2.The effects of offspring's behavior and SERT and TPH during the lactation exposure to fluoxetine
Shu CHEN ; Moxuan CHEN ; Ling JIANG ; Lei LEI ; Ya ZHOU ; Qian CHEN ; Lijuan AO
Chinese Journal of Nervous and Mental Diseases 2016;42(11):641-646
Objective To explore the influence of the lactation exposure to fluoxetine on offspring's behavior and serotonin transporter (SERT) and tryptophan hydroxylase (TPH). Methods Six SD pregnant rats were randomly divided into 2 groups (n=3 each group). Experimental maternal rats were intraperitoneally injected with fluoxetine at a dose of 12 mg/kg from postnatal day 5 to 21. The control group were injected with the same amount of normal saline. In infancy, the offspring's weight, hair length, eye opening and auditory development were measured. The free suspension test and bur?ied food pellets test were applied to evaluate the offspring's behaviors. After postnatal day 21, all the offspring were wean. At early childhood (P35d) and adulthood (P75d), 6 offspring rats from each group were executed to examine SERT and TPH in the prefrontal cortex by immunohistochemistry. Results The offspring's weight of experimental group was significantly lower than control group (P<0.05). The sensitivity of auditory in experimental group was significantly higher than control group (P<0.01). The time of free suspension in experimental group significantly was decreased comparing to control group (P<0.01). The SERT and TPH in prefrontal cortex was significantly lower in experimental group than those in control group either at childhood (P35d) or at adulthood (P75d) (P<0.05). Conclusion Lactation exposure to fluoxetine re?sults in offspring's abnormal development and behaviors through down-regulation of SERT and TPH in the prefrontal cor?tex.
3.Distribution and drug susceptibility analysis of pathogenic bacteria for fungal bloodstream infection in 19 tertiary first-class general hospitals in Sichuan
Ke-ping AO ; Jin DENG ; Ya LIU ; Ling SHU ; Mei KANG
China Tropical Medicine 2022;22(12):1188-
Abstract: Objective To understand the distribution and drug resistance of common pathogens of fungal bloodstream infection in Sichuan, and to provide reference for clinicians to empirically treat fungal bloodstream infection. Methods From November 1, 2019 to December 31, 2020, fungal strains isolated from blood culture of patients diagnosed with bloodstream infection in 19 tertiary first-class general hospitals in Sichuan Province were collected for mass spectrometry identification and drug susceptibility, and the results were statistically analyzed, along with a retrospective analysis of clinical data. Results A total of 255 fungal strains were received and identified by mass spectrometry, 215 strains of Candida spp (84.3%), 28 strains of Cryptococcus neoformans (11.0%), 4 strains of Talaromyces marneffei (1.6%) and 8 strains of others (3.1%). Among the Candida spp 90 strains of Candida albicans, 39 strains of Candida parapsilosis complex, 36 strains of Candida glabrata, 33 strains of Candida tropicalis, 8 strains of Candida guilliermondii, and 9 strains of other Candida. In the department, the ICU was predominant, accounting for 35.7%. The top four Candida (Candida albicans, Candida parapsilosis complex, Candida glabrata, Candida tropicalis) were analyzed for drug sensitivity, Candida albicans and Candida parapsilosis complex group were more sensitive to antifungal drugs, the sensitivity rates of Candida albicans to fluconazole, voriconazole, anidulafungin, caspofungin, micarafungin were 89.2%, 92.8%, 97.6%, 97.6%, 96.4%, respectively. The sensitivity rates of Candida parapsilosis to fluconazole and voriconazole were 89.7% and 94.9%, and to anidulafungin, caspofungin and micafungin were all 100%. Echinocandins had stronger antibacterial activity against Candida spp., Candida parapsilosis complex and Candida tropicalis had 100% sensitivity to echinocandins, Candida albicans had more than 95% sensitivity to echinocandins, and Candida glabrata had about 90% sensitivity to echinocandins. Candida tropicalis was less sensitive to fluconazole and voriconazole with 66.7% and 54.5%, and the sensitivity of Candida glabrata to fluconazole was mainly concentrated in susceptible dose dependent (SDD), accounting for 91.4%. The four Candida species did not show resistance to amphotericin B, all of them showed wild-type strains, Candida tropicalis showed the highest non-wild-type rate to posaconazole and itraconazole with 21.2% and 36.4%, and the drug sensitivity results of Cryptococcus neoformans showed that 4 out of 23 strains showed resistance to amphotericin B (non-wild-type) and 3 strains showed resistance to fluconazole (non-wild-type). Conclusions The fungus of bloodstream infection is mainly Candida spp.. Among of them, Candida albicans accounts for the highest percentage, echinocandins have good antibacterial effect on Candida, Candida is sensitive to amphotericin B as wild type, but Candida tropicalis has slightly higher resistance rate to fluconazole and voriconazole, and the non-wild type rate of Cryptococcus neoformans to amphotericin B is increasing, and clinicians should pay high attention to the rational use of antifungal drugs.
