Host-microbiota interactions contributing to the heterogeneous tumor microenvironment in colorectal cancer.

Colorectal cancer (CRC) exhibits pronounced heterogeneity and is categorized into four widely accepted consensus molecular subtypes (CMSs) with unique tumor microenvironments (TMEs). However, the intricate landscape of the microbiota and host-microbiota interactions within these TMEs remains elusive. Using RNA-sequencing data from The Cancer Genome Atlas, we analyzed the host transcriptomes and intratumoral microbiome profiles of CRC samples. Distinct host genes and microbial genera were identified among the CMSs. Immune microenvironments were evaluated using CIBERSORTx and ESTIMATE, and microbial coabundance patterns were assessed with FastSpar. Through LASSO penalized regression, we explored host-microbiota associations for each CMS. Our analysis revealed distinct host gene signatures within the CMSs, which encompassed ferroptosis-related genes and specific immune microenvironments. Moreover, we identified 293, 153, 66, and 109 intratumoral microbial genera with differential abundance, and host-microbiota associations contributed to distinct TMEs, characterized by 829, 1,270, 634, and 1,882 robust gene-microbe associations for each CMS in CMS1-CMS4, respectively. CMS1 featured inflammation-related HSF1 activation and gene interactions within the endothelin pathway and Flammeovirga. Integrin-related genes displayed positive correlations with Sutterella in CMS2, whereas CMS3 spotlighted microbial associations with biosynthetic and metabolic pathways. In CMS4, genes involved in collagen biosynthesis showed positive associations with Sutterella, contributing to disruptions in homeostasis. Notably, immune-rich subtypes exhibited pronounced ferroptosis dysregulation, potentially linked to tissue microbial colonization. This comprehensive investigation delineates the diverse landscapes of the TME within each CMS, incorporating host genes, intratumoral microbiota, and their complex interactions. These findings shed light on previously uncharted mechanisms underpinning CRC heterogeneity and suggest potential therapeutic targets.NEW & NOTEWORTHY This study determined the following: 1) providing a comprehensive landscape of consensus molecular subtype (CMS)-specific tumor microenvironments (TMEs); 2) constructing CMS-specific networks, including host genes, intratumoral microbiota, and enriched pathways, analyzing their associations to uncover unique patterns that demonstrate the intricate interplay within the TME; and 3) revealing a connection between immune-rich subtypes and ferroptosis activation, suggesting a potential regulatory role of the microbiota in ferroptosis dysregulation of the colorectal cancer TME.

NAFLDkb: A Knowledge Base and Platform for Drug Development against Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease with a broad spectrum of histologic manifestations. The rapidly growing prevalence and the complex pathologic mechanisms of NAFLD pose great challenges for treatment development. Despite tremendous efforts devoted to drug development, there are no FDA-approved medicines yet. Here, we present NAFLDkb, a specialized knowledge base and platform for computer-aided drug design against NAFLD. With multiperspective information curated from diverse source materials and public databases, NAFLDkb presents the associations of drug-related entities as individual knowledge graphs. Practical drug discovery tools that facilitate the utilization and expansion of NAFLDkb have also been implemented in the web interface, including chemical structure search, drug-likeness screening, knowledge-based repositioning, and research article annotation. Moreover, case studies of a knowledge graph repositioning model and a generative neural network model are presented herein, where three repositioning drug candidates and 137 novel lead-like compounds were newly established as NAFLD pharmacotherapy options reusing data records and machine learning tools in NAFLDkb, suggesting its clinical reliability and great potential in identifying novel drug-disease associations of NAFLD and generating new insights to accelerate NAFLD drug development. NAFLDkb is freely accessible at https://www.biosino.org/nafldkb and will be updated periodically with the latest findings.

Superconductivity in Ca-intercalated bilayer graphene: C2CaC2.

