1.Analysis of adverse events signaling of lurasidone by Open Vigil FDA2.1
Yu-Qing CHEN ; Zhan-Zhang WANG ; Xiu-Qing ZHU ; Ye YANG ; Li-Jing DAI ; Hao-Yang LU ; E-Mei SONG ; Yu-Guan WEN
The Chinese Journal of Clinical Pharmacology 2024;40(17):2567-2571
Objective To investigate the occurrence of adverse events of lurasidone in the U.S.Food and Drug Administration Adverse Event Reporting System(FAERS)database by using Open Vigil FDA2.1,to enrich the experience and provide the basis for the clinical use of the drug in China.Methods Using Open Vigil FDA2.1,adverse event data were extracted from the FAERS database for a total of 51 quarters from the 4th quarter of 2010 to the 3rd quarter of 2023,and the ratio of reporting ratio(ROR)method and the proportional reporting ratio(PRR)method were used for data mining and analysis.Results A total of 32 728 adverse event reports with lurasidone as the first suspected drug was obtained,with a larger proportion of females(54.26%)and occurring mostly in adults(18 to 59 years).After the screening,326 preferred term(PT)signals were obtained,involving 20 system-organ classifications(injury,poisoning and procedural complications,general disorders and administration site conditions,psychiatric disorders,etc.).Among them,PTs with the higher frequency of occurrence included off label use,feeling abnormal,crying,anxiety,depression,insomnia,etc.PTs with stronger signal strength included activation syndrome,mania,tongue movement disturbance,hypoprolactinaemia,akathisia,etc.Multiple new suspected adverse drug reactions were unearthed,including hypoprolactinaemia,emotional poverty,stiff tongue,etc.Conclusion Lurasidone has a favorable safety profile,and women need to closely monitor prolactin levels when taking this medication.The drug is relatively safe for use in pregnant,puerperal and perinatal women and patients with poor metabolic function.Hypoprolactinaemia and restless leg syndrome are new rare suspected adverse events with lurasidone.
2.Detection and characterization of the types of CYP21A1P/CYP21A2 and TNXA/TNXB fused genes by long-read sequencing among children with Steroid 21-hydroxylase deficiency.
Qingxian FU ; Zhen LI ; Shiyi XU ; Lingling DU ; Huishu E ; Limei GUAN
Chinese Journal of Medical Genetics 2024;41(12):1416-1425
OBJECTIVE:
To assess the diagnostic efficiency of long-read sequencing (LRS) for the determination of CYP21A1P/CYP21A2 and TNXA/TNXB fusion genotypes among children with 21-hydroxylase deficiency (21-OHD) and explore their clinical characteristics.
METHODS:
LRS sequencing was carried out on 30 children diagnosed with 21-OHD at the Department of Endocrinology, Fujian Children's Hospital between November 2022 and September 2023 by clinical symptoms or conventional Sanger sequencing combined with multiple ligation-dependent probe amplification (MLPA). The results of the two methods were compared. Clinical data of the children were collected and analyzed. This study has been approved by the Medical Ethics Committee of the Fujian Children's Hospital (Ethic No. 2022ETKLR10024).
RESULTS:
Of the 30 children with 21-OHD, 11 (36.7%) were found to carry CYP21A1P/CYP21A2 and TNXA/TNXB fusion genes by LRS. The most common type of fused CYP21A1P/CYP21A2 gene was CH-1 (72.7%), and 1 (3.3%) was found to harbor TNXA/TNXB CH-1. Eleven cases (36.7%) were found to carry large deletions by Sanger sequencing combined with MLPA, with the most common one being CYP21A2 exons 1-3 del (72.7%), which was followed by CYP21A2 exons 1-7 del (18.2%). Follow up of 11 patients carrying a fusion gene revealed that 6 were sale wasting (SW) types, 5 were simple virilizing (SV) types, whilst no non-classical (NC) type was found. Four girls had presented with central precocious puberty (CPP). One child carrying TNXA/TNXB CH-1 had presented with CAH-X syndrome.
