Increased risk of fetal left-right asymmetry disorders associated with maternal SARS-CoV-2 infection during the first trimester.

Our center has observed a substantial increase in the detection rate of fetal left-right(LR) asymmetry disorders between March and May 2023. This finding has raised concerns because these pregnant women experienced the peak outbreak of SARS-CoV-2 in China during their first trimester. To explore the relationship between maternal SARS-CoV-2 infection and fetal LR asymmetry disorders. A retrospective collection of clinical and ultrasound data diagnosed as fetal LR asymmetry disorders was conducted from January 2018 to December 2023. The case-control study involved fetuses with LR asymmetry disorders and normal fetuses in a 1:1 ratio. We evaluated and compared the clinical and fetal ultrasound findings in pregnant women with SARS-CoV-2 infection and pregnant women without infection. The Student t-test was utilized to compare continuous variables, while the chi-squared test was employed for univariable analyses. The incidence rate of LR asymmetry disorders from 2018 to 2023 was as follows: 0.17‰, 0.63‰, 0.61‰, 0.57‰, 0.59‰, and 3.24‰, respectively. A total of 30 fetuses with LR asymmetry disorders and 30 normal fetuses were included. This case-control study found that SARS-CoV-2 infection (96.67% vs 3.33%, P = .026) and infection during the first trimester (96.55% vs 3.45%, P = .008) were identified as risk factors. The odds ratio values were 10.545 (95% CI 1.227, 90.662) and 13.067 (95% CI 1.467, 116.419) respectively. In cases of SARS-CoV-2 infection in the first trimester, the majority of infections (88.1%, 37/42) occurred between 5 and 6 weeks of gestation. We found that 43.7% (66/151) of fetuses with LR asymmetry disorder had associated malformations, 90.9% (60/66) exhibited cardiac malformations. SARS-CoV-2 infection during the first trimester significantly increases the risk of fetal LR asymmetry disorders, particularly when the infection occurs between 5 and 6 gestation weeks. The most common associated malformation is heart malformation.

Prenatal ultrasonographic features and follow-up outcomes of 19 cases of congenital intrahepatic portosystemic venous shunts diagnosed during the foetal period.

BACKGROUND: To investigate the prenatal ultrasonographic features and case characteristics of the congenital intrahepatic portosystemic venous shunt (IHPSS) diagnosed during the foetal period and analyse its prognosis. METHODS: We conducted a retrospective cohort study of patients diagnosed with IHPSS between 2016 and 2021. IHPSS was defined as an abnormal connection between the foetal intrahepatic portal and the hepatic veins. RESULTS: In this study, 19 foetuses were identified, including 12 cases of single shunt and 7 cases of multiple shunts, with a gestational age of 33.8 ± 4.5 (range 25-40) weeks at diagnosis. In the single-shunt group, the origin position of the shunts was all from the left branch of the portal vein (LPV), whereas in the multiple-shunt group, the origin position of the shunts was from the LPV in six cases. Common concomitant intrauterine abnormalities of IHPSS include foetal growth restriction (47.4%) and foetal cardiac enlargement (21.1%). The postnatal manifestations of IHPSS include biochemical abnormalities (increased gamma-glutamyl transferase and bilirubin levels), neonatal hypoglycaemia, neonatal hyperammonaemia, pulmonary hypertension, multiple intrahepatic hyperechoic nodules, and cutaneous haemangiomas. Spontaneous closure of shunts occurred in ten cases, and the mean time to shunt closure was 8.1 months (1-28 months). CONCLUSIONS: Most IHPSS found during the foetal period is located in the left branch of the portal vein, and the gestational age at diagnosis is usually in the late second or third trimester. Spontaneous closure of shunts can occur in most live births, and the prognosis is good.

Dynamic carboxymethyl chitosan-based nano-prodrugs precisely mediate robust synergistic chemotherapy.

