Expanded diversity of Asgard archaea and their relationships with eukaryotes.

Asgard is a recently discovered superphylum of archaea that appears to include the closest archaeal relatives of eukaryotes1-5. Debate continues as to whether the archaeal ancestor of eukaryotes belongs within the Asgard superphylum or whether this ancestor is a sister group to all other archaea (that is, a two-domain versus a three-domain tree of life)6-8. Here we present a comparative analysis of 162 complete or nearly complete genomes of Asgard archaea, including 75 metagenome-assembled genomes that-to our knowledge-have not previously been reported. Our results substantially expand the phylogenetic diversity of Asgard and lead us to propose six additional phyla that include a deep branch that we have provisionally named Wukongarchaeota. Our phylogenomic analysis does not resolve unequivocally the evolutionary relationship between eukaryotes and Asgard archaea, but instead-depending on the choice of species and conserved genes used to build the phylogeny-supports either the origin of eukaryotes from within Asgard (as a sister group to the expanded Heimdallarchaeota-Wukongarchaeota branch) or a deeper branch for the eukaryote ancestor within archaea. Our comprehensive protein domain analysis using the 162 Asgard genomes results in a major expansion of the set of eukaryotic signature proteins. The Asgard eukaryotic signature proteins show variable phyletic distributions and domain architectures, which is suggestive of dynamic evolution through horizontal gene transfer, gene loss, gene duplication and domain shuffling. The phylogenomics of the Asgard archaea points to the accumulation of the components of the mobile archaeal 'eukaryome' in the archaeal ancestor of eukaryotes (within or outside Asgard) through extensive horizontal gene transfer.

Genome-wide identification, molecular evolution and gene expression of P450 gene family in Cyrtotrachelus buqueti.

BACKGROUND: Insect Cytochrome P450 monooxygenase (CYPs or P450s) plays an important role in detoxifying insecticides, causing insect populations to develop resistance. However, the molecular functions of P450 gene family in Cyrtotrachelus buqueti genome are still lacking. RESULTS: In this study, 71 CbuP450 genes have been identified. The amino acids length of CbuP450 proteins was between 183 aa ~ 1041 aa. They are proteins with transmembrane domains. The main component of their secondary structure is α-helix and random coils. Phylogenetic analysis showed that C. buqueti and Rhynchophorus ferrugineus were the most closely related. This gene family has 29 high-frequency codons, which tend to use A/T bases and A/T ending codons. Gene expression analysis showed that CbuP450_23 in the female adult may play an important role on high temperature resistance, and CbuP450_17 in the larval may play an important role on low temperature tolerance. CbuP450_10, CbuP450_17, CbuP450_23, CbuP450_10, CbuP450_16, CbuP450_20, CbuP450_23 and CbuP450_ 29 may be related to the regulation of bamboo fiber degradation genes in C. buqueti. Protein interaction analysis indicates that most CbuP450 proteins are mainly divided into three aspects: encoding the biosynthesis of ecdysteroids, participating in the decomposition of synthetic insecticides, metabolizing insect hormones, and participating in the detoxification of compounds. CONCLUSIONS: We systematically analyzed the gene and protein characteristics, gene expression, and protein interactions of CbuP450 gene family, revealing the key genes involved in the stress response of CbuP450 gene family in the resistance of C. buqueti to high or low temperature stress, and identified the key CbuP450 proteins involved in important life activity metabolism. These results provided a reference for further research on the function of P450 gene family in C. buqueti.

Near-Infrared Responsive Ag@Au Nanoplates with Exceptional Stability for Highly Sensitive Colorimetric and Photothermal Dual-Mode Lateral Flow Immunoassay.

