Valvuloplasty of fetal pulmonary atresia with intact ventricular septum and hypoplastic right heart: Mid-term follow-up results

ObjectiveThis study aimed to analyze and evaluate the results of mid-term follow-up after fetal pulmonary valvuloplasty (FPV) in fetuses with pulmonary atresia with intact ventricular septum (PA/IVS).MethodsFrom August 31, 2018, to May 31, 2019, seven fetuses with PA/IVS and hypoplastic right heart were included in this study. All underwent echocardiography by the same specialist and were operated on by the same team. Intervention and echocardiography data were collected, and changes in the associated indices noted during follow-up were analyzed.ResultsAll seven fetuses successfully underwent FPV. The median gestational age at FPV was 27.54 weeks. The average FPV procedural time was 6 ?min. Persistent bradycardia requiring treatment occurred in 4/7 procedures. Finally, five pregnancies were successfully delivered, and the other two were aborted. Compared to data before fetal cardiac interventions (FCI), tricuspid valve annulus diameter/mitral valve annulus diameter (TV/MV) and right ventricle diameter/left ventricle diameter (RV/LV) of all fetuses had progressively improved. The maximum tricuspid regurgitation velocity decreased from 4.60 ?m/s to 3.64 ?m/s. The average follow-up time was 30.40 ?± ?2.05 months. During the follow-up period, the diameter of the tricuspid valve ring in five children continued to improve, and the development rate of the tricuspid valve was relatively obvious from 6 months to 1 year after birth. However, the development of the right ventricle after birth was relatively slow. It was discovered that there were individual variations in the development of the right ventricle during follow-up.ConclusionThe findings support the potential for the development of the right ventricle and tricuspid valve in fetuses with PA/IVS who underwent FCI. Development of the right ventricle and tricuspid valve does not occur synchronously during pregnancy. The right ventricle develops rapidly in utero, but the development of tricuspid valve is more apparent after birth than in utero.     

Association Between Abnormal Fetal Head Growth and Autism Spectrum Disorder

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Prenatal diagnosis of fetal right ventricular diverticulum with massive pericardial effusion in one of monochorionic diamniotic twins: a case report with a favorable outcome following in utero pericardiocentesis

BackgroundCongenital ventricular diverticulum is a rare abnormality that may occur as an isolated malformation. Most cases are accompanied by pericardial effusion. Prenatal counseling can be difficult because the prognosis is uncertain and there is no consensus approach to prenatal management.Case presentation: We describe a case of congenital cardiac diverticulum complicated by large pericardial effusion in one of monochorionic diamniotic twins. The case was diagnosed by ultrasonography at 21 weeks of gestation. Therapeutic pericardiocentesis at 22 weeks resulted in complete resolution of the effusion and led to a favorable fetal outcome. We summarize the interventions and pregnancy outcomes in cases of cardiac diverticula reported in the literature.ConclusionsBetter awareness of clinical features, in utero therapies, and pregnancy outcomes could help define and improve prenatal management of congenital ventricular diverticula.     

Development of an IgG-Fc fusion COVID-19 subunit vaccine,AKS-452

AKS-452 is a biologically-engineered vaccine comprising an Fc fusion protein of the SARS-CoV-2 viral spike protein receptor binding domain antigen (Ag) and human IgG1 Fc (SP/RBD-Fc) in clinical development for the induction and augmentation of neutralizing IgG titers against SARS-CoV-2 viral infection to address the COVID-19 pandemic. The Fc moiety is designed to enhance immunogenicity by increasing uptake via Fc-receptors (FcγR) on Ag-presenting cells (APCs) and prolonging exposure due to neonatal Fc receptor (FcRn) recycling. AKS-452 induced approximately 20-fold greater neutralizing IgG titers in mice relative to those induced by SP/RBD without the Fc moiety and induced comparable long-term neutralizing titers with a single dose vs. two doses. To further enhance immunogenicity, AKS-452 was evaluated in formulations containing a panel of adjuvants in which the water-in-oil adjuvant, Montanide™ ISA 720, enhanced neutralizing IgG titers by approximately 7-fold after one and two doses in mice, including the neutralization of live SARS-CoV-2 virus infection of VERO-E6 cells. Furthermore, ISA 720-adjuvanted AKS-452 was immunogenic in rabbits and non-human primates (NHPs) and protected from infection and clinical symptoms with live SARS-CoV-2 virus in NHPs (USA-WA1/2020 viral strain) and the K18 human ACE2-trangenic (K18-huACE2-Tg) mouse (South African B.1.351 viral variant). These preclinical studies support the initiation of Phase I clinical studies with adjuvanted AKS-452 with the expectation that this room-temperature stable, Fc-fusion subunit vaccine can be rapidly and inexpensively manufactured to provide billions of doses per year especially in regions where the cold-chain is difficult to maintain.     