The deposition and intercalation of metal atoms can induce superconductivity in monolayer and bilayer graphenes. For example, it has been experimentally proved that Li-deposited graphene is a superconductor with critical temperature Tc of 5.9 K, Ca-intercalated bilayer graphene C6CaC6 and K-intercalated epitaxial bilayer graphene C8KC8 are superconductors with Tc of 2-4 K and 3.6 K, respectively. However, the Tc of them are relatively low. To obtain higher Tc in graphene-based superconductors, here we predict a new Ca-intercalated bilayer graphene C2CaC2, which shows higher Ca concentration than the C6CaC6. It is proved to be thermodynamically and dynamically stable. The electronic structure, electron-phonon coupling (EPC) and superconductivity of C2CaC2 are investigated based on first-principles calculations. The EPC of C2CaC2 mainly comes from the coupling between the electrons of C-pz orbital and the high- and low-frequency vibration modes of C atoms. The calculated EPC constant λ of C2CaC2 is 0.75, and the superconducting Tc is 18.9 K, which is much higher than other metal-intercalated bilayer graphenes. By further applying -4% biaxial compressive strain to C2CaC2, the Tc can be boosted to 26.6 K. Thus, the predicted C2CaC2 provides a new platform for realizing superconductivity with the highest Tc in bilayer graphenes.

First-principles prediction of superconducting properties of monolayer 1T'-WS2 under biaxial tensile strain.

High-purity 1T'-WS2 film has been experimentally synthesized [Nature Materials, 20, 1113-1120 (2021)] and theoretically predicted to be a two-dimensional (2D) superconducting material with Dirac cones [arXiv:2301.11425]. In the present work, we further study the superconducting properties of monolayer 1T'-WS2 by applying biaxial tensile strain. It is shown that the superconducting critical temperature Tc firstly increases and then decreases with respect to tensile strains, with the highest superconducting critical temperature Tc of 7.25 K under the biaxial tensile strain of 3%. In particular, we find that Dirac cones also exist in several tensile strained cases. Our studies show that monolayer 1T'-WS2 may provide a good platform for understanding the superconductivity of 2D Dirac materials.

Integrated Transcriptomics and Metabolomics Reveal Changes in Cell Homeostasis and Energy Metabolism in Trachinotus ovatus in Response to Acute Hypoxic Stress.

Trachinotus ovatus is an economically important mariculture fish, and hypoxia has become a critical threat to this hypoxia-sensitive species. However, the molecular adaptation mechanism of T. ovatus liver to hypoxia remains unclear. In this study, we investigated the effects of acute hypoxic stress (1.5 ± 0.1 mg·L-1 for 6 h) and re-oxygenation (5.8 ± 0.3 mg·L-1 for 12 h) in T. ovatus liver at both the transcriptomic and metabolic levels to elucidate hypoxia adaptation mechanism. Integrated transcriptomics and metabolomics analyses identified 36 genes and seven metabolites as key molecules that were highly related to signal transduction, cell growth and death, carbohydrate metabolism, amino acid metabolism, and lipid metabolism, and all played key roles in hypoxia adaptation. Of these, the hub genes FOS and JUN were pivotal hypoxia adaptation biomarkers for regulating cell growth and death. During hypoxia, up-regulation of GADD45B and CDKN1A genes induced cell cycle arrest. Enhancing intrinsic and extrinsic pathways in combination with glutathione metabolism triggered apoptosis; meanwhile, anti-apoptosis mechanism was activated after hypoxia. Expression of genes related to glycolysis, gluconeogenesis, amino acid metabolism, fat mobilization, and fatty acid biosynthesis were up-regulated after acute hypoxic stress, promoting energy supply. After re-oxygenation for 12 h, continuous apoptosis favored cellular function and tissue repair. Shifting from anaerobic metabolism (glycolysis) during hypoxia to aerobic metabolism (fatty acid ß-oxidation and TCA cycle) after re-oxygenation was an important energy metabolism adaptation mechanism. Hypoxia 6 h was a critical period for metabolism alteration and cellular homeostasis, and re-oxygenation intervention should be implemented in a timely way. This study thoroughly examined the molecular response mechanism of T. ovatus under acute hypoxic stress, which contributes to the molecular breeding of hypoxia-tolerant cultivars.

Ectopic endometriotic stromal cells-derived lactate induces M2 macrophage polarization via Mettl3/Trib1/ERK/STAT3 signalling pathway in endometriosis.

