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OBJECTIVE To provide reference for the clinically safe application of acalabrutinib by mining and analyzing the risk signals of adverse drug events （ADE）. METHODS The acalabrutinib-induced ADE reports were extracted from the U.S. FDA adverse event reporting system using the OpenVigil 2.1 platform from November 1， 2017 to March 31， 2023. The reporting odds ratio （ROR） method and composite criteria method from the Medicines and Healthcare Products Regulatory Agency （MHRA） were used for detection of ADE signals. RESULTS There were 7 869 ADE reports of acalabrutinib as the primary suspect drug and 142 ADE positive signals were detected from them， involving 20 system organ classes， which was generally consistent with the ADE recorded in the drug instruction of acalabrutinib， mainly involving general disorders and administration site conditions， various inspection， blood and lymphatic system disorders， various neurological disorders and cardiac disorders. In addition， this study identified several new potential ADE signals that were not mentioned in the drug instruction， including sudden cardiac death， pulmonary toxicity， tumor lysis syndrome， pleural effusion， dyspepsia， gastroesophageal reflux disease， bone pain， decreased blood pressure， and abnormal blood sodium， etc. CONCLUSIONS When using acalabrutinib， in addition to paying attention to the ADE recorded in its instructions， the risk of serious ADE that may lead to death， such as sudden cardiac death and pulmonary toxicity， should also be evaluated to avoid or reduce the occurrence of ADE as much as possible.
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Objective To explore the relationship between single nucleotide polymorphism (SNP) locus rs1058587,rs1059519 and rs1059369 polymorphisms of growth differentiation factor-15 (GDF-15)gene and susceptibility to chronic Keshan disease in Gansu Province.Methods Using the case-control study method,56 individuals with chronic Keshan disease were taken as case group,and 53 individuals without chronic Keshan disease from the same villages were selected as control group in Gansu Keshan disease areas,venous blood samples were collected,and ethylenediamine tetraacetic acid disodium salt (EDTA) was used for anticoagulation,and the samples were sent for gene sequencing.Univariate and multivariate logistic regression analyses were conducted to analyze the influence of genotypes of rs1058587,rs1059519 and rs1059369 on the prevalence of chronic Keshan disease,and the risk factors for disease were expressed as odds ratio (OR).Results The age of the 56 patients in the case group was (60.93 + 21.99) years old,15 males and 41 females;the age of the 53 residents in control group was (47.49-+ 33.61) years old,26 males and 27 females.There was no significant difference in age between the two groups (t =46.16,P ＞ 0.05);the difference in gender was statistically significant (x2=5.76,P ＜ 0.05).The differences of allele frequencies of case group and control group rs1058587 (C:36.6％,32.1％,G:63.4％,67.9％),rs1059369 (A:61.6％,72.6％,T:38.4％,27.4％) between the two groups were not significantly different (x2 =0.50,3.00,P ＞ 0.05);the differences of allele frequencies of GDF-15 rs1059319 (C:25.0％,40.6％,G:75.0％,59.4％) between the two groups were significantly different (x2 =6.01,P ＜ 0.05).The genotype frequency distribution of GDF-15 gene rs1058587,rs1059519 and rs1059369 in the case group and the control group was not significantly different between the groups (P ＞ 0.05).However,in the case group,the mutant GG frequency of rs1059519 locus was higher than wild type CC (x2 =5.33,P ＜ 0.05).In multivariate logistic regression analysis,women were 3.81 times more likely to suffer from chronic Keshan disease than men,and people aged 45 or older were 5.30 times more likely to suffer from chronic Keshan disease than those younger than 45.The heterozygous and mutant types of GDF-15 gene rs1058587 and rs1059369 were compared with wild type,and the difference was not statistically significant (ORrs1058587 =0.46,0.50,ORrs1059369 =1.30,2.59,P ＞ 0.05);there was no significant difference between the heterozygous type of GDF-15 gene rs1059519 and wild type (OR =3.34,P ＞ 0.05),and the difference between the mutant and wild type was statistically significant (OR =8.58,P ＜ 0.05).Conclusions In this study,we find women of the study population are more likely to have chronic Keshan disease than men,and aged≥45 is a risk factor for chronic Keshan disease.Genetic polymorphisms of GDF-15 gene rs1058587,rs1059369 are not associated with susceptibility to chronic Keshan disease,and a certain correlation between genetic polymorphism of rs1059519 locus and susceptibility to chronic Keshan disease.
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Objective:To optimize the formulation of HA-CA liposomes and to study the anti-tumor effect of HA-CA liposomes on uterine cervical carcinoma mice.Methods:The methods of preparing HA-CA liposomes were screened,and the optimal fomulation was selected by the orthogonal design experiment with the the phospholipids/cholesterol ratio,the drug/lipids ratio and the pH value of PBS buffer was 7.4 as entrapment enfficiency was the index.The release of HA-CA liposomes was studyed by dialysis bag method.Uterine cervical carcinoma cells were inoculated subcutaneously into right axillary ofBal b/c mice,after continuous treatment of 14 d,we weighed the tumor and calculated the rate of tumor growth inhibition.Results:HA-CA liposomes were prepared by thin film hydration methods.The optimal parameters were as follows:the phospholipids/cholesterol ratio was 4∶1,the drug/lipids ratio was 1∶ 30,the pH value of PBS buffer was 7.4.The release curve of HA-CA liposome and CA liposome was basically the same,both of which a sustained-release efficacy.The cumulative release of HA-CA liposomes and CA liposomes were 78.39％ and 83.01％ at 48h.The inhibition rate of HA-CA liposomes on U14 cervical cancer mice was 60.39％ and significantly higher than that of positive control group,which was higher than that of CA and CA liposomes.Conclusions:HA-CA liposomes can significantly inhibit the effect of U14 cervical cancer nude mice higher than that of CA and CA liposomes owe to the modification of the active target ligand HA.
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Objective In this paper,major issues for all those who have been selected in China national treatment program for patients with chronic Keshan disease (CNTP-CKD) were uncovered through evaluation of the annually reported data from participating provinces,in order to improve the performance quality of the program.Methods The datasets 2005-2012 were merged after cleaning them,and the composition of the treated patients was statistically analyzed,including gender and age distribution,diagnosis evidence for chronic Keshan disease (ECG,cardiothoracic ratio by X-ray,heart function grade of NYHA),and proportion of cases who had received treatment more than once.Results ①A total of 2 649 patients participated in the treatment,of them 1 115 patients were males accounting for 42.1％ (1 115/2 649),1 534 patients were females accounting for 57.9％ (1 534/2 649).Age of the patients were mainly distributed in 41 to 70 years old,and 24 CKD patients under 10 years accounting for 0.9％ (24/2 649).②2 313 cases of the involved patients were diagnosed with sufficient evidence,accounting for 81.9％ (2 313/2 823) and 121 cases with full misdiagnosis,accounting for 18.1％ (121/2 823).③There were 881 patients been treated for more than once,accounting for 38.3％ (881/2 301) of the number of treatment.Conclusions ① Diagnosis for CKD remains a key problem,suggesting that medical record for each patient diagnosed by province-level doctors' needs to be built up as early as possible.The rate of patient treatment for more than once is low which is not beneficial to the patients.② Treatment period for CKD patients is highly recommended to expand to at least one year,and the disease should be enrolled in the free cost list of the new rural cooperative medical system (NCMS).