Ultrasound-guided high-intensity focused ultrasound ablation for uterine arteriovenous fistula: a case series.

PURPOSE: To evaluate the efficacy and safety of high-intensity focused ultrasound (HIFU) ablation in the treatment of uterine arteriovenous fistula (UAVF). MATERIALS AND METHODS: This case series included three patients diagnosed with acquired UAVF. All patients underwent routine laboratory tests, electrocardiography (ECG), chest X-ray, ultrasound, and pelvic contrast-enhanced magnetic resonance imaging (MRI). HIFU treatment was performed under sedation and analgesia using a Model JC Focused Ultrasound Tumor Therapeutic System (made by Chongqing Haifu Medical Technology Co. Ltd., China) with a B mode ultrasound device for treatment guidance. The treatment time, sonication power, sonication time, and complications were recorded. Follow-up evaluations were scheduled at 1-, 3-, 6-, and 12-month to assess symptom improvement and evaluate the post-treatment imaging. RESULTS: All patients completed HIFU treatment in a single session without any major complication. All patients complained of mild lower abdominal and sacrococcygeal pain. Typically, no special treatment is required. Following HIFU treatment, there was a significant relief in clinical symptoms, particularly abnormal uterine bleeding. Ultrasound examinations conducted one month after the treatment revealed a notable reduction in the volume of the lesion, ranging from 57% to 100%. Moreover, the efficacy and safety of HIFU treatment remained consistent during the 12-month follow-up period. CONCLUSION: HIFU ablation appears to be an effective and safe treatment modality for UAVF. It provides a noninvasive approach with favorable clinical outcomes.

Higher Circulating Lymphocytes and the Incidence of Pre-eclampsia and Eclampsia.

Excessive immune activation contributes to the onset of early dysfunction of the maternal-fetal interface, and it is closely linked to the development of pre-eclampsia. However, the effect of specific immune cells on the risk of pre-eclampsia and eclampsia remains controversial. We investigated the causal relationship between immune cells and pre-eclampsia and eclampsia. For exposure, we extracted genetic variants associated with immune cell-related traits, and for outcomes, we used summary genetic data of pre-eclampsia/eclampsia. A two-sample Mendelian randomization (MR) analysis was then performed to assess the causal relationship. Robustness of the MR results was then evaluated through colocalization analysis. We found that genetically proxied circulating lymphocyte absolute count was causally associated with total eclampsia (odds ratio (OR) = 1.53, 95% confidence interval (CI) (1.31-1.79), p = 1.15E - 07) and pre-eclampsia (OR = 1.50, 95% CI (1.28-1.77), p = 9.18E - 07); T cell absolute count was causally associated with total eclampsia (OR = 1.49, 95% CI (1.28-1.73), p = 2.73E - 07) and pre-eclampsia (OR = 1.47, 95% CI (1.25-1.72), p = 1.76E - 06). And CD28- CD25+ CD8+ T cell absolute count was causally associated with total eclampsia (OR = 1.83, 95% CI (1.44-2.32), p = 7.11E - 07) and pre-eclampsia (OR = 1.77, 95% CI (1.38-2.26), p = 6.55E - 06). Colocalization analysis revealed that immune cell-related traits shared the same variant with pre-eclampsia/eclampsia. Our study suggested causal effects of genetic predisposition to high lymphocyte absolute count levels, T cell absolute count, and CD28- CD25+ CD8+ T cell absolute count on eclampsia, particularly pre-eclampsia risk, providing crucial new insights into the potential prevention target for eclampsia and pre-eclampsia.

Peri-implantation estradiol level has no effect on pregnancy outcome in vitro fertilization- embryo transfer.

