Research progress of microRNA-mediated immune function of CD4+T cells subsets in immune thrombocytopenia / 中国免疫学杂志

MicroRNA(miRNA)is a kind of small non-coding single stranded RNA that can participate in multiple biological processes.It also plays an important role in regulating the immune function of the body.Immune thrombocytopenia(ITP)is an autoim-mune disease,whose cause and deterioration are closely related to miRNA regulates immune function of CD4+T cells subsets.In ITP patients,different expression of miRNA can affect the immune function of CD4+T cells subsets,which causes not only unbalanced ex-pression of Th1/Th2,Th17/Treg and excessive differentiation of TFH,but also abnormal cytokine secretion furthermore.This paper summarizes the unbalanced mechanism of miRNA regulating immune function of CD4+T cells subsets in ITP,so as to provide inspira-tion for exploring the immunology and immunotherapy of ITP.

UHPLC-Q-TOF/MS Analysis of the Active Components of Total Flavonoids Extracts from Sarcandra glabra in Promoting Megakaryocyte Differentiation / 中药新药与临床药理

Objective To screen the active components of total flavonoid extracts of Sarcandra glabra to promote megakaryocyte differentiation.Methods(1)A model of megakaryocyte differentiation disorder was established by co-culturing human megakaryocytic leukaemia cells(Dami)with human bone marrow stromal cells(HS-5)as an evaluation system,and the experimental groupings were as follows:the Dami group(Dami),the control group(Dami+HS-5),and the PMA group[Dami+HS-5+5 ng·mL-1 foprolol 12-tetradecanoate 13-acetate(PMA)],and model group[Dami+HS-5+1%rabbit anti-rat platelet serum(APS)+5 ng·mL-1 PMA]were cultured for 48 hours.The expressions of megakaryocyte differentiation and maturation surface marker molecules,CD41a and CD61 were detected by flow cytometry.(2)Forty-nine SD male rats were randomly divided into blank plasma group,15-minute group,30-minute group,60-minute group,90-minute group,120-minute group,and 240-minute group,with 7 rats in each group.The rats in each administration group were gavaged with 1.26 g·kg-1 of total flavonoids extracts of Sarcandra glabra,and blood was collected at six set time points(15,30,60,90,120,240 minutes)for the preparation of time-dependent serum-containing plasma of total flavonoids extracts of Sarcandra glabra.(3)Ultra-high performance liquid chromatography-quadrupole tandem time-of-flight mass spectrometry(UHPLC-Q-TOF/MS)was used to analyze the plasma of the time-dependent serum-containing plasma of the total flavonoids extracts of Sarcandra glabra,and the peak area was used to construct a matrix(X-matrix)of the amount of chemical composition change over time in the time-dependent serum-containing plasma of the total flavonoids extracts of Sarcandra glabra.The collected time-dependent serum-containing plasma of the total flavonoids extracts of Sarcandra glabra at six different time points was used to intervene in the model of megakaryocyte differentiation and maturation disorder,and the expression of cell surface molecules CD41a and CD61 was detected by flow cytometry to construct the matrix of effect of time-dependent serum-containing plasma of the total flavonoids extracts of Sarcandra glabra(Y-matrix).(4)After the data of X and Y matrices were standardized,partial least squares(PLS)was used to calculate and analyze the quantitative and qualitative effect relationship,and variable importance for projection(VIP)>1 was used as the threshold to screen the effect components related to the changes of cell surface molecules CD41a and CD61,and chemical composition identification,as the potential effector components in the total flavonoid extracts of Sarcandra glabra were used to promote the differentiation of megakaryocytes,and finally the regression evaluation system was used to verify the efficacy of its medicinal effect.Results(1)Compared with the Dami group,the expression level of CD41a on the surface of Dami cells in the control group was significantly increased(P＜0.05).Compared with the control group,the expression levels of CD41a and CD61 on the surface of Dami cells in the PMA group were significantly increased(P＜0.01).Compared with the PMA group,the expression levels of CD41a and CD61 on the surface of Dami cells in the model group were significantly reduced(P＜0.01).(2)Compared with the blank plasma group,the expression levels of the molecules CD41a and CD61 on the surface of Dami cells at each time point of 15,30,60,90,120,and 240 minutes were significantly increased(P＜0.01),and the expression levels of CD41a and CD61 were both highest in the 30-minute group.The potential effective components with VIP value greater than 1 were screened out in the positive and negative ion mode,and 540.3638@12.25 and 559.2991@11.53 were selected for pharmacodynamic verification.559.2991@11.53 was identified as daucosterol(Dau),540.3638@12.25 was identified as rosmarinic acid 4-O-β-D-glucoside(Ros).After Ros and Dau intervened in the megakaryocyte differentiation and maturation disorder model respectively,the expression levels of CD41a and CD61 on the surface of Dami cells in the low-,medium-and high-dose groups(40,60 and 80 μg·mL-1)of Ros and Dau were significantly increased compared with the model group(P＜0.05,P＜0.01).Conclusion Ros and Dau may be the active components of the total flavonoids extracts of Sarcandra glabra to promote the differentiation of megakaryocytes.