Endometriosis is a gynaecological condition characterized by the growth of endometrium-like tissues within and outside of the pelvic cavity. Recent studies have demonstrated that aberrant infiltration of M2 macrophages is mainly responsible for the establishment of endometriotic lesions. A growing body of evidence shows that glycolysis and lactate accumulation have great impact on the regulation of immunomicroenvironment. However, the communication signal between glycolysis and macrophages is poorly defined in endometriosis. Hereby, we investigate the correlation between glycolysis and M2 macrophage infiltration in endometriosis. Next, we confirm that lactate is pivotal factor that drives macrophage M2-polarization to promote endometriotic stromal cells invasion in vitro and in vivo. In addition, we also identify that the activation of Mettl3 and its target gene Trib1 promote M2 macrophage polarization. Moreover, we also demonstrate that Trib1 induce M2 macrophage polarization via the activation of ERK/STAT3 signalling pathway. Finally, by injecting 2-DG into endometriosis mice model, we show that the restrain of glycolysis significantly reduces the progression of endometriosis, which provides evidence for lactate as a potential therapeutic strategy for the prevention and treatment of endometriosis.

Dr AFC: drug repositioning through anti-fibrosis characteristic.

Fibrosis is a key component in the pathogenic mechanism of a variety of diseases. These diseases involving fibrosis may share common mechanisms and therapeutic targets, and therefore common intervention strategies and medicines may be applicable for these diseases. For this reason, deliberately introducing anti-fibrosis characteristics into predictive modeling may lead to more success in drug repositioning. In this study, anti-fibrosis knowledge base was first built by collecting data from multiple resources. Both structural and biological profiles were then derived from the knowledge base and used for constructing machine learning models including Structural Profile Prediction Model (SPPM) and Biological Profile Prediction Model (BPPM). Three external public data sets were employed for validation purpose and further exploration of potential repositioning drugs in wider chemical space. The resulting SPPM and BPPM models achieve area under the receiver operating characteristic curve (area under the curve) of 0.879 and 0.972 in the training set, and 0.814 and 0.874 in the testing set. Additionally, our results also demonstrate that substantial amount of multi-targeting natural products possess notable anti-fibrosis characteristics and might serve as encouraging candidates in fibrosis treatment and drug repositioning. To leverage our methodology and findings, we developed repositioning prediction platform, drug repositioning based on anti-fibrosis characteristic that is freely accessible via https://www.biosino.org/drafc.

Hydrogenation induced high-temperature superconductivity in two-dimensional W2C3.

The discovery of highly crystalline two-dimensional (2D) superconductors provides a new alluring branch for exploring the fundamental significances. Based on first-principles calculations, we predict a new kind of 2D stable material W2C3, which is a semimetal but not a superconductor because of the weak electron-phonon coupling (EPC) strength. After hydrogenation, W2C3H2 possesses the intrinsic metallic properties with a large density of states (DOS) at the Fermi energy (EF). More interestingly, the EPC strength is greatly enhanced after hydrogenation and the calculated critical temperature (Tc) is 40.5 K. Furthermore, the compressive strain can obviously soften the low-frequency phonons and enhance the EPC strength. Then, the Tc of W2C3H2 can be increased from 40.5 K to 49.1 K with -4% compressive strain. This work paves the way for providing a new platform for 2D superconductivity.

Superconductivity of monolayer functionalized biphenylene with Dirac cones.

Monolayer biphenylene is a new two-dimensional (2D) carbon allotrope, which has been experimentally synthesized and theoretically predicted to show superconductivity. In this work, we investigate functionalized biphenylene with the adsorption of Li. The superconducting critical temperature (Tc) can be pushed from 0.59 K up to 3.91 K after Li adsorption. Our calculations confirm that the adsorption pushes the peak showing a high electronic density of states closer to the Fermi level, which usually leads to a larger Tc. Furthermore, the application of biaxial tensile strain can soften phonons and further enhance the Tc up to 15.86 K in Li-deposited biphenylene. Interestingly, a pair of type-II Dirac cones below the Fermi level has been observed, expanding the range of Dirac materials. It suggests that monolayer biphenylene deposited with Li may be a material with potential applications and improves the understanding of Dirac-type superconductors.

14-3-3ζ inhibits maladaptive repair in renal tubules by regulating YAP and reduces renal interstitial fibrosis.