Lateral flow immunoassay (LFIA) has played a vital role in point-of-care (POC) testing on account of its simplicity, rapidity, and low cost. However, the low sensitivity and difficulty of quantitation limit its further development. Sensitive markers with new detection modes are being developed to dramatically improve LFIA's performance. Herein, a ligand-complex approach was proposed to uniformly coat a thin layer of Au onto Ag triangular nanoplates (Ag TNPs) without etching the Ag cores, which not only retain the unique optical properties from Ag TNPs but also acquire the surface stability and biocompatibility of gold. The localized surface plasmon resonance absorption of these Ag@Au TNPs could be finely adjusted from visible (550 nm) to the second near-infrared region (NIR-II) (1100 nm), and even longer, by simply adjusting the ratio between edge length and thickness. Utilizing the Ag@Au TNPs as new markers for LFIA, a highly sensitive colorimetric and photothermal dual-mode detection of the SARS-CoV-2 nucleocapsid protein was achieved with a very low background. The Ag@Au TNPs showed an exceedingly high photothermal conversion efficiency of 61.4% (ca. 2 times higher than that of Au nanorods), endowing the LFIA method with a low photothermal detection limit (40 pg/mL), which was 25-fold lower than that of the colorimetric results. The generality of the method was further verified by the sensitive and accurate analysis of cardiac troponin I (cTnI). This method is robust, reproducible, and highly specific and has been successfully applied to SARS-COV-2 detection in 35 clinical samples with satisfactory results, demonstrating its potential for POC applications.

Irritable bowel syndrome in children: the placebo response rate and influencing factors a meta-analysis.

BACKGROUND: Irritable bowel syndrome is common in children and exhibits a high placebo response. This study was to explore the placebo response rate and its influencing factors in children with irritable bowel syndrome. METHODS: A systematic search was performed on Pubmed, Embase, MEDLINE, Cochrane Library, CNKI, Wanfang, and CBM from database inception to March 2022. Randomized controlled trials of irritable bowel syndrome in children were included in the study. The primary outcome was the placebo response rate of improvement. RESULTS: Thirteen studies were included, with 445 patients in the placebo group. The rate of improvement and abdominal pain disappearance were 28.2% (95% CI, 16.6-39.9%) and 5% (95% CI, 0-18.4%). The placebo response based on the abdominal pain score was 0.675 (95% CI, 0.203-1.147). The mode of administration (P < 0.01), dosing schedule (P < 0.01), and clinical outcome assessor (P = 0.04) have a significant impact on the magnitude of placebo effect. CONCLUSIONS: The placebo response rate for pediatric irritable bowel syndrome was 28.2%. In clinical trials, reducing dosing frequency, selecting appropriate dosage forms, and using patient-reported outcomes can help mitigate the placebo effect. IMPACT: This is the first meta-analysis to assess the placebo response rates for improvement and disappearance in children with IBS. The finding suggested that the mode of administration, dosing schedule, and clinical outcome assessor could potentially influence the magnitude of the placebo effect in children with IBS. This study would provide a basis for estimating sample size in clinical trial design with a placebo control.

Scutellarin inhibits oleic acid induced vascular smooth muscle foam cell formation via activating autophagy and inhibiting NLRP3 inflammasome activation.

Abnormalities in vascular smooth muscle cells (VSMCs) are pivotal in the pathogenesis of cardiovascular pathologies such as atherosclerosis and hypertension. Scutellarin (Scu), a flavonoid derived from marigold flowers, exhibits a spectrum of biological activities including anti-inflammatory, antioxidant, antitumor, immunomodulatory and antimicrobial effects. Notably, Scu has demonstrated the capacity to mitigate vascular endothelial damage and prevent atherosclerosis via its antioxidative properties. Nevertheless, the influence of Scu on the formation of VSMC-derived foam cells remains underexplored. In this study, Scu was evidenced to efficaciously attenuate oleic acid (OA)-induced lipid accumulation and the upregulation of adipose differentiation-associated protein Plin2 in a dose- and time-responsive manner. We elucidated that Scu effectively diminishes OA-provoked VSMC foam cell formation. Further, it was established that Scu pretreatment augments the protein expression of LC3B-II and the mRNA levels of Map1lc3b and Becn1, concurrently diminishing the protein levels of the NLRP3 inflammasome compared to the OA group. Activation of autophagy through rapamycin attenuated NLRP3 inflammasome protein expression, intracellular lipid droplet content and Plin2 mRNA levels. Scu also counteracted the OA-induced decrement of LC3B-II levels in the presence of bafilomycin-a1, facilitating the genesis of autophagosomes and autolysosomes. Complementarily, in vivo experiments revealed that Scu administration substantially reduced arterial wall thickness, vessel wall cross-sectional area, wall-to-lumen ratio and serum total cholesterol levels in comparison to the high-fat diet model group. Collectively, our findings suggest that Scu attenuates OA-induced VSMC foam cell formation through the induction of autophagy and the suppression of NLRP3 inflammasome activation.

