1.SiO2 Induces Iron Overload and Ferroptosis in Cardiomyocytes in a Silicosis Mouse Model
Wang YONGHENG ; Li NING ; Guan YI ; LI TONG ; Zhang YUXIU ; Cao HONG ; Yu ZHIHUA ; Li ZHIHENG ; Li SHUOYAN ; Hu JIAHAO ; Zhou WENXIN ; Qin SISI ; Li SHUANG ; Yao SANQIAO
Biomedical and Environmental Sciences 2024;37(6):617-627
Objective The aim of this study was to explore the role and mechanism of ferroptosis in SiO2-induced cardiac injury using a mouse model. Methods Male C57BL/6 mice were intratracheally instilled with SiO2 to create a silicosis model.Ferrostatin-1(Fer-1)and deferoxamine(DFO)were used to suppress ferroptosis.Serum biomarkers,oxidative stress markers,histopathology,iron content,and the expression of ferroptosis-related proteins were assessed. Results SiO2 altered serum cardiac injury biomarkers,oxidative stress,iron accumulation,and ferroptosis markers in myocardial tissue.Fer-1 and DFO reduced lipid peroxidation and iron overload,and alleviated SiO2-induced mitochondrial damage and myocardial injury.SiO2 inhibited Nuclear factor erythroid 2-related factor 2(Nrf2)and its downstream antioxidant genes,while Fer-1 more potently reactivated Nrf2 compared to DFO. Conclusion Iron overload-induced ferroptosis contributes to SiO2-induced cardiac injury.Targeting ferroptosis by reducing iron accumulation or inhibiting lipid peroxidation protects against SiO2 cardiotoxicity,potentially via modulation of the Nrf2 pathway.
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
;
Child
;
Humans
;
Female
;
Glycated Hemoglobin
;
Cohort Studies
;
Diabetes Mellitus/diagnosis*
;
Sensitivity and Specificity
;
ROC Curve
3.Comparison of the effects and safety of dydrogesterone and medroxyprogesterone acetate on endometrial hyperplasia without atypia: a randomized controlled non-inferior phase Ⅲ clinical study.
Yao Chen LOU ; Shuang ZHOU ; Jiong Bo LIAO ; Wen Yu SHAO ; Ying Ying HU ; Cheng Cheng NING ; Qian WANG ; Yierfulati GULINAZI ; Bing Yi YANG ; Ya Li CHENG ; Peng Fei WU ; Qin ZHU ; Xian Rong ZHOU ; Wei Wei SHAN ; Xiao Jun CHEN
Chinese Journal of Obstetrics and Gynecology 2023;58(7):526-535
Objective: To compare the effects and safety of dydrogesterone (DG) and medroxyprogesterone acetate (MPA) on the treatment in patients with endometrial hyperplasia without atypia (EH). Methods: This was a single-center, open-label, prospective non-inferior randomized controlled phase Ⅲ trial. From February 2019 to November 2021, patients with EH admitted to the Obstetrics and Gynecology Hospital of Fudan University were recruited. Enrolled patients were stratified according to the pathological types of simple hyperplasia (SH) or complex hyperplasia (CH), and were randomised to receive MPA or DG. Untill May 14, 2022, the median follow-up time after complete response (CR) was 9.3 months (1.1-17.2 months). The primary endpoint was the 6-month CR rate (6m-CR rate). The secondary endpoints included the 3-month CR rate (3m-CR rate), adverse events rate, recurrence rate, and pregnancy rate in one year after CR. Results: (1) A total of 292 patients with EH were enrolled in the study with the median age of 39 years (31-45 years). A total of 135 SH patients were randomly assigned to MPA group (n=67) and DG group (n=68), and 157 CH patients were randomly assigned to MPA group (n=79) and DG group (n=78). (2) Among 292 patients, 205 patients enrolled into the primary endpoint analysis, including 92 SH patients and 113 CH patients, with 100 patients in MPA group and 105 in DG group, respectively. The 6m-CR rate of MPA group and DG group were 90.0% (90/100) and 88.6% (93/105) respectively, and there were no statistical significance (χ2=0.11, P=0.741), with the rate difference (RD) was -1.4% (95%CI:-9.9%-7.0%). Stratified by the pathology types, the 6m-CR rate of SH patients was 93.5% (86/92), and MPA group and DG group were respectively 91.1% (41/45) and 95.7% (45/47); and the 6m-CR rate of CH patients was 85.8% (97/113), and MPA group and DG group were 89.1% (49/55) and 82.8% (48/58) respectively. The 6m-CR rates of the two treatments had no statistical significance either (all P>0.05). A total of 194 EH patients enrolled into the secondary endpoint analysis, including 88 SH patients and 106 CH patients, and 96 patients in MPA group and 98 in DG group, respectively. The 3m-CR rate of SH patients were 87.5% (77/88), while the 3m-CR rates of MPA group and DG group were 90.7% (39/43) and 84.4% (38/45), respectively; the 3m-CR rate of CH patients was 66.0% (70/106), and MPA group