Background: The necessity of monitoring luteal endocrine functions in in vitro fertilization- embryo transfer (IVF-ET) remains uncertain. Specifically, the significance of luteal phase estradiol (E2) levels is a matter of debate in current literature. Objective: To assess the impact of luteal phase (day 11 after HCG trigger) estradiol levels on IVF-ET outcomes. Design: Twelve thousand five hundred and thirty-five (n = 12,535) IVF-ET cycles performed in our center between 2015 and 2021 were divided into 5 groups based on the middle and late luteal phase serum E2 (MllPSE2) level percentiles as follows: Group A < 50 pg/mL (N=500), group B 50 pg/mL≤E2<150 pg/mL (N=2545), group C 150 pg/mL≤E2<250 pg/mL (N=1327), group D 250 pg/mL≤E2<500 pg/mL (N=925), group E E2≥500 pg/mL (n=668). The clinical pregnancy rates, abortion rates, and live birth rates of each group were compared. Binary logistic regression analysis was carried out to assess the potential impact of MllPSE2 on the live birth rate (LBR). Results: No significant differences were found in various parameters when comparing the five groups. The level of MllPSE2 showed no significant difference between the pregnant group and the non-pregnant group. The binary logistic regression analysis model demonstrated that MllPSE2 was not significantly related to LBR. Conclusion: The influence of E2 during the peri-implantation period (day 11) on clinical outcome in IVF-ET is not affected, even if E2<50 pg/mL. It is speculated that ovarian-derived E2 in MllPSE2 is not deemed necessary for endometrial receptivity. Although caution is warranted due to the retrospective nature of the analysis and the potential for unmeasured confounding, it is argued that the need for luteal E2 monitoring in IVF-ET may be of questionable value.

Molecular Characterization of Cuproptosis-related lncRNAs: Defining Molecular Subtypes and a Prognostic Signature of Ovarian Cancer.

Cuproptosis, a newly discovered form of programmed cell death, relies on mitochondrial respiration, the chain of which has been found to be altered in ovarian cancer (OC). The current work probed into the effects of Cuproptosis on the prognosis, immune microenvironment and therapeutic response of OC based on Cuproptosis-related lncRNAs. Data on OC gene expression and clinical characteristics were collected from TCGA, ICGC and GEO databases, and mRNA and lncRNA were distinguished. Cuproptosis-related lncRNAs were screened for consensus clustering analysis. Differentially expressed lncRNAs (DElncRNAs) were identified between clusters, and least absolute shrinkage and selection operator (LASSO) and Cox regression analysis were performed to establish a prognostic signature. Its potential value in OC was evaluated by Gene Set Enrichment Analysis (GSEA), tumor cell mutation and immune microenvironment analysis, and response to immunotherapy and antineoplastic drugs. According to the classification scheme of Cuproptosis-related lncRNAs, OC was divided into four molecular subtypes, which were different in survival time, immune characteristics and somatic mutation. The prognostic signature between subtypes included 10 lncRNAs, which were significantly correlated with the prognosis, immune microenvironment related indexes, the expression of immune checkpoint molecules and the sensitivity of antineoplastic drug Paclitaxel and Gefitinib of OC. We examined the expression of ten LncRNAs in OC cell lines and found that LINC00189, ZFHX4-AS1, RPS6KA2-IT1 and C9orf106 were expressed elevated in OC cell lines, and LINC00861, LINC00582, DEPDC1-AS1, LINC01556, LEMD1-AS1, TYMSOS expression was decreased in OC cell lines. The results of CCK8 showed that the cell viability of OC cells decreased after inhibition of C9orf106, whereas the cell viability of OC cells increased after inhibition of LEMD1-AS1. This work revealed new Cuproptosis-related lncRNA molecular subtypes exhibiting tumor microenvironment (TME) heterogeneity for OC and proposed a prognostic signature that may have benefits in understanding the prognosis, pathological features and immune microenvironment of OC patients.

How to enhance the applicability of a risk prediction model for term small-for-gestational-age neonates in clinical settings?

OBJECTIVE: To construct a simple term small-for-gestational-age (SGA) neonate prediction model that is clinically practical. METHODS: This analysis was based on the Born in Guangzhou Cohort Study (BIGCS). Mothers who had a singleton pregnancy, delivered a term neonate, and had an ultrasonography within 30 + 0 to 32 + 6 weeks of gestation were included. Term SGA was defined with customized population percentiles. Prediction models were constructed with backward selection logistic regression in a four-step approach, where model 1 contained fetal biometrics only, models 2 and 3 included maternal features and a time factor (weeks between ultrasonography and delivery), respectively; and model 4 contained all features mentioned. The prediction performance of individual models was evaluated based on area under the curve (AUC) and a calibration test was performed. RESULTS: The prevalence of SGA in the study population of 21 346 women was 11.5%. With a complete-case analysis approach, data of 19 954 women were used for model construction and validation. The AUC of the four models were 0.781, 0.793, 0.823, and 0.834, respectively, and all were well-calibrated. Model 3 consisted of fetal biometrics and corrected for time to delivery was chosen as the final model to build risk prediction graphs for clinical use. CONCLUSION: A prediction model derived from fetal biometrics in early third trimester is satisfactory to predict SGA.