Inhibiting cardiac autophagy suppresses Zika virus replication.

Zika Virus (ZIKV) infection is a global threat. Other than the congenital neurological disorders it causes, ZIKV infection has been reported to induce cardiac complications. However, the precise treatment plans are unclear. Thus, illustrating the pathogenic mechanism of ZIKV in the heart is critical to providing effective prevention and treatment of ZIKV infection. The mechanism of autophagy has been reported recently in Dengue virus infection. Whether or not autophagy participates in ZIKV infection and its role remains unrevealed. This study successfully established the in vitro cardiomyocytes and in vivo mouse models of ZIKV infection to investigate the involvement of autophagy in ZIKV infection. The results showed that ZIKV infection is both time and gradient-dependent. The key autophagy protein, LC3B, increased remarkably after ZIKV infection. Meanwhile, autophagic flux was detected by immunofluorescence. Applying autophagy inhibitors decreased the LC3B levels. Furthermore, the number of viral copies was quantified to evaluate the influence of autophagy during infection. We found that autophagy was actively involved in the ZIKV infection and the inhibition of autophagy could effectively reduce the viral copies, suggesting a potential intervention strategy for reducing ZIKV infection and the undesired complications caused by ZIKV.

Polycyclic aromatic hydrocarbon exposure burden: Individual and mixture analyses of associations with chronic obstructive pulmonary disease risk.

Accumulating data demonstrate that polycyclic aromatic hydrocarbons (PAH) exposure is linked to compromised respiratory diseases. This study aimed to analyze urinary PAH metabolites and their associations with chronic obstructive pulmonary disease (COPD) in a sample size of 3015 subjects from a total population of 50,588 from the National Health and Nutrition Examination Survey (NHANES) in 2007-2016. Results showed that the most predominant metabolite was 1-Hydroxynaphthalene (1-NAP, 84%) with a geometric mean concentration of 50,265 ng/L, followed by its homologue 2-NAP (10%), both of which arose from sources including road emission, smoking and cooking. Multiple logistic regression showed that seven of the ten major PAH metabolites were correlated with increased COPD risk: including 1-NAP (OR: 1.83, 95%CI: 1.25, 2.69), 2-Hydroxyfluorene (2-FLU, OR: 2.29, 95%CI: 1.42, 3.68) and 1-Hydroxyphenanthrene (1-PHE, OR: 2.79, 95%CI: 1.85, 4.21), when compared to the lowest tertile after adjusted for covariates. Total exposure burden per PAH congener sub-group demonstrated persistent positive correlation with COPD for ∑PHE (OR: 1.80, 95%CI: 1.34, 2.43) and ∑FLU (OR: 2.74, 95%CI: 1.77, 4.23) after adjusted for covariates. To address the contribution of PAH exposure as mixture towards COPD, weighted quantile sum (WQS) regression analyses revealed that 1-NAP, 9-Hydroxyfluorene (9-FLU), 3-Hydroxyfluorene (3-FLU) and 1-PHE were among the top contributors in the associations with COPD. Our results demonstrate the contemporary yet ongoing exposure burden of PAH exposure for over a decade, particularly towards NAPs and FLUs that contribute significantly to COPD risk, calling for more timely environmental regulation.

Colorimetric and photothermal dual-mode lateral flow immunoassay based on Au-Fe3O4 multifunctional nanoparticles for detection of Salmonella typhimurium.

