Visible-Light-Enabled Catalytic Approach to N,O-Spirocycles through Amidyl Radical Addition/Cyclization.

A rational combination of photoredox catalyst anthraquinone and hydrogen atom transfer (HAT) catalyst methyl thioglycolate allows for the rapid and straightforward conversion of a range of 2-amidated acetylenic alcohols to multifunctional N,O-spirocycles under visible light irradiation. With oxygen as the sole terminal oxidant, these reactions can be carried out efficiently at room temperature without the involvement of transition metals or strong oxidants. The successful application of this mild catalytic strategy in the late-stage functionalization of bioactive skeletons further highlights its practical value.

Ultrasound image segmentation based on Transformer and U-Net with joint loss.

Background: Ultrasound image segmentation is challenging due to the low signal-to-noise ratio and poor quality of ultrasound images. With deep learning advancements, convolutional neural networks (CNNs) have been widely used for ultrasound image segmentation. However, due to the intrinsic locality of convolutional operations and the varying shapes of segmentation objects, segmentation methods based on CNNs still face challenges with accuracy and generalization. In addition, Transformer is a network architecture with self-attention mechanisms that performs well in the field of computer vision. Based on the characteristics of Transformer and CNNs, we propose a hybrid architecture based on Transformer and U-Net with joint loss for ultrasound image segmentation, referred to as TU-Net. Methods: TU-Net is based on the encoder-decoder architecture and includes encoder, parallel attention mechanism and decoder modules. The encoder module is responsible for reducing dimensions and capturing different levels of feature information from ultrasound images; the parallel attention mechanism is responsible for capturing global and multiscale local feature information; and the decoder module is responsible for gradually recovering dimensions and delineating the boundaries of the segmentation target. Additionally, we adopt joint loss to optimize learning and improve segmentation accuracy. We use experiments on datasets of two types of ultrasound images to verify the proposed architecture. We use the Dice scores, precision, recall, Hausdorff distance (HD) and average symmetric surface distance (ASD) as evaluation metrics for segmentation performance. Results: For the brachia plexus and fetal head ultrasound image datasets, TU-Net achieves mean Dice scores of 79.59% and 97.94%; precisions of 81.25% and 98.18%; recalls of 80.19% and 97.72%; HDs (mm) of 12.44 and 6.93; and ASDs (mm) of 4.29 and 2.97, respectively. Compared with those of the other six segmentation algorithms, the mean values of TU-Net increased by approximately 3.41%, 2.62%, 3.74%, 36.40% and 31.96% for the Dice score, precision, recall, HD and ASD, respectively.

Milrinone for the treatment of heart failure caused by severe Pneumonia in children with congenital heart disease: a meta-analysis.

BACKGROUND: Children with congenital heart disease (CHD) are easily complicated by severe pneumonia and heart failure. We aimed to conduct a meta-analysis to evaluate the effects and safety of milrinone for the treatment of heart failure caused by severe pneumonia in children with CHD to provide evidence for the clinical CHD treatment. METHODS: Two authors searched MEDLINE, PubMed, Embase, Science Direct, Cochrane Central Register of Controlled Trials, the Cochrane Library, Wanfang database, Chinese Biomedical Literature Database, China National Knowledge Infrastructure (CNKI) for randomized controlled trials (RCTs) about the application of milrinone in the treatment of heart failure caused by severe pneumonia in children with CHD in children up to December 10, 2022. Two evaluators independently selected the literature, extracted data and evaluated the methodological quality, meta-analysis was carried out with RevMan 5.3 software. RESULTS: Eight RCTs involving 680 CHD children complicated by severe pneumonia and heart failure were included in this meta-analysis. Meta-analysis indicated that total effective rate of the milrinone group was higher than that of control group (RR = 1.25, 95%CI: 1.17 ~ 1.34, P < 0.001), the time to stable heart rate of the milrinone group was less than that of control group (RR=-0.88, 95%CI: -1.09~ -0.67, P < 0.001). The time to stable respiration of the milrinone group was less than that of control group (RR=-0.98, 95%CI: -1.17~ -0.78, P < 0.001). The LVEF of the milrinone group was higher than that of control group (RR = 6.46, 95%CI: 5.30 ~ 7.62, P < 0.001). There was no significant difference in the incidence of adverse reactions between the milrinone group and control group (RR = 0.85, 95%CI: 0.47 ~ 1.56, P = 0.061). Funnel plots and Egger regression test results indicated that there were no statistical publication bias amongst the synthesized outcomes (all P > 0.05). CONCLUSIONS: Milrinone is beneficial to improve clinical symptoms and cardiac function and increase the therapeutic effect and safety in children with CHD complicated by severe pneumonia and heart failure. However, more RCTs with large samples and rigorous design are needed to verify this finding.

