Objective:To investigate the mode and timing of delivery in pregnant women with complex fetal congenital heart disease (CHD) detected by prenatal ultrasound.Methods:The clinical data of 123 fetuses with complex CHD detected by prenatal ultrasound in Peking University People′s Hospital from January 2016 to December 2023 were retrospectively analyzed. Pregnant women with indications for prenatal diagnosis underwent G-banding karyotype analysis, single nucleotide polymorphism array (SNP arrry) or whole exome sequencing after informed consent. Integrated managements were provided for pregnant women with complex CHD during pregnancy and perinatal period, and to determine the mode and timing of delivery. Infants with complex CHD received timely treatment or referral after birth.Results:The gestational age at ultrasound diagnosis of the 123 fetuses with complex CHD was (23.7±3.4) weeks. There were 11 cases (8.9%) of total anomalous pulmonary venous connection (TAPVC), 14 cases (11.4%) of anomalous pulmonary valve (PVA), 7 cases (5.7%) of right ventricle double outlet (RVDO), 13 cases (10.6%) of anomalous aortic arch, 69 cases (56.1%) of transposition of the great arteries (TGA), 9 cases (7.3%) of other types. All cases were treated with fetal preservation after prenatal consultation. Among the 72 cases undergoing prenatal diagnosis, 9 cases (12.5%) had chromosomal variations. Fifty-five cases (44.7%, 55/123) underwent trial of labor, of which 46 cases (37.4%, 46/123) had successful vaginal delivery, including 6 cases of forceps delivery, and other 9 cases of failed trial of labor transferred to cesarean section. A total of 77 cases of pregnant women underwent cesarean section. Except for the 21 cases of pregnant women who asked for cesarean section, the cesarean section rate of pregnant women with complex CHD was 45.5% (56/123), which was not significantly different from the average cesarean section rate of the same period in our hospital (40.2%; χ2=7.34, P=0.270). The gestational age at delivery of the 123 fetuses with complex CHD was (37.9±1.4) weeks, the birth weight of the neonates was (3 099±480) g, and the umbilical artery blood pH value was 7.31±0.05. The oxygen saturation of 86 cases before and after alprostadil infusion were (72.8±6.0)% and (80.5±5.0)%, respectively, and the difference was statistically significant ( t=4.38, P<0.001). One hundred and fourteen children underwent surgical treatment, 112 of them (98.2%) had good postoperative reexamination. Only 2 cases (1.8%) died after surgery, and 14.0% (16/114) had the possibility of secondary surgery. Conclusions:Fetal complex CHD is not an indication for cesarean section, and the delivery mode could be selected according to the obstetric situation. If the mother and child are in stable condition, the delivery is planned after 39 weeks of gestation. For children with low oxygen saturation after birth, alprostadil could be pumped to maintain the open ductus arteriosus, and timely referral to the pediatric cardiac surgery for subsequent surgical treatment, which could achieve a good prognosis.

