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Objective To mine the adverse drug events(ADE)signal of avatrombopag,an effective drug for thrombocytopenia treatment,based on real world data in order to provide reference for its clinical safety application.Methods The OpenVigil2.1 pharmacovigilance platform was used to obtain the ADE report data of avatrombopag from May 2018 to March 2023 in the database of FDA adverse event reporting system(FAERS).The ADE signals were classified and described by the system organ class(SOC)and preferred term(PT)of the ADE terminology set in the Medical Dictionary for Regulatory Activities(MedDRA),and reporting odds ratio(ROR)and UK Medicines and Healthcare Products Regulatory Agency(MHRA)comprehensive standard were used to detect the positive ADE signals.Results A total of 1 879 ADE reports related to avatrombopag were obtained,24 SOCs were involved,and 28 positive ADE signals were detected at PT level.Among these signals,the strongest ones were renal vein thrombosis,portal vein thrombosis and graft versus host disease,while the reports accounting for the largest numbers were headache,fatigue and asthenia.There were 8 ADE signals discovered newly,that is,seasonal allergy,back disorder,musculoskeletal discomfort,flatulence,hypersomnia,rash macular,emotional disorder,and rhinorrhoea.Conclusion For clinical use of avatrombopag,clinicians should not only concern the risk of thrombosis,but also pay close attention to ADE signals such as seasonal allergy,back disorder,musculoskeletal discomfort,flatulence,hypersomnia,rash macular,emotional disorder,and rhinorrhoea that are not documented in the instructions.
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OBJECTIVE@#To explore the cause for the failure of non-invasive prenatal testing (NIPT) and feasibility of repeated testing.@*METHODS@#Clinical data, test results and pregnancy outcomes of 40 311 pregnant women who received NIPT test from January 2011 to December 2018 were reviewed.@*RESULTS@#Among all the pregnant women, 1116 cases failed in the first test, 9 cases (0.81%) had fetal free DNA concentration lower than 4%, 663 cases (59.41%) were retested after the establishment of Z value gray area, and the remainder 444 cases (39.78%) needed to be retested after the blood collection due to the fetal free DNA concentration lower than 4%. After retesting, 1069 cases (95.78%) obtained effective NIPT results. The results showed that 53 cases were at high risk (6 cases for trisomy 21, 6 cases for trisomy 18, 13 cases for trisomy 13, 16 cases for sex chromosomal abnormality, 12 cases for chromosomal copy number variation). Forty-eight cases were selected for invasive prenatal diagnosis, and 2 cases of 47, XXY and 2 CNV were confirmed. A total of 47 cases (0.12%) did not obtain results because the concentration of fetal free DNA was lower than 4%. Only 16 cases (34%) chose invasive prenatal diagnosis.@*CONCLUSION@#Repeated detection of the gray area of Z value can reduce the false positive rate of NIPT and invasive prenatal diagnosis, and the feasibility of repeated detection is high. In the case of fetal free DNA concentration lower than 4%, the success rate of obtaining effective NIPT results by re-sampling and re-detection increases with the increase of gestational age, but may delay the diagnosis for fetal aneuploidies. Therefore, personalized estimation should be made according to gestational age and clinical indications. It is suggested that pregnant women should choose invasive prenatal diagnosis when they have failed in the retest.
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OBJECTIVE:To investigate the current situation of unreasonable prescriptions in outpatient and emergency depart-ments of our hospital,and to provide reference for rational drug use in the clinic. METHODS:The evaluation of outpatient and emergency prescriptions in our hospital during 2013-2015 were summarized and analyzed. Irrational prescriptions were divided into 3 categories,involving 19 items. The main,secondary and general factors of irrational prescriptions were analyzed by Pareto chart. RESULTS:Among 19 types of irrational prescriptions,main factors included unsuitable drug selection,inappropriate usage and dosage,inappropriate drug combination,prescribing not in accordance with the antibiotics management regulations,incomplete di-agnosis. No indications of medication,drug dosage beyond the regulations ofthree urgent seven slowwere treated as the second-ary factors. Other 12 items were general factors. CONCLUSIONS:According to the main and secondary irrational drug use types, clinical pharmacists should carry out effective intervention and pharmaceutical care to improve the level of rational drug use and en-sure the safety of clinical drug use.
