Tetrabutylammonium Bromide (TBAB)-Promoted, Pd/Cu-Catalyzed Sonogashira Coupling of N-Tosyl Aryltriazenes.

Sonogashira coupling of N-tosyl aryltriazenes is reported to offer arylalkynes in yields up to 92% with the aid of tetrabutylammonium bromide (TBAB) as a dual activator for both the palladium catalyst and aryltriazenes. Common functional groups could be well tolerated, although large electronic effects from alkynes were observed. TBAB-assisted oxidative addition of palladium(0) to aryltriazene instead of in situ formed arylhalide has been proposed to initiate the catalytic cycle.

Mid-term Clinical Outcomes of "Light Bulb" Core Decompression with Arthroscopic Assistance in Peri-collapse Osteonecrosis of the Femoral Head: A Retrospective Comparative Study.

OBJECTIVE: Nontraumatic osteonecrosis of the femoral head (ONFH) is commonly encountered in orthopedics. Without early clinical intervention, most patients with peri-collapse of the ONFH will develop femoral head necrosis and eventually require hip replacement surgery. The aim of this study is to evaluate clinical outcomes in patients with ONFH who underwent "light bulb" core decompression (CD) with arthroscopic assistance and to compare them with the outcomes of those treated with traditional procedures. METHODS: A retrospective review of patients with Stage II and IIIA (Peri-collapse) radiographic findings based on the Association Research Circulation Osseous (ARCO) stage for ONFH who underwent "light bulb" CD with or without arthroscopic assistance by a single-surgeon team between March 2014 and December 2018 was performed. All patients were followed up for a minimum of 2 years. The visual analogue scale (VAS) pain score, Harris hip score (HHS), and radiological imaging were evaluated. The categorical parameters were analyzed by chi-square test and the continuous variables conforming to a normal distribution were analyzed by Student's t-test. RESULTS: The study included a total of 39 patients (18 and 21 patients in the with and without arthroscopic assistance groups, respectively), with a mean age of 40.3 years and a mean follow-up of 22.2 months. Overall, there was a better VAS score in the arthroscopic assistance group than in the control group (p < 0.05), There was a significant difference in HHS (80.1 ± 9.2 vs 75.1 ± 12.7) at the last follow-up (p < 0.05). The rate of good and excellent outcomes was 94%. Similarly, there was no significant difference in the total rate of complications or conversion to THA. CONCLUSION: With arthroscopic assistance, "light bulb" CD could be achieved via hip arthroscopy with less trauma, and it offered the opportunity for more precise evaluation and monitoring for therapy and yielded better VAS scores after surgery and better hip function outcomes at the last follow-up.

Cascaded momentum-space polarization filters enabled label-free black-field microscopy for single nanoparticles analysis.

Label-free optical imaging of single-nanometer-scale matter is extremely important for a variety of biomedical, physical, and chemical investigations. One central challenge is that the background intensity is much stronger than the intensity of the scattering light from single nano-objects. Here, we propose an optical module comprising cascaded momentum-space polarization filters that can perform vector field modulation to block most of the background field and result in an almost black background; in contrast, only a small proportion of the scattering field is blocked, leading to obvious imaging contrast enhancement. This module can be installed in various optical microscopies to realize a black-field microscopy. Various single nano-objects with dimensions smaller than 20 nm appear distinctly in the black-field images. The chemical reactions occurring on single nanocrystals with edge lengths of approximately 10 nm are in situ real-time monitored by using the black-field microscopy. This label-free black-field microscopy is highly promising for a wide range of future multidisciplinary science applications.

Comparative analysis of in-silico tools in identifying pathogenic variants in dominant inherited retinal diseases.