4.Significance of Multidrug Resistance-Associated Protein Gene and P-gp Expression in Malignant Lymphomas
Xi-Gui YANG ; Ling WEI ; Shu-Ping SONG ; Li-Ya JIA
Chinese Journal of Cancer 2001;20(4):379-382
Objective: This study was designed to investigate the relationship between expression level of multidrug resistance-associated protein (MRP) or P-glycoprotein (P-gp) genes and chemotherapy efficacy or clinical drug resistance in the patients with malignant lymphomas. Methods: Using the methods of semi quantitative reverse transcription polymerase chain reaction (RT-PCR) and flow cytometry (FCM), The authors examined the expression level of MRP and P-gp of 46 lymphoma patients. Results: The expression level and positive rate of P-gp in the recurrent patients was higher than that in untreated patients (P<0.001). There was no difference in MRP gene expression level and positive rate between recurrent and untreated patients (P>0.05). Chemotherapeutic effective rate in P-gp positive patients (26.67% ) was lower than that in P-gp negative patients (83.87% )(P<0.001). While there was no difference between MRP gene positive and negative patients, their chemotherapy effective rate had no difference. Relevant analysis showed that there was no correlation between MRP and P-gp (r-0.0808, P>0.05). Conclusion: P-gp expression correlates to multidrug resistance, and is the major mechanism of clinical drug resistance of lymphomas, whereas, MRP gene does not appears to play any role in that course.
5.Mutations in the epidermal growth factor receptor and targeted therapy of non-small-cell lung cancer.
Ren-Sheng LAI ; Ling XIE ; Long-Shu SHEN ; Ya-Min HE ; Chang-Le ZHU
Chinese Journal of Pathology 2005;34(11):745-746
Antineoplastic Agents
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therapeutic use
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Carcinoma, Non-Small-Cell Lung
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drug therapy
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genetics
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Drug Delivery Systems
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Erlotinib Hydrochloride
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Female
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Genes, erbB-1
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Humans
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Lung Neoplasms
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drug therapy
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genetics
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Male
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Mutation
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Protein Kinase Inhibitors
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therapeutic use
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Quinazolines
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therapeutic use
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Receptor, Epidermal Growth Factor
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antagonists & inhibitors
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genetics
6.Research status of small ubiquitin-like molecules modification in lung development
The Chinese Journal of Clinical Pharmacology 2024;40(4):624-628
Small ubiquitin-like molecules(SUMO)regulate the function of a variety of cells by binding to target proteins.SUMO modification plays an important role in embryonic development,including heart,brain,liver,etc.Factors involved in lung development and maturation are regulated by SUMO modification,such as hypoxia-inducible factor,CCAAT enhancer-binding protein α,forkhead box protein M1,vascular endothelial-derived growth factor,and bone morphogenetic protein 4,thus affecting their activities and stabilities.Therefore,the SUMO modification status of target protein is the key to explore the development process of fetal lung.In this paper,we reviewed the research literature of SUMO mediated lung development in recent years,and combined with the research basis of our research group for many years,reviewed the factors regulating lung development and the SUMO status,in order to provide ideas for the study of drugs for effective prevention and treatment of pulmonary dysplasia.