Functional brain activity in patients with amnestic mild cognitive impairment: an rs-fMRI study.

Background: Amnestic mild cognitive impairment (aMCI) is an early stage of Alzheimer's disease (AD). Regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) are employed to explore spontaneous brain function in patients with aMCI. This study applied ALFF and ReHo indicators to analyze the neural mechanism of aMCI by resting-state functional magnetic resonance imaging (rs-fMRI). Methods: Twenty-six patients with aMCI were included and assigned to the aMCI group. The other 26 healthy subjects were included as a healthy control (HC) group. Rs-fMRI was performed for all participants in both groups. Between-group comparisons of demographic data and neuropsychological scores were analyzed using SPSS 25.0. Functional imaging data were analyzed using DPARSF and SPM12 software based on MATLAB 2017a. Gender, age, and years of education were used as covariates to obtain ALFF and ReHo indices. Results: Compared with HC group, ALFF decreased in the left fusiform gyrus, left superior temporal gyrus, and increased in the left cerebellum 8, left inferior temporal gyrus, left superior frontal gyrus (BA11), and right inferior temporal gyrus (BA20) in the aMCI group (p < 0.05, FWE correction). In addition, ReHo decreased in the right middle temporal gyrus and right anterior cuneiform lobe, while it increased in the left middle temporal gyrus, left inferior temporal gyrus, cerebellar vermis, right parahippocampal gyrus, left caudate nucleus, right thalamus, and left superior frontal gyrus (BA6) (p < 0.05, FWE correction). In the aMCI group, the ALFF of the left superior frontal gyrus was negatively correlated with Montreal Cognitive Assessment (MoCA) score (r = -0.437, p = 0.026), and the ALFF of the left superior temporal gyrus was positively correlated with the MoCA score (r = 0.550, p = 0.004). The ReHo of the right hippocampus was negatively correlated with the Mini-Mental State Examination (MMSE) score (r = -0.434, p = 0.027), and the ReHo of the right middle temporal gyrus was positively correlated with MMSE score (r = 0.392, p = 0.048). Conclusion: Functional changes in multiple brain regions rather than in a single brain region have been observed in patients with aMCI. The abnormal activity of multiple specific brain regions may be a manifestation of impaired central function in patients with aMCI.

Visible-Light-Enabled Lanthanum-Mediated Intramolecular Epoxy-Ring Opening/Dehydrogenative Lactonization.

Catalytic C(sp3)-H functionalization has afforded great opportunities to prepare organic substances, facilitating the derivatization of complex drugs and natural molecules. This letter describes an efficient and practical protocol for lanthanum-catalyzed continuous epoxy-ring opening and oxidative dehydrogenative lactonization under visible-light irradiation. Notably, the lanthanum catalyst also acts as a photocatalyst while acting as a Lewis acid in this reaction; therefore, no additional photocatalyst is required. We can conveniently prepare a series of diverse isochromanones with oxygen-containing spirocyclic structural units under a balloon-oxygen atmosphere at room temperature. Mechanistic studies and control experiments reveal that the in situ-generated lanthanum bromide should be crucial in the reaction.

Using medical university websites for health education about COVID-19; an effective solution for public education during a pandemic.