Au-Fe3O4 multifunctional nanoparticles (NPs) were synthesized and integrated with lateral flow immunoassay (LFIA) for dual-mode detection of Salmonella typhimurium. The Au-Fe3O4 NPs not only combined excellent local surface plasmon resonance characteristics and superparamagnetic properties, but also exhibited good photothermal effect. In the detection, antibody-conjugated Au-Fe3O4 NPs first captured S. typhimurium from complex matrix, which was then loaded on the LFIA strip and trapped by the T-line. By observing the color bands with the naked eyes, qualitative detection was performed free of instrument. By measuring the photothermal signal, quantification was achieved with a portable infrared thermal camera. The introduction of magnetic separation achieved the enrichment and purification of target bacteria, thus enhancing the detection sensitivity and reducing interference. This dual-mode LFIA achieved a visual detection limit of 5 × 105 CFU/mL and a photothermal detection limit of 5 × 104 CFU/mL. Compared with traditional Au-based LFIA, this dual-mode LFIA increased the detection sensitivity by 2 orders of magnitude and could be directly applied to unprocessed milk sample. Besides, this dual-mode LFIA showed good reproducibility and specificity. The intra-assay and inter-assay variation coefficients were 3.0% and 7.9%, and with this dual-mode LFIA, other bacteria hardly produced distinguishable signals. Thus, the Au-Fe3O4 NPs-based LFIA has potential to increase the efficiency of pandemic prevention and control. Au-Fe3O4 nanoparticle proved to be a promising alternative reporter for LFIA, achieving multifunctions: target purification, target enrichment, visual qualitation, and instrumental quantification, which improved the limitations of traditional LFIA.

Design and Multiple Applications of Mixed-Ligand Metal-Organic Frameworks with Dual Emission.

Herein, we revealed the factors that affect the emission in mixed-ligand metal-organic frameworks (MOFs) with the combination of terephthalic acid (BDC), 2-aminoterephthalic acid (BDC-NH2), and 2,5-dihydroxylterephthalic acid [BDC-(OH)2] as models. The -NH2 and -(OH)2 groups change the π-conjugation and luminescence behaviors than BDC, so the ligands show different optical behaviors. The Zn2+ ion with a 3d10 full electronic structure shows little effect on the emission of the ligand and is selected as the metal node. We found that the emission of BDC is weak and incompatible to that of BDC-NH2, so only the emission of BDC-NH2 was observed in the BDC/BDC-NH2-MOF. Crosstalk occurs between the emissions from BDC and BDC-(OH)2 for the single emission from BDC/BDC-(OH)2-MOFs, even different ratios are selected. The MOFs prepared with BDC-NH2 and BDC-(OH)2 show dual emission at 450 and 550 nm, while the relative intensity was easily tuned with the ligand ratio and excitation wavelength. Thus, abundant optical behaviors and extensive applications were realized, including but not limited to (1) dual emission from single MOFs, (2) tunable color from blue to yellow with the excitation from 290 to 370 nm for information encryption and decryption, (3) white emission obtained under an excitation of 330 nm, and (4) response of -NH2 groups to HCHO and Fe3+ ions for ratiometric fluorescence sensing and visual detection. This work revealed the factors that affect the emission in mixed-ligand MOFs, studied their optical behaviors, and realized different applications with single MOFs.

Ag Nanoparticles with Ultrathin Au Shell-Based Lateral Flow Immunoassay for Colorimetric and SERS Dual-Mode Detection of SARS-CoV-2 IgG.