Currently, the polysaccharide-based nano-prodrug crosslinked by stimuli-responsive synergetic prodrug is of great demand, owing to its excellent stability, synergetic effect and tumor selectivity, and circumventing the dilemma of dose-limiting toxicity and immunogenicity induced by that crosslinked or grafted via a single drug. Herein, the dynamic carboxymethyl chitosan (CMCS)-based nano-prodrugs with precise structure were facilely fabricated, via crosslinking reaction between CMCS and water-soluble synergistic small molecule prodrug (cisplatin-demethylcantharidin conjugate) and further stabilization by glutaraldehyde. The pH/glutathione (GSH)-responsive double-crosslinked structure endowed the nano-prodrugs with long-term storge and circulation stability at physiological pH, and dynamic transitions at tumor sites including extracellular surface amino protonation and intracellular efficient drug release, which promoted selective tumor accumulation and synergistic cytotoxicity, therefore achieving robust tumor suppression while decreasing side effects. Thus, the dynamic precise CMCS-based nano-prodrugs crosslinked by water-soluble synergistic prodrug have great potential for highly selective robust chemotherapy attractive for clinical translation.

A multi-label learning framework for predicting antibiotic resistance genes via dual-view modeling.

The increasing prevalence of antibiotic resistance has become a global health crisis. For the purpose of safety regulation, it is of high importance to identify antibiotic resistance genes (ARGs) in bacteria. Although culture-based methods can identify ARGs relatively more accurately, the identifying process is time-consuming and specialized knowledge is required. With the rapid development of whole genome sequencing technology, researchers attempt to identify ARGs by computing sequence similarity from public databases. However, these computational methods might fail to detect ARGs due to the low sequence identity to known ARGs. Moreover, existing methods cannot effectively address the issue of multidrug resistance prediction for ARGs, which is a great challenge to clinical treatments. To address the challenges, we propose an end-to-end multi-label learning framework for predicting ARGs. More specifically, the task of ARGs prediction is modeled as a problem of multi-label learning, and a deep neural network-based end-to-end framework is proposed, in which a specific loss function is introduced to employ the advantage of multi-label learning for ARGs prediction. In addition, a dual-view modeling mechanism is employed to make full use of the semantic associations among two views of ARGs, i.e. sequence-based information and structure-based information. Extensive experiments are conducted on publicly available data, and experimental results demonstrate the effectiveness of the proposed framework on the task of ARGs prediction.

Ultrasonographic characteristics and outcome of Type III umbilical-portal-systemic venous shunt.

AIMS: According to a novel in-utero classification termed "umbilical-portal-systemic venous shunt (UPSVS)" recently proposed for an abnormal umbilical, portal and ductal venous system, the portal-systemic shunt belongs to type III UPSVS. This study was designed to examine the ultrasonographic characteristics and outcome of type III UPSVS.Material and methods: All cases of Type III UPSVS diagnosed at our department from April 2016 to December 2020 were retrospectively studied. RESULTS: Seventeen patients with type III UPSVS including 12 type IIIa and 5 IIIb cases were identified. Sonography showed a shunt between the inferior left portal vein and the left hepatic vein in all type IIIa cases. Three cases of type IIIb had a combination of another shunt (2 with type I and one with type IIIa). Integrate intrahepatic portal vein system was not seen in those 2 cases of type IIIb combined with type I UPSVS, leading to termination of pregnancy (TOP). TOP occurred in 4 patients with type IIIa as requested by the parents. Two cases (type IIIa and type IIIb each) underwent surgical procedure for the closure of the shunt. Spontaneous complete closure in 4 type IIIa cases and partial closure in one type IIIb case occurred during a period of 3-16 months. CONCLUSIONS: The majority of patients had type IIIa UPSVS presenting a good outcome. The lack of integrate intrahepatic portal vein system was the main reason for TOP in patients with type IIIb UPSVS. These data suggest the UPSVS classification is a useful tool for a prognosis prediction of type III UPSVS.

pH-triggered small molecule nano-prodrugs emulsified from tryptamine-cinnamaldehyde twin drug for targeted synergistic glioma therapy.