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Aim To explore the effect of connexin 43 ( Cx 4 3 ) on acquired gefitinib-resistance in human non small cell lung cancer ( NSCLC ) . Methods HCC827 GR, a gefitinib-resistant ( GR) NSCLC cell lines from their parental cells was established by gradually in-creasing the concentration of gefitinib. Gefitinib effica-cy in HCC827 and HCC827 GR cells was detected by MTT assay. Expression of Cx43 mRNA in HCC827 and HCC827 GR cells was determined by RT-PCR. The protein expressions of Cx43 and phospho-Akt ( p-Akt) in these cells were detected by Western blot. The func-tional gap junction intercellular communication ( GJIC ) was measured by parachute assay. The cellular locali-zation of Cx43 protein was evaluated by immunofluores-cence staining. Results MTT assay showed less ge-fitinib cytotoxicity in HCC827 GR cells than that in their parental cells with IC50 of (10. 84 ± 0. 021) μmol ·L-1 versus (0. 07 ± 0. 019) μmol·L-1 , respective-ly. Moreover, both mRNA and protein expressions of Cx43 in HCC827 GR cells were significantly lower than those in HCC827 cells ( P<0. 05 ) . However, the p-Akt protein in HCC827 GR cells was obviously higher than that in HCC827 cells ( P<0. 05 ) . Furthermore, treatment with LY294002 caused a significant reduced p-Akt expression, but a significant increased Cx43 ex-pression in HCC827 GR cells. Moreover, no detecta-ble GJIC was found in HCC827 and their GR cells with or without RA ( a well-defined GJIC enhancer ) treat-ment. Immunofluorescence staining clearly showed that Cx43 protein accumulated in the cytoplasm of HCC827 and their GR cells. Conclusion The down-regulation of Cx43 expression in cytoplasm of HCC827 GR cells may contribute to the acquired gefitinib resistance in NSCLC cells by GJIC-independent activation of PI3 K/Akt signaling pathway.
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Objective To investigate the effect of prostaglandin E1 (PGE1)on alveolar cells apoptosis in rat lung impact in-jury model.Methods SD rats were divided into 3 groups (normal control group,lung injury control group and PGE1 treated group).PaO2 and pulmonary coefficient were detected after 24 h of impact.TUNEL labeling was used to evaluate apoptosis and Western blot was used to estimate protein expression levels of beclin-1,LC3 Ⅱ/LC3 Ⅰand NIX.Results After 24 h of impacting, there were obvious structural damage and pneumonedema in rat lung.Compared to normal control group,the PaO2 of lung injury control group decreased and the apoptosis of alveolar cells increased significantly(P <0.05).Furthermore,the expression levels of Beclin-1,LC3Ⅱ/LC3Ⅰ and NIX in the impacting control group were increased (P <0.05 ).In the PGE1 treated group,the PaO2 were decreased compared to normal control group(P <0.05),but these expression levels were higher significantly than lung injury control group (P <0.05).The expression levels of apoptosis,Beclin-1,LC3Ⅱ/LC3Ⅰ and NIX in the PGE1 treated group were in-creased compared to normal control group(P <0.05),but these expression levels were lower significantly than lung injury control group (P <0.05).Conclusion PGE1 could alleviate alveolar cells apoptosis after lung impacting injury,and which effect may as-cribe to PGE1 inhibiting NIX-mediated autophagy and autophagic apoptosis of alveolar cells.
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<p><b>OBJECTIVE</b>To investigate the antitumor efficacy and mechanism of HSP90 inhibitor FW-04-806 against Bcr/Abl(+) leukemia K562 and HL60 cells and their mechanisms of action.</p><p><b>METHODS</b>MTT assay was used to assess the proliferation-inhibiting effect of FW-04-806. Cell cycle was analyzed with propidium iodide by flow cytometry. Cell apoptosis was determined using the FITC mV apoptosis detection kit. Western blot was applied to reveal the protein expression of related proliferative and apoptotic signaling pathways. The changes of mitochondrial membrane potential were detected by flow cytometry. Protein-protein interactions was shown by co-immunoprecipitation. The level of mRNA was assessed by real-time RT-PCR.</p><p><b>RESULTS</b>FW-04-806 obviously inhibited cell proliferation in the HL60, K562 and HL60/Bcr-Abl cell lines, with an IC50 of (30.89 ± 0.12) µmol/L, (9.76 ± 0.19) µmol/L and (8.03 ± 0.26) µmol/L, respectively (P<0.001). Compared with the vehicle group, the two increasing doses of FW-04-806 showed inhibition of tumor growth at a rate of (17.40 ± 0.34)% and (34.33 ± 5.00)%, respectively, in the K562 cell line groups (P=0.003), and (18.90 ± 1.45)% and (35.60 ± 3.55)% (P=0.001) in the HL60/Bcr-Abl cell line groups. FW-04-806 dissociated Hsp90/Cdc37 chaperon/co-chaperon complex, followed by degradation of the Hsp90 proteins through proteasome pathway without affecting mRNA expression. FW-04-806 induced apoptosis and led to G2/M arrest.</p><p><b>CONCLUSION</b>Our findings indicate that FW-04-806 displays potential antitumor effect by suppressing the proliferation and apoptosis in Bcr/Abl(+) leukemia cells in vivo.</p>