and DG group had the same 3m-CR rate of 66.0% (35/53). No statistical significance was found between the two treatments both in SH and CH patients (all P>0.05). (3) The incidence of adverse events between MPA group and DG group had no statistical significance (P>0.05). (4) A total of 93 SH patients achieved CR, and the cumulative recurrence rate in one year after CR were 5.9% and 0 in MPA group and DG group, respectively. While 112 CH patients achieved CR, and the cumulative recurrence rate in one year after CR were 8.8% and 6.5% in MPA group and DG group, respectively. There were no statistical significance between two treatment groups (all P>0.05). Among the 93 SH patients, 10 patients had family planning but no pregnancy happened during the follow-up period. Among the 112 CH patients, 21 were actively preparing for pregnancy, and the pregnancy rate and live-birth rate in one year after CR in MPA group were 7/9 and 2/7, while in DG group were respectively 4/12 and 2/4, and there were no statistical significance in pregnancy rate and live-birth rate between the two treatment groups (all P>0.05). Conclusions: Compared with MPA, DG is of good efficacy and safety in treating EH. DG is a favorable alternative treatment for EH patients.
Female
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Humans
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Adult
;
Medroxyprogesterone Acetate/adverse effects*
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Endometrial Hyperplasia/pathology*
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Dydrogesterone/adverse effects*
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Hyperplasia
;
Prospective Studies
4.A novel perspective of health risk assessment of heavy metals in Chinese herbal medicine—Probabilistic risk assessment, taking Plantago asiatica L. as an example
Tian-tian ZUO ; Jia-lin LIU ; Yi-ling LI ; Hong-yu JIN ; Yi-qin FEI ; Jing NIE ; Sheng WEI ; Shuang-cheng MA
Acta Pharmaceutica Sinica 2022;57(11):3365-3370
In order to establish the probabilistic risk assessment method for heavy metals and harmful elements in line with the characteristics of traditional Chinese medicine (TCM) and provide guidance for the safe use of TCM, the contents of lead (Pb), cadmium (Cd), arsenic (as), mercury (Hg) and copper (Cu) in 21 batches of
5.Clinical follow-up analysis of multidisciplinary treatment of children with spinal muscular atrophy.
Yu XIA ; Yi Jie FENG ; Mei YAO ; Jia Ning JIN ; Jia WEI ; Yi Qin CUI ; Ling Shuang WANG ; Ting Ting CHEN ; Xiao Yang CHEN ; Hai Bing LI ; Jing Fang XU ; Qi LONG ; Yuan JIANG ; Jin Ling LIU ; Jin Gan LOU ; Feng GAO ; Shan Shan MAO
Chinese Journal of Pediatrics 2022;60(11):1134-1139
Objective: To analyze the follow-up and clinical effect of multidisciplinary treatment on the children with spinal muscular atrophy (SMA). Methods: The clinical data including nutritional status, respiratory function, bone health and motor function of 45 children with SMA who received multidisciplinary management 1-year follow-up in the Children's Hospital, Zhejiang University School of Medicine from July 2019 to October 2021 were retrospectively collected. Comparisons before and after management were performed using paired-samples t-test or Wilcoxon rank-sum test, etc. Results: The age of 45 patients (25 boys and 20 girls) was 50.4 (33.6, 84.0) months at the enrollment, with 6 cases of type 1, 22 cases of type 2, and 17 cases of type 3 respectively. After the multidisciplinary management, the cases of SMA patients with malnutrition decreased from 22 to 12 (P=0.030), the level of vitamin D were significantly increased ((45±17) vs. (48±14) nmol/L, t=-4.13, P<0.001). There was no significant difference in the forced vital capacity %pred, the forced expiratory volume at 1 second %pred, and the peak expiratory flow %pred ((76±19)% and (76±21)%, (81±18)% and (79±18)%, (81±21)% and (78±17)%; t=-0.24, 1.36, 1.21; all P>0.05). The Cobbs angle of scoliosis also improved significantly (8.0°(0°, 13.0°) vs. 10.0°(0°, 18.5°), Z=-3.01, P=0.003). The Hammersmith functional motor scale expanded scores of children with SMA type 2 and type 3 both showed significant elevation (11.0 (8.0, 18.0) vs. 11.0 (5.0, 18.5) scores, 44.0 (36.5, 53.0) vs. 44.0 (34.0, 51.5) scores, Z=2.44, 3.11, P=0.015, 0.002). Conclusion: Multidisciplinary management is beneficial for delaying the progression of the multi-system impairments of SMA patients, such as malnutrition, restrictive ventilation dysfunction and scoliosis.