BACKGROUND: Medical universities use their websites to teach, research, and promote a culture of health. Therefore, this study aimed to evaluate the performance of medical universities in terms of health information and education regarding COVID-19 by surveying the website of Iranian medical universities. METHODS: This descriptive-analytical study was conducted in June to August 2020 on the websites of medical universities in three categories of universities (type 1, type 2 and type 3). The information of this study was collected from medical universities located in the east, west, north, south and center of Iran. Data were collected according to a checklist. The checklist contained 3 sections; the first part with 8 components regarding general information of the university websites, the second part with 11 components regarding the information and news related to the coronavirus and the third part with 12 components regarding the content of personal health education and environmental health for the prevention of coronavirus. To determine the status of each website in the two areas of health information and education, websites were divided into three categories based on scores (poor, average and good). Data were analyzed by chi-square. RESULTS: In this study, 1118 web pages related to 48 Iranian universities of medical sciences were reviewed, where 19 were type 1 universities, 21 type 2 universities, and 8 type 3 universities. The mean scores of the websites regarding the information and news related to the coronavirus (8.54 ± 1.750) and the mean scores of the websites regarding the personal and environmental health education related to coronavirus (10.96 ± 1.148) were in a favorable and positive condition. The ranking of medical universities by type showed that the scores in the two areas of health information and education about the coronavirus were in good condition and none of the universities were in bad condition. Chi-square showed that the information status and news related to the coronavirus had a significantly positive relationship with the type of medical universities (χ2 = 10.343, p = 0.006). CONCLUSIONS: The results of this study showed that type1 and type 2 and 62.5% of type 3 medical universities were in good condition in terms of total scores in the two areas of health information and education about coronavirus and none of the universities were in a bad situation. It is suggested that the website of medical universities can serve as a reliable and appropriate source of information not only for academics and students but also for the general public.

Causal associations between cardiorespiratory fitness and type 2 diabetes.

Higher cardiorespiratory fitness is associated with lower risk of type 2 diabetes. However, the causality of this relationship and the biological mechanisms that underlie it are unclear. Here, we examine genetic determinants of cardiorespiratory fitness in 450k European-ancestry individuals in UK Biobank, by leveraging the genetic overlap between fitness measured by an exercise test and resting heart rate. We identified 160 fitness-associated loci which we validated in an independent cohort, the Fenland study. Gene-based analyses prioritised candidate genes, such as CACNA1C, SCN10A, MYH11 and MYH6, that are enriched in biological processes related to cardiac muscle development and muscle contractility. In a Mendelian Randomisation framework, we demonstrate that higher genetically predicted fitness is causally associated with lower risk of type 2 diabetes independent of adiposity. Integration with proteomic data identified N-terminal pro B-type natriuretic peptide, hepatocyte growth factor-like protein and sex hormone-binding globulin as potential mediators of this relationship. Collectively, our findings provide insights into the biological mechanisms underpinning cardiorespiratory fitness and highlight the importance of improving fitness for diabetes prevention.

Cerebellar infarction caused by vertebral artery dissection: A case report.

RATIONALE: Vertebral artery dissection is an important cause of posterior circulation ischemic stroke in young and middle-aged people. We reported a young man with cerebellar infarction caused by dissection of the right vertebral artery. PATIENT CONCERNS: A 34-year-old man presented with intermittent dizziness, blurred vision, nausea, and transient tinnitus 10 days before admission. All these symptoms were gradually aggravated and followed by vomiting and unfavorable movement of the right limbs. All these symptoms gradually aggravated. DIAGNOSIS: Neurological examination on admission showed ataxia of the right limbs. Magnetic resonance imaging of the head revealed a right cerebellar infarction. High-resolution vessel wall magnetic resonance imaging showed dissection of the right vertebral artery. Whole-brain CT digital subtraction angiography revealed occlusion of the third segment (V3) of the right vertebral artery. This supports the diagnosis of vertebral artery dissection. INTERVENTIONS: The patient received anticoagulant treatment with warfarin. OUTCOMES: After 2 weeks of treatment, the patient showed remarkably alleviated dizziness and unfavorable movement of the right limbs. After 3 months of treatment, the modified Rankin Scale score was 0. MRI of the head revealed that the original right cerebellar focus was softened, and there were no newly formed infarct foci. LESSONS: When young and middle-aged patients without atherosclerotic risk factors encounter sudden dizziness, tinnitus, and unfavorable limb movement, vertebral artery dissection may be considered. Careful inquiry into the medical history may help make a final diagnosis. Further high-resolution vessel wall magnetic resonance imaging is an effective means to find arterial dissection. Early diagnosis and treatment for vertebral artery dissection has a favorable prognosis.

Heterogeneity of cancer-associated fibroblasts in head and neck squamous cell carcinoma.

