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In order to investigate the effect of intermediate principal stress on the progressive damage and permeability characteristics of unloading sandstone, the unloading test was carried out under different intermediate principal stress conditions based on a multifunctional true triaxial fluid-solid coupling test system with gas-bearing sandstone as the research object; the exponential permeability model related to the cracked volume strain and damage variable were obtained. The results show that the crack closure stress, crack initiation stress and damage stress increase with the increase of intermediate principal stress, and the percentage of elastic section and microcrack extension stage in the pre-peak strain increases. The deformation in the direction of the intermediate principal stress is restrained in the microcrack extension stage, and the compression effect on the direction of the minimum principal stress is enhanced with the increase of the intermediate principal stress; in the macroscopic crack extension stage, the damage stress is closer to the peak stress, and the damage of the specimen is brittle in character. With the increase of the intermediate principal stress, the initial permeability reduction shows a decreasing trend and the point of elevated permeability shifts backward.

ObjectiveThis study aims to evaluate the potential of using tongue image features as non-invasive biomarkers for diagnosing subthreshold depression and to assess the correlation between these features and acupuncture treatment outcomes using advanced deep learning models.MethodsWe employed five advanced deep learning models—DenseNet169, MobileNetV3Small, SEResNet101, SqueezeNet, and VGG19_bn—to analyze tongue image features in individuals with subthreshold depression. These models were assessed based on accuracy, precision, recall, and F1 score. Additionally, we investigated the relationship between the best-performing model’s predictions and the success of acupuncture treatment using Pearson’s correlation coefficient.ResultsAmong the models, SEResNet101 emerged as the most effective, achieving an impressive 98.5% accuracy and an F1 score of 0.97. A significant positive correlation was found between its predictions and the alleviation of depressive symptoms following acupuncture (Pearson’s correlation coefficient = 0.72, p

The aim was to evaluate the efficacy and safety between the watch-and-wait strategy (WW), radical surgery (RS), and local excision (LE) for rectal cancer with clinical complete response (cCR) after neoadjuvant radiotherapy (nCRT). We searched MEDLINE, EMBASE, the Cochrane Library, and clinical trials to compare WW with RS and LE for patients with cCR until March 2023 and collected the following data: local recurrence (LR), distant metastasis (DM), cancer-related death (CRD), overall survival (OS), and disease-free survival (DFS). In total, 2240 patients from 21 studies were included. Pairwise meta-analysis revealed no statistically significant differences between the three groups in terms of CRD and 2-, 3-, and 5-year OS (P

IntroductionAlcohol consumption alters the diversity and metabolic activities of gut microbiota, leading to intestinal barrier dysfunction and contributing to the development of alcoholic liver disease (ALD), which is the most prevalent cause of advanced liver diseases. In this study, we investigated the protective effects and action mechanism of an aqueous extraction of Pericarpium citri reticulatae and Amomi fructus (PFE) on alcoholic liver injury.MethodsC57BL/6 mice were used to establish the mouse model of alcoholic liver injury and orally administered 500 and 1,000 mg/kg/d of PFE for 2 weeks. Histopathology, immunohistochemistry, immunofluorescence, Western blotting, qRT-PCR, and 16S rDNA amplicon sequencing were used to analyze the mechanism of action of PFE in the treatment of alcohol-induced liver injury.ResultsTreatment with PFE significantly improved alcohol-induced liver injury, as illustrated by the normalization of serum alanine aminotransferase, aspartate aminotransferase, total triglyceride, and cholesterol levels in ALD mice in a dose-dependent manner. Administration of PFE not only maintained the intestinal barrier integrity prominently by upregulating mucous production and tight junction protein expressions but also sensibly reversed the dysregulation of intestinal microecology in alcohol-treated mice. Furthermore, PFE treatment significantly reduced hepatic lipopolysaccharide (LPS) and attenuated oxidative stress as well as inflammation related to the TLR4/NF-κB signaling pathway. The PFE supplementation also significantly promoted the production of short-chain fatty acids (SCFAs) in the ALD mice.ConclusionAdministration of PFE effectively prevents alcohol-induced liver injury and may also regulate the LPS-involved gut–liver axis; this could provide valuable insights for the development of drugs to prevent and treat ALD.

BackgroundUnbalanced inflammatory response is a critical feature of sepsis, a life-threatening condition with significant global health burdens. Immune dysfunction, particularly that involving different immune cells in peripheral blood, plays a crucial pathophysiological role and shows early warning signs in sepsis. The objective is to explore the relationship between sepsis and immune subpopulations in peripheral blood, and to identify patients with a higher risk of 28-day mortality based on immunological subtypes with machine-learning (ML) model.MethodsPatients were enrolled according to the sepsis-3 criteria in this retrospective observational study, along with age- and sex-matched healthy controls (HCs). Data on clinical characteristics, laboratory tests, and lymphocyte immunophenotyping were collected. XGBoost and k-means clustering as ML approaches, were employed to analyze the immune profiles and stratify septic patients based on their immunological subtypes. Cox regression survival analysis was used to identify potential biomarkers and to assess their association with 28-day mortality. The accuracy of biomarkers for mortality was determined by the area under the receiver operating characteristic (ROC) curve (AUC) analysis.ResultsThe study enrolled 100 septic patients and 89 HCs, revealing distinct lymphocyte profiles between the two groups. The XGBoost model discriminated sepsis from HCs with an area under the receiver operating characteristic curve of 1.0 and 0.99 in the training and testing set, respectively. Within the model, the top three highest important contributions were the percentage of CD38+CD8+T cells, PD-1+NK cells, HLA-DR+CD8+T cells. Two clusters of peripheral immunophenotyping of septic patients by k-means clustering were conducted. Cluster 1 featured higher proportions of PD1+ NK cells, while cluster 2 featured higher proportions of naïve CD4+T cells. Furthermore, the level of PD-1+NK cells was significantly higher in the non-survivors than the survivors (15.1% vs 8.6%, P