补肾壮督方联合阿仑膦酸钠及骨水泥分期灌注椎体后凸成形术对kummell病远期临床疗效和血清标志物的影响＊

目的 探讨补肾壮督方联合阿仑膦酸钠及骨水泥分期灌注椎体后凸成形术对kummell病远期临床疗效和血清标志物的影响。方法 选取90例2019年1月-2020年3月因kummell病住院手术治疗的患者，随机分为试验组45例和对照组45例。对照组给予骨水泥分期灌注椎体后凸成形术，术后口服阿仑膦酸钠治疗，试验组术后加用补肾壮督方口服治疗。记录两组术中骨水泥注入量。采用VAS疼痛评分标准评估术后疼痛改善情况，采用ODI评分评估功能障碍改善情况。采用伤椎前缘高度比值和伤椎椎体楔形角评估脊柱稳定性。采用碱性磷酸酶（ALP），骨钙素（OC），骨保护素（OPG）评估治疗前后血清骨形成情况。结果 与对照组比较，试验组术后第3天VAS疼痛评分明显低于对照组，差异有统计学意义（P<0.05）；试验组术后第3天、术后6个月和术后12个月ODI评分明显低于对照组，差异有统计学意义（P<0.05）；试验组术后6个月和术后12个月伤椎前缘高度比值明显高于对照组，差异有统计学意义（P<0.05）；试验组术后6个月和术后12个月伤椎椎体楔形角明显低于对照组，差异有统计学意义（P<0.05）。试验组术后6个月和术后12个月碱性磷酸酶（ALP），骨钙素（OC），骨保护素（OPG）明显高于对照组，差异有统计学意义（P<0.05）。结论 补肾壮督方联合阿仑膦酸钠及骨水泥分期灌注椎体后凸成形术治疗kummell病可加快术后患者疼痛改善和功能恢复，促进骨形成，有效抑制患者中远期椎体压缩塌陷，维持脊柱稳定性。     

丹青胶囊联合他扎罗汀倍他米松治疗银屑病的临床研究

目的 探讨丹青胶囊联合他扎罗汀倍他米松治疗银屑病的临床疗效.方法 选取2019年6月—2021年6月在天津市职业病防治院门诊皮肤科就诊治疗的114例银屑病患者,根据随机数字法分为对照组和治疗组,每组各57例.对照组患者给予他扎罗汀倍他米松乳膏,洗净患处,待皮肤干爽后,将适量本品均匀涂抹于患处,1次/d.治疗组患者在对照组治疗基础上口服丹青胶囊,4粒/次,3次/d.两组患者均连续治疗7 d.观察两组患者的临床疗效和临床症状好转时间,比较两组治疗前与治疗1、4、8周的皮损面积和严重程度指数(PASI)评分和血清炎性因子水平.结果 治疗后,治疗组总有效率是98.25％,显著高于对照组的82.46％(P<0.05).治疗后,治疗组患者皮损暗红、皮损肥厚、皮肤瘙痒、皮肤疼痛等症状好转时间均显著短于对照组(P<0.05).治疗后,两组PASI评分均较治疗前显著降低(P<0.05);治疗1、4、8周治疗组PASI评分显著低于对照组(P<0.05).治疗后,两组患者血清炎性因子白细胞介素6(IL-6)、白细胞介素17(IL-17)、肿瘤坏死因子α(TNF-α)、干扰素-γ(IFN-γ)水平均较治疗前显著降低(P<0.05);治疗后,治疗组血清炎性因子水平显著低于对照组(P<0.05).结论 丹青胶囊联合他扎罗汀倍他米松治疗银屑病效果明显,能显著降低炎性因子水平,并有助于改善皮损情况,值得临床推广应用.     