Child
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Male
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Female
;
Humans
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Child, Preschool
;
Scoliosis
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Retrospective Studies
;
Follow-Up Studies
;
Muscular Atrophy, Spinal
;
Malnutrition
6. Anthrahydroquinone-2,6-disulfonate alleviates paraquat-induced kidney injury via the apelin-APJ pathway in rats
Qi LI ; Tang DENG ; Qi-Feng HUANG ; Shuang-Qin XU ; Hang-Fei WANG ; Xin-Xin WU ; Nan LI ; Yang YI ; Ji-Chao PENG ; Yue HUANG ; Jin QIAN ; Xiao-Ran LIU ; Bo WANG ; Kai-Wen LIN
Asian Pacific Journal of Tropical Biomedicine 2022;12(8):333-342
Objective: To explore the protective effects of anthrahydroquinone-2,6-disulfonate (AH 2 QDS) on the kidneys of paraquat (PQ) poisoned rats via the apelin-APJ pathway. Methods: Male Sprague Dawley rats were divided into four experimental groups: control, PQ, PQ+sivelestat, and PQ+AH 2 QDS. The PQ+sivelestat group served as the positive control group. The model of poisoning was established via intragastric treatment with a 20% PQ pesticide solution at 200 mg/kg. Two hours after poisoning, the PQ+sivelestat group was treated with sivelestat, while the PQ+AH 2 QDS group was given AH 2 QDS. Six rats were selected from each group on the first, third, and seventh days after poisoning and dissected after anesthesia. The PQ content of the kidneys was measured using the sodium disulfite method. Hematoxylin-eosin staining of renal tissues was performed to detect pathological changes. Apelin expression in the renal tissues was detected using immunofluorescence. Western blotting was used to detect the expression levels of the following proteins in the kidney tissues: IL-6, TNF-α, apelin-APJ (the apelin-Angiotensin receptor), NF-κB p65, caspase-1, caspase-8, glucose-regulated protein 78 (GRP78), and the C/EBP homologous protein (CHOP). In in vitro study, a PQ toxicity model was established using human tubular epithelial cells treated with standard PQ. Twenty-four hours after poisoning, sivelestat and AH 2 QDS were administered. The levels of oxidative stress in human renal tubular epithelial cells were assessed using a reactive oxygen species fluorescence probe. Results: The PQ content in the kidney tissues of the PQ group was higher than that of the PQ+AH 2 QDS group. Hematoxylin-eosin staining showed extensive hemorrhage and congestion in the renal parenchyma of the PQ group. Vacuolar degeneration of the renal tubule epithelial cells, deposition of crescent-like red staining material in renal follicles, infiltration by a few inflammatory cells, and a small number of cast formation were also observed. However, these pathological changes were less severe in the PQ+sivelestat group and the PQ+AH 2 QDS group (P<0.05). On the third day after poisoning, immunofluorescence assay showed that the level of apelin in the renal tissues was significantly higher in the PQ+AH 2 QDS group than in the PQ group. Western blotting analysis results showed that IL-6, TNF-α, NF-κB p65, caspase-1, caspase-8, GRP78, and CHOP protein levels in the PQ group were higher than in the PQ+AH 2 QDS group (P<0.05). The expression of apelin-APJ proteins in the PQ+AH 2 QDS group was higher than in the PQ+sivelestat and PQ groups (P<0.05); this difference was significant on Day 3 and Day 7. The level of oxidative stress in the renal tubular epithelial cells of the PQ+AH 2 QDS group and the PQ+sivelestat group was significantly lower than in the PQ group (P<0.05). Conclusions: This study confirms that AH 2 QDS has a protective effect on PQ-poisoned kidneys and its positive effect is superior to that of sivelestat. The mechanism of the protective effects of AH 2 QDS may be linked to reduction in cellular oxidative stress, PQ content of renal tissue, inflammatory injury, endoplasmic reticulum stress, and apoptosis. AH 2 QDS may play a role in the treatment of PQ poisoning by upregulating the expression of the apelin-APJ.