ObjectiveTo investigate the mechanism of ferroptosis mediated by long-chain acyl-CoA synthetase 4 （ACSL4） signalling pathway in rats with coronary heart disease with blood stasis syndrome and the intervention effect of Xuefu Zhuyutang. MethodsSPF male SD rats were randomly divided into normal group， sham-operation group， model group， trimetazidine group （5.4 mg·kg^-1）， low-， medium-， and high-dose group （3.51， 7.02，14.04 g·kg^-1） of Xuefu Zhuyutang. The coronary artery left anterior descending ligation method was used to prepare a model of coronary heart disease with blood stasis syndrome， and continuous treatment for 7 d was conducted， while the sham-operation group was only threaded and not ligated. The general macroscopic symptoms of the rats were observed， and indicators such as electrocardiogram， echocardiography， and blood rheology were detected. The pathological morphology of myocardial tissue was observed by hematoxylin-eosin （HE） staining， and the changes in mitochondria in myocardial tissue were observed by transmission electron microscopy. The level of iron deposition in myocardial tissue was observed by Prussian blue staining. The levels of 12-hydroxyeicosatetraenoic acid （12-HETE） and 15-HETE were detected in serum by enzyme-linked immunosorbent assay. A biochemical colourimetric assay was used to detect the levels of Fe²⁺， lipid peroxidation （LPO）， glutathione （GSH）， and T-GSH/glutathione disulfide （GSSG） in myocardial tissue. DCFH-DA fluorescence quantitative assay was employed to detect the levels of reactive oxygen species （ROS）. Western blot and Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was adopted to detect the protein and mRNA expressions of glutathione peroxidase 4 （GPX4）， ferritin heavy chain 1 （FTH1）， ACSL4， and ly-sophosphatidylcholine acyltransferase3 （LPCAT3） in myocardial tissue. ResultsCompared with those in the normal group， the rats in the model group were poor in general macroscopic symptoms. The electrocardiogram showed widened QRS wave amplitude and increased voltage， bow-back elevation of the ST segments， elevated T waves， J-point elevation， and accelerated heart rate. Echocardiography showed a significant reduction in left ventricular ejection fraction （LVEF） and left ventricular fraction shortening （LVFS） （P<0.01）. Blood rheology showed that the viscosity of the whole blood （low， medium， and high rate of shear） was significantly increased （P<0.01）. HE staining showed an abnormal structure of myocardial tissue. There was a large area of myocardial necrosis and inflammatory cell infiltration and a large number of connective tissue between myocardial fibers. Transmission electron microscopy showed that the mitochondria were severely atrophy or swelling. The cristae were reduced or even broken， and the matrix was flocculent or even vacuolated. Prussian blue staining showed that there were a large number of iron-containing particles， and the iron deposition was obvious. The content of 12-HETE and 15-HETE in the serum was significantly increased （P<0.01）. The content of Fe²⁺， LPO， and ROS in myocardial tissue was significantly increased （P<0.01）. The content of GSH was significantly decreased （P<0.01）， and T-GSH/GSSG was decreased （P<0.01）. The protein and mRNA expressions of GPX4 and FTH1 in myocardial tissue were both significantly decreased （P<0.05， P<0.01）， while those of ACSL4 and LPCAT3 increased significantly （P<0.01）. Compared with the model group， the general macroscopic symptoms and electrocardiogram results of rats in low-， medium- and high-dose groups of Xuefu Zhuyutang were alleviated， and the differences in LVEF/LVFS ratios were all significantly increased （P<0.05， P<0.01）. The differences in whole-blood viscosity （low， medium， and high rate of shear） were all significantly decreased （P<0.01）. The results of HE staining and transmission electron microscopy showed that the morphology， structure， and mitochondria of cardiomyocytes were improved. The content of 12-HETE and 15-HETE in serum was reduced to different degrees in low-， medium-， and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）. The content of Fe²⁺， LPO， and ROS was significantly reduced in the medium- and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）， and the content of GSH and T-GSH/GSSG was significantly increased （P<0.05， P<0.01）. The protein and mRNA expressions of GPX4 and FTH1 were significantly increased to varying degrees in the medium- and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）， and ACSL4 and LPCAT3 were decreased to different degrees in the low-， medium-， and high-dose groups of Xuefu Zhuyutang （P<0.05， P<0.01）. ConclusionXuefu Zhuyutang can regulate iron metabolism and anti-lipid oxidation reaction to mediate ferroptosis through the ACSL4 signalling pathway， thus exerting a protective effect on rats with coronary heart disease with blood stasis syndrome.