A systematic review and meta-analysis: clinical outcomes of recurrent pregnancy failure resulting from preimplantation genetic testing for aneuploidy.

Background: Preimplantation genetic testing for aneuploidy (PGT-A) is an emerging technology that aims to identify euploid embryos for transfer, reducing the risk of embryonic chromosomal abnormalities. However, the clinical benefits of PGT-A in recurrent pregnancy failure (RPF) patients, particularly in young RPF patients, remains uncertain. Objective and rationale: This meta-analysis aimed to determine whether RPF patients undergoing PGT-A had better clinical outcomes compared to those not undergoing PGT-A, thus assessing the value of PGT-A in clinical practice. Search methods: We systematically searched PubMed, the Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Data, and VIP Database for Chinese Technical Periodicals (VIP) from 2002 to 2022. Thirteen published studies involving 930 RPF patients screened using PGT-A and over 1,434 RPF patients screened without PGT-A were included in this meta-analysis. Clinical outcomes were evaluated based on embryo transfers after PGT-A (n=1,015) and without PGT-A (n=1,799). Clinical outcomes: The PGT-A group demonstrated superior clinical outcomes compared to the in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) group. The PGT-A group had a significantly higher implantation rate (IR) (RR=2.01, 95% CI: [1.73; 2.34]), clinical pregnancy rate (CPR) (RR=1.53, 95% CI: [1.36; 1.71]), ongoing pregnancy rate (OPR) (RR=1.76, 95% CI: [1.35; 2.29]), live birth rate (LBR) (RR=1.75, 95% CI: [1.51; 2.03]), and significantly lower clinical miscarriage rate (CMR) (RR=0.74, 95% CI: [0.54; 0.99]). Subgroup analysis based on patient age (under 35 years and 35 years or older) showed that both PGT-A subgroups had significantly better CPR (P<0.01) and LBR (P<0.05) values compared to the IVF/ICSI groups. Summary: This meta-analysis demonstrates that PGT-A in RPF patients, is associated with improved clinical outcomes, including higher IR, CPR, OPR, and LBR values, and lower CMR compared to the IVF/ICSI group. These findings support the positive clinical application of PGT-A in RPF patients. Systematic Review Registration: http://INPLASY.com, identifier INPLASY 202320118.

Prenatal diagnosis of paternal uniparental disomy for chromosome 2 in two fetuses with intrauterine growth restriction.

Uniparental disomy (UPD) is when all or part of the homologous chromosomes are inherited from only one of the two parents. Currently, UPD has been reported to occur for almost all chromosomes. In this study, we report two cases of UPD for chromosome 2 (UPD2) encountered during prenatal diagnosis. The ultrasound findings of the fetuses from two unrelated families showed intrauterine growth restriction. The karyotype analyses were normal. The two fetuses both had complete paternal chromosome 2 uniparental disomy detected by whole-exome sequencing, but their clinical outcomes were significantly different, with fetal arrest in case 1 and birth in case 2. In this report, we analyzed and discussed the phenotypes of the fetuses in these two cases and reviewed the literature on UPD2.

TRMT61B rs4563180 G>C variant reduces hepatoblastoma risk: a case-control study of seven medical centers.