The increase in bone mineral density by bisphosphonate with active vitamin D analog is associated with the serum calcium level within the reference interval in postmenopausal osteoporosis

Objectives: To examine the factors associated with increase in lumbar spine bone mineral density (LS-BMD) by bisphosphonates (BPs) with active vitamin D analog (aVD).

Methods: Two independent postmenopausal osteoporotic patients treated by BPs with aVD for 24 months (Study 1: n?=?93, Study 2: n?=?99) were retrospectively analyzed.

Results: In Study 1, LS-BMD of the patients significantly increased for 24 m (5.4%, p?r²: 0.088, p?=?.02). While average sCa of the patients was 9.2?mg/dL before treatment, it increased time-dependently to 9.6?mg/dL for 24 m by treatment. As each patient had their LS-BMD five times during the study, there were four instances of %LS-BMD in each patient, resulting in 372 instances of %LS-BMD in Study 1. The smallest Akaike’s information criterion value for the most appropriate cut-off levels of sCa for %LS-BMD by treatment every 6 m was 9.3?mg/dL. The %LS-BMD by treatment for 6 m during 24 m period in patients with sCa ≥9.3?mg/dL (1.5%) was significantly higher than that in patients with sCa <9.3?mg/dL (0.8%, p?=?.038). The results of Study 2 were similar to those of Study 1, confirming the phenomena observed.

Conclusion: sCa was associated with an increased LS-BMD by BPs with aVD.     

Intrauterine fetal resuscitation

The delivery of oxygen to the fetus is dependent on adequate maternal blood oxygen concentration, uterine blood supply, placental transfer and fetal gas transport. Any disturbance in these factors, singly or in combination, can result in progressive fetal hypoxia and acidosis. The term fetal distress is non-specific but is usually applied to certain characteristic features on electronic fetal monitoring, confirmed if possible by fetal blood sampling. The aim of intrauterine fetal resuscitation (IUFR) measures is to increase oxygen delivery to the placenta and umbilical blood flow in an attempt to reverse fetal hypoxia and acidosis, so that labour may continue safely or to improve the fetal condition while arranging urgent delivery. IUFR measures include maternal re-positioning into left lateral or alternatives (i.e. right lateral or knee–elbow if necessary), rapid infusion of 1000 ml crystalloid (except in fluid-restricted or pre-eclamptic patients), decreasing uterine contractions by stopping oxytocics and administering acute tocolytics (terbutaline 250 μg SC or IV, glyceryl trinitrate 60–180 μg IV or sublingual spray, two puffs). A vasopressor (i.e. ephedrine) may be required in cases of maternal hypotension.     

Investigation of the mechanisms of Genkwa Flos hepatotoxicity by a cell metabolomics strategy combined with serum pharmacology in HL-7702 liver cells

1. To investigate Genkwa Flos hepatotoxicity, a cell metabolomics strategy combined with serum pharmacology was performed on human HL-7702 liver cells in this study.

2. Firstly, cell viability and biochemical indicators were determined and the cell morphology was observed to confirm the cell injury and develop a cell hepatotoxicity model. Then, with the help of cell metabolomics based on UPLC-MS, the Genkwa Flos group samples were completely separated from the blank group samples in the score plots and seven upregulated as well as two down-regulated putative biomarkers in the loading plot were identified and confirmed. Besides, two signal molecules and four enzymes involved in biosynthesis pathway of lysophosphatidylcholine and the sphingosine kinase/sphingosine-1-phosphate pathway were determined to investigate the relationship between Genkwa Flos hepatotoxicity and these two classic pathways. Finally, the metabolic pathways related to specific biomarkers and two classic metabolic pathways were analyzed to explain the possible mechanism of Genkwa Flos hepatotoxicity.

3. Based on the results, lipid peroxidation and oxidative stress, phospholipase A₂/lysophosphatidylcholine pathway, the disturbance of sphingosine-1-phosphate metabolic profile centered on sphingosine kinase/sphingosine-1-phosphate pathway and fatty acid metabolism might be critical participators in the progression of liver injury induced by Genkwa Flos.