Inherited retinal diseases (IRDs) are a group of rare genetic eye conditions that cause blindness. Despite progress in identifying genes associated with IRDs, improvements are necessary for classifying rare autosomal dominant (AD) disorders. AD diseases are highly heterogenous, with causal variants being restricted to specific amino acid changes within certain protein domains, making AD conditions difficult to classify. Here, we aim to determine the top-performing in-silico tools for predicting the pathogenicity of AD IRD variants. We annotated variants from ClinVar and benchmarked 39 variant classifier tools on IRD genes, split by inheritance pattern. Using area-under-the-curve (AUC) analysis, we determined the top-performing tools and defined thresholds for variant pathogenicity. Top-performing tools were assessed using genome sequencing on a cohort of participants with IRDs of unknown etiology. MutScore achieved the highest accuracy within AD genes, yielding an AUC of 0.969. When filtering for AD gain-of-function and dominant negative variants, BayesDel had the highest accuracy with an AUC of 0.997. Five participants with variants in NR2E3, RHO, GUCA1A, and GUCY2D were confirmed to have dominantly inherited disease based on pedigree, phenotype, and segregation analysis. We identified two uncharacterized variants in GUCA1A (c.428T>A, p.Ile143Thr) and RHO (c.631C>G, p.His211Asp) in three participants. Our findings support using a multi-classifier approach comprised of new missense classifier tools to identify pathogenic variants in participants with AD IRDs. Our results provide a foundation for improved genetic diagnosis for people with IRDs.

Celastrol ameliorates energy metabolism dysfunction of hypertensive rats by dilating vessels to improve hemodynamics.

The impact of hypertension on tissue and organ damage is mediated through its influence on the structure and function of blood vessels. This study aimed to examine the potential of celastrol, a bioactive compound derived from Tripterygium wilfordii Hook F, in mitigating hypertension-induced energy metabolism disorder and enhancing blood perfusion and vasodilation. In order to investigate this phenomenon, we conducted in vivo experiments on renovascular hypertensive rats, employing indirect calorimetry to measure energy metabolism and laser speckle contrast imaging to evaluate hemodynamics. In vitro, we assessed the vasodilatory effects of celastrol on the basilar artery and superior mesenteric artery of rats using the Multi Wires Myograph System. Furthermore, we conducted preliminary investigations to elucidate the underlying mechanism. Moreover, administration of celastrol at doses of 1 and 2 mg/kg yielded a notable enhancement in blood flow ranging from 6 to 31% across different cerebral and mesenteric vessels in hypertensive rats. Furthermore, celastrol demonstrated a concentration-dependent (1 × 10-7 to 1 × 10-5 M) arterial dilation, independent of endothelial function. This vasodilatory effect could potentially be attributed to the inhibition of Ca2+ channels on vascular smooth muscle cells induced by celastrol. These findings imply that celastrol has the potential to ameliorate hemodynamics through vasodilation, thereby alleviating energy metabolism dysfunctions in hypertensive rats. Consequently, celastrol may hold promise as a novel therapeutic agent for the treatment of hypertension.

Current state and challenges in respiratory syncytial virus drug discovery and development.

Human respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections (LRTI) in young children and elderly people worldwide. Recent significant progress in our understanding of the structure and function of RSV proteins has led to the discovery of several clinical candidates targeting RSV fusion and replication. These include both the development of novel small molecule interventions and the isolation of potent monoclonal antibodies. In this review, we summarize the state-of-the-art of RSV drug discovery, with a focus on the characteristics of the candidates that reached the clinical stage of development. We also discuss the lessons learned from failed and discontinued clinical developments and highlight the challenges that remain for development of RSV therapies.

De novel heterozygous copy number deletion on 7q31.31-7q31.32 involving TSPAN12 gene with familial exudative vitreoretinopathy in a Chinese family.

AIM: To investigate the genetic and clinical characteristics of patients with a large heterozygous copy number deletion on 7q31.31-7q31.32. METHODS: A family with familial exudative vitreoretinopathy (FEVR) phenotype was included in the study. Whole-exome sequencing (WES) was initially used to locate copy number variations (CNVs) on 7q31.31-31.32, but failed to detect the precise breakpoint. The long-read sequencing, Oxford Nanopore sequencing Technology (ONT) was used to get the accurate breakpoint which is verified by quantitative real-time polymerase chain reaction (QPCR) and Sanger Sequencing. RESULTS: The proband, along with her father and younger brother, were found to have a heterozygous 4.5 Mb CNV deletion located on 7q31.31-31.32, which included the FEVR-related gene TSPAN12. The specific deletion was confirmed as del(7)(q31.31q31.32)chr7:g.119451239_123956818del. The proband exhibited a phase 2A FEVR phenotype, characterized by a falciform retinal fold, macular dragging, and peripheral neovascularization with leaking of fluorescence. These symptoms led to a significant decrease in visual acuity in both eyes. On the other hand, the affected father and younger brother showed a milder phenotype. CONCLUSION: The heterozygous CNV deletion located on 7q31.31-7q31.32 is associated with the FEVR phenotype. The use of long-read sequencing techniques is essential for accurate molecular diagnosis of genetic disorders.