Immunoglobulin detection is essential for diagnosing progression of SARS-CoV-2 infection, for which SARS-CoV-2 IgG is one of the most important indexes. In this paper, Ag nanoparticles with ultrathin Au shells (∼2 nm) embedded with 4-mercaptobenzoic acid (MBA) (AgMBA@Au) were manufactured via a ligand-assisted epitaxial growth method and integrated into lateral flow immunoassay (LFIA) for colorimetric and SERS dual-mode detection of SARS-CoV-2 IgG. AgMBA@Au possessed not only the surface chemistry advantages of Au but also the superior optical characteristics of Ag. Moreover, the nanogap between the Ag core and the Au shell also greatly enhanced the Raman signal. After being modified with anti-human antibodies, AgMBA@Au recognized and combined with SARS-CoV-2 IgG, which was captured by the SARS-CoV-2 spike protein on the T line. Qualitative analysis was achieved by visually observing the color of the T line, and quantitative analysis was conducted by measuring the SERS signal with a sensitivity four orders of magnitude higher (detection limit: 0.22 pg/mL). The intra-assay and inter-assay variation coefficients were 7.7 and 10.3%, respectively, and other proteins at concentrations of 10 to 20 times higher than those of SARS-CoV-2 IgG could hardly produce distinguishable signals, confirming good reproducibility and specificity. Finally, this method was used to detect 107 clinical serum samples. The results agreed well with those obtained from enzyme-linked immunosorbent assay kits and were significantly better than those of the colloidal gold test strips. Therefore, this dual-mode LFIA has great potential in clinical practical applications and can be used to screen and trace the early immune response of SARS-CoV-2.

Photoswitches with different numbers of azo chromophores for molecular solar thermal storage.

We investigate three azo-chromophore-containing photoswitches (1, 2 and 3) for molecular solar thermal storage (MOST) based on reversible Z-E isomerization. 1, 2 and 3 are photoswitchable compounds that contain one, two and three azo chromophores, respectively. In solution, 1, 2 and 3 were charged via UV-light-induced E-to-Z isomerization. Among these three compounds, 2 exhibited an energy density as high as 272 ± 1.8 J g-1, which showed the best energy storage performance. This result originated from the low molecular weight, a high degree of photoisomerization, and moderate steric hindrance of 2, which demonstrated the advantages of the meta-bisazobenzene structure for MOST. In addition, we studied the performances of these photoswitches in the solvent-free state. Only 1 showed photoinduced reversible solid-to-liquid transitions, which enabled the charging of 1 in a solvent-free state. The stored energy density for 1 in a solvent-free state was 237 ± 1.5 J g-1. By contrast, 2 and 3 could not be charged in the solvent-free state due to the lack of solid-state photoisomerization. Our findings provide a better understanding of the structure-performance relationship for azobenzenebased MOST and pave the way for the development of high-density solar thermal fuels.

Case Report of Neonatal Sotos Syndrome with a New Missense Mutation in the NSD1 Gene and Literature Analysis in the Chinese Han Population.

Currently, no consensus exists regarding Sotos syndrome in the Chinese population. Here, we present a case of neonatal Sotos syndrome, followed by a retrospective analysis of five cases of neonatal Sotos syndrome, reported in China. The study subject was a twin premature infant, heavier than gestational age, with characteristic facial features, limb shaking, and hypertonia. Transient hypoglycemia, abnormal cranial magnetic resonance imaging, multiple nodules in polycystic kidneys and liver, abnormal hearing, patent ductus arteriosus, and an atrial septal defect were also noted. The subject showed overgrowth and developmental retardation at 3 months of age. Sequencing revealed a novel missense mutation, c.5000C>A, in the nuclear receptor binding the SET domain protein 1 gene, resulting in an alanine-to-glutamate substitution. The bioinformatics analysis suggested high pathogenicity at this site. This study provides insights into diagnosis of neonatal Sotos syndrome based on specific phenotypes. Subsequent treatment and follow-up should focus on developmental retardation, epilepsy, and scoliosis.

Magnetic Relaxation Switching Immunoassay Based on Hydrogen Peroxide-Mediated Assembly of Ag@Au-Fe3 O4 Nanoprobe for Detection of Aflatoxin B1.

