Objective To screen for differentially expressed apoptosis-related circular RNAs(circRNAs)in osteoblasts from steroid-induced osteonecrosis of the femoral head(SONFH)and to investigate their roles and mechanisms in osteoblast apoptosis.Methods MC3T3-E1 cells were cultured and divided into two groups:Control and DEX-treated.Western blot analysis was employed to evaluate the expression levels of BCL2-Associated X protein(Bax)and B-cell lymphoma 2(Bcl-2).Cell apoptosis was assessed using TUNEL staining and flow cytometry.RNA was extracted from both normal and DEX-treated MC3T3-E1 cells,followed by RNA-seq to identify differen-tially expressed circular RNAs(circRNAs).The functions and pathways of these circRNAs were analyzed using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG).The differentially expressed mmu_circ_0000818 was selected for further verification at the cellular level.Its chromosomal location and conservation were examined using the UCSC Genome Browser Gateway and circBase.Overexpression plasmids and small interfering RNAs(siRNAs)targeting mmu_circ_0000818 were constructed and transfected into the cells.Subsequently,apop-tosis in MC3T3-E1 cells from each group was evaluated by flow cytometry.Results Compared with the control group,the apoptosis rate of MC3T3-E1 cells was significantly increased in the DEX group(P<0.01).Differen-tially expressed circRNAs were identified based on log2foldchange(≥2)and P value(P<0.05).Relative to the control group,there were 234 differentially expressed circRNAs in the DEX group,including 138 up-regulated and 96 down-regulated circRNAs.GO and KEGG enrichment analyses of the target genes of these differentially expressed circRNAs revealed significant associations with apoptosis and the PI3K-Akt signaling pathway.qRT-PCR results demonstrated that the expression level of mmu_circ_0000818 was markedly higher in the DEX group com-pared to the control group(P<0.01).Analysis using the UCSC Genome Browser and CircBase indicated that mmu_circ_0000818,located at chromosome 17:78712463-78715086,is formed by the cyclization of exons 6-7 of the Crim1 gene and exhibits high conservation across species.Flow cytometry results indicated that knockdown of mmu_circ_0000818 attenuated DEX-induced apoptosis in MC3T3-E1 cells,while overexpression of mmu_circ_0000818 exacerbated apoptosis.Conclusions CircRNA mmu_circ_0000818 was significantly upregulated in DEX-treated MC3T3-E1 cells,and its downregulation mitigated DEX-induced apoptosis.Consequently,mmu_circ_0000818 may represent a promising therapeutic target for the prevention and treatment of SONFH.

Objective To screen for differentially expressed apoptosis-related circular RNAs(circRNAs)in osteoblasts from steroid-induced osteonecrosis of the femoral head(SONFH)and to investigate their roles and mechanisms in osteoblast apoptosis.Methods MC3T3-E1 cells were cultured and divided into two groups:Control and DEX-treated.Western blot analysis was employed to evaluate the expression levels of BCL2-Associated X protein(Bax)and B-cell lymphoma 2(Bcl-2).Cell apoptosis was assessed using TUNEL staining and flow cytometry.RNA was extracted from both normal and DEX-treated MC3T3-E1 cells,followed by RNA-seq to identify differen-tially expressed circular RNAs(circRNAs).The functions and pathways of these circRNAs were analyzed using Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG).The differentially expressed mmu_circ_0000818 was selected for further verification at the cellular level.Its chromosomal location and conservation were examined using the UCSC Genome Browser Gateway and circBase.Overexpression plasmids and small interfering RNAs(siRNAs)targeting mmu_circ_0000818 were constructed and transfected into the cells.Subsequently,apop-tosis in MC3T3-E1 cells from each group was evaluated by flow cytometry.Results Compared with the control group,the apoptosis rate of MC3T3-E1 cells was significantly increased in the DEX group(P<0.01).Differen-tially expressed circRNAs were identified based on log2foldchange(≥2)and P value(P<0.05).Relative to the control group,there were 234 differentially expressed circRNAs in the DEX group,including 138 up-regulated and 96 down-regulated circRNAs.GO and KEGG enrichment analyses of the target genes of these differentially expressed circRNAs revealed significant associations with apoptosis and the PI3K-Akt signaling pathway.qRT-PCR results demonstrated that the expression level of mmu_circ_0000818 was markedly higher in the DEX group com-pared to the control group(P<0.01).Analysis using the UCSC Genome Browser and CircBase indicated that mmu_circ_0000818,located at chromosome 17:78712463-78715086,is formed by the cyclization of exons 6-7 of the Crim1 gene and exhibits high conservation across species.Flow cytometry results indicated that knockdown of mmu_circ_0000818 attenuated DEX-induced apoptosis in MC3T3-E1 cells,while overexpression of mmu_circ_0000818 exacerbated apoptosis.Conclusions CircRNA mmu_circ_0000818 was significantly upregulated in DEX-treated MC3T3-E1 cells,and its downregulation mitigated DEX-induced apoptosis.Consequently,mmu_circ_0000818 may represent a promising therapeutic target for the prevention and treatment of SONFH.