Chemotherapy fails to achieve an ideal gliomas therapy due to the limited delivery of chemotherapeutics across the blood brain barrier (BBB), difficult accumulation of drugs in the gliomas area, and off-target toxicity. Herein, the pH-triggered small molecule nano-prodrugs (Try-CA-NPs) emulsified from hydrophobic tryptamine (Try)-cinnamaldehyde (CA) twin drug were successfully prepared through a facile method. Try-CA-NPs exhibited long-term storage and circulation stability. Furthermore, liposoluble Try-CA-NPs could easily cross BBB and efficiently accumulate in brain, selectively target to gliomas cells via Try-mediated cellular uptake, and enhance cytotoxicity through intracellular pH-triggered endosomal escape and efficient drug release, and synergistic effect between CA and Try, therefore achieving the complete destruction of SH-SY5Y multicellular spheroids (MCs). Thus, the pH-triggered small molecule nano-prodrugs emulsified from Try-CA twin drug have the great potential for clinically targeted synergistic glioma therapy.

Overexpression of MYBL2 predicts poor prognosis and promotes oncogenesis in endometrial carcinoma.

Endometrial cancer (EC) is the most common gynecologic malignancy and still remains clinically challenging. We aimed to explore the potential biomarkers of EC and provide a theoretical basis for early screening and targeted therapy. The available transcriptome data from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to identify differentially expressed genes. Immunohistochemistry was performed to detect gene expression. We analyzed the associations of MYBL2 with clinicopathological features and survival time and the biological effect of MYBL2 on the proliferation of EC cells. The effect of MYBL2 silencing on the transcriptome of EC cell model was analyzed by RNA-Seq. MYBL2 was significantly upregulated with obvious copy number alteration (CNA) in EC. Copy number amplification significantly increased MYBL2 mRNA expression, which led to a poor prognosis and severe pathological types of EC. Additionally, MYBL2 silencing significantly inhibited proliferation and induced apoptosis and G1-phase cell cycle arrest in EC cell lines. Our results indicate that MYBL2 is closely related to the cell cycle and apoptosis pathways in EC. The findings in this study provide evidence that MYBL2 can serve as a new candidate prognostic marker and a target for future therapeutic intervention in EC.

The effect of reproductive toxicity induced by ZnO NPs in mice during early pregnancy through mitochondrial apoptotic pathway.

The potential toxicity of Zinc oxide nanoparticles (ZnO NPs) to human beings has become a widespread concern. This study explored the reproductive toxicity and the mechanism of toxicity of ZnO NPs in early pregnant mice. The results showed that abnormal weight changes, induced inflammation, reduced level of serum sex hormones, damaged uterus, increased abortion, and abnormal development of fetus. In the uterus, the transcription levels of ZnT-1, HO-1, Bax, Bax/Bcl-2, JNK, and Caspase-3 were significantly up-regulated while Bcl-2, ER-1 and PR were significantly down-regulated. The TUNEL-positive cells increased that were exposed to high levels of ZnO NPs. In summary, those results indicated that Zn from high levels of exposure to ZnO NPs accumulated in the uterus that could have caused the formation of ROS that led to oxidative stress, which might have activated the mitochondrial apoptotic pathway that could have caused the uterine injury which induced the observed reproductive toxicity.

Prenatal Ultrasound Analysis of Umbilical-Portal-Systemic Venous Shunts Concurrent With Trisomy 21.

