BACKGROUND: T-cell lymphoblastic lymphoma/acute lymphoblastic leukemia (T-LBL/ALL) is an aggressive form of hematological malignancy associated with poor prognosis in adult patients. Histone deacetylases (HDACs) are aberrantly expressed in T-LBL/ALL and are considered potential therapeutic targets. Here, we investigated the antitumor effect of a novel HDAC inhibitor, chidamide, on T-LBL/ALL. METHODS: HDAC1, HDAC2 and HDAC3 levels in T-LBL/ALL cell lines and patient samples were compared with those in normal controls. Flow cytometry, transmission electron microscopy, and lactate dehydrogenase release assays were conducted in Jurkat and MOLT-4 cells to assess apoptosis and pyroptosis. A specific forkhead box O1 (FOXO1) inhibitor was used to rescue pyroptosis and upregulated gasdermin E (GSDME) expression caused by chidamide treatment. The role of the FOXO1 transcription factor was evaluated by dual-luciferase reporter and chromatin immunoprecipitation assays. The efficacy of chidamide in vivo was evaluated in a xenograft mouse. RESULTS: The expression of HDAC1, HDAC2 and HDAC3 was significantly upregulated in T-LBL/ALL. Cell viability was obviously inhibited after chidamide treatment. Pyroptosis, characterized by cell swelling, pore formation on the plasma membrane and lactate dehydrogenase leakage, was identified as a new mechanism of chidamide treatment. Chidamide triggered pyroptosis through caspase 3 activation and GSDME transcriptional upregulation. Chromatin immunoprecipitation assays confirmed that chidamide led to the increased transcription of GSDME through a more relaxed chromatin structure at the promoter and the upregulation of FOXO1 expression. Moreover, we identified the therapeutic effect of chidamide in vivo . CONCLUSIONS This study suggested that chidamide exerts an antitumor effect on T-LBL/ALL and promotes a more inflammatory form of cell death via the FOXO1/GSDME axis, which provides a novel choice of targeted therapy for patients with T-LBL/ALL.
Humans ; Pyroptosis/drug effects* ; Forkhead Box Protein O1/genetics* ; Aminopyridines/pharmacology* ; Animals ; Mice ; Benzamides/pharmacology* ; Cell Line, Tumor ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Phosphate-Binding Proteins/metabolism* ; Histone Deacetylase Inhibitors/pharmacology* ; Jurkat Cells ; Histone Deacetylases/metabolism* ; Apoptosis/drug effects* ; Gasdermins

Objective To explore the changes in serum energy metabolites in patients with peripheral T-cell lymphoma,and investigate serum biomarkers for monitoring peripheral T-cell lymphoma from the perspective of energy metabolism.Methods Multiple/selected reaction monitoring(MRM/SRM)was used to detect the energy-related metabolites in the sera of 16 patients with newly diagnosed peripheral T-cell lymphoma admitted in the Hematology Medical Center of the Second Affiliated Hospital of Army Medical University from November 2020 to December 2021,as well as 10 recruited healthy volunteers.The corresponding clinical data including medical history,laboratory results and image data were collected and retrospectively analyzed.Results Significant differences were seen in the contents and expression profiles of serum energy metabolism-related products between the patients and the healthy volunteers.The patients had significantly reduced serum contents of cyclic AMP,succinate,citrate and cis-aconitate(P＜0.05),and elevated D-glucose 6-phosphate content(P＜0.05).The serum contents of citrate and succinate were negatively correlated with the risk stratification(low-,moderate-and high-risk)and clinical stage of the disease(P＜0.05).Meanwhile,there was a negative correlation between the contents of L-malic acid and citrate and the mid-term efficacy evaluation results,such as complete/partial response(CR/PR)or stable disease(SD)(P＜0.05).For patients with extranodal NK/T cell lymphoma(n=10),there were also significant reductions in the contents of cyclic AMP,succinate,citrate,isocitrate and cis-aconitate in the sera of patients compared with healthy volunteers(P＜0.05),and the contents of citrate and succinate were negatively correlated with the clinical stage(P＜0.05)and were rather correlated with mid-term efficacy evaluation results(CR/PR or SD)(P＜0.05).For patients with angioimmunoblastic T-cell lymphoma(n=6),the serum contents of cyclic AMP,citrate and succinate were significantly lower,while the content of D-glucose 6-phosphate was higher when compared with the healthy volunteers(P＜0.05),and the content of succinate was negatively correlated with both clinical stage and risk grade of the patients(P＜0.05).Conclusion There are 5 serum differential metabolites identified between patients with peripheral T-cell lymphoma and healthy controls,and succinate and citrate are expected to be serum biomarkers of peripheral T-cell lymphoma.