Magnetic relaxation switching (MRS) sensors have shown great potential in food safety monitoring due to their high signal-to-noise ratio and simplicity, but they often suffer from insufficient sensitivity and stability due to the lack of excellent magnetic nanoprobes. Herein, dumbbell-like Au-Fe3 O4 nanoparticles are designed as magnetic nanoprobes for developing an aflatoxin B1-MRS immunosensor. The Fe3 O4 portion in the Au-Fe3 O4 nanoparticles functions as the magnetic probe to provide transverse relaxation signals, while the Au segments serve as a bridge to grow Ag shell and assemble the Au-Fe3 O4 nanoparticles, thus modulating transverse relaxation time of surrounding water molecular. The formation of Ag@Au-Fe3 O4 is triggered by hydrogen peroxide. After degraded by horseradish peroxidase, hydrogen peroxide reduces Ag+ to Ag nanoparticles which assemble dispersed Au-Fe3 O4 to aggregated Ag@Au-Fe3 O4 , thus dramatically improving the sensitivity of traditional MRS sensor. Combined with competitive immunoreaction, this Ag@Au-Fe3 O4 -MRS immunosensor can detect aflatoxin B1 with a high sensitivity (3.81 pg mL-1 ), which improved about 21 folds and 9 folds than those of enzyme-linked immunosorbent assay and high-performance liquid chromatography (HPLC), respectively. The good consistency with HPLC in real samples detection indicates the good accuracy of this immunosensor. This Ag@Au-Fe3 O4 -MRS immunosensor offers an attractive tool for detection of harmful substances.

Construction of NaYF4 Library for Morphology-Controlled Multimodality Applications.

Morphology and size of the nanoparticles are highly related to the properties; establishing a library to summarize the relationship between the morphology/size and property is very helpful for associated applications. However, the NaYF4 library and thus the correlation between the morphology and property are still absent. Here NaYF4 library is presented and their morphologies and structures are illustrated at atomic scale for the first time. How about the crystal formation affects the morphology is further used to guide the property. Through rational doping, upconversion luminescence, magnetic resonance (MR) and computed tomography are investigated with the nanoprisms, nanoflowers, and nanoplates as models to reveal the effect of the size and morphology. The difference of the properties provides strong evidence on the importance of the library. In particular, the "imperfect structure" of nanoflower is observed on atomic scale and enhances the MR response. The different upconversion intensity ratio for the emissions at 475 and 693 nm is observed from doped NaYF4 with different morphology. Thus, controllable fabrication of NaYF4 with desired morphology is indispensable to achieve the optimal properties as the guidance on how to choose matrix from the library to meet the specific applications.

AI detection of mild COVID-19 pneumonia from chest CT scans.

OBJECTIVES: An artificial intelligence model was adopted to identify mild COVID-19 pneumonia from computed tomography (CT) volumes, and its diagnostic performance was then evaluated. METHODS: In this retrospective multicenter study, an atrous convolution-based deep learning model was established for the computer-assisted diagnosis of mild COVID-19 pneumonia. The dataset included 2087 chest CT exams collected from four hospitals between 1 January 2019 and 31 May 2020. The true positive rate, true negative rate, receiver operating characteristic curve, area under the curve (AUC) and convolutional feature map were used to evaluate the model. RESULTS: The proposed deep learning model was trained on 1538 patients and tested on an independent testing cohort of 549 patients. The overall sensitivity was 91.5% (195/213; p < 0.001, 95% CI: 89.2-93.9%), the overall specificity was 90.5% (304/336; p < 0.001, 95% CI: 88.0-92.9%) and the general AUC value was 0.955 (p < 0.001). CONCLUSIONS: A deep learning model can accurately detect COVID-19 and serve as an important supplement to the COVID-19 reverse transcription-polymerase chain reaction (RT-PCR) test. KEY POINTS: • The implementation of a deep learning model to identify mild COVID-19 pneumonia was confirmed to be effective and feasible. • The strategy of using a binary code instead of the region of interest label to identify mild COVID-19 pneumonia was verified. • This AI model can assist in the early screening of COVID-19 without interfering with normal clinical examinations.