N1-methyladenosine (m1A) is an essential chemical modification of RNA. Dysregulation of RNA m1A modification and m1A-related regulators is detected in several adult tumors. Whether aberrant RNA m1A modification is involved in hepatoblast carcinogenesis has not been reported. tRNA methyltransferase 61B (TRMT61B) is responsible for mitochondrial RNA m1A modification. Some evidence has shown that genetic variants of TRMT61B might contribute to cancer susceptibility; however, its roles in hepatoblastoma are unknown. This study attempted to discover novel hepatoblastoma susceptibility loci. With the TaqMan method, we examined genotypes of the TRMT61B rs4563180 G>C polymorphism among germline DNA samples from 313 cases and 1446 controls. The association of the rs4563180 G>C polymorphism with hepatoblastoma risk was estimated based on odds ratios (ORs) and 95% confidence intervals (CIs). We found that the TRMT61B rs4563180 G>C polymorphism correlated significantly with a reduction in hepatoblastoma risk (GC vs. GG: adjusted OR=0.65, 95% CI=0.49-0.85, P=0.002; GC/CC vs. GG: adjusted OR=0.66, 95% CI=0.51-0.85, P=0.002). In stratified analysis, significant associations were detected in children younger than 17 months old, girls, and subgroups with stage I+II or III+IV tumors. False-positive report probability analysis validated that children with the GC or CC genotype, particularly in those <17 months of age, had a decreased risk of hepatoblastoma. The rs4563180 G>C polymorphism also correlated with expression of TRMT61B and the nearby gene PPP1CB. We identified a high-quality biomarker measuring hepatoblastoma susceptibility, which may contribute to future screening programs.

Identifying a Novel Eight-NK Cell-related Gene Signature for Ovarian Cancer Prognosis Prediction.

BACKGROUND: Ovarian cancer (OVC) is the most common and costly tumor in the world with unfavorable overall survival and prognosis. This study is aimed to explore the prognostic value of natural killer cells related genes for OVC treatment. METHODS: RNA-seq and clinical information were acquired from the TCGA-OVC dataset (training dataset) and the GSE51800 dataset (validation dataset). Genes linked to NK cells were obtained from the immPort dataset. Moreover, ConsensusClusterPlus facilitated the screening of molecular subtypes. Following this, the risk model was established by LASSO analysis, and immune infiltration and immunotherapy were then detected by CIBERSORT, ssGSEA, ESTIMATE, and TIDE algorithms. RESULTS: Based on 23 NK cell-related genes with prognosis, TCGA-OVC samples were classified into two clusters, namely C1 and C2. Of these, C1 had better survival outcomes as well as enhanced immune infiltration and tumor stem cells. Additionally, it was more suitable for immunotherapy and was also sensitive to traditional chemotherapy drugs. The eight-gene prognosis model was constructed and verified via the GSE51800 dataset. Additionally, a high infiltration level of immune cells was observed in low-risk patients. Low-risk samples also benefited from immunotherapy and chemotherapy drugs. Finally, a nomogram and ROC curves were applied to validate model accuracy. CONCLUSION: The present study identified a RiskScore signature, which could stratify patients with different infiltration levels, immunotherapy, and chemotherapy drugs. Our study provided a basis for precisely evaluating OVC therapy and prognosis.

Comparison of pregnancy outcomes in infertile patients with different types of adenomyosis treated with high-intensity focused ultrasound.

OBJECTIVE: This study assessed the improvement of symptoms and pregnancy outcomes in infertile patients with various types of adenomyosis who were treated with high-intensity focused ultrasound (HIFU). MATERIALS AND METHODS: Between October 2017 and January 2022, 129 infertile patients with adenomyosis who wished to conceive were treated with HIFU. Based on the relationship between the adenomyotic lesion, the endometrium, and the subserosa of the uterus on magnetic resonance imaging, the adenomyotic lesions were divided into internal, external, intramural, and full-thickness types. Menstruation pain score, menstruation blood volume score, anti-Müllerian hormone (AMH) levels, reproductive results, pregnancy and delivery complications, and other clinical variables were compared among these four groups. RESULTS: Patients with external adenomyosis had the greatest menstrual distress, whereas patients with internal adenomyosis had the greatest menstrual blood volume. Dysmenorrhea and heavy menstruation were significantly improved after HIFU treatment in all groups. AMH levels were not significantly different before and six months after HIFU. Of the 129 patients, 50 (38.7%) became pregnant after HIFU, and patients with internal adenomyosis had the highest pregnancy rate. Patients with adenomyotic lesions located in the posterior wall of the uterus had a higher pregnancy rate than those with lesions located in the fundus of the uterus. CONCLUSIONS: The classification of adenomyosis is closely related to distinctions in clinical symptoms and pregnancy outcomes. Infertile patients with different types of adenomyosis could be effectively treated with HIFU. HIFU can be considered as an option for infertile patients with adenomyosis who want to maintain their fertility.