7.Effects of matrix metalloproteinase-9 inhibitor in Lewis rats with experimental autoimmune myocarditis
Li-Na HAN ; Tie-Ling LI ; Ya-Jing ZHANG ; Ting-Shu YANG ; Yu DING ; Xiao-Ning ZHAO ; Shu-Li GUO
Chinese Journal of Cardiology 2011;39(2):118-123
Objective To investigate the effects of matrix metalloproteinase-9 (MMP-9) inhibitor minocyclin hydrochloride in Lewis rats with experimental autoimmune myocarditis (EAM). Methods EAM was induced by injection of cardiac C protein emulsified in completed Freund adjuvant in double footpad and intra peritoneal injection of pertussis toxin on 6- to 8-week old Lewis rats. Sixty EAM Lewis rats were dividedinto 3 groups (early, middle and late intervention groups, n =20 each: 10 minocyclin treated and 10 control rats). In early intervention group, rats in treatment group received intraperitoneal injection of minocyclin hydrochloride from 1st to 21st day after immunization; in middle intervention group, rats were treated from 8th to 28th day after immunization and in late intervention group, rats were treated from 15th to 35th day after immunization (50 mg/kg body weight, once daily). Control rats received intraperitoneal injection of same volumetric physiological saline at corresponding time periods. At the end of intervention, rats were euthanatized and hearts were harvested. Paraffin sections were used for hematoxylin and eosin stain to determine the inflammatory score, for picrosirius stain to determine fibrosis score and collagen content, and for immunohistological stain to determine macrophages and T lymphocytes. Real time PCR was used to detect mRNA expression of myocardial MMP-2 and MMP-9. Cryostat sections were used for in situ zymography to detect protein activity of gelatinase. Results Inflammatory score in cardiac paraffin slides, number of cardiac macrophages and T lymphocytes, cardiac interstitial fibrosis score and content, expression of MMP-2, 9 mRNA and activity of gelatinase in treatment group were all significantly lower than in control group for early and middle intervention groups ( inflammatory score: early control group vs. treatment group: 3.03 ± 1.35 vs. 1.51 ±0. 36,P <0. 05, middle control group vs. treatment group: 3.75 ±0. 29 vs. 2. 11 ±0. 82,P <0. 01; cardiac interstitial fibrosis score, early control group vs. treatment group: 2. 75 ±0. 29 vs. 1.51 ± 0.35, P<0.01, middle control group vs. treatment group: 2.50 ±0.41 vs. 1.61 ±0.42, P<0.05;gelatinase, early control group vs. treatment group: 162 367 ±5095 vs. 62 366 ±2131, P <0. 01, middle control group vs. treatment group: 184 256 ±5427 vs. 113 197 ±4809, P <0. 01 ) while these parameters were similar between minocyclin-treated and control rats in late intervention group ( all P > 0. 05 ).Conclusions MMP-9 plays an important role in the pathogenesis of autoimmune myocarditis. Inhibition of MMP-9 in early and middle stage could significantly attenuate inflammatory responses and myocardial fibrosis in this experimental EAM model.
8.Clinical study on acupuncture for treatment of chronic functional constipation.
Xun JIN ; Yi-jiang DING ; Ling-ling WANG ; Shu-qing DING ; Lin SHU ; Ya-wen JIANG ; Wei-yu HUO
Chinese Acupuncture & Moxibustion 2010;30(2):97-101
OBJECTIVETo discuss the effect of acupuncture for treatment of chronic functional constipation (CFC).
METHODSNinety cases were treated with acupuncture. The following two groups of acupoints were used alternatively once every other day. The acupoints in the first group were Tianshu (ST 25), Qihai (CV 6), Shangjuxu (ST 37) etc., and Zhongliao (BL 33), Xialiao (BL 34), Dachangshu (BL 25) etc. in the second group, electroacupuncture was used at Zhongliao (BL 33), Xialiao (BL 34), Tianshu (ST 25) and Shangjuxu (ST 37), once a day, 10 times constituting one course. The defecation frequency, difficulty degree of defecation, defecation time, endless sensation of defecation, stool quality and awareness of defecation were observed and the Patient Assessment of Constipation Quality of Life (PAC-QOL) was evaluated by constipation patients' diaries.
