Associations between genomic aberrations, increased nuchal translucency, and pregnancy outcomes: a comprehensive analysis of 2,272 singleton pregnancies in women under 35.

Objectives: Regarding increased nuchal translucency (NT), the cutoff values used are heterogeneous in clinical practice, this study aims to assess the efficacy of prenatal detection for chromosomal abnormalities and pregnancy outcomes in fetuses with varying NT thicknesses, in order to provide data that supports informed prenatal diagnosis and genetic counseling for such cases. Methods: We included 2,272 pregnant women under 35 with singleton pregnancies who underwent invasive prenatal diagnosis between 2014 and 2022. The cohort comprised 2,010 fetuses with increased NT (≥2.5 mm) and 262 fetuses with normal NT but exhibiting a single soft marker. Prenatal diagnoses were supported by chromosomal microarray (CMA) and copy number variation sequencing (CNV-seq) analyses. Results: The detection rates of numerical chromosomal abnormalities were 15.4% (309/2,010) and 17.3% (297/1,717) in the NT ≥2.5 and ≥ 3.0 groups, respectively. Pathogenic/likely pathogenic CNV incidence increased with NT thickness (χ2 = 8.60, p < 0.05), peaking at 8.7% (22/254) in the NT 4.5-5.4 mm group. Structural defects were found in 18.4% of fetuses with NT values between 2.5 mm and 2.9 mm. Chromosomal abnormality rates in the isolated increased NT groups of 2.5-2.9 mm and 3.0-3.4 mm were 6.7% (16/239) and 10.0% (47/470), respectively, with no statistical significance (χ2 = 2.14, p > 0.05). Fetuses with NT thickness between 2.5 and 2.9 mm combined with the presence of soft markers or non-lethal structural abnormalities exhibited a significantly higher chromosomal abnormality risk (19.0%) compared to fetuses with isolated increased NT ranging from 3.5 to 4.4 mm (13.0%). Pregnancy termination rates increased with NT thickness (χ2 = 435.18, p < 0.0001), ranging from 12.0% (30/249) in the NT 2.5-2.9 mm group to 87.0% (141/162) in the NT ≥ 6.5 mm group. Conclusion: CMA or CNV-seq exhibited good performance in identifying genomic aberrations in pregnancies with increased NT thickness. NT ranging from 2.5 mm to 2.9 mm elevated the risk of fetal chromosomal abnormalities, particularly when combined with other soft markers.

Increased Prevalence of Thyroid Nodules Across Nearly 10 Years in Shanghai, China.

OBJECTIVE: This study aimed to determine whether the prevalence of thyroid nodules (TNs) increased due to modern lifestyles or other factors, despite the advances in screening and diagnostic tools. METHODS: This study included 3474 pairs of participants, who were matched by gender and age (±3 years) from two cross-sectional sampling surveys: (1) the program on the iodine nutritional status and related health status of residents in Shanghai in 2009; (2) the thyroid disease screening program for adults in Shanghai between 2017 and 2018. The prevalence of TNs and thyroid diseases in 2009 and 2017-2018 were compared, and the potential risk factors of TNs were detected. RESULTS: The prevalence of TNs in 2009 was 28.9%: 22.5% in males and 34.5% in females. In 2017, this increased to 43.8%: 37.9% in males and 49.1% in females. The prevalence of TNs significantly increased from 2009 to 2017 (odds ratio, 1.486; 95% confidence interval, 1.238-1.786). In addition, female gender, thyroid disease history, and age were the main risk factors for TNs after adjusting for confounders in the logistic regression across the time period. CONCLUSION: The prevalence of TNs significantly increased across nearly 10 years in Shanghai.

[Exploration and Application of ESB High-availability Architecture Construction Based on Hospital Information System].

OBJECTIVE: To solve the ESB bus performance and safety problems caused by the explosive growth of the hospital's business, and to ensure the stable interaction of the hospital's business system. METHODS: Taking the construction of our hospital's information system as an example, we used AlwaysOn, load balancing and other technologies to optimize the ESB bus architecture to achieve high availability and scalability of the hospital's ESB bus. RESULTS: The ESB bus high-availability architecture effectively eliminates multiple points of failure. Compared with the traditional dual-machine Cluster solution, the security is significantly improved. The nodes based on load balancing can be scaled horizontally according to the growth of the hospital's business volume. CONCLUSIONS: The construction of the ESB bus high-availability architecture effectively solves the performance and security issues caused by business growth, and provides practical experience for medical information colleagues. It has certain guiding significance for the development of regional medical information.