Investigation on the risk of recurrent immune thrombocytopenia in children and establishment of a predictive model / 基础医学与临床

Objective To investigate the recurrence of immune thrombocytopenia(ITP)in children and to establish a predictive model.Methods A total of 288 children with ITP admitted to Children's Hospital of Wujiang District and Children's Hospital Affiliated to Suzhou University from January 2018 to April 2022 were collected.The factors potentially related to the recurrence of ITP in children were screened.The children in the model group were divided into 2 groups according to the presence or absence of recurrence and the indicators of the 2 groups were compared.After screening the potential influencing factors by LASSO regression and the independent influencing factors of relapse in children with ITP patients by Logstic regression analysis,we constructed a column-line graph model by using R language and validated it.Results A total of 37(18.47%)of 201 patients in the model group experienced relapse.The age,blood type,duration of disease before treatment,antecedent infections,bleeding,initial treatment regimen,antinuclear antibody titer,initial count and mean platelet volume,initial platelet distri-bution width,initial peripheral blood lymphocyte count and time length to effective platelet count after treatment were found in the recurrence group versus the non-recurrence group The difference was statistically significant(P＜0.05).The results of multifactorial logistic regression analysis performed on the basis of LASSO regression showed that blood type,duration of illness before treatment,antecedent infection,initial treatment regimen,ini-tial peripheral blood lymphocyte count,and time to effective platelet count after treatment were independent influ-ences on the conversion of cough variant asthma to classic asthma in children.Based on the results of the multifac-torial analysis,a column chart model for predicting ITP recurrence in children was developed in R.The results of the receiver operating characteristic(ROC)analysis showed that the area under curve(AUC)of the column chart model for predicting ITP recurrence in children in the modeling group was 0.867[95%CI(0.796,0.938)]with a sensitivity of 84.2%and a specificity of 73.1%,and that in the validation group,the AUC was 0.838[95%CI(0.765),0.911]with a sensitivity of 82.3%and a specificity of 78.4%,0.911)]sensitivity was 82.3%and specificity was 78.4%.The Bootstrap method was used to repeat the sampling 1000 times,and the validation group was used for validation.The results of the calibration curve showed that the prediction curves of the model group and the validation group were basically fitted with the standard curve,suggesting that the model prediction accuracy was high.The results of the decision curve analysis of the model group showed that the net benefit rate of patients was greater than zero when the probability threshold of the column line graph model of pre-dicting ITP recurrence in children was 0.15-0.75.Conclusions ITP recurrence in children is mainly affected by the patient's age,blood type,and pre-treatment course of the disease,and the column-line diagram model based on these factors has a high accuracy and differentiation for ITP recurrence in parenting children.

A case of chronic myelomonocytic leukemia complicated with immune thrombocytopenia / 上海交通大学学报（医学版）

Chronic myelomonocytic leukemia(CMML)complicated with immune thrombocytopenia(ITP)is rare.This article reports the clinical data of a patient with CMML complicated with ITP treated with a combination of venetoclax,ripertamab(an anti-CD20 monoclonal antibody),and hetrombopag.The coexistence mechanism of CMML and ITP needs to be further clarified.Venetoclax combined with anti-CD20 monoclonal antibody and thrombopoietin receptor agonist may be an effective strategy for the treatment of this complication.

Study on the diagnostic value of lymphocyte subpopulations combined with chemokines in children with immunologic thrombocytopenic purpura / 安徽医科大学学报