CONCLUSION
Compared with Sanger sequencing combined with MLPA detection method, LRS sequencing was able to differentiate the subtypes of CYP21A1P/CYP21A2 and TNXA/TNXB fusion genes, pinpoint the breakpoints of the deletions, and directly determine the cis-trans position without the need to analyze the genotype of the pedigree members, which has provided a reliable method for the typing of 21-OHD. As some fusion genes may retain 21-hydroxylase activity, female carriers may have a higher incidence of CPP.
Humans
;
Steroid 21-Hydroxylase/genetics*
;
Adrenal Hyperplasia, Congenital/genetics*
;
Child
;
Female
;
Male
;
Child, Preschool
;
Tenascin/genetics*
;
Infant
;
Genotype
;
Sequence Analysis, DNA/methods*
;
Pseudogenes
3.Detection and characterization of the types of CYP21A1P/CYP21A2 and TNXA/TNXB fused genes by long-read sequencing among children with Steroid 21-hydroxylase deficiency
Qingxian FU ; Zhen LI ; Shiyi XU ; Lingling DU ; Huishu E ; Limei GUAN ; Hui LIU
Chinese Journal of Medical Genetics 2024;41(12):1416-1425
Objective:To assess the diagnostic efficiency of long-read sequencing (LRS) for the determination of CYP21A1P/ CYP21A2 and TNXA/ TNXB fusion genotypes among children with 21-hydroxylase deficiency (21-OHD) and explore their clinical characteristics. Methods:LRS sequencing was carried out on 30 children diagnosed with 21-OHD at the Department of Endocrinology, Fujian Children′s Hospital between November 2022 and September 2023 by clinical symptoms or conventional Sanger sequencing combined with multiple ligation-dependent probe amplification (MLPA). The results of the two methods were compared. Clinical data of the children were collected and analyzed. This study has been approved by the Medical Ethic Committee of the Fujian Children Hospital(Ethic No. 2022ETKLR10024).Results:Of the 30 children with 21-OHD, 11 (36.7%) were found to carry CYP21A1P/ CYP21A2 and TNXA/ TNXB fusion genes by LRS. The most common type of fused CYP21A1P/ CYP21A2 gene was CH-1 (61.5%), and 1 (3.3%) was found to harbor TNXA/ TNXB CH-1. 11 cases (36.7%) were found to carry large deletions by Sanger sequencing combined with MLPA, with the most common one being CYP21A2 exons 1-3 del (61.5%), which was followed by CYP21A2 exons 1-7 del (23.1%). Follow up of 11 patients carrying a fusion gene revealed that 6 were sale wasting (SW) types, 5 were simple virilizing (SV) types, whilst no non-classical (NC) type was found. Four girls had presented with central precocious puberty (CPP). One child carrying TNXA/ TNXB CH-1 had presented with CAH-X syndrome. Conclusion:Compared with Sanger sequencing combined with MLPA detection method, LRS sequencing was able to differentiate the subtypes of CYP21A1P/ CYP21A2 and TNXA/ TNXB fusion genes, pinpoint the breakpoints of the deletions, and directly determine the cis-trans position without the need to analyze the genotype of the pedigree members, which has provided a reliable method for the typing of 21-OHD. As some fusion genes may retain 21-hydroxylase activity, female carriers may have a higher incidence of CPP.