Objective:To investigate the mode and timing of delivery in pregnant women with complex fetal congenital heart disease (CHD) detected by prenatal ultrasound.Methods:The clinical data of 123 fetuses with complex CHD detected by prenatal ultrasound in Peking University People′s Hospital from January 2016 to December 2023 were retrospectively analyzed. Pregnant women with indications for prenatal diagnosis underwent G-banding karyotype analysis, single nucleotide polymorphism array (SNP arrry) or whole exome sequencing after informed consent. Integrated managements were provided for pregnant women with complex CHD during pregnancy and perinatal period, and to determine the mode and timing of delivery. Infants with complex CHD received timely treatment or referral after birth.Results:The gestational age at ultrasound diagnosis of the 123 fetuses with complex CHD was (23.7±3.4) weeks. There were 11 cases (8.9%) of total anomalous pulmonary venous connection (TAPVC), 14 cases (11.4%) of anomalous pulmonary valve (PVA), 7 cases (5.7%) of right ventricle double outlet (RVDO), 13 cases (10.6%) of anomalous aortic arch, 69 cases (56.1%) of transposition of the great arteries (TGA), 9 cases (7.3%) of other types. All cases were treated with fetal preservation after prenatal consultation. Among the 72 cases undergoing prenatal diagnosis, 9 cases (12.5%) had chromosomal variations. Fifty-five cases (44.7%, 55/123) underwent trial of labor, of which 46 cases (37.4%, 46/123) had successful vaginal delivery, including 6 cases of forceps delivery, and other 9 cases of failed trial of labor transferred to cesarean section. A total of 77 cases of pregnant women underwent cesarean section. Except for the 21 cases of pregnant women who asked for cesarean section, the cesarean section rate of pregnant women with complex CHD was 45.5% (56/123), which was not significantly different from the average cesarean section rate of the same period in our hospital (40.2%; χ2=7.34, P=0.270). The gestational age at delivery of the 123 fetuses with complex CHD was (37.9±1.4) weeks, the birth weight of the neonates was (3 099±480) g, and the umbilical artery blood pH value was 7.31±0.05. The oxygen saturation of 86 cases before and after alprostadil infusion were (72.8±6.0)% and (80.5±5.0)%, respectively, and the difference was statistically significant ( t=4.38, P<0.001). One hundred and fourteen children underwent surgical treatment, 112 of them (98.2%) had good postoperative reexamination. Only 2 cases (1.8%) died after surgery, and 14.0% (16/114) had the possibility of secondary surgery. Conclusions:Fetal complex CHD is not an indication for cesarean section, and the delivery mode could be selected according to the obstetric situation. If the mother and child are in stable condition, the delivery is planned after 39 weeks of gestation. For children with low oxygen saturation after birth, alprostadil could be pumped to maintain the open ductus arteriosus, and timely referral to the pediatric cardiac surgery for subsequent surgical treatment, which could achieve a good prognosis.

Objective To prepare nifedipine nanocrystals(NDP-NCs)and evaluate their in vivo pharmacokinetics in rats.Methods The NDP-NCs was prepared by medium grinding method,and the formulation and preparation technology of NDP-NCs were determined by single factor experiment.The microstructure of NDP-NCs and its solid powder was observed under scanning electron microscope.The particle size distribution and Zeta potential of NDP-NCs before and after spray drying were compared.The stability of the spray drying granules of NDP-NCS was investigated.The dissolution rates of the NDP raw material and NDP-NCs granules were compared.The in vivo pharmacokinetics of NDP suspension and NDP-NCs granules were evaluated after oral administration in rats.Results Using hydroxypropyl cellulose(HPC-SL)and sodium dodecyl sulfate(SDS)as stabilizers,the ratio of drug to stabilizer was 5∶1,the size of grinding medium was 0.2 mm,the ratio of grinding medium to liquid volume was 1∶1,the grinding speed was 2 000 r/min,and the grinding time was 3 h.The NDP-NCs showed an irregular granular distribution,and the NDP-NCs granules were porous and spherical.The average particle size and polydispersity index had no change before and after spray drying.The NDP-NCs granules had good stability after 6 months under the condition of accelerated testing.The solubility of NDP-NCs in different pH media was obviously improved.The dissolution rate of NDP-NCs granules increased significantly,and the drug could dissolve more than 90％within 15 min.The oral bioavailability of NDP was significantly improved after it was prepared into nanocrystals.Conclusion In this study,the nifedipine is prepared into nanocrystals with reasonable formulation design and feasible preparation technology,which can significantly improve the oral bioavailability of nifedipine.