Objective @#To explore the diagnostic value of lymphocyte subpopulations combined with chemokines in children with immunologic thrombocytopenic purpura ( ITP) . @*Methods @#132 children with proposed diagnosis of ITP were collected , and the children were divided into ITP and non ITP groups according to the diagnostic results of ITP related clinical diagnostic criteria. 6 ml of peripheral venous blood was drawn , the levels of CD4 + CD8 + and CD3 + were detected using flow cytometry , and the levels of chemokine (C-C motif) ligand 5 (CCL5) , Recombi nant Chemokine (C-X-C Motif) Ligand 1 (CXCL11) , and monocyte chemotactic protein 1 (MCP-1) were detec ted using enzyme linked immunosorbent assay , the blood platelet (PLT) was measured by a fully automated cell an alyzer. The children were divided into ITP and non ITP groups according to the clinical diagnostic criteria related to ITP. The lymphocyte subpopulations and chemokine levels of the two groups of children were compared , and the correlation between lymphocyte subpopulations and chemokine levels and PLT was analyzed . The ROC method was used to evaluate the diagnostic efficacy of individual and combined detection of each indicator for ITP. @*Results@#The levels of CD4 + and CD3 + in the ITP group were lower than those in the non ITP group (P < 0.05) , while the levels of CD8 + were higher than those in the non ITP group (P < 0.05) . The levels of CCL5 , CXCL11 , and MCP-1 in the ITP group were higher than those in the non ITP group (P < 0.05) . The correlation analysis results showed that CD4 + , CD3 + and platelet count were positively correlated in the ITP group(P < 0.05) , while CD8 + , CCL5 , CXCL11 , MCP-1 were negatively correlated with PLT (P < 0.05) . The ROC analysis results showed that the cut off values of CD4 + , CD8 + , CD3 + , CCL5 , CXCL11 , and MCP-1 for the diagnosis of ITP in children were 27.13% , 24.02% , 59.88% , 41.02 ng/L , 30.18 ng/L , and 188.27 ng/L , respectively. The AUC values were 0.893 , 0.880 , 0.629 , 0.801 , 0.892 , and 0.751 , respectively , The AUC of the parallel diagnosis ( meaning that one or more of CD4 + , CD3 + was below the cut off value and/or one or more of CD8 + , CCL5 , CXCL11 , MCP-1 was above the cut off value at the time of parallel testing) was 0.967 , indicating that one or more of them was lower than the cut off value and/or one or more of them was higher than the cut off value when tested separately. Its diag nostic efficacy was higher than that of each indicator tested separately (P < 0.05) .@*Conclusion @#There are signifi cant differences in lymphocyte subpopulations and chemokines between pediatric ITP patients and non ITP patients . CD4 + , CD8 + , CD3 + , CCL5 , CXCL11 , and MCP-1 can be used for the diagnosis of pediatric ITP. Combined de tection of various indicators can improve detection efficiency.

Efecto de las vacunas inactivada y de ARNm contra la COVID-19 sobre la trombocitopenia en pacientes con trombocitopenia inmunitaria / Effect of inactivated and mRNA COVID-19 vaccines on thrombocytopenia in immune thrombocytopenia patients

Este estudio observacional retrospectivo tuvo como objetivo abordar los posibles efectos de las vacunas inactivada y de ARNm en pacientes con trombocitopenia inmunitaria relacionados con la exacerbación. Para definir exacerbación, se consideró una disminución de más del 30 por ciento en el recuento de plaquetas con respecto al valor basal o un recuento de plaquetas disminuido a menos de 30×109/L o el desarrollo de una nueva hemorragia. Cincuenta y nueve (hombres 30,5 por ciento, mujeres 69,5 por ciento) de 208 pacientes con trombocitopenia inmunitaria, se inscribieron en el estudio. La mediana de edad fue de 47 años (rango 18-86). Se realizó un total de 171 vacunaciones en 59 pacientes. El 38 por ciento y el 62 por ciento de los pacientes fueron vacunados con Sinovac® y BioNTech®, respectivamente. En total, 10 (16,9 por ciento) pacientes experimentaron una disminución del recuento de plaquetas por debajo de 30×109/L tras la vacunación. Durante el último año antes de la pandemia, 19 de la misma cohorte (32,2 por ciento) experimentaron dicha disminución. Después de la primera, segunda y la dosis de refuerzo de la vacunación, el 12,7 por ciento, 13,8 por ciento y 15 por ciento de los pacientes experimentaron exacerbaciones, respectivamente; las exacerbaciones con hemorragias leves fueron del 2,3 por ciento y todos los episodios hemorrágicos se trataron con éxito comenzando con esteroides o aumentando la dosis de esteroides. No se registró ninguna hemorragia grave o potencialmente mortal. Se documentó una diferencia estadística en la exacerbación en los pacientes vacunados con la vacuna de ARNm (p =0,041) sólo después de la primera dosis y los pacientes más jóvenes experimentaron una mayor tasa de exacerbación sin significación estadística (p=0,06) después de la primera dosis. En conclusión, tanto la vacuna de ARNm como la inactivada parecen ser seguras para los pacientes con trombocitopenia inmunitaria con complicaciones hemorrágicas poco frecuentes. Especialmente los pacientes más jóvenes y los vacunados con vacunas de ARNm deben ser objeto de un seguimiento estrecho durante 1-2 meses después de la vacunación para detectar trombocitopenia(AU)