4.Detection and characterization of the types of CYP21A1P/CYP21A2 and TNXA/TNXB fused genes by long-read sequencing among children with Steroid 21-hydroxylase deficiency
Qingxian FU ; Zhen LI ; Shiyi XU ; Lingling DU ; Huishu E ; Limei GUAN ; Hui LIU
Chinese Journal of Medical Genetics 2024;41(12):1416-1425
Objective:To assess the diagnostic efficiency of long-read sequencing (LRS) for the determination of CYP21A1P/ CYP21A2 and TNXA/ TNXB fusion genotypes among children with 21-hydroxylase deficiency (21-OHD) and explore their clinical characteristics. Methods:LRS sequencing was carried out on 30 children diagnosed with 21-OHD at the Department of Endocrinology, Fujian Children′s Hospital between November 2022 and September 2023 by clinical symptoms or conventional Sanger sequencing combined with multiple ligation-dependent probe amplification (MLPA). The results of the two methods were compared. Clinical data of the children were collected and analyzed. This study has been approved by the Medical Ethic Committee of the Fujian Children Hospital(Ethic No. 2022ETKLR10024).Results:Of the 30 children with 21-OHD, 11 (36.7%) were found to carry CYP21A1P/ CYP21A2 and TNXA/ TNXB fusion genes by LRS. The most common type of fused CYP21A1P/ CYP21A2 gene was CH-1 (61.5%), and 1 (3.3%) was found to harbor TNXA/ TNXB CH-1. 11 cases (36.7%) were found to carry large deletions by Sanger sequencing combined with MLPA, with the most common one being CYP21A2 exons 1-3 del (61.5%), which was followed by CYP21A2 exons 1-7 del (23.1%). Follow up of 11 patients carrying a fusion gene revealed that 6 were sale wasting (SW) types, 5 were simple virilizing (SV) types, whilst no non-classical (NC) type was found. Four girls had presented with central precocious puberty (CPP). One child carrying TNXA/ TNXB CH-1 had presented with CAH-X syndrome. Conclusion:Compared with Sanger sequencing combined with MLPA detection method, LRS sequencing was able to differentiate the subtypes of CYP21A1P/ CYP21A2 and TNXA/ TNXB fusion genes, pinpoint the breakpoints of the deletions, and directly determine the cis-trans position without the need to analyze the genotype of the pedigree members, which has provided a reliable method for the typing of 21-OHD. As some fusion genes may retain 21-hydroxylase activity, female carriers may have a higher incidence of CPP.
5.Analysis of Clinical Features and Risk Factors for Oral Ulcers and Bloodstream Infection in Patients with Hematopoietic Stem Cell Transplantation.
Ke WU ; Li-Na GUAN ; Jie-Yong ZHANG ; Ran ZHANG ; Zhi-Lei BIAN ; Chong WANG ; Ding-Ming WAN ; Wei-Jie CAO
Journal of Experimental Hematology 2023;31(3):866-870
OBJECTIVE:
To investigate the risk factors of oral ulcers and bloodstream infection in patients with hematopoietic stem cell transplantation.
METHODS:
The clinical data of 401 hematopoietic stem cell transplant patients in the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2021 were retrospective analyzed, and the risk factors of oral ulcers and bloodstream infection statistical and analyzed.
RESULTS:
Among the 401 patients, the incidence of oral ulcers was 61.3% (246/401), and the incidence of bloodstream infection was 9.0% (36/401). A total of 40 strains of pathogenic bacteria were isolated from 36 patients, including 26 strains of Gram negative strains (65%), 13 strains of Gram positive strains (32.5%), and 1 strain of fungi (2.5%). Single-factor analysis showed that oral hygiene was associated with the occurrence of bloodstream infection, and the Multi-factor analysis showed that age ≥14 years old, disease diagnosis of leukemia, and allogeneic hematopoietic stem cell transplantation were risk factors for oral ulcers.
CONCLUSION
The incidence of oral ulcers in patients with hematopoietic stem cell transplantation is high. The age ≥14 years, disease diagnosis of leukemia, and allogeneic hematopoietic stem cell transplantation were risk factors for oral ulcers in patients, and oral hygiene was associated with the occurrence of bloodstream infection.