Focused ultrasound: a novel therapy for improving vaginal microecology in patients with high-risk HPV infection.

OBJECTIVES: To investigate changes in vaginal microecology in women with high-risk human papillomavirus (HR-HPV) infection after focused ultrasound (FU) treatment. MATERIALS AND METHODS: We collected vaginal secretions at the time of admission and 3 months after FU treatment from 169 women who received FU treatment for cervical HR-HPV infection between July 2020 and September 2022. Among them, there were 101 patients with cute vaginitis, we also collected their vaginal secretions after one week of drug treatment. These samples were evaluated for vaginal microecology and HPV-DNA examination. RESULTS: Of the 169 patients, 101 (59.7%) suffered from acute vaginitis at the time of admission. After one week of targeted antibiotics drug treatment, there were no pathogens or pus cells on the field of microscopic vision, but there was no significant difference(p > 0.05) in the diversity and density of vaginal flora, the proportion and function of Lactobacillus (H2O2 negative rate) between one week after treatment and at the time of admission. At the time of admission of the 169 patients, the normal flora rate was 40.3%, which increased to 93.5% three months after FU treatment. The differences in vaginal secretion parameters at the time of admission and 3 months after FU treatment were as follows: H2O2 negative rate (37.3% vs. 3.6%), leukocyte esterase positive rate (54.4% vs. 5.9%), sialidase positive rate (38.5% vs. 4.1%), bacterial vaginitis positive rate (55% vs. 4.7%), fungal vaginitis positive rate (44.4% vs. 5.9%), and trichomonal vaginitis positive rate (7.1% vs. 0). The difference was statistically significant (p < 0.01). The pH value and Nagent score at the time of admission were significantly higher than those three months after FU. Three months after FU, the positive rate of HPV was 5.8% in the group of patients with normal vaginal microecology at the time of admission and post-FU; it was 6.7% in the group of patients with abnormal vaginal microecology at the time of admission and normal vaginal microecology post-FU; and it was 100% in the group patients with abnormal vaginal microecology at the time of admission and post-FU. A significant difference was observed among the three groups (p < 0.01). CONCLUSION: FU is an effective treatment for patients with cervical HR-HPV infection. FU does not interfere with the vaginal microecology of HR-HPV positive patients with normal vaginal microecology.FU followed by antibiotic drug therapy for pathogens is beneficial to restore the function of Lactobacillus vaginalis in HR-HPV positive patients with acute vaginitis,so as to improve the vaginal microecology of HR-HPV positive patients with abnormal vaginal microecology.

HIFU as an alternative modality for patients with uterine fibroids who require fertility-sparing treatment.

OBJECTIVES: To compare pregnancy outcomes after high-intensity focused ultrasound ablation (HIFU), myomectomy and uterine artery embolization (UAE) for fertility-sparing patients with uterine fibroids and to investigate the possible mechanism of improving pregnancy by HIFU. MATERIALS AND METHODS: A meta-analysis of 54 studies containing 12,367 patients was conducted to compare the pregnancy outcomes of three fertility-sparing therapies. And a retrospective self-control study of 26 patients with uterine fibroids from May 2019 to December 2020 was performed to assess the blood flow impedance of bilateral uterine arteries before and after HIFU. RESULTS: In the analysis by treatment option, the pregnancy rate after myomectomy was 0.43 (95% CI 0.36-0.49), which was higher than 0.18 (95% CI 0.10-0.26) after HIFU, the latter was significantly higher than that after UAE (ratio 0.08, 95% CI 0.06-0.10). The miscarriage rate after HIFU was 0.08 (95% CI 0.04-0.12), which was similar to 0.15 (95% CI 0.09-0.21) after myomectomy and also similar to 0.16 after UAE (95% CI 0.01-0.30). In the subgroup analysis, women who received ultrasound guided HIFU (USgHIFU) were more likely to have ideal pregnancy outcomes than that after magnetic resonance imaging-guided HIFU. The pulsatility index and resistance index on the right side were significantly higher 3 months after HIFU than before (1.637 ± 0.435 vs. 1.845 ± 0.469; p = 0.033; 0.729 ± 0.141 vs. 0.784 ± 0.081, p = 0.039). CONCLUSIONS: HIFU, especially USgHIFU, may be an alternative fertility-sparing modality for patients with uterine fibroids over 40 years old. HIFU may contribute to improving pregnancy rates by elevating uterine blood flow impedance.