Cancer-associated fibroblasts (CAFs) consist of heterogeneous cellular populations that contribute critical roles in head and neck squamous cell carcinoma (HNSCC). A series of computer-aided analyses were performed to determine various aspects of CAFs in HNSCC, including their cellular heterogeneity, prognostic value, relationship with immune suppression and immunotherapeutic response, intercellular communication, and metabolic activity. The prognostic significance of CKS2+ CAFs was verified using immunohistochemistry. Our findings revealed that fibroblasts group demonstrated prognostic significance, with the CKS2+ subset of inflammatory CAFs (iCAFs) exhibiting a significant correlation with unfavorable prognosis and being localized in close proximity to cancer cells. Patients with a high infiltration of CKS2+ CAFs had a poor overall survival rate. There is a negative correlation between CKS2+ iCAFs and cytotoxic CD8+ T cells and natural killer (NK) cells, while a positive correlation was found with exhausted CD8+ T cells. Additionally, patients in Cluster 3, characterized by a high proportion of CKS2+ iCAFs, and patients in Cluster 2, characterized by a high proportion of CKS2- iCAFs and CENPF-/MYLPF- myofibroblastic CAFs (myCAFs), did not exhibit significant immunotherapeutic responses. Moreover, close interactions was confirmed to exist between cancer cells and CKS2+ iCAFs/ CENPF+ myCAFs. Furthermore, CKS2+ iCAFs demonstrated the highest level of metabolic activity. In summary, our study enhances the understanding of the heterogeneity of CAFs and provided insights into improving the efficacy of immunotherapies and prognostic accuracy for HNSCC patients.

Structural and functional activities of brain in patients with vascular cognitive impairment: A case-controlled magnetic resonance imaging study.

This study aimed to identify abnormal brain regions and imaging indices of vascular cognitive impairment (VCI) and explore specific imaging diagnostic markers of VCI. In this study, 24 patients with VCI were allocated to the VCI group and 25 healthy subjects were assigned to the healthy control (HC) group. Demographic data and neuropsychological test scores were compared using SPSS 25.0. The structural and functional imaging data were post-processed and statistically analyzed using CAT12, DPARSF and SPM12 software, based on the MATLAB platform. The structural and functional indices of gray matter volume (GMV) and regional homogeneity (ReHo) were obtained, and inter-group data were analyzed using an independent-sample t test. Sex, age, years of education, and total brain volume were used as covariates. Compared to the HC group, the GMV of VCI in the VCI group decreased significantly in the rectus muscles of the bilateral gyrus, left superior temporal gyrus, left supplementary motor area (SMA), right insula, right superior temporal gyrus, right anterior cuneiform lobe, and right anterior central gyrus (PRECG) (P < .05, FWE correction), without GMV enlargement in the brain area. ReHo decreased in the right inferior temporal gyrus (ITG), right parahippocampal gyrus, and left temporal pole (middle temporal gyrus, right lingual gyrus, left posterior central gyrus, and right middle temporal gyrus), the areas of increased ReHo were the left caudate nucleus, left rectus gyrus, right anterior cingulate gyrus and lateral cingulate gyrus (P < .05, FWE correction). Correlation analysis showed that the GMV of the left superior temporal gyrus was positively correlated with the Montreal Cognitive Assessment (MoCA) score (P < .05), and the GMV of the right insula was positively correlated with the MESE and long delayed memory scores (P < .05). There was a significant positive correlation between the ReHo and short-term delayed memory scores in the middle temporal gyrus of the left temporal pole (P < .05). The volume of GMV and ReHo decreased in VCI patients, suggesting that impairment of brain structure and function in specific regions is the central mechanism of cognitive impairment in these patients. Meanwhile, the functional indices of some brain regions were increased, which may be a compensatory mechanism for the cognitive impairment associated with VCI.

Naturally occurring substitution of an amino acid in a plant virus gene-silencing suppressor enhances viral adaptation to increasing thermal stress.