Humans ; Pregnancy ; Female ; Umbilical Cord/diagnostic imaging* ; Pregnancy Outcome ; Ultrasonography ; Ultrasonography, Prenatal

Sepsis is characterized by a severe and life-threatening host immune response to polymicrobial infection accompanied by organ dysfunction.Studies on the therapeutic effect and mechanism of immunomod-ulatory drugs on the sepsis-induced hyperinflammatory or immunosuppression states of various im-mune cells remain limited.This study aimed to investigate the protective effects and underlying mechanism of artesunate(ART)on the splenic microenvironment of cecal ligation and puncture-induced sepsis model mice using single-cell RNA sequencing(scRNA-seq)and experimental validations.The scRNA-seq analysis revealed that ART inhibited the activation of pro-inflammatory macrophages recruited during sepsis.ART could restore neutrophils'chemotaxis and immune function in the septic spleen.It inhibited the activation of T regulatory cells but promoted the cytotoxic function of natural killer cells during sepsis.ART also promoted the differentiation and activity of splenic B cells in mice with sepsis.These results indicated that ART could alleviate the inflammatory and/or immunosuppressive states of various immune cells involved in sepsis to balance the immune homeostasis within the host.Overall,this study provided a comprehensive investigation of the regulatory effect of ART on the splenic microenvironment in sepsis,thus contributing to the application of ART as adjunctive therapy for the clinical treatment of sepsis.

Diabetic gastroparesis (DGP) is characterized by delayed gastric emptying caused by reduction of gastrointestinal motility. Its clinical manifestations include vomiting, nausea, belching, early satiety, postprandial fullness, and abdominal distention, etc. The mechanism of DGP is still not clear. Depletion of interstitial cells of Cajal, myopathy and neuropathy are considered to be the main pathogenic factors. Gastric prokinetics, gastric electric stimulation and endoscopic therapy are the main treatment options, but the long-term efficacy of these symptomatic treatment is not very satisfactory, which seriously affects patients' quality of life. This article reviewed the advances in study on pathogenesis and treatment of DGP.

Objective To explore the clinical characteristics of interrupted of the inferior vena cava with azygous continuation and the prognosis.Methods Retrospective analysis of 21 fetuses diagnosed with interrupted inferior vena cava with azygous continuation among 28 567 pregnant women who underwent routine ultrasound scan.The clinical data,ultrasonographic features,genetic information and prognosis were collected. Results Interrupted of the inferior vena cava with azygous continuation occurred in 21(0.07%, 21/28 567)of 28 567 patients.Three fetuses(14%,3/21)complicated with heart and extracardiac malformations, including endocardiac cushion defect,single atrium and single ventricle,double superior vena cava,dextrocardia, asplenia syndrome,visceral heterotaxy,duodenal atresia;six fetuses(29%,6/21)were associated with cardiac anomalies, such as hypoplastic left heart syndrome, double outlet right ventricle, pulmonary stenosis, ventricular septal defect,persistent left superior vena cava,endocardiac cushion defect and transposition of the great arteries;six cases(29%,6/21)were only combined with extracardiac malformations,includingasplenia syndrome, visceral heterotaxy, duodenal atresia. Three fetuses (14%,3/21) were nonorganic abnormalities included thickening of the right ventricle wall, fetal bradycardia, pericardial effusion, hydrops abdominis, increased peak systolic velocity/end diastolic velocity and single umbilical artery.Three fetuses(14%,3/21) were isolated interrupted inferior vena cava with azygous continuation,but without other anomalies and 2 of them had normal fetal karyotype.Five cases(24%,5/21)were successfully vaginal delivery,1 case(5%,1/21) had cesarean section. After 12-40 months follow-up, we didn′t obeserve obviously abnormality, nor any chromosomal abnormality.Ten patients(48%,10/21)opted for termination of the pregnancy and the autopsies were not done.Five cases(24%,5/21)were lost to follow up.Conclusions Interrupted inferior vena cava with azygous continuation are associated with cardiovascular and extracardiac anomalies, cardiac malformation and visceral heterotaxy are the most common anomalies. Visceral heterotaxy should be considered and fetal karyotype should be suggested. In the cases of isolated interrupted inferior vena cava with azygous continuation and normal karyotype,the outcome is favorable.