Arsenic Trioxide Rescues Structural p53 Mutations through a Cryptic Allosteric Site.

TP53 is the most frequently mutated gene in cancer, yet these mutations remain therapeutically non-actionable. Major challenges in drugging p53 mutations include heterogeneous mechanisms of inactivation and the absence of broadly applicable allosteric sites. Here we report the identification of small molecules, including arsenic trioxide (ATO), an established agent in treating acute promyelocytic leukemia, as cysteine-reactive compounds that rescue structural p53 mutations. Crystal structures of arsenic-bound p53 mutants reveal a cryptic allosteric site involving three arsenic-coordinating cysteines within the DNA-binding domain, distal to the zinc-binding site. Arsenic binding stabilizes the DNA-binding loop-sheet-helix motif alongside the overall ß-sandwich fold, endowing p53 mutants with thermostability and transcriptional activity. In cellular and mouse xenograft models, ATO reactivates mutant p53 for tumor suppression. Investigation of the 25 most frequent p53 mutations informs patient stratification for clinical exploration. Our results provide a mechanistic basis for repurposing ATO to target p53 mutations for widely applicable yet personalized cancer therapies.

Pseudodominant inheritance of autosomal recessive congenital stationary night blindness in one family with three co-segregating deleterious GRM6 variants identified by next-generation sequencing.

BACKGROUND: The congenital stationary night blindness (CSNB) affects the patients' dim light vision or dark adaption by impairing the normal function of retina. It is a clinically and genetically heterogeneous disorder and can be inherited in an X-linked, autosomal dominant or autosomal recessive pattern. Several genetic alterations to the genes involved in visual signal transduction of photoreceptors and/or bipolar cells underlie its pathogenesis. METHODS: In this study, we used Sanger sequencing and next-generation sequencing (NGS)-based gene panel screening to investigate a family of three patients with CSNB inherited in an apparent autosomal dominant pattern. We expected to find out the disease-causing gene defects carried by this family. RESULTS: We found that the patients in this family did not carry the RHO, GNAT1, or PDE6B mutation, but carried compound heterozygotes mutations of GRM6. Three deleterious GRM6 variants, p.Arg621Ter, p.Gly51Val, and p.Gly464Arg, were found to be co-segregating with the disease, causing a pseudodominant inheritance of GRM6-related autosomal recessive complete CSNB. CONCLUSION: This study presents a rare case of autosomal recessive CSNB (arCSNB) pseudodominant inheritance, which potentially leads us to expand our gene candidate list in future genetic testing for apparent dominant pedigrees. The discovery of the two novel likely pathogenic variants p.Gly51Val and p.Gly464Arg could broaden our knowledge about the genetics of CSNB and provide insights into the structure and function of the GRM6 protein.

Anti-inflammatory properties of lipoxin A4 protect against diabetes mellitus complicated by focal cerebral ischemia/reperfusion injury.

Lipoxin A4 can alleviate cerebral ischemia/reperfusion injury by reducing the inflammatory reaction, but it is currently unclear whether it has a protective effect on diabetes mellitus complicated by focal cerebral ischemia/reperfusion injury. In this study, we established rat models of diabetes mellitus using an intraperitoneal injection of streptozotocin. We then induced focal cerebral ischemia/reperfusion injury by occlusion of the middle cerebral artery for 2 hours and reperfusion for 24 hours. After administration of lipoxin A4 via the lateral ventricle, infarction volume was reduced, the expression levels of pro-inflammatory factors tumor necrosis factor alpha and nuclear factor-kappa B in the cerebral cortex were decreased, and neurological functioning was improved. These findings suggest that lipoxin A4 has strong neuroprotective effects in diabetes mellitus complicated by focal cerebral ischemia/reperfusion injury and that the underlying mechanism is related to the anti-inflammatory action of lipoxin A4.

Drinking Behavior and Associated Factors among Middle School Students in Shanghai, China.

The purpose of our study was to assess drinking status in middle school students and to understand the associated factors. The adjusted drinking rates were 50.9%, 39.8%, and 15.1% for lifetime, past-year, and current drinking, respectively. Multivariable logistic regression revealed the following variables positively related to drinking during the past year: family income, maternal educational level, family members who drink, parents who support drinking, best friends who drink, friends who encourage drinking, frequently attending friends' parties, smoking, and actuation trend (P<0.05). The main risk factors were friends (OR=6.77, 95% CI: 6.17, 7.43) and smoking (OR=4.70, 95% CI: 3.44, 6.43). These results contribute to obtaining the potential associated factors and aid in targeted intervention into the drinking behavior of middle school students.