[Finite element analysis of artificial ankle elastic improved inserts].

Objective: To discuss the influence of artificial ankle elastic improved inserts (hereinafter referred to as "improved inserts") in reducing prosthesis micromotion and improving joint surface contact mechanics by finite element analysis. Methods: Based on the original insert of INBONE Ⅱ implant system (model A), four kinds of improved inserts were constructed by adding arc or platform type flexible layer with thickness of 1.3 or 2.6 mm, respectively. They were Flying goose type_1.3 elastic improved insert (model B), Flying goose type_2.6 elastic improved insert (model C), Platform type_1.3 elastic improved insert (model D), Platform type_2.6 elastic improved insert (model E). Then, the CT data of right ankle at neutral position of a healthy adult male volunteer was collected, and finite element models of total ankle replacement (TAR) was constructed based on model A-E prostheses by software of Mimics 19.0, Geomagic wrap 2017, Creo 6.0, Hypermesh 14.0, and Abaqus 6.14. Finally, the differences of bone-metal prosthesis interface micromotion and articular surface contact behavior between different models were investigated under ISO gait load. Results: The tibia/talus-metal prosthesis interfaces micromotion of the five TAR models gradually increased during the support phase, then gradually fell back after entering the swing phase. The improved models (models B-E) showed lower bone-metal prosthesis interface micromotion when compared with the original model (model A), but there was no significant difference among models A-E ( P>0.05). The maximum micromotion of tibia appeared at the dome of the tibial bone groove, and the ​​micromotion area was the largest in model A and the smallest in model E. The maximum micromotion of talus appeared at the posterior surface of the central bone groove, and there was no difference in the micromotion area among models A-E. The contact area of the articular surface of the insert/talus prosthesis in each group increased in the support phase and decreased in the swing phase during the gait cycle. Compared with model A, the articular surface contact area of models B-E increased, but there was no significant difference among models A-E ( P>0.05). The change trend of the maximum stress on the articular surface of the inserts/talus prosthesis was similar to that of the contact area. Only the maximum contact stress of the insert joint surface of models D and E was lower than that of model A, while the maximum contact stress of the talar prosthesis joint surface of models B-E was lower than that of model A, but there was no significant difference among models A-E ( P>0.05). The high stress area of the lateral articular surface of the improved inserts significantly reduced, and the articular surface stress distribution of the talus prosthesis was more uniform. Conclusion: Adding a flexible layer in the insert can improve the elasticity of the overall component, which is beneficial to absorb the impact force of the artificial ankle joint, thereby reducing interface micromotion and improving contact behavior. The mechanical properties of the inserts designed with the platform type and thicker flexible layer are better.

Inverse design of chiral functional films by a robotic AI-guided system.

Artificial chiral materials and nanostructures with strong and tuneable chiroptical activities, including sign, magnitude, and wavelength distribution, are useful owing to their potential applications in chiral sensing, enantioselective catalysis, and chiroptical devices. Thus, the inverse design and customized manufacturing of these materials is highly desirable. Here, we use an artificial intelligence (AI) guided robotic chemist to accurately predict chiroptical activities from the experimental absorption spectra and structure/process parameters, and generate chiral films with targeted chiroptical activities across the full visible spectrum. The robotic AI-chemist carries out the entire process, including chiral film construction, characterization, and testing. A machine learned reverse design model using spectrum embedded descriptors is developed to predict optimal structure/process parameters for any targeted chiroptical property. A series of chiral films with a dissymmetry factor as high as 1.9 (gabs ~ 1.9) are identified out of more than 100 million possible structures, and their feasible application in circular polarization-selective color filters for multiplex laser display and switchable circularly polarized (CP) luminescence is demonstrated. Our findings not only provide chiral films with the highest reported chiroptical activity, but also have great fundamental value for the inverse design of chiroptical materials.

