cells (P<0.05, P<0.01). Moreover, compared with the blank group, XLJDP (1.625, 3.25, 6.50 g·L-1) suppressed glucose uptake and lactic acid production in a dose-dependent manner (P<0.05, P<0.01). The expression of p-mTOR/mTOR, LDHA, and GLUT1 was down-regulated by XLJDP (P<0.05, P<0.01). ConclusionXLJDP can significantly inhibit the proliferation and the Warburg effect of glycolysis in colorectal cancer cells by regulating the mTOR signaling pathway and the down-regulating the expression of LDHA, GLUT1, and other key proteins and enzymes in glycolysis.
10.Effect and Mechanism of Xianlian Jiedu Prescription Against Proliferation of Colorectal Cancer Cells in Hypoxic Microenvironment
Rui-yang JIANG ; Chang-liang XU ; Hai-bo CHENG ; Wei-xing SHEN ; Min-min FAN ; Jia-ni TAN ; Yue-yang LAI ; Cheng-tao YU ; Dong-dong SUN ; Liu LI
Chinese Journal of Experimental Traditional Medical Formulae 2022;28(8):79-85
ObjectiveTo study the effect of Xianlian Jiedu prescription (XLJDP) on the activation of nuclear transcription factor-κB (NF-κB) signaling pathway induced by bromodomain-containing protein 4 (Brd4) in hypoxic microenvironment and to explore its mechanism in inhibiting the proliferation of colorectal cancer HT-29 cells. MethodThe human colorectal cancer HT-29 cells were cultured in a hypoxic incubator or normoxia incubator and treated with XLJDP at 0.8,1,1.2,1.6,3.2,6.4,and 12.8 g·L-1 for 48 h, respectively. Following the detection of cell vitality using methyl thiazolyl tetrazolium (MTT) colorimetry, the effects of XLJDP (1.25,2.5,and 5 g·L-1) on the cell mitochondrial membrane potential were determined using a fluorescent probe (JC-1), and the apoptosis of colorectal cancer HT-29 cells was detected by flow cytometry. The cell colony formation assay and 5-ethynyl-2'-deoxyuridine (EDU) staining were conducted to test the proliferation of colorectal cancer HT-29 cells. The Western blot was carried out to measure the expression levels of Brd4 and its downstream relevant proteins such as c-Myc and hexamethylene bisacetamide-inducible protein 1 (HEXIM1), as well as the effects of XLJDP on related proteins in the NF-κB signaling pathway. ResultCompared with the blank control group, XLJDP at 0.8,1,1.2,1.6,3.2,6.4,and 12.8 g·L-1 inhibited the vitality of colorectal cancer HT-29 cells (P<0.05 , P<0.01), with the median inhibitory concentration (IC50) under the hypoxic condition higher than that under the normoxia condition. Compared with the blank control group, XLJDP at 1.25,2.5,and 5 g·L-1 significantly decreased the mitochondria membrane potential, enhanced the apoptosis (P<0.05,P<0.01), and lowered the number of cell colonies and also the EDU-positive cells (P<0.05, P<0.01). The results of Western blot showed that compared with the blank control group, XLJDP at 1.25,2.5,and 5 g·L-1 down-regulated Brd4, c-Myc, p-NF-κB p65, and p-IκBα protein expression to varying degrees and up-regulated the expression of HEXIM1 (P<0.05, P<0.01). ConclusionIn the hypoxic microenvironment, XLJDP inhibits the proliferation of colorectal cancer HT-29 cells regulated by Brd4, which may be related to its inhibition of the activation of NF-κB signaling pathway.


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