BACKGROUND: Massive bleeding is the main concern for the management of placenta percreta (PP). Intra-abdominal aortic balloon occlusion (IABO) is one method for pelvic devascularization, but the efficacy of IABO is uncertain. This study aims to investigate the outcomes of IABO in PP patients. METHODS: We retrospectively reviewed the clinical data of PP cases from six tertiary centers in China between January 2011 and December 2015. PP cases with/without the use of IABO were analyzed. Propensity score matching analysis was performed to reduce the effect of selection bias. Postpartum hemorrhage (PPH) and the rate of hysterectomy, as well as neonatal outcomes, were analyzed. RESULTS: One hundred and thirty-two matched pairs of patients were included in the final analysis. Compared with the control group, maternal outcomes, including PPH (68.9% vs. 87.9%, χ2 = 13.984, P < 0.001), hysterectomy (8.3% vs. 65.2%, χ2 = 91.672, P < 0.001), and repeated surgery (1.5% vs. 12.1%, χ2 = 11.686, P = 0.001) were significantly reduced in the IABO group. For neonatal outcomes, Apgar scores at 1 minute (8.67 ± 1.79 vs. 8.53 ± 1.68, t = -0.638, P = 0.947) and 5 minutes (9.43 ± 1.55 vs. 9.53 ± 1.26, t = 0.566, P = 0.293) were not significantly different between the two groups. CONCLUSIONS IABO can significantly reduce blood loss, hysterectomies, and repeated surgeries. This procedure has not shown harmful effects on neonatal outcomes.
Aorta ; Balloon Occlusion/methods* ; Blood Loss, Surgical ; Female ; Humans ; Hysterectomy ; Infant, Newborn ; Placenta Accreta/surgery* ; Placenta Previa/surgery* ; Postpartum Hemorrhage ; Pregnancy ; Retrospective Studies

Objective:To summarize the clinical features, treatment and prognosis of asparaginase (ASP) related cerebral venous sinus thrombosis (CVST).Methods:Clinical profiles including age, sex, first symptoms, coagulation function, imaging findings, ASP type, treatment and prognosis of eight acute lymphoblastic leukemia (ALL) or lymphoblastic lymphoma (LBL) children with ASP related CVST at the Department of Pediatrics, First Affiliated Hospital of Zhengzhou University from November 2016 to October 2021 were analyzed retrospectively.Results:Eight CVST children were all male, including 6 ALL and 2 LBL, with the onset age ranged from 5 to 15 years, 6 cases occurred in the stage of first induction remission, and the initial symptom were mainly epileptic seizures (7 cases). Magnetic resonance imaging combined magnetic resonance venography (MRV) showed the most common site of venous sinus enlargement was superior sagittal sinus (8 cases). Secondary cerebral hemorrhage was found in 5 cases. D-dimer elevated on the day of onset in all cases. Three patients were treated with intravascular mechanical thrombectomy and thrombolysis combined with anticoagulant therapy, 3 patients were treated with continuous anticoagulant therapy only, 2 patients were not treated with anticoagulant therapy. MRV follow-up for 3 months showed that the thrombi in patients were almost completely absorbed except in 2 patients who were not treated with anticoagulant therapy. Thrombolysis combined with anticoagulant therapy was the fastest way for thrombosis absorption. Among 8 patients, 1 died of early recurrence of ALL, and 7 patients accepted further asparaginase and no CVST recurrence or progression was found. There were no sequelae of nervous system except 1 patient with left upper limb muscle strength impairment.Conclusions:ASP related CVST is more common in older male children and the prognosis is good. ASP related CVST occurred mostly in the stage of first induction remission, and most initial manifestation is epileptic seizure. The superior sagittal region is a common site of thrombus, magnetic resonance imaging combined with MRV is helpful for accurately diagnosis. Timely anticoagulant treatment can improve the prognosis, and mechanical thrombectomy and thrombolysis can quickly recanalize the vessel.