[The relationship between within-day drinking occasion and intake amount of water of primary and middle school students in four cities of China].

OBJECTIVE: To investigate the number of drinking occasions per day and average amount consumed per drinking occasion of primary and middle school students in four cities of China, and understand the relationship among drinking occasion, average amount consumed per drinking occasion and total drinking water. METHODS: A total of 5914 primary and middle school students from Beijing, Shanghai, Guangzhou and Chengdu were selected using multiple-stage random sampling method, and 5868 students completed the study from September to October in 2011. The detailed information of amounts and types of daily drinking water was recorded by subjects using a 24 hours measurement for seven consecutive days. Analysis of the relationship among drinking occasion, average amount consumed per drinking occasion and total drinking water was carried out. RESULTS: The daily total drinking water of subjects was (1089 ± 540) ml; the daily number of drinking occasions was (4.7 ± 1.8) times, with 79.1% (4639/5868) of subjects reporting 6 or less drinking occasions. The amount consumed per drinking occasion was (239 ± 96) ml, plain water (231 ± 112) ml, and beverages (237 ± 112) ml. The number of drinking occasions of subjects was positively correlated with total drinking water (r = 0.614, P < 0.05), and negatively correlated with the average amount consumed per drinking occasion (r = -0.211, P < 0.05). Total drinking water and the average amount consumed per drinking occasion was positively correlated (r = 0.598, P < 0.05). CONCLUSION: The number of drinking occasion of primary and middle school students more than 6 times was fewer in four cities of China, but the average amount of beverages consumed per drinking occasion was relatively more. With the increasing of drinking occasion, the average amount consumed per drinking occasion decreased, but total drinking water increased.

Exactly solvable fermion chain describing a ν=1/3 fractional quantum Hall state.

We introduce an exactly solvable fermion chain that describes a ν=1/3 fractional quantum Hall (FQH) state beyond the thin-torus limit. The ground state of our model is shown to be unique for each center-of-mass sector, and it has a matrix product representation that enables us to exactly calculate order parameters, correlation functions, and entanglement spectra. The ground state of our model shows striking similarities with the BCS wave functions and quantum spin-1 chains. Using the variational method with matrix product ansatz, we analytically calculate excitation gaps and vanishing of the compressibility expected in the FQH state. We also show that the above results can be related to a ν=1/2 bosonic FQH state.

[Time-dependent expression of astroglial S100beta following diffuse brain injury in rats].

OBJECTIVE: To investigate the dynamics of the induction of S100beta in different parts of rat brain following the diffuse brain injury. METHODS: Immunohistochemistry and auto-image analysis were to determine the expression of astroglial S100beta after diffuse brain injury in rats. Forty rats were distributed into groups according to injury time of 30min, and2,4,12,24h, and 3,6 d after diffuse brain injury, and normal rats as control. RESULTS: The number of S100beta positive cells in the four areas increased significantly followed by a decrease, and then a further increase. The expression of S100beta could be detected increasing in 2h, and increased significantly in 4h, and it reached apex 12h after DBI, and decreased gradually to the level less than normal 3d, and returned to normal 7d following injury. In the postmortem injury groups, there were no significant changes in anti-S100beta immunoreactivities in four areas of brain compared to the control group. CONCLUSION: The present study showed the time-dependent expression of S100beta is obvious following diffuse brain injury, and suggested S100beta be suitable as a marker for brain injury age determination.

[Synthesis of partial glycerol caprates by using lipase in nonaqueous media].

Enzymatic esterification by reacting caparic acid with glycerol in solvent-free system was studied. Lipases from Pseudomonas fluoresces(PFL), Mucor miehei(MML) and Candida antarictica(CAL) possessed good catalytic activity. The optimal reaction conditions to convert capric acid with CAL are: 60 degrees C, 20-100 u of CAL per gram capric acid, 12% (W/W) of initial water content in glycerol. CAL does not express its 1,3-specificity in final product. Mechanical fraying denatured CAL partly. 96.4% of catalytic activity of CAL recovered after 5 batches of reaction. Extraction with sodium carbonate solution can decrease acid value of product from 9.8 mg KOH/g to 0.68 mg KOH/g. Applying the enzymatic esterification in open system, under vacuum or dehydrating with molecular sieves all dehydrate effectively. Molar ratio of reactants does not influence the total conversion of capric acid but influences the yield of monoglyceride. With certain protocols, the reaction period could be shortened dramatically; conversion of capric acid reached 96.9% in 5 h.