This retrospective observational study was aimed to address the possible effects of inactivated and mRNA vaccines in immune thrombocytopenia patients related to exacerbation. To define exacerbation, more than 30percent decrease in platelet counts from baseline or platelet counts decreased to less than 30×109/L and/or development of new bleeding were considered. Fifty-nine (male 30.5percent, female 69.5percent) out of 208 immune thrombocytopenia patients, were enrolled in the study. The median age was 47 (range18-86). A total of 171 vaccinations were performed in 59 patients. Thirty-eight and 62percent of patients were vaccinated with Sinovac® and BioNTech®, respectively. Overall, 10 (16.9percent) patients experienced decrease in platelet count below 30×109/L after vaccination. During the last year before pandemic, 19 of the same cohort (32.2percent) experienced such decrease. After first, second and booster dose vaccinations, 12.7percent, 13.8percent and 15percent of patients experienced exacerbation respectively; exacerbation with minor bleeding was 2.3percent and all bleeding episodes were successfully treated by starting with steroid or increasing the steroid dose. We did not report any severe and life-threatening bleeding. A statistical difference in exacerbation was documented in patients vaccinated with mRNA vaccine (p =0.041) only after the first dose and younger patients experienced a higher rate of exacerbation without statistical significance (p=0.06) after the first dose. In conclusion, both mRNA and inactivated vaccines seem to be safe for immune thrombocytopenia patients with rare bleeding complications. Especially younger patients and those vaccinated with mRNA vaccines should be followed up closely for 1-2 months post vaccination for thrombocytopenia(AU)

Efficacy and safety of biosimilar romiplostim in Indian patients with chronic immune thrombocytopenia: A multicentric retrospective study

Context and Aims: To evaluate the efficacy and safety of biosimilar romiplostim in Indian patients with immune thrombocytopenic purpura (ITP). Settings and Design: Multicentre, retrospective observational study. Methods and Material: Patients with chronic ITP who received biosimilar romiplostim from July 2019 to March 2020 across 3 major hospitals in Guwahati, India, were included. The study outcomes were the platelet response (platelet count > 50 × 109/L), time to first response, number of dose-limiting events, and the median effective dose. Statistical Analysis Used: Descriptive. Results: Of 32 patients included in this analysis, majority (59.4%) were females. The mean (SD) age was 40.37 (15.79) years, and mean age at ITP diagnosis was 38.53 years. The median number of romiplostim doses were 27.5 (range: 10-42) over a period of 10 months; median romiplostim dose used was 4.2 ?g/kg (range: 2.8-5 ?g/kg). Platelet response was achieved as early as after one week in 9 (28.12%) patients, which continued to increase to 24 (75%) patients after the second, 30 (93.75%) patients after the third and all 32 (100%) patients after four weeks of romiplostim administration. The median platelet count was 161 × 109/L. Dose reduction was done in a total of 21 patients. Thrombocytosis (46.88%), elevated liver enzymes (15.63%) and myalgia (15.63%) were the most common adverse events. Conclusions: Biosimilar romiplostim was effective in achieving and maintaining platelet response without any new safety concerns in Indian adult patients with chronic ITP. The median effective dose of romiplostim required in our patients was lower as compared with the standard prescribed dose.

Acute Acquired Immune Thrombocytopenia After Cardiac Surgery: A Challenging Case

Thrombocytopenia is a common condition that recognizes an infinite number of possible causes, especially in specific settings like the one covered in this case report: the postoperative period of cardiac surgery. We report a case of an old male with multiple comorbidities who underwent a coronary angioplasty procedure and aortic valve replacement. He showed severe thrombocytopenia in the postoperative days. Differential diagnosis required a big effort, also for the experts in the field. Our goal was to aggressively treat the patient with prednisolone, platelets, and intravenous immunoglobulins to maximize the prognosis. Our patient developed no complications and was discharged successfully

FcγRIIa and Fcγ RIIIa genes polymorphism in Egyptian children with primary immune thrombocytopenia