Acute kidney injury (AKI) refers to a group of common clinical syndromes characterized by acute renal dysfunction, which may lead to chronic kidney disease (CKD), and this process is called the AKI-CKD transition. The transcriptional coactivator YAP can promote the AKI-CKD transition by regulating the expression of profibrotic factors, and 14-3-3 protein zeta (14-3-3ζ), an important regulatory protein of YAP, may prevent the AKI-CKD transition. We established an AKI-CKD model in mice by unilateral renal ischemia-reperfusion injury and overexpressed 14-3-3ζ in mice using a fluid dynamics-based gene transfection technique. We also overexpressed and knocked down 14-3-3ζ in vitro. In AKI-CKD model mice, 14-3-3ζ expression was significantly increased at the AKI stage. During the development of chronic disease, the expression of 14-3-3ζ tended to decrease, whereas active YAP was consistently overexpressed. In vitro, we found that 14-3-3ζ can combine with YAP, promote the phosphorylation of YAP, inhibit YAP nuclear translocation, and reduce the expression of fibrosis-related proteins. In an in vivo intervention experiment, we found that the overexpression of 14-3-3ζ slowed the process of renal fibrosis in a mouse model of AKI-CKD. These findings suggest that 14-3-3ζ can affect the expression of fibrosis-related proteins by regulating YAP, inhibit the maladaptive repair of renal tubular epithelial cells, and prevent the AKI-CKD transition.

Advances in G-quadruplexes-based fluorescent imaging.

G-quadruplexes (G4s), the noncanonical nucleic acid secondary structure, form within guanine-rich DNA or RNA sequences. G4s formation can affect chromatin architecture and gene regulation and has been associated with various cellular functions, including DNA replication, transcription, and genome maintenance. Visualizing and detecting G4s precisely in such processes is essential to increasing our understanding of G4s biology. Considerable attention has focused on the G4s targeting molecular imaging studies. Besides, fluorescent light-up aptamers (FLAPs, also referred to as fluorogenic aptamers) have gained momentum, which commonly have a G4 scaffolding for imaging intracellular RNAs and metabolites. In this review, we first introduce several representative fluorescent imaging approaches for tracking G4s in cells and in vivo. We also discuss the potential of G4-containing FLAPs in bioimaging and summarize current developments in this field from the standpoint of fluorescent molecules. Finally, we discuss the present challenges and future potential of G4 imaging and G4-containing FLAPs development.

Phonon-mediated superconductivity in two-dimensional hydrogenated phosphorus carbide: HPC3.

In recent years, three-dimensional (3D) high-temperature superconductors at ultrahigh pressure have been reported, typical examples are the polyhydrides H3S, LaH10, YH9, etc. To find high-temperature two-dimensional (2D) superconductors at atmospheric pressure is another research hotspot. Here, we investigated the possible superconductivity in a hydrogenated monolayer phosphorus carbide based on first-principles calculations. The results reveal that monolayer PC3 transforms from a semiconductor to a metal after hydrogenation. Interestingly, the C-π-bonding band contributes most to the states at the Fermi level. Based on the electron-phonon coupling mechanism, it is found that the electron-phonon coupling constant of HPC3 is 0.95, which mainly originates from the coupling of C-π electrons with the in-plane vibration modes of C and H. The calculated critical temperature Tc is 31.0 K, which is higher than those in most 2D superconductors. By further applying a biaxial tensile strain of 3%, the Tc can be boosted to 57.3 K, exceeding the McMillan limit. Thus, hydrogenation and strain are effective ways for increasing the superconducting Tc of 2D materials.

Theoretical prediction of superconductivity in two-dimensional MXenes of molybdenum carbides.

Theoretically and experimentally, MXenes consisting of Mo and C have aroused much interest due to superconductivity in their films and even monolayer forms. Here, based on first-principles calculations, we systematically calculate the electronic structure, phonon dispersion, and electron-phonon coupling (EPC) of monolayer Mo2C (both T- and H-phases), Mo3C2, and Mo3C3. The results show that H-MoxCy (x = 2 or 3, y = 1-3) always have lower total energies than their corresponding T phase and other configurations. All these two-dimensional (2D) molybdenum carbides are metals and some of them display weak phonon-mediated superconductivity at different superconducting transition temperatures (Tc). The Mo 4d-orbitals play a critical role in their electronic properties and the Mo atomic vibrations play a dominant role in their low-frequency phonons, EPC, and superconductivity. By comparison, we find that increasing the Mo content can enhance the EPC and Tc. Besides, we further explore the impact of strain engineering on their superconducting related physical quantities. With increasing biaxial stretching, the phonon dispersions are gradually softened to form some soft modes, which can trigger some peaks of α2F(ω) in the low-frequency region and evidently increase the EPC λ. The Tc of H-Mo2C can be increased up to 11.79 K. Upon further biaxial stretching, charge density waves may appear in T-Mo2C, H-Mo3C2, and H-Mo3C3.