Objective:To investigate the clinical characteristics, management and outcome of aortic dissection (AD) in pregnant women with pre-eclampsia.Methods:Clinical characteristics, management, and prognosis of nine patients with pre-eclampsia complicated by AD who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2013 to April 2021 were retrospectively summarized using descriptive statistical analysis.Results:(1) Clinical features: The incidence of pre-eclampsia complicated by AD among the total deliveries and pre-eclampsia deliveries were 18/100 000 (9/49 166) and 182/100 000 (9/4 943), respectively. All the nine cases of pre-eclampsia complicated by AD, with an average age of (36.6±4.2) years, presented clinical symptoms in the second or the third trimester that were mainly manifested as chest and back pain (8/9) and the average gestational week at onset was (31.0±4.7) weeks. Seven cases were confirmed by transthoracic echocardiography (TTE) and computed tomography angiography (CTA), one by TTE and magnetic resonance angiography, and one by TTE+MRI+CTA. The main classification of AD was Stanford B (8/9). In the grading of blood pressure during pregnancy, except for one case without data, eight cases were severe. (2) Management: Four women did not receive any antihypertensive treatment. However, blood pressure remained uncontrolled in the other five cases despite antihypertensive managment. Except for one death before operation due to rapid deterioration, the other eight cases all received initial treatment and thoracic endovascular aortic repair (TEVAR). Four cases underwent TEVAR prior to the termination of pregnancy. Two cases were delivered by cesarean section first, and TEVAR was performed 5 and 6 days after delivery, respectively. The other two cases undenwent cesarean section and TEVAR at the same time. Lung infection ( n=6) was the main postoperative complication. (3) Delivery: Among the nine patients, one patient died, and the average termination time of the eight patients (six underwent cesarean section, including two cases with fetal death, two underwent vaginal delivery following fetal death) was (32.9±3.6) weeks and none of them had postpartum hemorrhage. (4) Maternal-infant outcomes: Follow-up of the eight surviving women showed that one had numbness in one side of the limbs, one with occasional heart palpitations, and the rest had good outcomes. There were four live births, including two with low birth weight and one with neonatal asphyxia, and five stillbirths. During the 7-83 months of follow-up, all four children grew well. Conclusions:Pregnant women with pre-eclampsia should actively control blood pressure to avoid AD. Once symptoms such as chest and back pain occur, the possibility of AD should be considered. Active treatment after diagnosis of AD can improve maternal and fetal survival rate.