Abstract Introduction Phagocytosis of autoantibody-sensitized coated platelets through Fc gamma receptors on phagocytic cells is an important mechanism of thrombocytopenia in primary immune thrombocytopenia (ITP). Objective We aimed to investigate the contribution of the FcγRIIa and FcγRIIIa genes polymorphism to the risk of ITP and their association with disease characteristics in Egyptian children. Methods A case control study was conducted on eighty children with primary ITP and eighty age and sex healthy matched subjects as a control group. The FcγRIIa and FcγRIIIa genes polymorphism was detected using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results We found that the FcγRIIa‐131H and ‐131R allele frequencies were 51.3 % and 48.7%, respectively, in children with ITP, versus 75% and 25%, respectively, in controls (p= 0.002). The compound heterozygous HR genotype was significantly higher in ITP patients (p < 0.05). The FcγRIIIa-158F and ‐158V allele frequencies were 46.3% and 53.7%, respectively, in children with ITP, versus 70% and 30%, respectively, in controls (p= 0.002). The compound heterozygous VF genotype was significantly higher in ITP patients (p < 0.05). The combined HR/FV genotype was 47.5% in ITP patients, versus 10% in controls (p < 0.001). No significant difference was found between children with newly diagnosed ITP and those who developed chronic ITP, regarding the frequency distribution of the FcγRIIa and FcγRIIIa alleles and genotypes (p > 0.05). Conclusion There is a possible association of the FcγRIIa and FcγRIIIa genes polymorphism with the risk for, and genetic susceptibility to ITP in Egyptian children, but large-scale studies are still needed to support our findings.

Cytomegalovirus Infection-related Immune Thrombocytopenia: A Case Report / Púrpura Trombocitopênica Imune Associada à Infecção por Citomegalovírus: Relato de Caso

Immune thrombocytopenia (ITP) is an acquired cause of thrombocytopenia characterized by the presence of autoantibodies against platelets. It may be primary or secondary to several conditions. We present the case of a 63-year-old woman with a diagnosis of immune thrombocytopenia refractory to conventional therapy. After she was tested for secondary causes of ITP, a diagnosis of acute cytomegalovirus (CMV) infection was made. She was treated with ganciclovir and presented normalization of platelet count. CMV-related Immune Thrombocytopenia should always be considered in certain cases of refractory ITP. If the diagnosis of ITP secondary to acute CMV infection is made, specific antiviral therapy with ganciclovir should be considered. In these cases, immunosuppressive agents, such as steroids, may worsen the ITP and should be tapered or withdrawn as rapidly as feasible.

A Púrpura Trombocitopênica Imune (PTI) é uma causa de trombocitopenia adquirida caracterizada pela presença de autoanticorpos contra plaquetas. A doença pode ser primária ou secundária a diversas condições. Apresentamos o caso de uma mulher de 63 anos com diagnóstico de PTI refratária à terapêutica convencional. A investigação de causas secundárias evidenciou infecção aguda por citomegalovírus (CMV). A paciente foi tratada com ganciclovir e evoluiu com normalização no nível de plaquetas. A PTI relacionada ao CMV deve sempre ser investigada em pacientes com PTI refratária, sendo a terapia antiviral específica com ganciclovir o tratamento de escolha. Nestes casos, os agentes imunossupressores, como os corticosteroides, podem piorar a PTI e devem ser reduzidos gradualmente ou retirados o mais rapidamente possível.

Expression of interleukin-37, vascular endothelial growth factor A, and transforming growth factor-β1 and their correlation with T cells in children with primary immune thrombocytopenia / 中国当代儿科杂志

OBJECTIVES@#To investigate the expression of interleukin-37 (IL-37), vascular endothelial growth factor A (VEGFA), and transforming growth factor-β1 (TGF-β1) in children with primary immune thrombocytopenia (ITP) and their correlation with T cells.@*METHODS@#A retrospective analysis was conducted on 45 children with ITP (ITP group) who were admitted to Handan Central Hospital from January 2020 to April 2022, and 30 healthy children who underwent physical examination during the same period were included as the healthy control group. The mRNA expression levels of IL-37, VEGFA, and TGF-β1 and the levels of regulatory T cells (Treg) and helper T cells 17 (Th17) were measured before and after treatment, and the correlation between the mRNA expression levels of IL-37, VEGFA, and TGF-β1 and the levels of Treg, Th17, and Treg/Th17 ratio were analyzed.@*RESULTS@#Compared with the healthy control group, the ITP group had a significantly higher mRNA expression level of IL-37 and a significantly higher level of Th17 before and after treatment, as well as significantly lower mRNA expression levels of VEGFA and TGF-β1 and significantly lower levels of Treg and Treg/Th17 ratio (P<0.05). After treatment, the ITP group had significant reductions in the mRNA expression level of IL-37 and the level of Th17 and significant increases in the mRNA expression levels of VEGFA and TGF-β1 and the levels of Treg and Treg/Th17 ratio (P<0.05). Correlation analysis showed that in the ITP group, the mRNA expression levels of IL-37 and TGF-β1 were negatively correlated with the levels of Treg and Treg/Th17 ratio (P<0.05) and were positively correlated with the level of Th17 (P<0.05) before and after treatment; the mRNA expression level of VEGFA was positively correlated with the levels of Treg and Treg/Th17 ratio (P<0.05) and was negatively correlated with the Th17 level (P<0.05) before and after treatment.@*CONCLUSIONS@#Abnormal expression levels of IL-37, VEGFA, and TGF-β1 may be observed in children with ITP, which is significantly associated with the imbalance of Treg/Th17 ratio. It is speculated that the cytokines such as IL-37, VEGFA, and TGF-β1 may be involved in the development and progression of ITP or may become important potential targets for the treatment of children with ITP. Citation:Chinese Journal of Contemporary Pediatrics, 2023, 25(11): 1131-1136.