The effect of doping and strain on superconductivity of T-graphene.

As an allotrope of graphene, T-graphene was predicted to be an intrinsic two-dimensional (2D) superconductor with a superconducting critical temperature (Tc) of about 20.8 K [Gu et al., Chin. Phys. Lett. 36, 097401 (2019)]. In this work, based on first-principles calculations, hole doping and biaxial tensile strain (BTS) are considered to modulate the electron-phonon coupling (EPC) and superconductivity of T-graphene. It is found that the EPC constant of T-graphene is 0.807 and the calculated critical temperature Tc is 28.2 K at a doping level of 0.5 hole per unit cell (3.31 × 1014 cm-2) and 12% BTS. Furthermore, when 0.8 hole per unit cell (5.43 × 1014 cm-2) doping and 10% BTS are applied, the EPC constant is 0.939, and the Tc can be boosted to 35.2 K, which is higher than those of the pristine T-graphene and many other 2D carbon-based superconductors.

Alterations in bile acid metabolizing gut microbiota and specific bile acid genes as a precision medicine to subclassify NAFLD.

Multiple mechanisms for the gut microbiome contributing to the pathogenesis of nonalcoholic fatty liver disease (NAFLD) have been implicated. Here, we aim to investigate the contribution and potential application for altered bile acids (BA) metabolizing microbes in NAFLD by post hoc analysis of whole metagenome sequencing (WMS) data. The discovery cohort consisted of 86 well-characterized patients with biopsy-proven NAFLD and 38 healthy controls. Assembly-based analysis was performed to identify BA-metabolizing microbes. Statistical tests, feature selection, and microbial coabundance analysis were integrated to identify microbial alterations and markers in NAFLD. An independent validation cohort was subjected to similar analyses. NAFLD microbiota exhibited decreased diversity and microbial associations. We established a classifier model with 53 differential species exhibiting a robust diagnostic accuracy [area under the receiver-operator curve (AUC) = 0.97] for detecting NAFLD. Next, eight important differential pathway markers including secondary BA biosynthesis were identified. Specifically, increased abundance of 7α-hydroxysteroid dehydrogenase (7α-HSDH), 3α-hydroxysteroid dehydrogenase (baiA), and bile acid-coenzyme A ligase (baiB) was detected in NAFLD. Furthermore, 10 of 50 BA-metabolizing metagenome-assembled genomes (MAGs) from Bacteroides ovatus and Eubacterium biforme were dominant in NAFLD and interplayed as a synergetic ecological guild. Importantly, two subtypes of patients with NAFLD were observed according to secondary BA metabolism potentials. Elevated capability for secondary BA biosynthesis was also observed in the validation cohort. These bacterial BA-metabolizing genes and microbes identified in this study may serve as disease markers. Microbial differences in BA-metabolism and strain-specific differences among patients highlight the potential for precision medicine in NAFLD treatment.

Differential effect of pre-pregnancy low BMI on fetal macrosomia: a population-based cohort study.