Humans
;
Adolescent
;
Retrospective Studies
;
Oral Ulcer/etiology*
;
Bacteremia/microbiology*
;
Hematopoietic Stem Cell Transplantation/adverse effects*
;
Sepsis
;
Risk Factors
;
Leukemia
6.Clinical Characteristics and Risk Factors of Invasive Fungal Infections in Acute Leukemia Patients in Tropical Regions.
Wen-Shuai ZHENG ; Li-Xun GUAN ; Shen-Yu WANG ; Ya-Lei HU ; Bo PENG ; Jian BO ; Quan-Shun WANG ; Xiao-Ning GAO
Journal of Experimental Hematology 2022;30(1):99-106
OBJECTIVE:
To analyze the clinical characteristics and risk factors of invasive fungal infection (IFI) occurenced in patients with acute leukemia (AL) during treatment in tropical regions.
METHODS:
The clinical data of 68 AL patients admitted to the Hainan Hospital of PLA General Hospital from April 2012 to April 2019 was retrospectively analyzed. Logistic regression analysis was used to analyze the factors affecting the occurrence of IFI in AL patients.
RESULTS:
Among the 68 patients, 44 were acute myeloid leukemia, 24 were acute lymphoblastic leukemia, 39 were male, 29 were female and the median age was 41(13-75) years old. The 68 patients received 242 times of chemotherapy or hematopoietic stem cell transplantation(HSCT), including 73 times of initial chemotherapy or inducting chemotherapy after recurrence, 14 times of HSCT, 155 times of consolidating chemotherapy. Patients received 152 times of anti-fungal prophylaxis, including 77 times of primary anti-fungal prophylaxis and 75 times of secondary anti-fungal prophylaxis. Finally, the incidence of IFI was 31 times, including 24 times of probable diagnosis, 7 times of proven diagnosis, and the total incidence of IFI was 12.8%(31/242), the incidence of IFI in inducting chemotherapy was 24.66%(18/73), the incidence of IFI in HSCT patients was 28.57% (4/14), the incidence of IFI in consolidating chemotherapy was 5.80% (9/155). Multivariate analysis showed that inducting chemotherapy or HSCT, the time of agranulocytosis ≥7 days, risk stratification of high risk were the independent risk factors for IFI in AL patients during treatment in tropical regions.
CONCLUSION
The incidence of IFI in patients with AL in the tropics regions is significantly higher than that in other regions at homeland and abroad. Anti-fungal prophylaxis should be given to the patients with AL who have the high risk factors of inducting chemotherapy or HSCT, time of agranulocytosis ≥7 days and risk stratification of high risk.
Adult
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Aged
;
Antifungal Agents/therapeutic use*
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Female
;
Hematopoietic Stem Cell Transplantation
;
Humans
;
Invasive Fungal Infections/epidemiology*
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Leukemia, Myeloid, Acute/drug therapy*
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Male
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Middle Aged
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Retrospective Studies
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Risk Factors
7.Study on Thalassemia in Han Population in Sanya of Hainan Province.
Yuan-Yuan XU ; Meng LI ; Lin-Xun GUAN ; Song-He XIANG ; Long-Can CHENG ; Yu-Hui YANG ; Xiao-Ning GAO ; Hong-Mei NING
Journal of Experimental Hematology 2022;30(1):232-236
OBJECTIVE:
To study the distribution characteristics of thalassemia genotype in Han Population in Sanya of Hainan Province.
METHODS:
Gap PCR and reverse dot hybridization were used to detect and analyze the thalassemia gene in 572 suspected thalassemia carriers of Han Population in Sanya.