RESULTSThe scores of defecation frequency, difficulty degree of defecation, defecation time, endless sensation of defecation, stool quality, awareness of defecation and PAC-QOL were obviously improved after treatment (all P < 0.01). The total effective rate was 67.7% (61/90). The effect of acupuncture for chronic functional constipation in different dynamic mechanism was different. The effect of slow transit constipation (STC) was better than that of spastic pelvic floor syndrome (SPFS) (P < 0.05), and the effect of constipation caused by irritable bowel syndrome (IBS-C) was better than that of SPFS and relaxant pelvic floor syndrome (RPFS) (both P < 0.05). Fifty-two cases were effectively followed up. Three cases were cured, 6 cases were remarkably effective, 23 cases were effective and 20 cases were ineffective after 1 month of treatment. Three cases were cured, 5 cases were remarkably effective, 16 cases were effective and 28 cases were ineffective after 3 months.
CONCLUSIONThe effect of acupuncture for CFC with exact etiology, disease location and classification diagnosis is definite, but different dynamic mechanism has different effect. The treatment programs for SPFS and RPFS need to be optimized to improve the therapeutic effect.
Acupuncture Points ; Acupuncture Therapy ; Adult ; Aged ; Constipation ; physiopathology ; therapy ; Defecation ; Female ; Humans ; Male ; Middle Aged ; Treatment Outcome ; Young Adult
9.Effect of ozonized saline on signaling passway of Keap1-Nrf2-ARE in rat hepatocytes.
Dan-dan QU ; Fu-jiang PENG ; Li LIU ; Shu-ling YANG ; Ya-bing GUO
Chinese Journal of Hepatology 2011;19(5):367-371
OBJECTIVETo study the effect of ozonized saline on the activation of the Keap1-Nrf2-ARE signaling pathway in rat liver cells.
METHODSTwenty male Sprague-Dawley rats were randomly divided into ozonized saline (OS) group, model group, ozonized saline control (OSC) group and normal control (NC) group. The rats in OS group and model group were intravenously administered with OS or oxygen saline (5 ml/kg) respectively, once a day for 15 days, and then intraperitoneally injected with CCl4 dissolved in oliver oil. The rats in OSC group were pretreated with OS for 15 days. The rats in NC group were fed normally for 15 days. On the 16th day, the rats in OSC group and NC group were intraperitoneally injected with oliver oil (2 ml/kg) without CCl4. After 24 hours of CCl4 or olive oil intraperitoneal injection, the serum levels of alanine transaminase (ALT) and aspertate aminotransferase (AST) were measured. The liver tissues were also collected for detection of total anti-oxygen capability (TAOC), glutathione (GSH), catalase (CAT), Glutathione peroxidase (GPx). Western Blot was used to detect Nrf2 and immunofluorescence staining assay to display intracelluar distribution of Nrf2.
RESULTSCompared with the rats in model group,the serum ALT and AST levels of rats in OS group were significantly lower (P < 0.01) ,which were (1240.4 ± 188.2) U/L and (1245.4 ± 176.9) U/L vs (539.8 ± 175.3) U/L and (546.0 ± 130.2) U/L, and the TAOC, CAT, GPx and GSH activity of rats in OS group were significantly higher, which were (0.72 ± 0.24) U/mg, (1.05 ± 0.21) mg/g, (676.9 ± 115.1) U/mg and (45.2 ± 14.3) U/mg vs (1.37 ± 0.19) U/mg, (2.23 ± 0.55) mg/g, (1024.6 ± 162.9) U/mg and (68.2 ± 9.9) U/mg, respectively. In contrast with NC group, pretreatment of OS in OSC group elevated TAOC, CAT, GPx and GSH activity (P < 0.01 or P < 0.05). Ozonized saline can strengthen the Nrf2 expression in liver cells.