PurposeThis study aims to investigate the differences in binocular corneal parameters and their interrelation with binocular biometric parameters asymmetry in patients with simple myopic anisometropia, thereby elucidating the influence of myopia process on various corneal parameters.MethodsIn this cross-sectional study, 65 patients with anisometropia in monocular myopia were included. They were divided into low anisometropia group: 3.00D

Abstract The continuous increase of saline-alkali areas worldwide has led to the emergence of saline-alkali conditions, which are the primary abiotic stress or hindering the growth of plants. Beet is among the main sources of sugar, and its yield and sugar content are notably affected by saline-alkali stress. Despite sugar beet being known as a salt-tolerant crop, there are few studies on the mechanisms underlying its salt tolerance, and previous studies have mainly delineated the crop’s response to stress induced by NaCl. Recently, advancements in miRNA-mRNA network analysis have led to an increased understanding of how plants, including sugar beet, respond to stress. In this study, seedlings of beet variety "N98122" were grown in the laboratory using hydroponics culture and were exposed to salt stress at 40 days of growth. According to the phenotypic adaptation of the seedlings' leaves from a state of turgidity to wilting and then back to turgidity before and after exposure, 18 different time points were selected to collect samples for analysis. Subsequently, based on the data of real-time quantitative PCR (qRT-PCR) of salt-responsive genes, the samples collected at the 0, 2.5, 7.5, and 16 h time points were subjected to further analysis with experimental materials. Next, mRNA-seq data led to the identification of 8455 differentially expressed mRNAs (DEMs) under exposure to salt stress. In addition, miRNA-seq based investigation retrieved 3558 miRNAs under exposure to salt stress, encompassing 887 known miRNAs belonging to 783 families and 2,671 novel miRNAs. With the integrated analysis of miRNA-mRNA network, 57 miRNA-target gene pairs were obtained, consisting of 55 DEMIs and 57 DEMs. Afterwards, we determined the pivotal involvement of aldh2b7, thic, and δ-oat genes in the response of sugar beet to the effect of salt stress. Subsequently, we identified the miRNAs novel-m035-5p and novel-m0365-5p regulating the aldh gene and miRNA novel-m0979-3p regulating the thic gene. The findings of miRNA and mRNA expression were validated by qRT-PCR.

In recent years, Internet of Things security incidents occur frequently, which is often accompanied by malicious events. Therefore, anomaly detection is an important part of Internet of Things security defense. In this paper, we create a process whitelist based on the K-Core decomposition method for detecting anomalous processes in IoT devices. The method first constructs an IoT process network according to the relationships between processes and IoT devices. Subsequently, it creates a whitelist and detect anomalous processes. Our work innovatively transforms process data into a network framework, employing K-Core analysis to identify core processes that signify high popularity. Then, a threshold-based filtering mechanism is applied to formulate the process whitelist. Experimental results show that the unsupervised method proposed in this paper can accurately detect anomalous processes on real-world datasets. Therefore, we believe our algorithm can be widely applied to anomaly process detection, ultimately enhancing the overall security of the IoT.

Abstract Spermatogenesis is a complex process related to male infertility. Till now, the critical genes and specific mechanisms have not been elucidated clearly. Our objective was to determine the hub genes that play a crucial role in spermatogenesis by analyzing the differentially expressed genes (DEGs) present in non-obstructive azoospermia (NOA) compared to OA and normal samples using bioinformatics analysis. Four datasets, namely GSE45885, GSE45887, GSE9210 and GSE145467 were used. Functional enrichment analyses were performed on the DEGs. Hub genes were identified based on protein–protein interactions between DEGs. The expression of the hub genes was further examined in the testicular germ cell tumors from the TCGA by the GEPIA and validated by qRT-PCR in the testes of lipopolysaccharide-induced acute orchitis mice with impaired spermatogenesis. A total of 203 DEGs including 34 up-regulated and 169 down-regulated were identified. Functional enrichment analysis showed DEGs were mainly involved in microtubule motility, the process of cell growth and protein transport. PRM2, TEKT2, FSCN3, UBQLN3, SPATS1 and GTSF1L were identified and validated as hub genes for spermatogenesis. Three of them (PRM2, FSCN3 and TEKT2) were significantly down-regulated in the testicular germ cell tumors and their methylation levels were associated with the pathogenesis. In summary, the hub genes identified may be related to spermatogenesis and may act as potential therapeutic targets for NOA and testicular germ cell tumors.