Synthesis and vasorelaxant evaluation of novel 7-methoxyl-2,3-disubstituted-quinoxaline derivatives.

An array of novel 7-methoxyl-2,3-disubstituted quinoxaline derivatives was designed, synthesized and their potential antihypertensive activities were examined, in an attempt to discover potent small molecules with vasorelaxant effects. The vasoactivities of these compounds on vascular tone, as well as underlying mechanisms were hereby explored. Results showed that five compounds (7s, 7t, 7v, 7w, 7γ) could induce endothelium-independent relaxation in high extracellular K+- and phenylephrine-precontracted C57 mice aortic rings. These five compounds, unlike other commonly used vasodilators, could slowly but effectively inhibit vasoconstriction.

Butyrolactone and sesquiterpene derivatives as inhibitors of iNOS from the roots of Lindera glauca.

Nine previously undescribed butyrolactone and sesquiterpene derivatives, named cyclopentanone A (1), subamolides F and G (2 and 3), secosubamolide F (4), rupestonic acids J - L (5-7), linderaguaianols A and B (8 and 9), together with six known ones 10-15 were isolated from the roots of Lindera glauca. Their structures, including their absolute configurations were elucidated by extensive spectroscopic analysis, quantum chemical calculations, and Mo2(AcO)4-induced circular dichroism. Compound 1 that possessed a unique five-membered cyclopentane skeleton with a side chain was rarely found from natural sources. The biogenetic pathway for 1-4 was postulated. Secosubamolide F (4) inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-activated RAW264.7 cells with IC50 value of 1.73 ± 0.18 µM and also significantly suppressed the production of iNOS. The binding interactions between 4 and iNOS were investigated using docking analyses.

Effects of Low-Dose Amitriptyline on Epigastric Pain Syndrome in Functional Dyspepsia Patients.

AIM: To observe the therapeutic effect of low-dose amitriptyline (AMT) on epigastric pain syndrome (EPS) in patients with functional dyspepsia. METHODS: Sixty patients with EPS were randomly divided into the following two groups for a four-week clinical trial: routine treatment with pantoprazole (RT group) and the AMT group. The RT group was treated with 40 mg of pantoprazole once daily. The AMT group received 25 mg of AMT once daily before bedtime. The Nepean Dyspepsia Index (NDI) checklist, Hamilton Rating Scale of Anxiety/Depression (HAMA/HAMD), and Pittsburgh Sleep Quality Index (PSQI) were employed to evaluate dyspepsia symptoms, psychological distress, and sleep, respectively. RESULTS: All items were similar between the two groups before treatment (0 week). After 4 weeks of treatment, the NDI-symptom checklist score as well as the severity and bothersomeness of EPS in the AMT group was significantly decreased compared with those in the RT group (p < 0.05). However, no differences were found in the frequency of NDI checklist, psychological status (HAMD/HAMA scores) of EPS, or sleep quality (PSQI score) between the two groups after treatment. In addition, the time to fall asleep was shorter in the AMT group compared with the RT group after 4 weeks of treatment (p < 0.05). CONCLUSION: Low-dose AMT effectively improved the dyspepsia symptoms and the time to fall asleep in the EPS patients, compared with pantoprazole, although it did not reduce the psychological distress. Therefore, AMT could be considered as a good candidate for EPS treatment in the clinic.

Predicting factors of central lymph node metastasis and BRAFV600E mutation in Chinese population with papillary thyroid carcinoma.