Mechanoredox/Nickel Co-Catalyzed Cross Electrophile Coupling of Benzotriazinones with Alkyl (Pseudo)halides.

An air-tolerant mechanoredox/nickel cocatalyzed cross electrophile coupling of benzotriazinones with alkyl (pseudo)halides is developed by liquid-assisting grinding in the presence of manganese powders and strontium titanate as a reductant and a cocatalyst, respectively. Mechanical activation of metal surfaces via ball milling eliminates the chemical activator for manganese, while mechanoredox cocatalysis of strontium titanate remarkably improves the aryl/alkyl cross electrophile coupling via piezoelectricity-mediated radical generation from alkyl halides. Both benzotriazinones and alkyl (pseudo)halides display reactivities in the mechanoredox/nickel cocatalysis different from those of conventional thermal chemistry in solution. The scope of the reaction is demonstrated with 26 examples, showing a high chemoselectivity of bromides vs chlorides.

Identification of circRNA-associated ceRNA networks in peripheral blood mononuclear cells as potential biomarkers for chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD), which is a common respiratory disorder with high morbidity and mortality globally, has a complex pathogenesis that is not fully understood. Some circular RNAs (circRNAs) have been recognized to serve as miRNA sponges for regulating target RNA transcripts during the processes of human diseases. In the present study, we aimed to investigate novel circRNA-associated biomarkers for COPD, 245 differentially expressed circRNAs were identified, including 111 up-regulated and 134 down-regulated circRNAs. These candidate circRNAs were enriched in inflammation-associated pathways (such as mTOR, B-cell receptor, and NF-κB signaling pathways) via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. A combination of two circRNAs (up-regulated hsa_circ_0067209 and down-regulated hsa_circ_0000673) demonstrated good diagnostic value (area under the receiver operating characteristic curve [AUC] = 0.866) for COPD by receiver operating characteristic curve (ROC) analysis and qRT-PCR validation. Subsequently, hsa-miR-8082 and hsa-miR-1248 were identified as targets for hsa_circ_0067209 and hsa_circ_0000673, respectively, via bioinformatics analysis and a dual-luciferase reporter assay, and the combination of these two miRNAs displayed better diagnosis potential for COPD (AUC = 0.967) than each other. Evaluation of COPD-related mRNA profiles revealed that the up-regulated genes ABR and TRPM6 were predicted downstream targets for hsa_circ_0067209/hsa-miR-8082, whereas the down-regulated gene RORC was a predicted downstream target for hsa_circ_0000673/hsa-miR-1248. In summary, hsa_circ_0067209 and hsa_circ_0000673 have potential as novel diagnostic biomarkers of COPD. In addition, competing endogenous RNA networks of hsa_circ_0067209/hsa-miR-8082/ABR/TRPM6 and hsa_circ_0000673/hsa-miR-1248/RORC may play critical regulation roles for COPD pathogenesis.

Safety and efficacy of AK0529 in respiratory syncytial virus-infected infant patients: A phase 2 proof-of-concept trial.

Background: Respiratory syncytial virus (RSV) infection is a cause of substantial morbidity and mortality in young children. There is currently no effective therapy available. Methods: This was a Phase 2 study of the oral RSV fusion protein inhibitor AK0529 in infants aged 1-24 months, hospitalized with RSV infection. In Part 1, patients (n = 24) were randomized 2:1 to receive a single dose of AK0529 up to 4 mg/kg or placebo. In Part 2, patients (n = 48) were randomized 2:1 to receive AK0529 at 0.5, 1, or 2 mg/kg bid or placebo for 5 days. Sparse pharmacokinetic samples were assessed using population pharmacokinetics modelling. Safety, tolerability, viral load, and respiratory signs and symptoms were assessed daily during treatment. Results: No safety or tolerability signals were detected for AK0529: grade ≥3 treatment-emergent adverse events occurring in 4.1% of patients in AK0529 and 4.2% in placebo groups, respectively, and none led to death or withdrawal from the study. In Part 2, targeted drug exposure was reached with 2 mg/kg bid. A numerically greater reduction in median viral load with 2 mg/kg bid AK0529 than with placebo at 96 h was observed. A -4.0 (95% CI: -4.51, -2.03) median reduction in Wang Respiratory Score from baseline to 96 h was observed in the 2 mg/kg group compared with -2.0 (95% CI: -3.42, -1.82) in the placebo group. Conclusions: AK0529 was well tolerated in hospitalized RSV-infected infant patients. Treatment with AK0529 2 mg/kg bid was observed to reduce viral load and Wang Respiratory Score. Clinical Trials Registration: NCT02654171.