OBJECTIVES: A classification termed umbilical-portal-systemic venous shunt (UPSVS) for an abnormal umbilical vein (UV), portal vein (PV), and ductus venosus (DV) was proposed recently. According to this classification, there are 3 types of UPSVSs: types I, II, and III. Trisomy 21 associated with UV-PV-DV anomalies has been described, but the incidence of trisomy 21 in UPSVS cases, the relationship between UPSVS types and trisomy 21, and the pregnancy outcome are poorly documented. This study aimed to address these issues. METHODS: All UPSVS cases diagnosed at our department from 2016 to 2019 were retrospectively studied. The English literature describing UV-PV-DV anomalies and trisomy 21 from 2000 to 2019 was searched, and the retrieved cases were analyzed. RESULTS: Four of 20 UPSVS cases identified by us also had trisomy 21, with 2 type I and 2 type II UPSVSs. Ultrasound markers of Down syndrome were observed in all 4 cases that underwent termination of pregnancy (TOP). The literature search retrieved 12 reports including 279 patients, with 29 also having trisomy 21, giving a pooled trisomy 21 incidence rate of 10.4%. Of the 29 cases, 16 had type I, and 9 had type II, whereas UPSVS types in 4 were undeterminable, and 22 cases underwent TOP. CONCLUSIONS: There is a high incidence of trisomy 21 in UPSVS cases. Trisomy 21 is associated with a type I or II UPSVS. Most cases with the combined defect underwent TOP. These findings may be used to direct prenatal counseling and management of the combined condition.

Osteoprotegerin, interleukin and hepatocyte growth factor for prediction of diabetes and hypertension in the third trimester of pregnancy.

BACKGROUND: Gestational diabetes mellitus (GDM) raises the risk of high blood pressure and may cause a series of life-threatening complications in pregnant women. Screening and management of GDM and gestational hypertension (GH) in pregnancy helps to control and reduce these risks and prevent adverse effects on mothers and their fetuses. Currently, the majority criteria used for screening of diabetes mellitus is oral glucose tolerance tests, and blood pressure test is usually used for the screening and diagnosis of hypertension. However, these criteria might not anticipate or detect all GDM or GH cases. Therefore, new specific predictive and diagnostic tools should be evaluated for this population. This study selected three biomarkers of osteoprotegerin (OPG), interleukin (IL) and hepatocyte growth factor (HGF) for GDM and GH predication and diagnosis. AIM: To explore the feasibility of changes in placental and serum OPG, IL and HGF as tools for prediction and diagnosis of diabetes and hypertension in pregnant women. METHODS: From January 2018 to January 2019, 44 pregnant women with GDM and GH were selected as an observation group, and 44 healthy pregnant women were selected as a control group in the same period. Serum OPG, IL and HGF were compared between the two groups. RESULTS: The levels of OPG and HGF in the observation group were lower than in the control group, and the level of IL-1ß was higher in the observation group than in the control group (all P < 0.05). Furthermore, OPG and HGF were negatively associated with gestational diabetes and gestational hypertension, while IL-1ß was positively associated with GDM complicated with GH (all P < 0.05). CONCLUSION: The evaluation of serum OPG, HGF and IL-1ß levels in patients with coexistent gestational diabetes complicated with hypertension can predict the degree of disease and play an important role in the follow-up treatment and prognosis prediction.

Exposure to silver nanoparticles induces immunological dysfunction in pregnant mice.

The adverse outcomes of silver nanoparticles (AgNPs) on pregnancy have been studied in murine animals. However, the potential toxicity of AgNPs to immune balance, which is essential for maintaining a normal pregnancy, still requires further exploration. Therefore, this study assessed the effect of AgNPs on the immune balance during gestation time. Pregnant mice were given a dose of 1 mg/kg of AgNPs and silver ion on gestation days 3.5 to 9.5 by tail vein injection. Results showed that the AgNPs and silver ion decreased the number of CD4+ CD25+ Treg cells which were the important cells in the immune system, thereby disrupting the balance of normal immune tolerance function, activated the inflammatory responses, together with the reductive production of placental immunoregulatory genes, and the expression of inflammatory factors in the placenta in the Ag-treated groups increased. These effects increased the absorption rate. Furthermore, the inflammatory signaling pathway p38MAPK/AP-1/MMP-9 in the placenta was activated, indicating that Ag induced inflammation through this signaling pathway. All results indicated that undesirable pregnancy outcome caused by AgNPs could be happened by stimulating immunological dysfunction. Therefore, the potential risks to embryogenesis exposure to AgNPs that caused immune imbalance should be given sufficient attention.