Objective:To investigate the mechanism of programmed death 1(PD-1)/ programmed death ligand 1(PD-L1) signaling pathway and its feasibility as a potential therapeutic target and prognostic predictor by detecting the expressions, of PD-1 and PD-L1 in bone marrow mononuclear cells of children with acute lymphoblastic leukemia (ALL), and to provide new ideas for the diagnosis and treatment of ALL as well.Methods:Bone marrow samples were collected from 59 children with ALL in the First Affiliated Hospital of Zhengzhou University from September 2018 to July 2019.Flow cytometry was applied to detect the expression of PD-1 and PD-L1 in bone marrow mononuclear cells in 59 ALL patients, including 47 newly-diagnosed ALL patients and 12 relapsed ALL patients, respectively, at initial diagnosis, after induction therapy and early intensive treatment.Their relevant clinical data were collected and compared with the bone marrow specimens of 12 children suffering from non-malignant blood diseases as the control group of the same hospital during the same period.Results:There was no significant difference in the expression of PD-1 in the bone marrow mononuclear cells of the primary diagnosis group, recurrence group and control group ( H=2.402, P>0.05). The expression of PD-L1 in the relapsed and refractory group [(7.32±3.60)%] and the newly diagnosed group [(3.18±2.37)%] was higher than that in the control group [(0.84±0.39)%], and the differences were statistically significant ( H= 28.048, P<0.05). In the initial treatment group, the expression of PD-L1 in the bone marrow mononuclear cells was the strongest expression before treatment ( B=1.293), followed by after induction treatment ( B=0.036) and after early intensive treatment ( B=0.000), suggesting that there was a downward trend as the continued treatment.The expression of PD-L1 was the weakest expression in the low-risk group ( B=-3.912) than in the medium-risk group ( B=-3.595) and high-risk group ( B=0.000), revealing that the expression of PD-L1 is related to the risk grades of ALL.The higher the risk rating is, the higher the PD-L1 protein expression is. Conclusions:The high expression of PD-L1 may be involved in the pathogenesis and be used as an adverse predictor of ALL childhood and an evaluation index of chemotherapy efficacy.PD-1 / PD-L1 signaling pathway may be a potential therapeutic target of ALL childhood.

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 evaluate the risk factors and sonographic findings of pregnancies complicated by placenta increta or placenta percreta. Methods Totally, 2219 cases were retrospectively analyzed from 20 tertiary hospitals in China from January 2011 to December 2015. The data were collected based on the original case records. All cases were divided into two groups, the placenta increta (PI) group (79.1％, 1755/2219) and the placenta percreta (PP) group (20.9％, 464/2219), according to the degree of placental implantation. The risk factors and sonographic findings of placenta increta or percreta were analyzed by uni-factor and logistic regression statistic methods. Results The risk factors associated with the degree of placental implantation were age, gravida, previous abortion or miscarriage, previous cesarean sections, and placenta previa (all P<0.05), especially, previous cesarean sections (χ2=157.961) and placenta previa (χ2=91.759). Sonographic findings could be used to predict the degree of placental invasion especially the boundaries between placenta and uterine serosa, the boundary between placenta and myometrium, the disruption of the placental-uterine wall interface and loss of the normal retroplacental hypoechoic zone(all P<0.01). Conclusions Previous cesarean sections and placenta previa are the main independent risk factors associated with the degree of placenta implantation. Ultrasound could be used to make a prenatal suggestive diagnosis of placenta accreta spectrum disorders.

Objective To explore the impact of WeChat-assisted follow-up on self-administer medication capability of stroke survivors.Methods Seventy patients were recruited from a tertiary hospital and randomly divided into intervention group (n=35) and control group (n=35).Patients in intervention group were given WeChat-assisted follow-up including health education program and behavior guidance,and patients in control group received regular discharge care.The effects of WeChat-assisted follow-up and regular care on self-administer medication ability,cognitive and behavior level were assessed.Results After three months' follow-up,the scores of self-administer medication capability (38 (32,42)),experience (25 (20,28) and the integral level (87 (71,92)) in intervention group were significantly higher than those in control group (capability 25(16,38),experience 21 (8.75,27),total score 68 (38,87)) (Z=-2.511,-2.033,-2.209,P＜0.05).The self-administer medication experience,cognitive,capability and total scores increased significantly in intervention group after intervention(Z=-4.525,-4.610,-3.806,-4.718,all P＜ 0.01),while only the cognitive level increased slightly in control group (18 (10,24) vs 13 (11,18),Z =-1.794,P=0.073).Conclusions Follow-up intervention based on WeChat platform can improve the stroke patients' self-administration medication capability,however,the long-term effects on cognitive level and further reform need to be strengthened.