Exploration the global single-cell ecological landscape of adenomyosis-related cell clusters by single-cell RNA sequencing.

Background: Adenomyosis (AM) is a common benign uterine disease that threatens the normal life of patients. Cells associated with microenvironmental immune ecology are crucial in AM, although they are not as well understood at the cellular level. Methods: Single-cell sequencing (scRNA-seq) data were used to construct an AM global single-cell map, to further identify relevant cell clusters and infer chromosomal copy number variation (CNV) in AM samples. The biological functions of cell clusters were explored and cellular evolutionary processes were inferred by enrichment analysis and pseudotime analysis. In addition, a gene regulatory network (GRN) analysis was constructed to explore the regulatory role of transcription factors in AM progression. Results: We obtained the expression profiles of 42260 cells and identified 10 cell clusters. By comparing the differences in cell components between AM patients and controls, we found that significant abundance of endometrial cells (EC), epithelial cells (Ep), endothelial cells (En), and smooth muscle cells (SMC) in AM patients. Cell clusters with high CNV levels possessing tumour-like features existed in the ectopic endometrium samples. Moreover, the Ep clusters were significantly involved in leukocyte transendothelial cell migration and apoptosis, suggesting an association with cell apoptosis and migration. En clusters were mainly involved in pathways in cancer and apoptosis, indicating that En has certain malignant features. Conclusion: This study identified cell clusters with immune-related features, investigated the changes in the immune ecology of the microenvironment of these cells during AM, and provided a new strategy for the treatment of AM.

[Birth weights of singleton neonates of 14 Chinese ethnic groups in 11 cities of China]. / 中国11市14ä¸ªæ°‘æ—å•èƒŽå„¿å‡ºç”Ÿä½“é‡ç ”ç©¶.

OBJECTIVES: To develop the birth weight curves of the Chinese Han (26-41 weeks of gestation) and Zhuang (28-41 weeks of gestation) singleton neonates in 11 cities of China, as well as the birth weight means of full-term neonates of 14 Chinese ethnic groups. METHODS: The live singleton neonates who were born in 11 maternal and child health care hospitals from 11 cities of China between January 2017 and December 2020 were classified according to the mother's ethnic group. Birth weight means were calculated for the full-term neonates of each ethnic group. For the Han and Zhuang singleton neonates with a large sample size, the Lambda-Mu-Sigma (LMS) method was used to establish the birth weight percentile curves of the Han and Zhuang singleton neonates with different gestational ages. RESULTS: A total of 105 365 live singleton neonates were included, among whom the Han neonates had the highest number of 84 851 (26-41 weeks of gestation), followed by the Zhuang neonates (12 803 neonates with a gestational age of 28-41 weeks). The neonates of the other Chinese ethnic groups enrolled were live full-term singleton neonates, with a sample size of more than 100 neonates for each ethnic group. The 3rd-97th percentile curves of birth weight were established for the Han singleton neonates with a gestational age of 26-41 weeks and the Zhuang singleton neonates with a gestational age of 28-41 weeks. The birth weight curves of the Han singleton neonates at each gestational age were higher than those of the Zhuang singleton neonates. Birth weight means (3 199-3 499 g) and standard deviations were determined for 14 Chinese ethnic groups, i.e., Li, Mulao, Zhuang, Yao, Dong, Miao, Han, Buyi, Mongolian, Tujia, Yi, Hui, Man, and Korean ethnic groups. The Li ethnic group had the lowest birth weight, followed by the Mulao, Zhuang, Yao, Dong, Miao, Han, Buyi, Mongolian, Tujia, Yi, Hui, Man, and Korean ethnic groups. CONCLUSIONS: The 3rd-97th percentile curves of birth weight are developed for the Han (26-41 weeks of gestation) and Zhuang (28-41 weeks of gestation) singleton neonates in 11 cities of China, and birth weight means are determined for the full-term neonates of 14 Chinese ethnic groups in 11 cities of China, which provides a reference for evaluating the intrauterine growth of neonates in these ethnic groups.

Detection of four rare thalassemia variants using Single-molecule realtime sequencing.