Objective::This study aimed to determine the likelihood of gestational diabetes mellitus (GDM) in subsequent pregnancy among women without GDM history and to identify risk factors for GDM in subsequent pregnancy.Methods::This retrospective cohort study involved participants who delivered twice in same hospital of 18 research centers when delivered the second baby from January 2018 to December 2018. Finally 6204 women were enrolled and 5180 women without GDM history were analyzed further. Women were categorized as non-GDM or GDM based on the blood glucose values of the subsequent pregnancy, and the characteristics and GDM risk of these groups were compared. A univariate analysis of potential risk factors was performed using the Chi-squared test and/or t-test for qualitative or quantitative variables, respectively. Associations with P values <0.1 were chosen to be included in the multivariate binary logistic regression model. Results::In primary analysis of 6204 women, the incidence of GDM in subsequent pregnancy is 48.9% (490/1002) in women with GDM history and 16.1% (835/5202) in women without GDM history. In a further analysis for 5180 women without GDM at index pregnancy, compared with the non-GDM group, the GDM group had a significantly higher age, prepregnancy body mass index, and blood glucose value at each oral glucose tolerance test (OGTT) timepoint (fasting, 1 h and 2 h) during the index and subsequent pregnancies, as well as higher weight retention during the interval between the two pregnancies ( P<0.001). Age above 35 years in subsequent pregnancy (odds ratio ( OR)=1.540, 95% confidence interval ( CI) = 1.257-1.886, P<0.001), macrosomia in index pregnancy ( OR=1.749, 95% CI=1.277-2.395, P=0.001), OGTT blood glucose values in index pregnancy (fasting, OR=2.487, 95% CI=1.883-3.285, P<0.001; 1 h, OR=1.142, 95% CI=1.051-1.241, P=0.002; 2 h, OR=1.290, 95% CI=1.162-1.432, P<0.001) and weight retention ( OR=1.052, 95% CI=1.035-1.068, P<0.001) were independent risk factors for GDM in subsequent pregnancy. Conclusion::For women without GDM history, GDM risk factors including age, macrosomia history, OGTT value, and weight retention, these can be evaluated before a subsequent pregnancy. Early warning and interventions are needed for women at high risk.

Objective::This study aimed to determine the likelihood of gestational diabetes mellitus (GDM) in subsequent pregnancy among women without GDM history and to identify risk factors for GDM in subsequent pregnancy.Methods::This retrospective cohort study involved participants who delivered twice in same hospital of 18 research centers when delivered the second baby from January 2018 to December 2018. Finally 6204 women were enrolled and 5180 women without GDM history were analyzed further. Women were categorized as non-GDM or GDM based on the blood glucose values of the subsequent pregnancy, and the characteristics and GDM risk of these groups were compared. A univariate analysis of potential risk factors was performed using the Chi-squared test and/or t-test for qualitative or quantitative variables, respectively. Associations with P values <0.1 were chosen to be included in the multivariate binary logistic regression model. Results::In primary analysis of 6204 women, the incidence of GDM in subsequent pregnancy is 48.9% (490/1002) in women with GDM history and 16.1% (835/5202) in women without GDM history. In a further analysis for 5180 women without GDM at index pregnancy, compared with the non-GDM group, the GDM group had a significantly higher age, prepregnancy body mass index, and blood glucose value at each oral glucose tolerance test (OGTT) timepoint (fasting, 1 h and 2 h) during the index and subsequent pregnancies, as well as higher weight retention during the interval between the two pregnancies ( P<0.001). Age above 35 years in subsequent pregnancy (odds ratio ( OR)=1.540, 95% confidence interval ( CI) = 1.257-1.886, P<0.001), macrosomia in index pregnancy ( OR=1.749, 95% CI=1.277-2.395, P=0.001), OGTT blood glucose values in index pregnancy (fasting, OR=2.487, 95% CI=1.883-3.285, P<0.001; 1 h, OR=1.142, 95% CI=1.051-1.241, P=0.002; 2 h, OR=1.290, 95% CI=1.162-1.432, P<0.001) and weight retention ( OR=1.052, 95% CI=1.035-1.068, P<0.001) were independent risk factors for GDM in subsequent pregnancy. Conclusion::For women without GDM history, GDM risk factors including age, macrosomia history, OGTT value, and weight retention, these can be evaluated before a subsequent pregnancy. Early warning and interventions are needed for women at high risk.