CONCLUSIONPreconditioning injection of ozonized saline can reduce rat's liver injury induced by CCl4. The ozonized saline, as a novel Nrf2 activator, can reduce the oxidative damage of radical oxygen species (ROS) and the deleterious substance by activating the Keap1-Nrf2-ARE signaling pathway and its downstream genes expression.
Alanine Transaminase ; metabolism ; Animals ; Glutathione ; metabolism ; Glutathione Peroxidase ; metabolism ; Hepatocytes ; drug effects ; metabolism ; Intracellular Signaling Peptides and Proteins ; Kelch-Like ECH-Associated Protein 1 ; Liver ; metabolism ; Male ; Malondialdehyde ; metabolism ; NF-E2-Related Factor 2 ; metabolism ; Oxidative Stress ; Ozone ; pharmacology ; Proteins ; metabolism ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; Superoxide Dismutase ; metabolism
10.Effects of hydroquinone on expression of human 8-oxo-guanine DNA glycosylase mRNA in human A549 lung adenocarcinoma cell strains.
Ya SHU ; Yue-bin KE ; Ling WANG ; Zun-zhen ZHANG
Chinese Journal of Preventive Medicine 2009;43(5):428-433
OBJECTIVETo explore the effects of hydroquinone (HQ) on reactive oxygen species (ROS) generation, antioxydase activities and the expression of human 8-oxo-guanine DNA glycosylase (hOGG1) mRNA in human A549 lung adenocarcinoma cell strains.
METHODSA549 cells were treated with different concentrations of HQ. Cell survival was determined by methyl thiazolyl tetrazolium (MTT). Changes of ROS were detected by fluorescent probe. The contents of malonaldehyde and activities of antioxydase were determined through colorimetry. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to assess the level of hOGG1 mRNA.
RESULTSWith the increased concentration of HQ, the findings were as follows. (1) The absorbance value of A549 cell decreased. There was significant difference between 160 micromol/L (0.584+/-0.098) and 320 micromol/L (0.328+/-0.066) of HQ (q=5.56 and 9.07, P<0.05) with the control group (0.989+/-0.150), and the cell survival rate were less than 80%. (2) The ROS in A549 cell increased. 40 micromol/L (39.80+/-4.15) and 80 micromol/L (101.99+/-9.45) had statistical significance (q=10.74 and 30.32, P<0.05) with the control group (5.71+/-0.50). (3) It was found that the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) decreased and malonaldehyde (MDA) increased. Compared with the control group [(25.62+/-0.28) U/mg prot and (38.97+/-2.61) U/mg prot], the activities of SOD and GSH-Px had a significant decrease (q=12.17 and 8.78, P<0.05) in 80 micromol/L [(22.93+/-0.56) U/mg prot and (25.60+/-2.31) U/mg prot]. And MDA had a significant increase (q=10.90 and 15.49, P<0.05) in 40 micromol/L [(1.07+/-0.01) nmol/mg prot] and 80 micromol/L [(1.19+/-0.08) nmol/mg prot] as compared with the control group [(0.77+/-0.04) nmol/mg prot]. The decrease of SOD (r=-0.95, F=20.00, P=0.04) and GSH-Px activities (r=-0.99, F=115.48, P=0.01) and the increase of MDA contents (r=0.96, F=21.31, P=0.04) all had a dose-response relationship. (4) RT-PCR results showed that the expression of hOGG1 mRNA decreased. The significant difference was observed between the expression of hOGG1 mRNA in 80 micromol/L (0.478+/-0.017) (q=11.70, P<0.05) with the control group (0.715+/-0.038).
CONCLUSIONThis study suggests that HQ could induce oxidative damage and changes of the expression of hOGG1 mRNA in A549 cells.
Cell Line, Tumor ; DNA Glycosylases ; genetics ; Down-Regulation ; Gene Expression ; Gene Expression Regulation, Enzymologic ; drug effects ; Humans ; Hydroquinones ; toxicity ; RNA, Messenger ; genetics