7.A multicenter retrospective study on survival rate and complications of very preterm infants.
Xin-Ping WU ; Chuan-Li GU ; Shu-Ping HAN ; Xiao-Yi DENG ; Xiao-Qing CHEN ; Huai-Yan WANG ; Shuang-Shuang LI ; Jun WANG ; Qin ZHOU ; Wei-Wei HOU ; Yan GAO ; Liang-Rong HAN ; Hong-Jie LIU ; Zhang-Bin YU ; Zeng-Qin WANG ; Na LI ; Hai-Xin LI ; Jin-Jun ZHOU ; Shan-Shan CHEN ; Shan-Yu JIANG ; Xing-Xing LU ; Zhao-Jun PAN ; Xiao-Hui CHEN
Chinese Journal of Contemporary Pediatrics 2021;23(8):814-820
OBJECTIVES:
To study the survival rate and the incidence of complications of very preterm infants and the factors influencing the survival rate and the incidence of complications.
METHODS:
The medical data of the very preterm infants with a gestational age of <32 weeks and who were admitted to the Department of Neonatology in 11 hospitals of Jiangsu Province in China from January 2018 to December 2019 were retrospectively reviewed. Their survival rate and the incidence of serious complications were analyzed. A multivariate logistic regression analysis was used to evaluate the risk factors for death and serious complications in very preterm infants.
RESULTS:
A total of 2 339 very preterm infants were enrolled, among whom 2 010 (85.93%) survived and 1 507 (64.43%) survived without serious complications. The groups with a gestational age of 22-25
CONCLUSIONS
The survival rate is closely associated with gestational age in very preterm infants. A low 1-minute Apgar score (≤3) may increase the risk of death in very preterm infants, while high gestational age, high birth weight, and prenatal use of glucocorticoids are associated with the reduced risk of death. A low 5-minute Apgar score (≤3) and maternal chorioamnionitis may increase the risk of serious complications in these infants, while high gestational age and high birth weight may reduce the risk of serious complications.
Female
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Gestational Age
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Humans
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Infant, Newborn
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Infant, Premature
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Infant, Premature, Diseases
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Infant, Very Low Birth Weight
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Pregnancy
;
Retrospective Studies
;
Survival Rate
8.Humulus lupulus L. Extract Prevents Ovariectomy-Induced Osteoporosis in Mice and Regulates Activities of Osteoblasts and Osteoclasts.
Tian-Shuang XIA ; Liu-Yue LIN ; Qiao-Yan ZHANG ; Yi-Ping JIANG ; Chang-Hui LI ; Xiao-Yan LIU ; Lu-Ping QIN ; Hai-Liang XIN
Chinese journal of integrative medicine 2021;27(1):31-38
OBJECTIVE:
To systematically evaluate the protective effects of Humulus lupulus L. extract (HLE) on osteoporosis mice.
METHODS:
In vivo experiment, a total of 35 12-week-old female ICR mice were equally divided into 5 groups: the sham control group (sham); the ovariectomy with vehicle group (OVX); the OVX with estradiol valerate [EV, 0.2 mg/(kg•d)] the OVX with low- or high-dose HLE groups [HLE, 1 g/(kg•d) and 3 g/(kg•d)], 7 in each group. Treatment began 1 week after the ovariectomized surgery and lasted for 12 weeks. Bone mass and trabecular bone mircoarchitecture were evaluated by micro computed tomography, and bone turnover markers in serum were evaluated using enzyme-linked immunosorbent assay (ELISA) kits. In vitro experiment, osteoblasts and osteoclasts were treated with HLE at doses of 0, 4, 20 and 100 µg/mL. Biomarkers for bone formation in osteoblasts and bone resorption in osteoclasts were analyzed.