Cereal yellow dwarf virus (CYDV-RPV) encodes a P0 protein that functions as a viral suppressor of RNA silencing (VSR). The strength of silencing suppression is highly variable among CYDV-RPV isolates. In this study, comparison of the P0 sequences of CYDV-RPV isolates and mutational analysis identified a single C-terminal amino acid that influenced P0 RNA-silencing suppressor activity. A serine at position 247 was associated with strong suppressor activity, whereas a proline at position 247 was associated with weak suppressor activity. Amino acid changes at position 247 did not affect the interaction of P0 with SKP1 proteins from Hordeum vulgare (barley) or Nicotiana benthamiana. Subsequent studies found P0 proteins containing a P247 residue were less stable than the P0 proteins containing an S247 residue. Higher temperatures contributed to the lower stability and in planta and the P247 P0 proteins were subject to degradation via the autophagy-mediated pathway. A P247S amino acid residue substitution in P0 increased CYDV-RPV replication after expression in agroinfiltrated plant leaves and increased viral pathogenicity of P0 generated from the heterologous Potato virus X expression vector system. Moreover, an S247 CYDV-RPV could outcompete the P247 CYDV-RPV in a mixed infection in natural host at higher temperature. These traits contributed to increased transmission by aphid vectors and could play a significant role in virus competition in warming climates. Our findings underscore the capacity of a plant RNA virus to adapt to climate warming through minor genetic changes in gene-silencing suppressor, resulting in the potential for disease persistence and prevalence.

Functional analysis of polymorphism haplotypes of MGMT in residents of high background radiation area.

To investigate the distribution of polymorphisms and their frequent haplotypes in the regulatory region of MGMT in residents of high background radiation area (HBRA) and their impacts on transcriptional activity, we collected DNA samples from 83 healthy Chinese residents in HBRA and searched for genetic polymorphisms in the regulatory region of MGMT. Haplotypes were characterized by Haploview analysis. Transcriptional activities of different polymorphism haplotypes were detected by using a dual-luciferase reporter assay. Six genetic polymorphisms were identified within the regulatory region (1024 bp) of MGMT. Linkage disequilibrium (LD) patterns and haplotype profiles were analyzed using the identified genetic polymorphisms. These polymorphisms we found to be in high LD, with a D' of 0.928 (r2 = 0.581) for -808 T>C and -19 C>T, 0.928 (r2 = 0.581) for -797 G>A and -19 C>T in Han Chinese HBRA residents. Complete LD with a D' of 1.0 (r2 = 1.0) was observed between -808 T>C and -797 G>A. Haploview analysis revealed the existence of three polymorphism haplotypes in the core region of regulatory region of MGMT. Using serially truncated regulatory region of human MGMT luciferase reporter gene constructs, we found a 1002 bp (-637 nt to +365 nt) fragment in the MGMT gene was the core region. Dual-luciferase reporter assays showed that different polymorphism haplotypes bearing different variant alleles exhibit distinct transcriptional activities, especially the polymorphism haplotype carrying -19 T has the strongest transcriptional activity. In summary, the present study obtained genetic characteristics of the six polymorphisms in the regulatory region of the MGMT gene in HBRA residents, and the results suggest that different polymorphism haplotypes have significant effects on the transcriptional activity of the MGMT and that the -19 C>T polymorphism may be a functional variant involved in the transcriptional regulation of the MGMT gene.

Syntheses of functionalized benzocoumarins by photoredox catalysis.

Direct functionalization of inert C(sp3)-H bonds is an attractive synthetic technology for the preparation of pharmaceutically significant compounds in modern synthetic organic chemistry. In this work, we report a new method for the synthesis of functionalized benzocoumarins through the strategy of activation of multiple C-H bonds on 2-aryl toluenes under visible-light-enabled photoredox conditions. This method has the advantages of high functional group compatibility, mild reaction conditions, and effectively avoiding the use of strong oxidants and precious metal catalysts. Detailed mechanistic investigations, including spectroscopic and electrochemical studies, support the reaction's mechanistic course.

MicroRNA-382-5p Promotes Oral Squamous Cell Carcinoma Development and Progression by Negatively Regulating PTEN Expression.