Effect of head circumference in combination with facial profile line on ultrasonic diagnosis of microcephaly.

Objective: Recently, microcephaly has usually been misdiagnosed only by ultrasound via measurement of head circumference (HC). Therefore, the aim of this study is to find another diagnostic index to supplement the original diagnostic method of microcephaly, to improve the detection rate of fetal microcephaly and to reduce the misdiagnosis rate.Methods: We retrospectively analyzed 123 pregnant women from February 2012 to January 2017 with fetal HC less than two standard deviations (SD). The facial profile line (FPL) was determined by ultrasonography. The first method (M1) was only used HC to determine whether the fetus was microcephaly, the second one (M2) was to combine HC and FPL for the diagnosis of microcephaly. Results were classified into five orderly categories by experienced sonographers. ROC curve was drawn to evaluate the diagnostic effect.Results: Among the pregnant women, 14 cases of fetal head circumference were less than 3SD, 109 were -2SD < HC≤ -3SD. A total of 12 cases were confirmed of microcephaly by magnetic resonance imaging (MRI) or postnatal, 10 cases of HC were less than 3SD, 2 were -2SD < HC≤ -3SD. The area under the ROC curve for M1 and M2 were 0.751 and 0.983 respectively.Conclusion: The HC in combination with FPL can be used to evaluate the fetal HC and forehead development quickly, and to improve the sensitivity and specificity of diagnosing fetal microcephaly.

Prenatal sonographic characteristics and postnatal outcomes of umbilical-portal-systemic venous shunts under the new in-utero classification: A retrospective study.

An in-utero re-classification of umbilical-portal-systemic venous shunt (UPSVS) has recently been proposed. We retrospectively reviewed the sonograms of a large cohort of fetuses, identified and analyzed UPSVS cases, and presented the prenatal sonographic characteristics, birth outcomes, and follow-up results following the new classification system.Sonograms and clinical data of all participants who visited our departments from April 2016 to July 2018 were retrospectively reviewed. Identified cases of UPSVS were analyzed according to the new classification: Type I: umbilical-systemic shunt (USS); Type II: ductus venosus-systemic shunt (DVSS); Type IIIa: intrahepatic portal-systemic shunt (IHPSS) and Type IIIb: extrahepatic portal-systemic shunt (EHPSS). Postnatal follow-ups ranged from 3 months to 1 year.A total of 10 UPSVS cases were identified in 61,082 fetuses: 4 with Type I, 3 with Type II and 3 with Type IIIa. All 4 cases of USS had complete agenesis of the portal venous system, and had the umbilical vein drained into the inferior vena cava. Two USS cases also had trisomy 21. Pregnancy was terminated in all cases with a Type I shunt. Two fetuses with DVSS had normal portal venous system and were born full term. The pregnancy of 1 DVSS case was terminated due to the detection of trisomy 21. Three cases were IHPSS with full-term birth. One had chromosomal abnormality and 1 had surgery to repair the shunt 12-days post birth. In the 2 cases that did not receive repair surgery, sonographic examination revealed the portal-hepatic venous shunt was not closed at the 6-month follow-up period. However, the 1 case that had repair surgery appeared healthy at the 3-month follow-up period.UPSVS is extremely rare. Type I shunts have the poorest prognosis, and the presence of the intrahepatic portal venous system is key to live birth in UPSVS regardless of types. Chromosomal abnormalities and other organ anomalies can occur in any types of UPSVS. Therefore, karyotyping and examination of other organs should be performed once UPSVS is detected.