Objective:To explore the effects of pregnancy complicated with Takayasu arteritis (TA) on maternal and fetal outcomes.Methods:The clinical data of 17 TA patients with pregnancy and finally terminated admitted to the First Affiliated Hospital of Zhengzhou University from January 2012 to December 2020 were collected and the maternal and infant outcomes were retrospectively analyzed.Results:Among the 24 pregnancies in 17 TA patients in our hispital, 11 patients in our hospital were primiparous (46%, 11/24) and 13 patients were multiparous (54%, 13/24); 4 cases of chronic hypertension before pregnancy (17%, 4/24), and 20 cases of non-hypertension (83%, 20/24) were abserved. Apart from the thoracoabdominal artery type, 15 cases (63%, 15/24) of brachiocephalic type, 8 cases (33%, 8/24) of extensive type, and 1 case of pulmonary artery type (4%, 1/24) were included in TA classification; the renal artery was damaged in 7 cases (7/8) of the extensive type. Among the 24 pregnancies of 17 TA patients, 8 cases of pregnancy complications occurred, including 4 cases (17%, 4/24) of preeclampsia, one case of (4%, 1/24) new-onset hypertension during pregnancy, exacerbation of existing hypertension, thrombocytopenia and ischemic stroke respectively; 3 cases of induced abortion, 1 case of induced labor, and 20 cases of final delivery were found. Of the 20 final deliveries, 3 cases (15%, 3/20) were delivered through the vagina; 17 cases (85%, 17/20) were delivered by cesarean section; 3 cases (15%, 3/20) of fetal growth restriction and 6 cases of oligohydramnios (30%, 6/20) were occurred. The median gestational age of pregnancy termination of 17 full-term neonates (85%, 17/20) and 3 premature neonates (15%, 3/20) was 38.4 weeks (range:29.6-40.9 weeks). All premature women were complicated with pre-eclampsia or severe pre-eclampsia, which lead to premature birth; the birth weight of the neonates was (2 791±783) g. Neonatal asphyxia occurred in 3 cases (15%, 3/20), and 6 cases (30%, 6/20) were admitted to the neonatal intensive care unit. None of the newborns died. The patients were followed up for 3 months to 7 years. Except for one case who underwent surgical treatment 3 years after delivery and died of intraoperative hemorrhage, the other 16 patients were in stable condition; all the newborns grew and developed well. The incidences of maternal and infant adverse events were higher in those with chronic hypertension, renal artery involvement, and no use of hormones and aspirin during pregnancy, but the differences were not statistically significant (all P>0.05). Conclusions:Pregnancy with TA has adverse effects on maternal and infant outcomes. To reduce the occurrence of maternal and child adverse events, the condition of TA patients should be fully assessed before pregnancy, multidisciplinary cooperation, regular treatment, strengthened monitoring of the condition, timely treatment of complications, selection of appropriate delivery methods after pregnancy, and vigilance of postpartum complications should be properly carried out.