Ligand-protected metal nanoclusters as low-loss, highly polarized emitters for optical waveguides.

Photoluminescent molecules and nanomaterials have potential applications as active waveguides, but such a use has often been limited by high optical losses and complex fabrication processes. We explored ligand-protected metal nanoclusters (LPMNCs), which can have strong, stable, and tunable emission, as waveguides. Two alloy LPMNCs, Pt1Ag18 and AuxAg19-x (7 ≤ x ≤ 9), were synthesized and structurally determined. Crystals of both exhibited excellent optical waveguide performance, with optical loss coefficients of 5.26 × 10-3 and 7.77 × 10-3 decibels per micrometer, respectively, lower than those demonstrated by most inorganic, organic, and hybrid materials. The crystal packing and molecular orientation of the Pt1Ag18 compound led to an extremely high polarization ratio of 0.91. Aggregation enhanced the quantum yields of Pt1Ag18 and AuxAg19-x LPMNCs by 115- and 1.5-fold, respectively. This photonic cluster with low loss and high polarization provides a generalizable and versatile platform for active waveguides and polarizable materials.

Chromosomal abnormalities in recurrent pregnancy loss and its association with clinical characteristics.

OBJECTIVE: To evaluate the distribution of chromosomal abnormalities in a recurrent pregnancy loss (RPL) cohort and explore the associations between chromosomal abnormalities and clinical characteristics. METHOD: Over a 5-year period, fresh products of conception (POC) from women with RPL were analyzed by single-nucleotide polymorphism (SNP) array at our hospital. After obtaining the information on clinical characteristics, we investigated the associations between the causative chromosomal abnormalities and clinical characteristics by the chi-squared test or Fisher's exact test and logistic regression. RESULTS: A total of 2383 cases were enrolled. Overall, 56.9% (1355/2383) were identified with causative chromosomal abnormalities, of which 92.1% (1248/1355) were numerical abnormalities, 7.5% (102/1355) were structural variants, and 0.4% (5/1355) were loss of heterozygosity (LOH). The risk of numerical abnormalities was increased in women with maternal age ≥ 35 years (OR, 1.71; 95% CI, 1.41-2.07), gestational age at pregnancy loss ≤ 12 weeks (OR, 2.78; 95% CI, 1.79-4.33), less number of previous pregnancy losses (twice: OR, 2.32; 95% CI, 1.84-2.94; 3 times: OR, 1.59; 95% CI, 1.23-2.05, respectively), and pregnancy with a female fetus (OR, 1.37; 95% CI, 1.15-1.62). The OR of pregnancy loss with recurrent abnormal CMA was 4.00 (95% CI: 1.87-8.58, P < 0.001) and the adjusted OR was 5.05 (95% CI: 2.00-12.72, P = 0.001). However, the mode of conception was not associated with the incidence of numerical abnormality. No association was noted between structural variants and clinical characteristics. CONCLUSION: Chromosomal abnormality was the leading cause of RPL. Numerical chromosome abnormality was more likely to occur in cases with advanced maternal age, an earlier gestational age, fewer previous pregnancy losses, and pregnancy with a female fetus.

Nickel-Catalyzed Suzuki Coupling of Phenols Enabled by SuFEx of Tosyl Fluoride.

A practical and efficient Suzuki coupling of phenols has been developed by using trans-NiCl(o-Tol)(PCy3)2/2PCy3 as a catalyst in the presence of tosyl fluoride as an activator. The key for the direct use of phenols lies in the compatibility of the nickel catalyst with tosyl fluoride (TsF) and its sulfur(VI) fluoride exchange (SuFEx) with CAr-OH. Water has been found to improve the one-pot process remarkably. The steric and electronic effects and the functional group compatibility of the one-pot Suzuki coupling of phenols appear to be comparable to the conventional one of pre-prepared aryl tosylates. A series of electronically and sterically various biaryls could be obtained in good to excellent yields by using 3-10 mol% loading of the nickel catalyst. The applications of this one-pot procedure in chemoselective derivatization of complex molecules have been demonstrated in 3-phenylation of estradiol and estrone.