PURPOSE: Oral squamous cell carcinoma (OSCC) local recurrence and distant metastasis remain a poorly understood clinical challenge. The objective of this study was to investigate how dysregulation of miR-382-5p impacts invasion and dissemination of OSCC. METHODS: Tissue samples were collected from 20 subjects with OSCC. Expression levels of miR-382-5p were determined by quantitative real-time polymerase chain reaction (qRT-PCR), and correlations with clinical characteristics were investigated. qRT-PCR was used to determine the miR-382-5p and peptidyl-prolyl cis/trans isomerase (PTEN) expression in tumor tissues, adjacent normal tissues, normal human oral keratinocyte line, and OSCC line (SCC-9). Cell proliferation, invasion, and migration of knock-in and knock-down miR-382-5p transfectants were assessed using cell counting kit-8 and Transwell assays. PTEN was confirmed to be a downstream target using a TargetScan prediction, dual-luciferase reporter assays, and western blot analysis. Statistical analysis of experimental data was performed with SPSS 22.0 software. RESULTS: We found high expression of miR-382-5p and significant downregulation of PTEN in tumor tissues and SCC-9 cells from OSCC patients (P < .05). miR-382-5p expression was lower in early stage (I + II) than in late stage (III + IV), while PTEN exhibited higher expression in early stage (I + II) instead of in late stage (III + IV) (P < .05). In addition, overexpression of miR-382-5p promoted the proliferation, invasion, and migration of OSCC cells. However, the proliferation, invasion, and migration of OSCC cells were inhibited after suppression of miR-382-5p. Finally, PTEN is downregulated by miR-382-5p. CONCLUSION: MiR-382-5p supports proliferation, invasion, and migration of OSCC cells through the PTEN pathway. Further investigation may improve our understanding of OSCC local recurrence and distant metastasis.

A bibliometric analysis of neuroimaging biomarkers in Parkinson disease based on Web of Science.

BACKGROUND: This study aimed to analyze and summarize the research hotspots and trends in neuroimaging biomarkers (NMBM) in Parkinson disease (PD) based on the Web of Science core collection database and provide new references for future studies. METHODS: Literature regarding NMBM in PD from 1998 to 2022 was analyzed using the Web of Science core collection database. We utilized CiteSpace software (6.1R2) for bibliometric analyses of countries/institutions/authors, keywords, keyword bursts, references, and their clusters. RESULTS: A total of 339 studies were identified with a continually increasing annual trend. The most productive country and collaboration was the United States. The top research hotspot is PD cognitive disorder. NMBM and artificial intelligence medical imaging have been applied in the clinical diagnosis, differential diagnosis, treatment, and prognosis of PD. The trends in this field include research on T1 weighted structure magnetic resonance imaging in accordance with voxel-based morphometry, PD cognitive disorder, and neuroimaging features of Lewy body dementia and Alzheimer disease. CONCLUSION: The development of NMBM in PD will be effectively promoted by drawing on international research hotspots and cutting-edge technologies, emphasizing international collaboration and institutional cooperation at the national level, and strengthening interdisciplinary research.

Artery of Percheron Occlusion in China: A Case Report and Chinese Literature Review.

INTRODUCTION: The artery of Percheron (AOP) is a rare anatomical variant in which bilateral paramedian thalami are supplied by a single vascular branch arising from the P1 segment of the posterior cerebral artery. We present a case of AOP occlusion presenting as loss of consciousness and summarize the literature in Chinese to find the clinical characteristics. CASE REPORT: An 83-year-old woman was found unconscious for 1 day at home and was sent to the hospital the next day. Cerebral magnetic resonance imaging on day 1 of the patient showed a recent bilateral paramedian thalamic infarction. Simultaneously, magnetic resonance angiography found evident artery stenosis of the right P1 segment of the posterior cerebral artery, suggesting that the patient was diagnosed with AOP occlusion. Since the patient has missed the best time for thrombolytic therapy, anticoagulant therapy was given immediately; as the patient was then found to have pulmonary infections, antibiotic therapy was also initiated. The neurological status of this patient improved very slow. In about 2 weeks, the patient becomes more conscious but still could not speak or move. CONCLUSION: Our report suggests that unusual mood disorder and language disorder of aged patients might indicate the AOP occlusion, and cerebral imaging of magnetic resonance imaging (better with magnetic resonance angiography) should be performed to establish the diagnosis of AOP occlusion. The fast and accurate diagnosis of stroke because of AOP occlusion could best benefit the patients.

Identification of Rare Loss-of-Function Genetic Variation Regulating Body Fat Distribution.