Objective: Hepatocyte nuclear factor 1 homeobox b (HNF1B) -associated disease is an autosomal dominant inherited disorder with a variable, multi-systemic phenotype. In China, five adult probands and one child proband with HNF1B-associated disease had been reported, whereas few fetuses are described. The aims of this retrospective study were to understand about the clinical manifestations of HNF1B-associated disease and to further improve the recognition of this disorder. Method: Four patients (3 males, 1 female) and three fetuses with HNF1B mutations were included in this study. They were admitted to our hospital from January 2013 to March 2017. HNF1B mutations were detected using targeted next generation sequencing and quantitative real-time PCR or Sanger sequencing. HNF1B heterozygous deletion of exons 1-9 was found in 4 patients and 2 fetuses, and HNF1B heterozygous missense mutation in 1 fetus. These two mutations had been reported. Two patients and 1 fetus had de novo mutations. Results of renal ultrasonography with or without magnetic resonance imaging, biochemical investigations, urine routine examination and other necessary investigations in 7 cases were analyzed. Result: Three patients were Han Chinese ethnicity, and one patient was Mongolian. In patients 1 and 4, abnormal fetal kidneys were discovered by routine ultrasonography, and the age at first feature identified in Patients 2 and 3 were 13 years and 28 years. Patient 3 had normal renal function and the remainder had reduced glomerular filtration rate. In addition, patient 4 presented with nephrotic syndrome and glycosuria, patient 2 with early onset hyperparathyroidism and renal osteodystrophy, and patient 3 with diabetes mellitus. All the 4 patients had renal structural abnormalities including bilateral multiple renal cysts, dysplasia and hyperechogenic kidneys. Only patient 3 had a positive family history of renal diseases, the remainder had a negative family history of renal diseases. In 3 fetuses, prenatal ultrasound anomalies were detected during the second trimester. These 3 fetuses had hyperechogenic kidneys with or without renal cysts. Polyhydramnios was detected in only one of the 3 fetuses. Two of the 3 fetuses had a positive family history of renal diseases. Conclusion Clinical phenotypes of HNF1B-related disease are heterogeneous, renal malformations clearly appear to be the most common manifestation, multiple renal cysts are characteristic, and patients can progress to impaired kidney function during childhood; HNF1B mutation is a differential diagnosis of fetal hyperechogenic kidneys or multiple renal cysts.

Objective To investigate the clinical effect of McDonald cervical cerclage and the affecting factors. Methods Between January 2002 to December 2013 in Peking University First Hospital we performed McDonald cervical cerclage for 116 single pregnant women. They were defined as the successful group who deliveried the live babies after 28 weeks after the cerclage and the failure group who deliveried in the second trimester. According to the surgical indications they were divided into preventive cerclage group and therapeutic cerclage group. Then we analyzed the curative effect and the affecting factors in the groups. Results (1) In the 116 cases, 12 cases (10.3%) failed, and 104 cases (89.7%) succeeded. In the successful group, 37 cases (35.6%,37/104) deliveried pretermly and 67 cases (64.4%) deliveried termly. And there were 56 cases of vaginal delivery (53.8%), and 48 cases (46.2%) of cesarean section. (2) Among the 116 cases, 48 cases (41.4%) were included in prophylactic cerclage group, the gestational age was (16.3± 2.2) weeks, 68 (58.6%) cases were included in therapeutic group, the gestational age was (24.0±2.2) weeks. The operation time was (22±9) minutes in preventive group and (24±13) minutes in therapeutic group,there was no statistical difference between the two groups (P>0.05). Live-birth rate between preventive cerclage group and therapeutic cerclage group was no statistically significant difference (P>0.05). The term birth rate (72.9%, 35/48) in preventive group was higher than that in therapeutic group (47.1%, 32/68), the difference was statistically significant (P<0.01). Neonatal hospitalization rate was lower in preventive group (14.6%, 7/48) than therapeutic group (36.8%, 25/68) , the difference was statistically significant (P< 0.01). (3) In the failure group placental pathology was examed in 7 cases. The placental tissue showed a large number of neutrophils infiltrating in 6 cases (6/7). In the successful group, 27 pregnant women deliveried between 28 to 33+6 weeks (26.0%,27/104), 10 pregnant women deliveried between 34 to 36+6 weeks 10 cases (9.6%, 10/104), 67 cases deliveried after 37 weeks (64.4%, 67/104). A lot of factors including maternal age, the previous cervix operation history, perioperative application of progesterone, operation time and preoperative invasive procedure were compared between the successful group and the failure group. Only maternal age and preoperative invasive proedcure were statistically significant (P<0.05) and the others had no statistical significance (P>0.05). (4) There were 68 cases in the therapeutic group, 7 cases failed, and 61 cases succeeded;the preoperative cervical os in failure group [ (21 ± 20) mm] was wider than that in successful group [(14±5) mm], the difference was statistically significant (P<0.05);and preoperative vaginal ultrasound measurement of cervical canal length were (18 ± 8) mm versus (19 ± 10) mm, there was no statistically significant difference (P>0.05). Conclusions The McDonald cervical cerclage for cervical incompetence is a simple, safe and high successful rate of intervention measures. The term labor rate of prophylactic cervical cerclage was higher than that of the therapeutic cerclage. Older maternal age and preoperative invasive procedure may be the risk factors for cerclage. The infection may play an important factor leading to the failure of McDonald cervical cerclage.