Anticancer effects and mechanisms of astragaloside­IV (Review).

Astragalus membranaceus Bunge is widely used in Traditional Chinese Medicine to treat various cancers. Astragaloside­IV (AS­IV) is one of the major compounds isolated from A. membranaceus Bunge and has been demonstrated to have antitumor effects by inhibiting cell proliferation, invasion and metastasis in various cancer types. Numerous studies have used in vitro cell culture and in vivo animal models of cancer to explore the antitumor activities of AS­IV. In the present study, the antitumor effects and mechanisms of AS­IV reported in studies recorded in the PubMed database were reviewed. First, the antitumor effects of AS­IV on proliferation, cell cycle, apoptosis, autophagy, invasion, migration, metastasis and epithelial­mesenchymal transition processes in cancer cells and the tumor microenvironment, including angiogenesis, tumor immunity and macrophage­related immune responses to cancer cells, were comprehensively discussed. Subsequently, the molecular mechanisms and related signaling pathways associated with antitumor effects of AS­IV as indicated by in vitro and in vivo studies were summarized, including the Wnt/AKT/GSK-3ß (glycogen synthase kinase­3ß)/ß­catenin, TGF­ß/PI3K/AKT/mTOR, PI3K/MAPK/mTOR, PI3K/AKT/NF­κB, Rac family small GTPase 1/RAS/MAPK/ERK, TNF­α/protein kinase C/ERK1/2­NF­κB and Tregs (T­regulatory cells)/IL­11/STAT3 signaling pathways. Of note, several novel mechanisms of Toll­like receptor 4 (TLR4)/NF­κB/STAT3, pSmad3C/3L, nuclear factor erythroid 2­related factor (NrF2)/heme oxygenase 1, circDLST/microRNA­489­3p/eukaryotic translation initiation factor 4A1 and macrophage­related high­mobility group box 1­TLR4 signaling pathways associated with the anticancer activity of AS­IV were also included. Finally, the limitations of current studies that must be addressed in future studies were pointed out to facilitate the establishment of AS­IV as a potent therapeutic drug in cancer treatment.

Perinatal outcome and timing of selective fetal reduction in dichorionic diamniotic twin pregnancies: a single-center retrospective study.

Objective: The study aimed to evaluate the pregnancy outcomes of dichorionic diamniotic twin pregnancies that were reduced to singletons at different gestational ages. Study design: This was a retrospective cohort study of twin pregnancies that underwent fetal reduction to singletons in a single tertiary referral center between 2011 and 2020. A total of 433 cases were included. The cohort was divided into five groups according to gestational age at surgery: Group A: <16 weeks (125 cases); Group B: 16-19+6 weeks (80 cases); Group C: 20-23+6 weeks (74 cases); Group D: 24-26+6 weeks (48 cases); and Group E: ≥27 weeks (106 cases). Outcome data were obtained by reviewing the electronic medical records or interviews. Results: Selective reduction was technically successful. The clinical characteristics of the population were not different. The overall live birth rate and the survival rate were 96.5 and 95.4%, respectively. Although the rate of spontaneous miscarriage was comparable, gestational age at delivery significantly differed among groups (p < 0.001). Additionally, there was a trend that gestational age at delivery decreased with the increasing gestational age at surgery in Groups A, B, C, and D, whereas gestational age at delivery in Group E was later than that in Group D. In Groups A, B, C, and D, the rates of preterm birth at <32 weeks and <34 weeks increased with the increasing gestational age at surgery, while the rates in Group E were significantly lower than that in Group D. Regression analysis showed that timing of reduction may be an independent factor after adjusting for maternal age, parity, pre-pregnancy BMI, ART, and cervical length. Conclusion: Selective reduction performed by experienced hands for a dizygotic abnormal twin is safe and effective. Gestational age at surgery (<26+6 weeks) was inversely correlated with gestational age at delivery and positively with the rate of preterm birth. Reduction after 27 weeks, where legal, can be performed with a good outcome for the retained fetus.

Safety and efficacy of COVID-19 vaccine immunization during pregnancy in 1024 pregnant women infected with the SARS-CoV-2 Omicron virus in Shanghai, China.