RESULTS:
Among the 572 Han Population in Sanya, 271 cases of thalassemia gene abnormality were detected, among which 161 cases were founded to be carriers of α-thalassemia gene. A total of 9 genotypes were detected, in the following order of the detection rate was --SEA/αα,-α3.7/αα,-α4.2/αα,--SEA/-α3.7,--SEA/-α4.2,-α4.2/-α4.2,-α3.7/-α4.2,-α3.7/-α3.7,--SEA/--SEA. Among them, the deletion type (--SEA/αα) in southeast Asia was the most common, accounting for 66 cases. 99 cases of β-thalassemia were detected, there were 7 genotypes, all of which were heterozygous. The order of the detection rate was CD41-42/βN, IVS-II-654/βN, CD17/βN, CD71-72/βN, -28/βN, -29/βN, CD27-28/βN. Among them, CD41-42/βN was the most common, accounting for 51 cases. In addition, 11 cases of combined α and β thalassemia were detected. Five kinds of genotypes were checked out, the order of detection rate was -α3.7/αα composite CD41-42/βN, --SEA/αα composite IVS-II-654/βN, -α4.2/-α4.2 composite CD41-42/βN, -α4.2/αα composite -29/βN , --SEA/ -α4.2 composite CD41-42/βN.
CONCLUSION
Han Population in Sanya of Hainan Province is a high-risk population of thalassemia, the genotype characteristics are different from other areas with high incidence of thalassemia in China. The main type of α-thalassemia is the deficiency mutation of southeast Asia, while CD41-42 heterozygous mutation is the main type of β-thalassemia.
China/epidemiology*
;
Genotype
;
Heterozygote
;
Humans
;
Mutation
;
alpha-Thalassemia/genetics*
;
beta-Thalassemia
8.Clinical Study of miRNAs Derived from Serum Exosomes in Multiple Myeloma.
Lin ZHOU ; Xiao-Li LIU ; Yu-Wu LI ; Liang WU ; Guang-Zhou WANG ; Zheng-Fang WANG ; Li MA ; Jun GUAN ; Chong-Xu HAN
Journal of Experimental Hematology 2022;30(5):1490-1495
OBJECTIVE:
To investigate the expression level and prognostic value of miR-21, miR-18a, miR-146a, and Let-7b derived from serum exosomes in patients with multiple myeloma (MM).
METHODS:
Serum exosomes were extracted from 57 MM patients and 20 healthy persons using ExoQuick exosome precipitation solution kit, and the relative expression level of miR-21, miR-18a, miR-146a, and Let-7b derived from serum exosomes was measured by RT-qPCR. Correlations of the expression levels of all miRNAs mentioned above with routine laboratory parameters were analyzed by Spearman correlation analysis. The relationship between the expression level of miR-21, miR-18a, miR-146a, and Let-7b derived from serum exosomes and overall survival of patients with MM was analyzed using the Kaplan-Meier survival curve.
RESULTS:
The expression levels of miR-21, miR-18a, and Let-7b derived from serum exosomes in patients with MM were significantly lower than those in the normal control group (P<0.001), while the expression level of miR-146a between the two groups was not significantly different (P>0.05). The expression level of miR-21 was strongly negatively correlated with serum β2-microglobulin concentration (r=-0.830), and weakly negatively correlated with serum creatinine, corrected serum calcium, and cystatin C (r=-0.488, -0.282, -0.627). The expression levels of Let-7b and miR-18a were also weakly negatively correlated with the corrected serum calcium, β2-microglobulin, and cystatin C concentration (r=-0.305, -0.362, -0.461; -0.317, -0.542, -0.434). However, there was no significant correlation between the expression level of miR-146a and routine laboratory parameters in MM patients. The overall survival rate of MM patients with low expression level of miR-21, miR-18a, and Let-7b significantly decreased compared with high expression level group (P<0.05), however, the expression level of miR-146a was not related to the overall survival rate.
CONCLUSION
Aberrant low expression levels of miR-21, miR-18a, and Let-7b derived from serum exosomes exist in patients with MM, which are associated with a worse overall survival rate.