RESULTS:
Compared with the OVX group, HLE exerted bone protective effects by the increase of estradiol (P<0.05), the improvement of cancellous bone structure, bone mineral density (P<0.01) and the reduction of serum alkaline phosphatase (ALP), tartrate resistant acid phosphatase (TRAP), bone gla-protein, c-terminal telopeptides of type I collagen (CTX-I) and deoxypyridinoline levels (P<0.01 for all). In vitro experiment, compared with the control group, HLE at 20 µg/mL promoted the cell proliferation (P<0.01), and increased the expression of bone morphogenetic protein-2 and osteopontin levels in osteoblasts (both P<0.05). HLE at 100 µg/mL increased the osteoblastic ALP activities, and HLE at all dose enhanced the extracellular matrix mineralization (both P<0.01). Furthermore, compared with the control group, HLE at 20 µg/mL and 100 µg/mL inhibited osteoclastic TRAP activity (P<0.01), and reduced the expression of matrix metalloproteinase-9 and cathepsin K (both P<0.05).
CONCLUSION
HLE may protect against bone loss, and have potentials in the treatment of osteoporosis.
9.Automatic Framework Acquisition and Visualization Analysis of Ancient Chinese Medicine Literature Relating to Tumor
Yan-lan KANG ; Rui-heng XIAO ; Shi ZHANG ; Yi JIANG ; Li-ping SHEN ; Ju-hua YIN ; Xiao-li XIN ; Peng ZHANG ; Ruo-yan QIN ; Ling-shuang LIU
Chinese Journal of Experimental Traditional Medical Formulae 2021;27(10):152-160
Objective:To obtain ancient traditional Chinese medicine(TCM)literatures relating to tumor and visual analysis by an automatic framework tool, in order to systematically sort out the development of ancient Chinese medicine oncology. Method:Based on the database platform of ancient TCM books,names of tumor-related diseases in ancient TCM books were retrieved by Selenium WebDriver, an automation framework tool under Python 3.8. Lxml's etree library was used to parse the data. Statistics was made for "classification", "authors", "completion time" and "summary" of relevant ancient books automatically. After the data was checked and processed, Tableau 2019.2 software was used for data visualization analysis. And ancient Chinese medicine literatures relating to tumor were consulted at the database manually,with the dynasties as the clue,and the symptoms,etiology,pathogenesis and prognosis as the emphasis,this paper explores the development process of TCM oncology. Result:A total of 774 349 bytes of text data of 1 128 entries in 242 ancient books were included automatically. According to the findings, there were simple classification and time distribution of tumor diseases in ancient TCM books in the pre-Qin period, with a simple view on the pathogenesis of tumor diseases. From the Han dynasty to the Tang dynasty, the number of relevant literature records and the types and disease names had gradually increased,which further enriched the cognition of tumor nature,signs,classification methods,differential diagnosis;in Song and Ming dynasties,the proportion of Chinese prescription books and surgery books had increased gradually,with the largest number of abdominal organ tumor names among all dynasties;from Qing dynasty to the Republic of China,literatures relating to tumor name and classification were the most improved,and then the TCM tumor syndrome differentiation and treatment system had been formed. Conclusion:It was found that TCM oncology originated in the pre-Qin dynasty,and was improved in the Han and Tang dynasties, mature in the Song and Ming dynasties and completed in the Qing dynasty and the Republic of China. The data visualization method with integrated automation framework and parsing tools is helpful to analyze the subdivision characteristics of ancient TCM literatures,which is convenient,efficient and innovative,in the expectation to provide a classic reference for contemporary TCM studies.