Background: Large sample of pregnant women vaccinated with COVID-19 vaccine has not been carried out in China. The objective of this study was to evaluate the safety and effectiveness of COVID-19 inactivated vaccine in pregnant women infected with the SARS-CoV-2 Omicron variant. Methods: A total of 1,024 pregnant women and 120 newborns were enrolled in this study. 707 pregnant women received one to three doses of the inactivated COVID-19 vaccine, and 317 unvaccinated patients served as the control group. A comparison was made between their clinical and laboratory data at different stages of pregnancy. Results: The incidence rate of patients infected with Omicron variant in the first, the second, and the third trimesters of pregnancy was 27.5%, 27.0%, and 45.5% in patients during, respectively. The corresponding length of hospital stay was 8.7 ± 3.3 days, 9.5 ± 3.3 days, and 11 ± 4.3 days, respectively. The hospitalization time of pregnant women who received 3 doses of vaccine was (8.8 ± 3.3) days, which was significantly shorter than that of non-vaccinated women (11.0 ± 3.9) days. (P<0.0001). The positive rate of SARS-CoV-2 IgG in patients in the early stage of pregnancy was 28.8%, while that in patients in the late stage of pregnancy was 10.3%. However, three-doses of vaccination significantly increased the SARS-CoV-2 IgG positive rate to 49.5%. The hospitalization time of SARS-CoV-2 IgG-positive patients was shorter than that of negative patients (9.9 ± 3.5 days), which was 7.4 ± 2.0 days. 12.2% of vaccinated women experienced mild adverse reactions, manifested as fatigue (10.6%) and loss of appetite (1.6%). The vaccination of mother did not affect her choice of future delivery mode and the Apgar score of their newborn. All newborns tested negative for SARS-CoV-2 nucleic acid, as well as for IgG and IgM antibodies. Conclusions: Women in the third trimester of pregnancy are highly susceptible to infection with the Omicron strain. The vaccination of pregnant women with COVID-19 vaccine can accelerate the process of eliminating SARS-CoV-2 virus, and is considered safe for newborns. The recommended vaccination includes three doses.

An Investigation of the Etiologies of Non-Immune Hydrops Fetalis in the Era of Next-Generation Sequence-A Single Center Experience.

(1) Background: Numerous etiologies may lead to non-immune hydrops fetalis (NIHF). However, the causes remain unclear in half of NIHF cases following current standard assessment. The application of prenatal chromosomal microarray analysis (CMA) and exome sequencing (ES) can improve the identification of the etiologies. This study aimed to investigate the etiologies of NIHF in the era of next-generation sequence (NGS) following a unified prenatal work-up flow for diagnosis. (2) Methods: A retrospective analysis was conducted on NIHF cases that were collected prospectively to explore the underlying etiologies according to a unified prenatal diagnosis work-up flow at Shanghai First Maternity and Infant Hospital between Jan 2016 and Dec 2019. The medical records for all NIHF cases were reviewed, and the causes of NIHF were classified as confirmed (diagnostic), suspected, or unknown. (3) Results: Prenatal and postnatal medical records for a total of 145 NIHF cases were reviewed, 48.3% (70/145) of the cases were identified to be with confirmed etiologies, and 10.3% (15/145) with suspected etiologies. Among 85 cases with confirmed or suspected etiologies, 44.7% were diagnosed with genetic disorders, 20% with chylothorax/chyloascites diagnosed postnatally, 12.9% with fetal structural anomalies, 12.9% with fetal anemia, 7% (6 cases) with fetal arrhythmia, and 2.3% (2 cases) with placenta chorioangioma. In cases with genetic disorders, 8 aneuploidies were detected by CMA, and 30 cases had single-gene disorders identified by ES (29/30) or targeted gene panel (1/30). There were still 41.4% cases (60/145) with unknown causes after this unified prenatal diagnostic work-up flow. (4) Conclusions: In the era of NGS, the causes of NIHF were identified in 58.6% of cases, with genetic disorders being the most common ones. NGS is helpful in determining the genetic etiology of NIHF when CMA results cannot explain NIHF, but 41.4% of cases were still with unknown causes under the unified prenatal diagnostic work-up flow in this single-center study.