Calcium/metabolism*
;
Creatinine/metabolism*
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Cystatin C/metabolism*
;
Exosomes/metabolism*
;
Humans
;
MicroRNAs/metabolism*
;
Multiple Myeloma/metabolism*
9.Research Progress in Anti-alcoholic Effect of Puerariae Lobatae Radix
Yong-mei GUAN ; Pan XU ; Qian SHEN ; E JIANG ; Li-hua CHEN ; Wei-feng ZHU ; Wen-ting WU ; Zhen-zhong ZANG
Chinese Journal of Experimental Traditional Medical Formulae 2021;27(2):210-217
With advanced brewing technology and contemporary table culture, alcohol drinking, which can be traced back to Dukang wine in the Xia dynasty, is very common in China. However, excessive alcohol intake can easily cause alcohol liver damage, ranging from abdominal pain and venous thrombosis to severe hypoglycemia and fat embolism, coma shock and even life-threatening cases. Puerariae Lobatae Radix has a cool property and sweet taste, with functions of antipyretic, promoting the secretion of saliva or body fluid, rash and hangover alleviation, and so on. It was first recorded in
10.Single Center Analysis of Bloodstream Infection Clinical Characteristics and Prognosis in Patients with Hematological Malignancies in the Tropics.
Long-Can CHENG ; Ting YANG ; Hui-Hui KUANG ; Shuai YU ; Li-Xun GUAN ; Zhen-Yang GU ; Yuan-Yuan XU ; Wen-Shuai ZHENG ; Lu WANG ; Ya-Lei HU ; Xiao-Ning GAO ; Quan-Shun WANG
Journal of Experimental Hematology 2021;29(1):265-271
OBJECTIVE:
To analyze the characteristics, prognosis and risk factors of bloodstream infection in patients with hematological malignancies in the tropics, so as to provide evidence for the prevention and treatment of bloodstream infection.
METHODS:
The clinical features, blood culture results and prognosis of patients with bloodstream infection in patients with hematological malignancies admitted to Hainan Hospital of PLA General Hospital were retrospectively studied.
RESULTS:
The most common primary infection site of the 81 patients with hematological malignancies was lung (46.91%), followed by PICC (11.11%). The detection rate of Gram-positive bacteria and Gram-negative bacteria in the blood culture was 60.98% and 30.02%, respectively. Coagulase-negative staphylococci was the most common Gram-positive bacteria resulting in bloodstream infection in our study. Of the Gram-negatives, Klebsiella pneumoniae (34.38%) was predominant, followed by Escherichia coli (18.75%) and Pseudomonas aeruginosa (18.75%). Gram-positive bacteria was highly sensitive (100%) to vancomycin, linezolid and tigecycline. Study showed that Gram-negative bacteria had low sensitive to quinolones, in particular, the resistance rate of Escherichia coli to quinolones was as high as 83.33%. In terms of overall survival (OS), the 30-days OS of patients with Gram-negative and Gram-positive septicemia was 77.42% and 92.00%, respectively. There was no statistically significant difference between the two groups. Multivariate analysis revealed that septic shock (P=0.001, RR=269.27) was an independent risk factor for 30-day mortality, and remission status (P=0.027, RR=0.114) was an independent predictor of a favourable outcome of bloodstream infection in patients with hematological malignancies.
CONCLUSION
Gram-positive bacteria are the main pathogens causing bloodstream infections in patients with hematological malignancies in the tropics. Improving the care of PICC is an important measure to reduce the incidence of bloodstream infection in patients with hematological malignancies in the tropics. A correct treatment relieving disease and effective prevention and treatment of septic shock can reduce mortality of patients with bloodstream infection in patients with hematological malignancies in the tropics.
Anti-Bacterial Agents/therapeutic use*
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Bacteremia/drug therapy*
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Drug Resistance, Bacterial
;
Gram-Negative Bacteria
;
Hematologic Neoplasms/drug therapy*
;
Humans
;
Microbial Sensitivity Tests
;
Prognosis
;
Retrospective Studies
;
Sepsis

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