Immune Thrombocytopenia Induced by Sintilimab in Lung Cancer: A Case Report and Literature Review / 中国肺癌杂志

Immune checkpoint inhibitors (ICIs) show unique advantages in the treatment of lung cancer, making the treatment of lung cancer enter the era of immunotherapy, but ICIs will also have adverse reactions, and the incidence of immune-induced hematological toxicity is not very high. Immunotherapy-induced thrombocytopenia is a rare adverse event.We report one case of thrombocytopenia induced by ICIs and review the literature on thrombocytopenia associated with ICIs and discuss the clinical features, possible mechanisms, and optimal treatment. 
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Recent Advances in SARS-CoV-2-Induced Immune Thrombocytopenia --Review / 中国实验血液学杂志

SARS-CoV-2-induced immune thrombocytopenia (SARS-CoV-2-induced ITP) is an autoimmune disease secondary to virus infections. Its diagnosis is often based on exclusion of other possible causes of thrombocytopenia in COVID-19 patients. Common laboratory examinations include coagulation function, thrombopoietin and drug-dependent antibodies. Since both bleeding and thrombosis risks are seen in SARS-CoV-2-induced ITP patients, individual remedy is essential for the treatment of this disease. Because thrombopoietin receptor agonist(TPO-RA) has the side effect of accelerating thrombosis and may aggravate the pulmonary embolism symptoms of patients, it should be used for refractory SARS-CoV-2-induced ITP patients only. This review briefly summarizes the recent research progress in the pathogenesis, diagnosis and treatment of SARS-CoV-2-induced ITP.

Advances in the Treatment of Glucocorticoid Resistance and Relapsed Immune Thrombocytopenia --Review / 中国实验血液学杂志

Immune thrombocytopenia (ITP) is an immune-mediated acquired hemorrhagic autoimmune disease. At present, the first-line therapeutic drugs for ITP include glucocorticoids and intravenous immunoglobulins. However, about 1/3 of the patients had no response to the first-line treatment, or relapsed after dose reduction or withdrawal of glucocorticoids. In recent years, with the gradual deepening of the understanding on the pathogenesis of ITP, the drugs targeting different pathogenesis continually emerge, including immunomodulators, demethylating agents, spleen tyrosine kinase (SYK) inhibitors and neonatal Fc receptor (FcRn) antagonist. However, most of these drugs are in clinical trials. This review summarized briefly the recent advances in the treatment of glucocorticoids resistance and relapsed ITP, so as to provide reference for the clinical treatments.

Screening of key genes and pathway and analytical research of traditional Chinese medicines for primary immune thrombocytopenia based on bioinformatics analysis / 中国免疫学杂志

Objective:To preliminarily screen the key genes of primary immune thrombocytopenia(ITP)by bioinformatics method and explore the pathogenesis,so as to predict the potential traditional Chinese medicine(TCM)for the treatment of ITP.Methods:Based on the original microarray data set GSE80401 under the National Center for Biotechnology Information(NCBI),the differential miRNA of ITP were obtained by analyzing the adjusted P<0.05 and |logFC|≥1 as the screening criteria for differential miRNA.miRTarBase,miRDB and TargetScan were used to predict miRNA target genes.The target of ITP was searched in Genecards database,and the predicted up-regulated target genes and down-regulated target genes were intersected with disease targets.On this basis,the mapped target genes were respectively constructed into PPI network through String database and Cytoscape to screen core target genes,and the core target genes were enriched and analyzed in DAVID and Omicsbean databases for GO and KEGG pathways.The key genes were imported into the Coremine Medical database to analyze the TCM for the treatment of key genes.Results:Total of 422 differential genes and 17 key genes were finally screened,including BCL2L1,CCND1,CD44,CDKN1A,CREB1,GRB2,MAPK1,MAPK8,PIK3R1,CDK2,CAV1,FGF2,IGF1,SMAD2,SMAD4,TLR4 and VEGFA,mainly involving proteoglycan,FoXO,PI3K-Akt,human T cell leukemia virus 1 infection,endocrine resistance,focal adhesion and other signal pathways.A total of 12 TCM for ITP prevention and treatment,including ginseng,Radix Paeoniae Rubra,Angelica sinensis,bee venom,cobra,Psoralea corylifolia,Rehmannia glutinosa,buffalo horn,hemp seed,dodder seed,Wulingzhi and Jinji NaPi were screened.TLR4 maps the most TCM,followed by CCND1 and VEGFA.Among many TCM,ginseng acts on 17 targets at the same time,Radix Paeoniae Rubra,Angelica sinensis and bee venom act on 11 targets at the same time,cobra and Psoralea corylifolia act on 9 and 8 targets at the same time,Rehmannia glutinosa and buffalo horn act on 7 targets at the same time,hemp seed act on 4 targets at the same time,dodder seed act on 3 targets at the same time,and wulingzhi act on 2 targets at the same time.It is suggested that these drugs had the potential of multi-target prevention and treatment of ITP.Conclusion:The key pathogenic genes of ITP and the TCM with preventive and thera-peutic effects could be preliminarily predicted based on the analysis of genetic information,which can provide targets and research ideas for the development of related TCM.