Conventional methods for the diagnosis of thalassemia include gap polymerase chain reaction (Gap-PCR), reverse membrane hybridization (RDB), multiplex ligation-dependent probe amplification (MLPA) and Sanger sequencing. In this study, we used single molecule real-time technology (SMRT) sequencing and discovered four rare variants that have not been identified by conventional diagnostic methods for thalassemia. We also performed genotype and phenotype analyses on family members of thalassemia patients. The SMRT technology detected five cases in which the proband had abnormal results by conventional diagnostic methods or inconsistencies between the genotype and phenotype. The variants included two cases of an α-globin gene cluster 27,311 bp deletion, --27.3/αα (hg38 chr16:158664-185974), one case of an HS-40 region 16,079 bp deletion (hg38 chr16:100600-116678), one case of a rearrangement of -α3.7α1α2 on one allele and one case of a ß-globin gene cluster HBG1-HBG2 4,924 bp deletion (hg38 chr11:5249345-5254268). This study clarified the hematological phenotypes of four rare variants and indicated the application value of SMRT in the diagnosis of rare α-globin and ß-globin gene cluster deletions, gene recombination and deletion breakpoints. The SMRT method is a comprehensive one-step technology for the genetic diagnosis of thalassemia and is particularly suitable for the diagnosis of thalassemia with rare deletions or genetic recombination.

Decreased plasma levels of PDGF-BB, VEGF-A, and HIF-2α in preterm infants after ibuprofen treatment.

Introduction: Ibuprofen is one of the most common non-steroidal anti-inflammatory drugs used to close patent ductus arteriosus (PDA) in preterm infants. PDA is associated with bronchopulmonary dysplasia (BPD), while PDA closure by ibuprofen did not reduce the incidence of BPD or death. Previous studies have indicated an anti-angiogenesis effect of ibuprofen. This study investigated the change of angiogenic factors after ibuprofen treatment in preterm infants. Methods: Preterm infants with hemodynamically significant PDA (hsPDA) were included. After confirmed hsPDA by color doppler ultrasonography within 1 week after birth, infants received oral ibuprofen for three continuous days. Paired plasma before and after the ibuprofen treatment was collected and measured by ELISA to determine the concentrations of platelet-derived growth factor-BB (PDGF-BB) and vascular endothelial growth factor A (VEGF-A), and hypoxia-inducible factor-2α (HIF-2α). Results: 17 paired plasma from infants with hsPDA were collected. The concentration of PDGF-BB and VEGF-A significantly decreased after ibuprofen treatment (1,908 vs. 442 pg/mL for PDGF-BB, 379 vs. 174 pg/mL for VEGF-A). HIF-2α level showed a tendency to decrease after ibuprofen treatment, although the reduction was not statistically significant (p = 0.077). Conclusion: This study demonstrated decreased vascular growth factors after ibuprofen exposure in hsPDA infants.

Birth weight curves of twin neonates with a gestational age of 25-40 weeks and their regional differences in 11 cities of China: an analysis of 17 256 cases. / 中国11市17 256例胎龄25~40周双胎儿出生体重曲线及地区差异特征.

OBJECTIVES: To develop the birth weight curve of twin neonates with a gestational age of 25-40 weeks, and to investigate the regional differences of the birth weight curve. METHODS: A total of 11 maternal and child health care hospitals with more than 7 000 neonates delivered annually were selected in 11 cities of China (Haikou, Guangzhou, Liuzhou, Guilin, Quanzhou, Shenzhen, Chongqing, Chengdu, Changsha, Ningbo, and Lianyungang), and all live twin neonates delivered in the 11 hospitals from January 1, 2017 to December 31, 2020 were enrolled for the development of birth weight curves. RESULTS: A total of 17 256 twin neonates with a gestational age of 25-40 weeks from the 11 cities were included in the study. The reference values of the 3rd-97th percentiles of birth weight of twin neonates for the total of the 11 cities and for each of the 11 cities in China were established, and the birth weight percentile curves were drawn. The birth weight curve level of twin neonates in Liuzhou was lower than the average level of the 11 cities; the birth weight curve level of twin neonates in Ningbo was higher than the average level of the 11 cities; the birth weight curve level of twin neonates in Lianyungang was obviously higher than the average level of the 11 cities; the birth weight curve level of twin neonates in other 8 cities was almost the same as the average level of the 11 cities. CONCLUSIONS: The reference values of the 3rd-97th percentiles of birth weight of twin neonates for the total of the 11 cities and for each of the 11 cities are developed, which can be used as a reference for evaluating the intrauterine growth of twin neonates in the region. The level of intrauterine growth of twin neonates in some cities is different from the average level of the 11 cities of China.