Objective To investigate the effects of different concentrations and adsorption methods of aluminum hydroxide adjuvant produced by different manufacturers on the immunogenicity of the diphtheria-tetanus-acellular pertussis and inactivated poliovirus combined vaccine ( DTaP-sIPV) . Methods Five anti-gens of DTaP were adsorbed onto different concentrations (0. 42 mg/ml, 0. 47 mg/ml and 0. 52 mg/ml) of aluminum hydroxide from different manufacturers through sequential and separate adsorption. Adsorbability, anti-pertussis toxin ( PT)/filamentous hemagglutinin ( FHA)/pertactin ( PRN)/diphtheria toxoid ( DT)/tet-anus toxoid ( TT) antibodies and the potency of vaccines were detected. Results The adsorbability of alu-minum hydroxide adjuvant slightly decreased with the reduction of concentration. No significant difference in potency and antibody level was observed between sequential and separate adsorption. Moreover, no signifi-cant difference in antibody level was observed between vaccines prepared with aluminum hydroxide adjuvant produced by General Chemical Corp and our institute. Conclusion Aluminum hydroxide adjuvant produced by our institute at the concentration of 0. 52 mg/ml and separate adsorption method are suitable for prepara-tion of DTaP-sIPV.

Objective To compare the clinical efficacies between warm needling and Ibuprofen sustained release capsules (a nonsteroidal anti-inflammatory drug, NSAID) in treating patients with dysmenorrhea in adenomyosis. MethodSixty-five patients with dysmenorrhea induced by adenomyosis were randomized into a treatment group of 33 cases and a control group of 32 cases. The control group was intervened by oral administration of Ibuprofen sustained release capsules, while the treatment group was intervened by warm needling.The intervention lasted 3 menstrual cycles and a 3-month follow-up was studied. The Visual Analogue Scale (VAS), dysmenorrhea symptoms scores and clinical efficacy were compared between the two groups.ResultThe VAS scores after the intervention and inthe first and second months of the follow-up study were significantly different from the pre-treatment score in the two groups (P<0.01); the VAS score of the 3-month follow-up was significantly different from the score before the intervention in the treatment group (P<0.01). There were significant differences in comparing the VAS score after the intervention and in the follow-up study between the two groups (P<0.01), and the treatment group was superior to the control group. The dysmenorrhea symptoms scoresdeclined significantly after the intervention and in the first and second months of the follow-up study in both groups (P<0.01); the dysmenorrhea symptoms score of the 3-month follow-up study decreased in the treatment group and was significantly different from the pre-treatment score (P<0.01). There were significant differences in comparing the dysmenorrhea symptoms scores in the second and third months of the follow-up study between the two groups (P<0.01). The total effective rate was 93.9% in the treatment group, significantly better than 62.5% in the control group (P<0.01).ConclusionWarm needling is effective in easing pain and improving the symptoms of dysmenorrhea in adenomyosis, and can produce a consistent efficacy after the termination of thetreatment; it's superior to NSAIDs in comparing both short-term and long-term treatment efficacies.