Objective:To explore the effects of interpregnancy interval (IPI) on pregnancy outcomes of subsequent pregnancy.Methods:A multicenter retrospective study was conducted in 21 hospitals in China. Information of age, height, pre-pregnancy weight, IPI, history of diseases, complications of pregnancy, gestational age of delivery, delivery mode, and pregnancy outcomes of the participants were collected by consulting medical records of pregnant women who had two consecutive deliveries in the same hospital during 2011 to 2018. The participants were divided into 4 groups according to IPI:<18 months, 18-23 months, 24-59 months and ≥60 months. According to the WHO′s recommendation, with the IPI of 24-59 months group as a reference, to the effects of IPI on pregnancy outcomes of subsequent pregnancy were analyzed. Stratified analysis was further carried out based on age, history of gestational diabetes mellitus (GDM), macrosomia, and premature delivery, to explore the differences in the effects of IPI on pregnancy outcomes among women with different characteristics.Results:A total of 8 026 women were included in this study. There were 423, 623, 5 512 and 1 468 participants in <18 months group, 18-23 months group, 24-59 months group and ≥60 months group, respectively. (1) The age, pre-pregnancy body mass index (BMI), history of cesarean section, GDM, gestational hypertension and cesarean section delivery rate of <18 months group, 18-23 months group, 24-59 months group and ≥60 months group were gradually increased, and the differences were statistically significant ( P<0.05). (2) After adjusting for potential confounding factors, compared with women in the IPI of 24-59 months group, the risk of premature delivery, premature rupture of membranes, and oligohydramnios were increased by 42% ( OR=1.42, 95% CI: 1.07-1.88, P=0.015), 46% ( OR=1.46, 95% CI: 1.13-1.88, P=0.004), and 64% ( OR=1.64, 95% CI: 1.13-2.38, P=0.009) respectively for women in the IPI≥60 months group. No effects of IPI on other pregnancy outcomes were found in this study ( P>0.05). (3) After stratified by age and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of oligohydramnios for women with advanced age ( OR=2.87, 95% CI: 1.41-5.83, P=0.004); and <18 months could increase the risk of premature rupture of membranes for women under the age of 35 ( OR=1.59, 95% CI: 1.04-2.43, P=0.032). Both the risk of premature rupture of membranes ( OR=1.58, 95% CI: 1.18-2.13, P=0.002) and premature delivery ( OR=1.52, 95% CI: 1.07-2.17, P=0.020) were significantly increased in the IPI≥60 months group. After stratified by history of GDM and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would lead to an increased risk of postpartum hemorrhage for women with a history of GDM ( OR=5.34, 95% CI: 1.45-19.70, P=0.012) and an increased risk of premature rupture of membranes for women without a history of GDM ( OR=1.44, 95% CI: 1.10-1.90, P=0.009). After stratified by history of macrosomia and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months could increase the proportion of cesarean section for women with a history of macrosomia ( OR=4.11, 95% CI: 1.18-14.27, P=0.026) and the risk of premature rupture of membranes for women without a history of macrosomia ( OR=1.46, 95% CI: 1.12-1.89, P=0.005). After stratified by history of premature delivery and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of premature rupture of membranes for women without a history of premature delivery ( OR=1.47, 95% CI: 1.13-1.92, P=0.004). Conclusions:Both IPI≥60 months and <18 months would increase the risk of adverse pregnancy outcomes in the subsequent pregnancy. Healthcare education and consultation should be conducted for women of reproductive age to maintain an appropriate IPI when they plan to pregnant again, to reduce the risk of adverse pregnancy outcomes in the subsequent pregnancy.

Placenta percreta with bladder bleeding can occur during gestation or postpartum, posing a great threat to both mother and fetus. But it is rare and lacks standard management strategies. We reported four cases suffering from bladder bleeding caused by placenta percreta even with hemorrhagic shock admitted between January 1 st, 2011 and December 31 th, 2020 in The First Affiliated Hospital of Zhengzhou University. Clinical information, including age, gravidity and parity, ultrasound and magnetic resonance imaging manifestations, onset gestational age, bladder bleeding volume, clinical manifestations under bleeding, diagnosis, hemostatic methods, hospital stay, treatment cost, and prognosis, are presented. Two cases had bladder bleeding during the second trimester, respectively on the 22 +3 and 23 +5 weeks. Pregnancy was terminated timely. The other two cases had bladder bleeding on the 2 nd day post near-term cesarean section when activity. All the four cases achieved successful hemostasis following angiography and concomitant embolization for iliac vessels, and one of them received electrocoagulation hemostasis under cystoscopy, but failed. They all had favorable clinical outcomes and had no long-term complications. The neonatal outcome in the two cases that bladder hemorrhage occurred after near-term c-section was good. The newborns did not survive in two cases in which bladder hemorrhage occurred at the second trimester of pregnancy. Timely termination of pregnancy is recommended when such a condition develops during gestation. Diagnosis of bladder bleeding is relatively easy, for it is characterized by fast speed and large volume, with concomitant distension of the lower abdomen, blood discharge from the urethral orifice, or the indwelling catheter. Interventional embolization is an effective means to treat bladder bleeding caused by placenta percreta, while electrocoagulation hemostasis under cystoscopy must be applied with great caution. For the pregnant women with a high risk of placenta percreta, timely and accurate diagnosis should be achieved during the gestational age, and bladder bleeding should be concerned when placenta penetrates through the anterior wall of uterus.