BACKGROUND: The differential effect of pre-pregnancy low BMI on macrosomia has not been fully addressed. Herein, we conducted a city-wide population-based cohort study to illuminate the association between pre-pregnancy low BMI and macrosomia, stratifying by maternal age, parity, and GDM status. METHODS: All pregnant women who paid their first prenatal visit to the hospital in Qingdao during August 1, 2018, to June 30, 2020, were recruited to this study. The interactive effect of maternal age and pre-pregnancy low BMI on macrosomia was evaluated using logistic regression models, followed by strata-specific analyses. RESULTS: A total of 105,768 mother-child pairs were included, and the proportion of fetal macrosomia was 11.66%. The interactive effect of maternal pre-pregnancy BMI and age was statistically significant on macrosomia irrespective of parity (nullipara: Padjusted=0.0265; multipara: Padjusted=0.0356). The protective effect of low BMI on macrosomia was most prominent among nullipara aged 35 years and above (aOR=0.16, 95% CI 0.05-0.49) and multipara aged 25 years and below (aOR=0.17, 95% CI 0.05-0.55). In nullipara without GDM, the risk estimates gradually declined with increasing conception age (20-to-24 years: aOR=0.64, 95% CI 0.51-0.80; 25-to-29 years: aOR=0.43 95% CI 0.36-0.52; 30-to-34 years: aOR=0.40 95% CI 0.29-0.53; and ≥35 years: aOR=0.19, 95% CI 0.06-0.60). A similar pattern could also be observed in nullipara with GDM, where the aOR for low BMI on macrosomia decreased from 0.54 (95% CI 0.32-0.93) in pregnant women aged 25-29 years to 0.30 (95% CI 0.12-0.75) among those aged 30-34 years. However, younger multiparous mothers, especially those aged 25 years and below without GDM (aOR=0.21, 95% CI 0.06-0.68), were more benefited from a lower BMI against the development of macrosomia. CONCLUSIONS: Maternal low BMI is inversely associated with macrosomia irrespective of maternal age and parity. The impact of pre-pregnancy low BMI on macrosomia varied by maternal age and parity. The protective effect of a lower maternal BMI against fetal macrosomia was more prominent in nulliparous mothers aged 35 years and above, whereas multiparous mothers younger than 25 years of age were more benefited.

Association of VEGFA polymorphisms with chronic obstructive pulmonary disease in Chinese Han and Mongolian populations.

NEW FINDINGS: What is the central question of this study? Vascular endothelial growth factor A (VEGFA) is an important growth factor involved in changes in the bronchial microvascular and airway inflammation in chronic obstructive pulmonary disease (COPD) progression. What is the association of single nucleotide polymorphisms (SNPs) in VEGFA with the risk of COPD in the Chinese Han and Mongolian populations? What is the main finding and its importance? The effect of five SNPs in the VEGFA gene was analysed and compared between the Chinese Han and Mongolian populations. A contribution of risk alleles rs833068, rs833070 and rs3024997 to COPD was detected in the Chinese Mongolian population only. The study provided data from different populations to validate the role of VEGFA polymorphisms in COPD and provided reliable SNPs to predict the risk of COPD. ABSTRACT: We attempted to define the associations between single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor A (VEGFA) gene and chronic obstructive pulmonary disease (COPD) in Chinese Han and Mongolian cohorts. Five SNPs were genotyped in cohorts of 684 COPD patients (350 Mongolian and 334 Han) and 784 healthy controls (350 Mongolian and 434 Han) using SNPscan multiplex PCR. SNP frequencies, genetic models and haplotypes were analysed using the chi-square test. The associations of SNPs with COPD and linkage disequilibrium were analysed using logistic regression and HaploView, respectively. We found that only rs833068G>A, rs833070T>C and rs3024997G>A were significantly associated with the risk of COPD in the Mongolian population (rs833068: P < 0.001, rs833070: P < 0.001, rs3024997: P = 0.002). In the analysis of genotype distributions, the A/A and G/A genotypes in rs833068 (A/A: odds ratio (OR) = 0.313, P < 0.001; G/A: OR = 0.724, P < 0.001) and rs3024997 (A/A: OR = 0.513, P = 0.008; G/A: OR = 0.671, P = 0.008) and the C/C and T/C genotypes in rs833070 (C/C: OR = 0.435, P = 0.007; T/C: OR = 0.593, P = 0.007) were associated with protection against COPD in the Mongolian population. The haplotype frequencies of GCCAT and GTCGC were significantly different between the patients and controls (GCCAT: P = 0.001; GTCGC: P < 0.001) in the Mongolian population. Our findings indicate that five SNPs in the VEGFA gene play divergent roles in the Han and Mongolian populations. rs833068A, rs833070C and rs3024997A were observed to be associated with the risk of COPD in the Mongolian population.

Incidence and risk factors of congenital heart disease in Qingdao: a prospective cohort study.