10.Changes of microRNA-153 expression and its regulatory role in arsenic-induced hepatocytes apoptosis
Yi YANG ; Li LIU ; Rujia XIE ; Lei TANG ; Lu ZHENG ; Shuang CAI ; Yusi CHEN ; Cai LIANG ; Yixin GUO ; Qin YANG ; Bing HAN
Chinese Journal of Endemiology 2020;39(10):703-709
Objective:To investigate the changes of microRNA-153 (miR-153) expression and the mechanism of regulating histone H3 lysine 4 (H3K4) methyltransferase (SET7/9) and histone H3K4 methylation (H3K4me1) in the process of arsenic-induced endoplasmic reticulum stress-related hepatocytes apoptosis.Methods:Human normal hepatocytes (L-02 cells) were cultured in vitro and divided into control, arsenic treatment, arsenic + negative transfection, arsenic + miR-153 up-regulation and arsenic+ miR-153 down-regulation groups according to different treatment methods. Arsenic+ negative transfection, arsenic+ miR-153 up-regulation and arsenic+ miR-153 down-regulation groups were transfected with transfection plasmid and transfection reagent according to a certain proportion (3 μg: 8 μl). After 24 h, arsenic treatment, arsenic+ negative transfection, arsenic+ miR-153 up-regulation and arsenic+ miR-153 down-regulation groups were all treated with 100 μmol/L sodium arsenite (NaAsO 2) as the final concentration for 24 h. The control group was treated with phosphate buffer solution (PBS) of the same volume as NaAsO 2 for 24 h. The expression of miR-153 was detected by real-time quantitative polymerase chain reaction (RT-qPCR); cell apoptosis and cell cycle were detected by flow cytometry; real-time cell dynamic analyzer (RTCA) was used to detect cell proliferation; Western blotting was used to detect the expression of endoplasmic reticulum marker proteins glucose regulatory protein 78 (GRP78), SET7/9 and H3K4me1. Results:The expression levels of miR-153 in each group were significantly different ( F = 10.73, P < 0.05). Compared with the control group [(41.10 ± 6.08)%], the expression level of miR-153 in arsenic treatment group [(4.35 ± 0.20)%] was significantly decreased ( P < 0.05); compared with the arsenic+ negative transfection group [(10.00 ± 2.40)%], the expression level of miR-153 in arsenic+ miR-153 up-regulation group [(157.70 ± 42.70)%] was significantly increased ( P < 0.05), and that in arsenic+ miR-153 down-regulation group [(4.20 ± 0.28)%] was significantly decreased ( P < 0.05). There were significant differences in the total cell apoptosis rate and G1 phase cell proportion among the five groups ( F = 29.69, 104.32, P < 0.05). Compared with the control group, the total cell apoptosis rates and G1 phase cell proportions in arsenic treatment, arsenic+ miR-153 up-regulation and arsenic+ miR-153 down-regulation groups were significantly increased ( P < 0.05); compared with the arsenic+ negative transfection group, the total cell apoptosis rate and G1 phase cell proportion in arsenic+ miR-153 up-regulation group were significantly decreased ( P < 0.05), and those in arsenic+ miR-153 down-regulation group were significantly increased ( P < 0.05). The difference of cell proliferation rate in each group was statistically significant ( F = 799.35, P < 0.05). Compared with the control group, the cell proliferation rates in arsenic treatment, arsenic+ miR-153 up-regulation and arsenic+ miR-153 down-regulation groups were significantly decreased ( P < 0.05); compared with the arsenic+ negative transfection group, the cell proliferation rate in arsenic+ miR-153 up-regulation group was significantly increased ( P < 0.05), and that in arsenic+ miR-153 down-regulation group was significantly decreased ( P < 0.05). The protein expression levels of SET7/9, GRP78 and H3K4me1 in each group were significantly different ( F = 78.52, 52.13, 54.32, P < 0.05). Compared with the control group, the protein expression levels of SET7/9, GRP78 and H3K4me1 in arsenic treatment group were significantly increased ( P < 0.05); compared with the arsenic+ negative transfection group, the protein expression levels of SET7/9, GRP78 and H3K4me1 in arsenic+ miR-153 up-regulation group were significantly decreased ( P < 0.05), and those in arsenic + miR-153 down-regulation group were significantly increased ( P < 0.05). Conclusion:miR-153 plays an important role in arsenic-induced endoplasmic reticulum stress-related hepatocytes apoptosis, the expression and regulation are related to the changes of SET7/9 and H3K4me1 levels.

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