Placenta percreta with bladder bleeding can occur during gestation or postpartum, posing a great threat to both mother and fetus. But it is rare and lacks standard management strategies. We reported four cases suffering from bladder bleeding caused by placenta percreta even with hemorrhagic shock admitted between January 1 st, 2011 and December 31 th, 2020 in The First Affiliated Hospital of Zhengzhou University. Clinical information, including age, gravidity and parity, ultrasound and magnetic resonance imaging manifestations, onset gestational age, bladder bleeding volume, clinical manifestations under bleeding, diagnosis, hemostatic methods, hospital stay, treatment cost, and prognosis, are presented. Two cases had bladder bleeding during the second trimester, respectively on the 22 +3 and 23 +5 weeks. Pregnancy was terminated timely. The other two cases had bladder bleeding on the 2 nd day post near-term cesarean section when activity. All the four cases achieved successful hemostasis following angiography and concomitant embolization for iliac vessels, and one of them received electrocoagulation hemostasis under cystoscopy, but failed. They all had favorable clinical outcomes and had no long-term complications. The neonatal outcome in the two cases that bladder hemorrhage occurred after near-term c-section was good. The newborns did not survive in two cases in which bladder hemorrhage occurred at the second trimester of pregnancy. Timely termination of pregnancy is recommended when such a condition develops during gestation. Diagnosis of bladder bleeding is relatively easy, for it is characterized by fast speed and large volume, with concomitant distension of the lower abdomen, blood discharge from the urethral orifice, or the indwelling catheter. Interventional embolization is an effective means to treat bladder bleeding caused by placenta percreta, while electrocoagulation hemostasis under cystoscopy must be applied with great caution. For the pregnant women with a high risk of placenta percreta, timely and accurate diagnosis should be achieved during the gestational age, and bladder bleeding should be concerned when placenta penetrates through the anterior wall of uterus.

Objective:To investigate and analyze disease status and risk factors of venous thromboembolism (VTE) during pregnancy and puerperium in our country.Methods:Clinical datas were collected from 575 patients diagnosed with VTE during pregnancy and puerperium and hospitalized in nine medical institutions in our country from January 1, 2015 to November 30, 2019, and retrospectively analyzed it′s disease status and risk factors.Results:(1) The proportion of VTE in pregnancy and puerperium was 50.6% (291/575) and 49.4% (284/575), respectively. Four patients died, the mortality rate was 0.7% (4/575). The cause of death was pulmonary embolism. (2) The location of VTE during pregnancy and puerperium was mainly in the lower limb vascular (76.2%, 438/575), followed by pulmonary vessels (7.1%, 41/575). (3) In the risk factors of VTE, cesarean section accounted for 32.3% (186/575), maternal advance age accounted for 27.7% (159/575), braking or hospitalization during pregnancy accounted for 13.6% (78/575), other risk factors accounted for more than 5% were previous VTE, obesity, preterm birth, assistant reproductive technology conception and so on, pre-eclampsia and multiple pregnancy accounted for 4.9% (28/575) respectively. In addition, some patients with VTE did not have any of the above risk factors, and the incidence rate was as high as 23.1% (133/575).Conclusions:The occurrence of VTE during pregnancy and puerperium is related to multiple risk factors, and could lead to matemal death, It is very necessary to screen VTE risk factors for all pregnant women, to make corresponding prevention and control measures.