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: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.

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.

Radiotherapy is the most common treatment for nasopharyngeal carcinoma, and the radiotherapy technique is essential for the prognosis of nasopharyngeal carcinoma. Due to the complexity of the structure of the intensity-modulated device and the accuracy of the clinical requirements of radiotherapy, it is inevitable that higher requirements will be imposed on the process of intensity-modulated radiotherapy. Currently, gaps exist in the radiotherapy equipment and personnel qualification among radiotherapy units, and thus the homogenization in the radiotherapy remains to be strengthened in China. With the application of radiotherapy information management system, digital medicine and artificial intelligence technologies in the field of radiotherapy, the original process fails to meet the application needs of the new precise radiotherapy technology. Therefore, this process is designed based on the existing radiotherapy procedures for nasopharyngeal carcinoma in combination with the latest developments in the field of radiotherapy, aiming to establish a novel standard process recommendation, ensuring the standardization and homogenization of radiotherapy and achieve the individualized intensity-modulated radiotherapy for nasopharyngeal carcinoma patients.

Objective To investigate the prevalence of iron deficiency(ID)and iron deficiency anemia (IDA) in pregnant women in urban areas of China. Methods The study was a national cross-sectional survey conducted from September 19th, 2016 to November 20th, 2016. According to the classification of the National Bureau of Statistics, all survey sites were set up in 6 regions of the country. Pregnant women were continuously selected using multistage stratified sampling. A total of 12 403 pregnant women were collected and examined for serum ferritin and hemoglobin levels. Results The median serum ferritin level during pregnancy was 20.60 μg/L(11.78-36.98 μg/L), the hemoglobin level was(118±12)g/L. With the progress of pregnancy, the levels of serum ferritin and hemoglobin decreased gradually. The median serum ferritin levels in the first, second trimester and third trimester were 54.30 μg/L(34.48-94.01 μg/L), 28.60 μg/L(16.40-50.52 μg/L), and 16.70 μg/L(10.20-27.00 μg/L)respectively(P<0.01). The mean hemoglobin levels were(127 ± 10)g/L,(119 ± 11)g/L and(117 ± 11)g/L respectively(P<0.01). The prevalence of ID in urban pregnant women was 48.16%(5 973/12 403), and IDA prevalence was 13.87% (1 720/12 403). The prevalence of IDA in the first, second trimester and third trimester were 1.96% (20/1 019), 8.40%(293/3 487)and 17.82%(1 407/7 897), respectively(P<0.01). The prevalence of standardized ID and IDA were significantly different in various regions of China(P<0.01). The standardized prevalence of ID were relatively higher in East China and Northeast China, 57.37% and 53.41% respectively, while it was the lowest in Southwest China, 30.51%. The standardized prevalence of IDA in South Central, Northwest, and East China were relatively high, 21.30%, 16.97% and 17.53% respectively, and the standardized prevalence of IDA in Southwest China was the lowest, 5.44%,the differents in various regions were significant(all P<0.01). Conclusion The current phenomenon of ID and IDA in pregnant women is still very common,and nutrition and health care during pregnancy should be strengthened.

Objective To investigate the therapeutic effect of uteroplasty aided with temporary balloon occlusion of abdominal aorta in treating pernicious placenta previa combined with placenta percreta.Methods Sixty-two third-trimester gravidas who were diagnosed as pernicious placenta previa combined with placenta percreta by prenatal ultrasound and magnetic resonance imaging (MRI) in the First Affiliated Hospital of Zhengzhou University from January 1,2013 to May 31,2016 were enrolled in this study.All of them received cesarean section and then underwent uteroplasty following temporary balloon occlusion of abdominal aorta.Efficacy of that treatment was evaluated from the perspectives of blood loss,operation time,complications and postoperative recovery.All data were analyzed by descriptive analysis.Results All of the 62 cases were diagnosed with placenta percreta during operation including 10 cases (16.1％) with perimetrium invasion,46 cases (74.2％) with invasion to the muscular layer of bladder and six cases (9.7％) with bladder invasion.The average blood loss of all cases during and within 24 hours after operation was (1 377.3±605.2) ml and (140.6±66.3) ml,respectively.The average operation time was (72.3 ±24.5) min and the average length of postoperative hospital stay was (5.8± 1.6) d.The six cases of placenta percreta with bladder invasion received bladder repair.Sixty-one cases had their uterus preserved and the other one case had a sub-total hysterectomy due to amniotic fluid embolism.One woman developed phlebothrombosis in her lower limbs after operation.No intestinal or ureteral injury,puerperal infection,uterine ischemia necrosis or death was reported.In addition to three cases lost to follow-up,the other 59 patients were followed up to May 31,2017.Results of physical examination indicated that the 59 cases had normal uterine involution after operation.Menses returned in 58 of the 59 cases without any difference from before,and did not return in one case due to breastfeeding.Conclusion Uteroplasty aided with temporary balloon occlusion of abdominal aorta is a safe and effective uterus-preserving surgery for patients with pernicious placenta previa combined with placenta percreta.

Objective To explore the relationship among clinicians' work pressure,perceived social support and compassion fatigue,and to provide a new prospective for the localization studying of intervention and treatment to compassion fatigue.Methods Data of scale for occupational stressors on clinician,perceived social support scale and professional quality of life scale were collected from a sample of 533 clinicians and analyzed with structural equation modeling to study the relationship among clinicians' work pressure,perceived social support and compassion fatigue.Results (1)Work pressure(2.40±0.45),burnout (2.14±0.54) and secondary traumatic stress(1.93±0.60) scores of the clinicians with high perceived social support were significantly lower than that of the clinicians with low perceived social support (2.78±3.67,2.73± 0.59,2.32±0.71;t=7.68,-9.44,8.77,5.07;P＜0.01).Compassion satisfaction scores (4.15±0.63) of the clinicians with high perceived social support were significantly higher than that of the clinicians with low perceived social support (3.40±0.71,t =-9.44,P＜0.01).(2) According to relevant results,work pressure was significantly negative correlation with both perceived social support (r=-0.34,P＜0.01) and compassion satisfaction (r=-0.44,P＜0.01),and significantly positive correlation with both burnout (r=0.69,P＜0.01) and secondary traumatic stress(r=0.53,P＜0.01);while perceived social support was significantly positive correlation with compassion satisfaction (r=0.42,P＜0.01),and significantly negative correlation with burnout (r=-0.40,P＜0.01) and secondary traumatic stress(r=-0.26,P＜0.01).(3) According to the results of structural equation modeling,perceived social support played a partly mediating role in the effect of work pressure toward compassion satisfaction and fatigue with the intermediary effect of 55.4％ and 12.5％.Conclusion Perceived social support plays a mediation role between work pressure and compassion fatigue for clinicians,and better social support of the clinician is beneficial to clinicians mental health level.