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Humanos , Apoptose , Ciclo Celular , Proliferação de Células , Proteínas de Fusão bcr-abl , Células HL-60 , Proteínas de Choque Térmico HSP90 , Células K562 , Leucemia , Tratamento Farmacológico , Metabolismo , Patologia , Potencial da Membrana Mitocondrial , Oxazóis , Farmacologia , RNA Mensageiro , Metabolismo , Transdução de SinaisRESUMO
Aim To investigate the efficacy and mech-anism of FW-04-806 against HER2-positive gastric cancer cell lines,and the combination effect of FW-04-806 with lapatinib. Methods MTT assay was used to assess cell proliferous inhibition of FW-04-806 . The in-hibitory effect of colony formation was tested by colony formation. The protein expression, apoptotic induction and cell cycle arrest were detected by flow cytometry. Co-immunoprecipitation was used to investigate protein-protein interactions. The expression change of proteins was showed by immunohistochemistry. Western blot was applied to reveal the protein expression of related pro-liferous and apoptotic signaling pathway. The tumor growth inhibition was evaluated in tumor xenograft model. Results FW-04-806 obviously inhibited cell proliferation and colony formation in HER2 positive gastric cancer cell lines NCI-N87, OE19, with IC50 of (24. 17 ± 0. 02 ) , ( 29. 61 ± 0. 03 ) μmol · L-1 , re-spectively;FW-04-806 induced G2-M arrest and apop-tosis in a dose-dependent manner;200 mg · kg-1 of FW-04-806 showed tumor growth inhibition of 48. 0%( P < 0. 01 ) . In addition, FW-04-806 dissociated Hsp90/CDC37 complex, followed by degradation of HER2 and Akt,inhibiting the phosporylation of HER2, Akt and ERK, and increasing expression of apoptotic proteins,such as cleaved caspase-3 and cleaved parp. Furthermore,the combination of FW-04-806 with lapa-tinib in vitro was synergistic in NCI-N87 , which en-hanced the inhibition of cell proliferation and increased apoptotic rates. Conclusions FW-04-806 shows po-tent efficacy against HER2-positive gastric cancer cell lines in vitro and in vivo;FW-04-806 is synergistic with lapatinib.
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Objective To analysis 2 years follow-up clinical effects in endodontic lesion combined periodontal in treatment with Vitapex .Methods 112 patients with periodontal endodontic lesion combined periodontal were randomly divided into control group (56 cases ,75 teeth) and study group(56 cases ,77 teeth) .Treatment of Zinc oxide glycerin paste combined with gutta percha filling root canal was used in control group ,while Vitapex combined with gutta percha filling root canal was used in study group .After 2 years ,the clinical data of the two groups were analysed .Results The total effective rate of anterior and posterior in study group were significant higher than in control group(P<0 .05) .The total effective rate of of I type ,II type and III type lesions in study group were higher than in control group(P<0 .05) .Conclusion Treatment of Vitapex combined with gutta percha filling root canal in endodontic lesion combined periodontal has better clinical effectiveness to promote periapical and periodontal tissue healing than control group .
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Objective To establish the best technological condition of Guanzhoukang Oral Liquid. Method Based on the evaluation marker of extraction amount and gentiopicroside content in prescription, the factors influencing the effect of water decoction and alcohol reflux procedure were selected by orthogonal design. Results The best technological condition of Guanzhoukang Oral Liquid should be as follows:radix gentianae, radix isatidis and radix scutellariae contained in prescription were extracted by alcohol in which the concentration was 65%, 8 times of total amount of material herb, extracted 3 times, 1 h for each time. The left material herbs were extracted by water decoction in which amount was 12 times of total amount of material herb, soaked for half hour and decocted 3 times, 1 h for each time. Conclusion The result provides experimental basis for the preparation technology of Guanzhoukan Oral Liquid.
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Objective To establish a method for determination of rutin in Xueguankang Tea. Methods RP-HPLC method and C18 column were used for determination. Methanol-water-acetic acid (40∶60∶1) was the mobile phase with a flow rate of 1.0 mL/min. The detection wavelength was set at 257 nm. Results There was a good linear relationship of rutin within the range of 0.06~0.3 ?g with r=0.999 2. The average recovery of rutin was 98.48 % with RSD=0.87% (n=5). Conclusion This method is convenient,sensitive,accurate and reproducible,and can be used for the quality control of Xueguankang Tea.