BACKGROUND: Many studies have been conducted to assess the incidence of congenital heart disease (CHD). However, results were greatly inconsistent among these studies with a broad range of findings. METHODS: A prospective census-based cohort study was conducted in Qingdao, China, from August 1, 2018 to April 30, 2019. All of the local registered pregnant women were continuously investigated and followed from 15 to 20 weeks of gestation to delivery, tracking the CHD cases in both the fetal and neonatal stages. A logistic regression model was applied to assess the association between CHD and possible risk factors. RESULTS: The positive rate of prenatal CHD screening was 14.36 per 1000 fetuses and the incidence of CHD was 9.38 per 1000 live births. Results from logistic regression indicated that, living in the countryside (odds ratio, (OR): 0.771; 95% confidence interval, (CI): 0.628-0.946) and having a childbearing history (OR: 0.802; 95%CI: 0.676-0.951) were negatively associated with CHD. However, twin pregnancy (OR: 1.957, 95% CI: 1.245-3.076), illness in the first trimester (OR: 1.306; 95% CI: 1.048-1.628), a family history of CHD (OR: 7.156; 95% CI: 3.293-15.552), and having a child with a birth defect (OR: 2.086; 95% CI: 1.167-3.731) were positively associated with CHD. CONCLUSION: CHD is a serious health problem in Qingdao. The CHD incidence found in this study was similar to existing research. The positive rate of prenatal CHD screening was higher than the incidence of neonatal CHD. Moreover, CHD risk factors were identified in our study, and our findings may have great implications for formation CHD intervention strategies.

[Value of Contrast-enhanced Ultrasound Parameters in Evaluating K-W Nodule Formation in Diabetic Nephropathy].

Objective To discuss the value of contrast-enhanced ultrasound(CEUS)parameters in evaluating the formation of Kimmelstiel-Wilson(K-W)nodules in diabetic nephropathy(DN).Methods Sixty-two patients pathologically diagnosed with DN and undergoing CEUS in the First Medical Center of Chinese PLA General Hospital from March 2017 to January 2020 were assigned into two groups according to whether K-W nodules were formed.The cortical CEUS parameters and the ratios of cortical to medullary CEUS parameters were compared between the two groups.Results The 62 patients included 19 patients without K-W nodules(group A)and 43 patients with K-W nodules(group B).The median rise time(U=209,P=0.013)and fall time(U=197,P=0.007)in group B were significantly longer than those in group A.The median wash-in rate(WiR)(U=228,P=0.031)and wash-out rate(WoR)(U=229,P=0.032)in group B were significantly lower than those in group A.The median peak enhancement(PE)1/PE2(U=224,P=0.026),WiR1/WiR2(U=235,P=0.041),and WoR1/WoR2(U=230,P=0.043)ratios in group B were significantly lower than those in group A.The median FT1/FT2 ratio in group B was significantly higher than that in group A(U=227,P=0.038).Conclusion CEUS parameters can be used to quantitatively evaluate renal cortical microperfusion in DN patients with K-W nodules.

Risk factors for the critical illness in SARS-CoV-2 infection: a multicenter retrospective cohort study.

BACKGROUND: Prior studies reported that 5 ~ 32% COVID-19 patients were critically ill, a situation that poses great challenge for the management of the patients and ICU resources. We aim to identify independent risk factors to serve as prediction markers for critical illness of SARS-CoV-2 infection. METHODS: Fifty-two critical and 200 non-critical SARS-CoV-2 nucleic acid positive patients hospitalized in 15 hospitals outside Wuhan from January 19 to March 6, 2020 were enrolled in this study. Multivariable logistic regression and LASSO logistic regression were performed to identify independent risk factors for critical illness. RESULTS: Age older than 60 years, dyspnea, respiratory rate > 24 breaths per min, leukocytosis > 9.5 × 109/L, neutrophilia > 6.3 × 109/L, lymphopenia < 1.1 × 109/L, neutrophil-to-lymphocyte ratio > 3.53, fibrinogen > 4 g/L, d-dimer > 0.55 µg/mL, blood urea nitrogen > 7.1 mM, elevated aspartate transaminase, elevated alanine aminotransferase, total bilirubin > 21 µM, and Sequential Organ Failure Assessment (SOFA) score ≥ 2 were identified as risk factors for critical illness. LASSO logistic regression identified the best combination of risk factors as SOFA score, age, dyspnea, and leukocytosis. The Area Under the Receiver-Operator Curve values for the risk factors in predicting critical illness were 0.921 for SOFA score, 0.776 for age, 0.764 for dyspnea, 0.658 for leukocytosis, and 0.960 for the combination of the four risk factors. CONCLUSIONS: Our findings advocate the use of risk factors SOFA score ≥ 2, age > 60, dyspnea and leukocytosis > 9.5 × 109/L on admission, alone or in combination, to determine the optimal management of the patients and health care resources.