OBJECTIVE: The aim of this study was to evaluate the predictive factors of central lymph node metastasis (CLNM) and BRAFV600E mutation in Chinese patients with papillary thyroid carcinoma (PTC). METHODS: A total of 943 PTC patients who underwent thyroidectomy from 2014 to 2016 at our hospital were enrolled. Those patients were divided into PTC > 10 mm and papillary thyroid microcarcinoma (PTMC) groups by tumor size. The BRAFV600E mutation was examined by quantitative real-time PCR. Univariate and multivariate analyses were used to examine risk factors associated with CLNM and the BRAFV600E mutation. RESULTS: The frequency of CLNM was 53% (505/943). Both univariate and multivariate analyses suggested that the risk factors for CLNM in PTC patients were male, younger age, and larger tumor size (P < 0.05). Coexistent Hashimoto thyroiditis (HT) was an independent protective factor against CLNM when the tumor was > 10 mm (P = 0.006). Stratified analysis revealed that male, age ≤ 30 years, and tumor size > 5 mm were independent risk factors for CLNM. The BRAFV600E mutation rate was 85%. Multivariate logistic regression analysis revealed that age (P < 0.001) and coexistent HT (P = 0.005) were independent predictive factors of BRAFV600E mutation in PTC patients. Only age was a risk factor for the BRAFV600E mutation when the tumor was > 10 mm (P = 0.004). In the PTMC group, the BRAFV600E mutation was significantly correlated with tumor size (P < 0.001) and coexistent HT (P = 0.03). Stratified analysis revealed that age > 30 years and tumor size > 5 mm were independent predictive factors of BRAFV600E mutation. Furthermore, the incidence of CLNM was significantly higher in BRAFV600E mutation-positive patients (P = 0.009) when the tumor was ≤ 5 mm. CONCLUSION: The factors male, younger age (≤ 30 years), large tumor size (> 5 mm), and coexistent HT are independent predicative factors for CLNM. The BRAFV600E mutation is associated with both large size and without HT in PTMC patients, age > 30 years in the PTC > 10 mm group. The BRAFV600E mutation was an independent risk factor for CLNM when the tumor was ≤ 5 mm. For optimal management, these features should be comprehensively evaluated to determine the initial surgical approach for PTC patients.

Diurnal Blood Pressure and Heart Rate Variability in Hypertensive Patients with Cerebral Small Vessel Disease: A Case-Control Study.

BACKGROUND: Whether autonomic dysfunction contributes to cerebral small vessel disease (CSVD) remains unclear. This study aimed to explore the relationship between CSVD and blood pressure variability (BPV) and heart rate variability (HRV). METHODS: This case-control study recruited 50 patients with CSVD and 50 non-CSVD hypertensive age- and gender-matched controls. All participants completed a 24-h ambulatory electrocardiogram recording and ambulatory BP monitoring (ABPM). Differences in HRV and BPV between the two groups were examined. BPV indices assessed by ABPM included mean systolic BP (SBP), mean diastolic BP (DBP), coefficient of variation and weighted standard deviation of SBP and DBP. RESULTS: CSVD patients had significant higher 24-h mean systolic BP (SBP), 24-h mean diastolic BP (DBP), daytime mean SBP, nocturnal mean SBP, and nocturnal mean DBP (P < .05 for all). CSVD patients had a significant lower nocturnal SBP fall rate compared with controls (median: 1.0 versus 6.2, respectively; P < .001) and were more likely to be non-dippers and reverse dippers. There were no differences in HRV variables between the two groups. Five logistic models were built to explore the correlations between BPV indices and CSVD. BPV indices were separately entered into the logistic regression models, together with hyperlipidemia, ischemic stroke history, current use of anti-hypertensive agents, and serum blood urea nitrogen. In models 1-3, 24-h mean SBP and nocturnal mean SBP and DBP were significantly correlated with CSVD (r2 = 0.308-0.340). In model 4, the nocturnal SBP fall rate was negatively correlated with CSVD (odds ratio [OR] = 0.871, 95% confidence interval [CI] = 0.804-0.943; P = .001), with r2 = 0.415 fitting the model. In model 5, the pattern of SBP dipping was significantly associated with CSVD, with non-dipper (OR = 8.389, 95%CI = 1.489-47.254; P = .016) and reverse dipper (OR = 27.008, 95%CI = 3.709-196.660; P = .001) having the highest risks of CSVD (r2 = 0.413). CONCLUSIONS: Lower nocturnal SBP fall rate is associated with CSVD. Non-dipper and reverse dipper hypertensive patients have a higher risk of CSVD.