CONTEXT: Biological and translational insights from large-scale, array-based genetic studies of fat distribution, a key determinant of metabolic health, have been limited by the difficulty in linking predominantly noncoding variants to specific gene targets. Rare coding variant analyses provide greater confidence that a specific gene is involved, but do not necessarily indicate whether gain or loss of function (LoF) would be of most therapeutic benefit. OBJECTIVE: This work aimed to identify genes/proteins involved in determining fat distribution. METHODS: We combined the power of genome-wide analysis of array-based rare, nonsynonymous variants in 450 562 individuals in the UK Biobank with exome-sequence-based rare LoF gene burden testing in 184 246 individuals. RESULTS: The data indicate that the LoF of 4 genes (PLIN1 [LoF variants, P = 5.86 × 10-7], INSR [LoF variants, P = 6.21 × 10-7], ACVR1C [LoF + moderate impact variants, P = 1.68 × 10-7; moderate impact variants, P = 4.57 × 10-7], and PDE3B [LoF variants, P = 1.41 × 10-6]) is associated with a beneficial effect on body mass index-adjusted waist-to-hip ratio and increased gluteofemoral fat mass, whereas LoF of PLIN4 (LoF variants, P = 5.86 × 10-7 adversely affects these parameters. Phenotypic follow-up suggests that LoF of PLIN1, PDE3B, and ACVR1C favorably affects metabolic phenotypes (eg, triglycerides [TGs] and high-density lipoprotein [HDL] cholesterol concentrations) and reduces the risk of cardiovascular disease, whereas PLIN4 LoF has adverse health consequences. INSR LoF is associated with lower TG and HDL levels but may increase the risk of type 2 diabetes. CONCLUSION: This study robustly implicates these genes in the regulation of fat distribution, providing new and in some cases somewhat counterintuitive insight into the potential consequences of targeting these molecules therapeutically.

Surgical site infection after delayed sternal closure in neonates with congenital heart disease: retrospective case-control study.

OBJECTIVES: To determine the prevalence of surgical site infections (SSIs) in neonatal congenital heart disease patients undergoing delayed sternal closure (DSC) and evaluate risk factors for SSI. METHODS: Hospital records of 483 consecutive neonates who underwent surgical intervention between January 2013 and December 2017 were reviewed, and perioperative variables were recorded. RESULTS: We found that the prevalence of SSI was 87.5% when the body weight was less than 1500 g. When the operative age was between seven and 14 days, the probability of no SSI is about 93.9%. When the duration of the aortic cross-clamp was more than 60 min, the prevalence of SSI was 91.2%. The prevalence without SSI was 96.6% when the duration of DSC was less than 24 h. However, when the duration of DSC was more than 120 h, the prevalence of SSI was 88.9% (p = 0.000). CONCLUSIONS: With the prolongation of aortic clamping duration, the probability of occurrence of SSI increased in neonatal CHD with DSC. The age at operation and body weight are closely related to the occurrence of SSI in neonatal CHD patients with DSC.

[Prevalence of Human T-Cell Lymphotropic Virus Type 1 and 2 among Blood Donors in Jiangsu from 2016 to 2019].

OBJECTIVE: To investigate the prevalence of human T-cell lymphotropic virus (HTLV) type-I/II infection among voluntary blood donors in Jiangsu (Nanjing, Suzhou, Xuzhou). METHODS: From 2016 to 2019, 408 262 samples of voluntary blood donors from four blood stations in Jiangsu Province (Jiangsu Province Blood Center, Nanjing Red Cross Blood Center, Suzhou Central Blood Station, and Xuzhou Central Blood Station) were screened for HTLV-I/II antibody by ELISA. The positive samples were sent to National Center for Clinical Laboratories for confirmation by RT-PCR and Western blot. RESULTS: The positive rate of HTLV-I/II screened by ELISA was 0.20‰ (82/408 262), and three HTLV-I positive samples were confirmed. The prevalence of HTLV-1 infection was 0.74 per 100 000 (3/408 262). All three donors were female repeated blood donors of childbearing ages. CONCLUSION: Jiangsu is a low prevalence area of HTLV, and a reasonable blood screening strategy for HTLV can further reduce the risk of transfusion-transmitted virus infection.