[Birth weight curves of singleton neonates with a gestational age of 24-42 weeks and their regional differences in 11 cities of China: an analysis of 93 720 cases]. / 中国11市93 720例胎龄24~42å‘¨å•èƒŽå„¿å‡ºç”Ÿä½“é‡æ›²çº¿åŠå ¶åœ°åŒºå·®å¼‚ç‰¹å¾.

OBJECTIVES: To develop the birth weight curve of singleton neonates with a gestational age of 24-42 weeks, and to investigate the regional differences of the birth weight curve. METHODS: A total of 11 maternal and child health hospitals with more than 7 000 neonates delivered annually were selected in 11 cities of China (Haikou, Guangzhou, Shenzhen, Liuzhou, Guilin, Quanzhou, Chongqing, Chengdu, Changsha, Ningbo, and Lianyungang), and all live singleton neonates delivered in the 11 hospitals from January 1, 2017 to December 31, 2020 were enrolled for the development of birth weight curves. RESULTS: A total of 93 720 singleton neonates with a gestational age of 24-42 weeks from the 11 cities were included in the study. The reference values of the 3rd-97th percentiles of birth weight of singleton neonates for the total of the 11 cities and for each of the 11 cities were established, and the birth weight percentile curves were drawn. The birth weight curve level of singleton neonates in Shenzhen and Quanzhou was almost the same as the average level of the 11 cities; the birth weight curve level of singleton neonates in Haikou, Guangzhou, Guilin, and Liuzhou was slightly lower than the average level of the 11 cities; the birth weight curve level of singleton neonates in Chongqing, Chengdu, and Changsha was slightly higher than the average level of the 11 cities; the birth weight curve level of singleton neonates in Ningbo and Lianyungang was higher than the average level of the 11 cities. The average birth weight curve level of singleton neonates in the 11 cities were very close to that of China Neonatal Cooperation Network in 2011-2014. CONCLUSIONS: The reference values of the 3rd-97th percentiles of birth weight of singleton neonates for the total of the 11 cities and for each of the 11 cities are developed, which can be used as a reference for evaluating the intrauterine growth of singleton neonates in the region. The level of intrauterine growth of neonates in some cities is different from the national level.

Effectiveness of containment strategies in preventing SARS-CoV-2 transmission.

BACKGROUND: Despite substantial resources deployed to curb SARS-CoV-2 transmission, controlling the COVID-19 pandemic has been a major challenge. New variants of the virus are frequently emerging leading to new waves of infection and re-introduction of control measures. In this study, we assessed the effectiveness of containment strategies implemented in the early phase of the pandemic. METHODS: Real-world data for COVID-19 cases was retrieved for the period Jan 1 to May 1, 2020 from a number of different sources, including PubMed, MEDLINE, Facebook, Epidemic Forecasting and Google Mobility Reports. We analyzed data for 18 countries/regions that deployed containment strategies such as travel restrictions, lockdowns, stay-at-home requests, school/public events closure, social distancing, and exposure history information management (digital contact tracing, DCT). Primary outcome measure was the change in the number of new cases over 30 days before and after deployment of a control measure. We also compared the effectiveness of centralized versus decentralized DCT. Time series data for COVID-19 were analyzed using Mann-Kendall (M-K) trend tests to investigate the impact of these measures on changes in the number of new cases. The rate of change in the number of new cases was compared using M-K z-values and Sen's slope. RESULTS: In spite of the widespread implementation of conventional strategies such as lockdowns, travel restrictions, social distancing, school closures, and stay-at-home requests, analysis revealed that these measures could not prevent the spread of the virus. However, countries which adopted DCT with centralized data storage were more likely to contain the spread. CONCLUSIONS: Centralized DCT was more effective in containing the spread of COVID-19. Early implementation of centralized DCT should be considered in future outbreaks. However, challenges such as public acceptance, data security and privacy concerns will need to be addressed.