Analysis of influencing factors for failure of glucocorticoid treatment in immune thrombocytopenia / 中国医师杂志

Objective:To explore the influencing factors of failure to receive glucocorticoid (GC) treatment for newly diagnosed immune thrombocytopenia (ITP).Methods:A retrospective selection was made of 82 patients who were initially diagnosed with ITP in the Hematology Department of the First Hospital of Baoding from January 2018 to December 2020 and received standardized GC treatment as the training set. They were divided into a success group (46 cases) and a failure group (36 cases) based on treatment results; Forty patients admitted from January 2021 to July 2021 were selected as the validation set according to the same criteria. We compared the clinical data of patients in the successful and failed groups, analyzed the risk factors for GC treatment failure in newly diagnosed ITP patients through multiple logistic regression, established a column chart prediction model, and evaluated it.Results:There were statistically significant differences in age, gender, platelet (PLT) count, interleukin-17 (IL-17), P-glycoprotein (P-gp), CD4 + T lymphocytes, bone marrow megakaryocyte count, serum antinuclear antibody (ANA), PLT related antibodies, and neutrophil alkaline phosphatase (NAP) positivity rates between the successful and failed groups of patients (all P<0.05); IL-17 levels ( OR=2.336, 95% CI: 1.452-4.165, P=0.005), P-gp expression levels ( OR=3.723, 95% CI: 1.224-5.118, P=0.013), bone marrow megakaryocyte count ( OR=4.778, 95% CI: 3.178-5.889, P=0.028), and PLT related antibody expression ( OR=0.347, 95% CI: 0.133-0.938, P=0.031) were independent influencing factors for GC treatment failure (all P<0.05). The C-index calculation results of the training set and validation set column chart models were 0.822(95% CI: 0.735-0.891) and 0.809(95% CI: 0.711-0.856), respectively. The area under the receiver operating characteristic (ROC) curve is 0.815(95% CI: 0.745-0.902) and 0.843(95% CI: 0.733-0.887), respectively. The clinical decision curve threshold probability of the column chart model is within the range of 0.01-0.95, and the net benefit rate was >0. Conclusions:Elevated L-17 levels, high expression of P-gp, decreased number of bone marrow megakaryocytes, and positive PLT related antibodies are independent influencing factors for GC treatment failure.

Clinical observation of herombopag combined with recombinant human thrombopoietin in the treatment of primary immune thrombocytopenia / 中国药房

OBJECTIVE To investigate the clinical efficacy and safety of herombopag combined with recombinant human thrombopoietin （rhTPO） in the treatment of primary immune thrombocytopenia （ITP） in the real world. METHODS A retrospective study was conducted on the patients diagnosed with ITP in the Second Affiliated Hospital of Bengbu Medical College from January 2021 to December 2022. Among them， 98 patients who were treated with a combination of herombopag and rhTPO were included in the observation group， and 157 patients who were treated with rhTPO alone were included in the control group. The changes in platelet count， clinical efficacy， bleeding， platelet transfusion rate and adverse drug reactions before and after treatment were observed and compared between the two groups. RESULTS Since the 8th day of treatment， there was a statistically significant difference in platelet count between the two groups （[ 61.04±13.46）×109 L－1 in observation group， （52.11±12.06）× 109 L－1 in control group] （P＜0.05）， and there also was a statistically significant difference in the peak and stable values of platelet count between the two groups （P＜0.05）. The total effective rates of the observation group and the control group were 79.59% and 66.88%， with cumulative response rates of 81.32% and 68.68%， and median response durations of 8 days and 10 days， respectively； these differences were statistically significant （P＜0.05）. During the treatment period， the bleeding rates of the observation group and control group were 3.06% and 8.28% （P＜0.05）， bleeding events were categorized as grade 1 or 2， and platelet transfusion rates were 31.63% and 40.76%； the differences in bleeding rates and platelet transfusion rates between the two groups was statistically significant （P＜0.05）. The incidences of adverse drug reactions in the two groups were 11.22% and 9.55%， respectively， with no statistically significant difference （P＞0.05）， and no moderate to severe adverse drug reaction was found. CONCLUSIONS The combination of herombopag and rhTPO can significantly increase platelet levels and response rate， and reduce bleeding rate and platelet transfusion rate in ITP patients， with good safety.

NLRP3 inflammasome mediated macrophage polarization in ITP / 安徽医科大学学报

Objective@#To investigate the activation level of NLRP3 inflammasome in immune thrombocytopenia ( ITP) and the effect of inhibiting NLRP3 mediated inflammasome activation on polarization and immune function of M1 macrophages.@*Methods @#The expression of NLRP3 mRNA in peripheral blood mononuclear cells (PBMC) and CD14 + monocytes of ITP patients (ITP group) and Control group (Control group) was detected by RT⁃qPCR. The levels of IL⁃1β and IL⁃18 in serum of the two groups were determined by ELISA. M0 macrophages (MDMs) from ITP group were divided into 4 groups : IgG control group ( IgG group) , MCC950 treatment group ( MCC950 group) , LPS , IFN⁃γ and IgG treatment group (LPS + IFN⁃γ + IgG group) and LPS , IFN⁃γ and MCC950 treatment group (LPS + IFN⁃γ + MCC950 group) ; mRNA and protein levels of M1 macrophage markers CD86 , iNOS and MCP⁃ 1 were detected by RT⁃qPCR and Western blot. Western blot was used to detect the expression of NLRP3 inflammasome associated protein , ASC , Cleaved caspase⁃1 and IL⁃ β . Flow cytometry was used to detect the phagocytosis of MDMs on platelets in each group , and CFSE was used to detect the proliferation of CD4 + T and CD8 + T.@*Results@#Compared with the control group , the expression of NLRP3 mRNA in PBMC and CD14 + monocytes , and the concentration of IL⁃1β and IL⁃18 in serum of ITP group increased significantly ( P < 0. 05 ) . Platelet counts were negative correlated with NLRP3 mRNA expression in CD14 + monocyte and the concentration of IL⁃1β , IL⁃18 in serum in patients with ITP ( P < 0. 05) . Compared with IgG group , the mRNA and protein expressions of M1 macrophage markers CD86 , iNOS , MCP⁃1 , and the protein expression level of NLRP3 , ASC , cleaved caspase⁃1 and IL⁃ β , the platelet phagocytosis and the proliferation promoting ability of CD4 + T and CD8 + T cells significantly increased in LPS + IFN⁃γ + IgG group and LPS + IFN⁃γ + MCC950 group ( all P < 0. 05) . Compared with LPS + IFN⁃γ + IgG group , the above indexes significantly decreased in LPS + IFN⁃γ + MCC950 group (P < 0. 05) .@*Conclusion @#The activation level of NLRP3 inflammasome in ITP is abnormally elevated , which was related to the excessive M1 polarization of MDMs. Inhibiting NLRP3 mediated inflammasome activation could attenuate the M1 polarization and immune function of macrophages.

Immune thrombocytopenia associated with lymph node tuberculosis: a case report

ABSTRACT Extrapulmonary tuberculosis associated with immune thrombocytopenia (ITP) is extremely rare. A likely association between ITP and pulmonary and lymph node tuberculosis was reported in a 29-year-old male patient. His platelet count decreased to 4,000/µL. Chest tomography revealed mediastinal adenomegaly, lymph node clusters in the aorta, and consolidation in the left upper lung lobe. Immunoglobulin and methylprednisolone were administered intravenously. The histopathology of the left upper lung lobe confirmed tuberculosis. The rifampicin/isoniazid/pyrazinamide/ethambutol regimen was initiated, and the corticosteroids were tapered off. This case suggests an association of tuberculosis with ITP, since the platelet count effectively normalized after tuberculosis treatment.

The role of autophagy in the pathogenesis of children immune thrombocytopenia / 国际儿科学杂志

Immune thrombocytopenia (ITP) is a common hemorrhagic disorder among children.Its pathogenesis is mainly based on impaired platelet production or increased platelet destruction.The development of ITP is not just due to abnormalities in the immune system.With the role of autophagy being revealed, more and more studies have proven its importance in hematopoietic stem cells, megakaryocytes and platelets.The paper aims to review the role of autophagy in the pathogenesis of ITP.