Abstract Due to the relatively brief domestication history of sugar beet (Beta vulgaris ssp. vulgaris), our understanding of the genomic diversity and functional genes in its cultivars is limited, resulting in slow breeding progress. To address this issue, a total of 306 germplasm materials of major cultivars and breeding lines from China, the USA, and Europe were selected for genome resequencing. We investigated population structure and genetic diversity and performed selective scanning of genomic regions, identifying six novel genes associated with important agronomic traits: the candidate genes DFAX2 and P5CS for skin roughness; the candidate genes FRO5, GL24, and PPR91 for root yield and sugar yield, and the pleiotropic candidate gene POLX for flourishing growth vigour, plant height, crown size, flesh coarseness, and sugar yield. In addition, we constructed a protein–protein interaction network map and a phenotype-gene network map, which provide valuable information for identifying and characterizing functional genes affecting agronomic traits in sugar beet. Overall, our study sheds light on the future improvement of sugar beet agronomic traits at the molecular level.

Abstract Background Clinical decision-making involves ethical issues that become more and more complex. Nurse interns must be more skilled in making rational and timely decisions when facing ethical dilemmas. The contributing factors and their relationships that challenge ethical decision-making among nurse interns must be fully understood, as this level of knowledge can support the development of strategies and interventions that improve the ethical decision-making ability of nurse interns. Objective This study examined the relationships between moral courage, moral sensitivity, and ethical decision-making by nurse interns. In addition, we investigated whether moral sensitivity mediates the relationship between moral courage and ethical decision-making. Design A descriptive cross-sectional study using an online questionnaire. Setting The study sampled nurse interns from Class iii Grade A general hospitals in Sichuan Province, China. Participants A convenience sampling method was used to select 1334 nurse interns from March 2022 to May 2022. Methods A general information questionnaire, the Nurses’ Moral Courage Scale (NMCS), the Chinese Moral Sensitivity Questionnaire (MSQ), and the Judgement About Nursing Decision (JAND) were used for data collection. Data was processed and analysed using SPSS 26.0 and Amos 28.0. Data analysis included descriptive statistics, Pearson correlation analysis, and structural equation modelling. Results Moral courage was found to be positively correlated with ethical decision-making (P

Abstract The purpose of the present study is to develop and validate the hypertension scale of the Quality of Life Instruments (QoL) for Chronic Diseases system, QLICD-HY (V2.0). The QLICD-HY (V2.0) was developed via a programmed decision method with several focus groups, nominal discussions and pilot testing. The data was collected from 370 hypertensive inpatients and measured their QoL three times before and after treatment. Using correlation, factor analyses, as well as t-tests, the psychometric properties of the scale were assessed with regard to validity, reliability and responsiveness. Correlation and factor analysis supported good construct validity and criterion-related validity when using Short Form 36 as a criterion. Test–retest reliability coefficients for the overall scale score and all domains, with the exception of the psychological and social domain (0.77, 0.78), were greater than 0.80, with a range of 0.77–0.92. The internal consistency for all domains was higher than 0.70. With the exception of the psychological domain and social domain, the overall score and scores for the majority of aspects within each domain underwent statistically significant changes (t-tests) after the treatment. The QLICD-HY (V2.0) has good validity, reliability and responsiveness and can be used as a QoL measure for hypertensive patients.

Background: Nirsevimab is approved in the US for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants during their first RSV season and in children aged ≤24 months who remain vulnerable to severe RSV disease through their second RSV season. We summarize a pre-specified analysis of nirsevimab safety data from three randomized controlled trials: Phase 2b (NCT02878330; healthy infants born ≥29 to n = 3184; placebo, n = 1284; palivizumab, n = 304). Most AEs were mild to moderate in severity, with ≥98% unrelated to treatment. AEs of special interest occurred infrequently (

The Internet of Things (IoT) is rapidly transforming our lives and work, enabling a wide range of emerging services and applications. However, as the scale of the IoT expands, its security issues are becoming increasingly prominent. Malicious actors can exploit vulnerabilities in IoT devices to launch attacks. Protecting the IoT begins with device identification. Identified devices can have corresponding protective measures selected based on the information, thereby enhancing network security. In this study, we propose a dual-machine-learning-based IoT device identification algorithm, Dual-IoTID, which identifies devices based on the payload of IoT device sessions. In contrast to existing methods that rely on extracting header fields or network layer features, our approach attempts to obtain identification information from session payloads. Dual-IoTID first extracts frequent items from sessions and uses a first-layer classifier to obtain a confidence matrix for initial classification. Then, the confidence matrix, along with extracted session communication features, is fed into a second-layer classifier for IoT device identification. Our proposed method is applicable to any IoT device, and it is also suitable for networks with NAT enabled. Experimental results demonstrate that Dual-IoTID has higher accuracy than existing methods, achieving 99.48% accuracy in the UNSW dataset and accurately identifying IoT devices even in environments containing non-IoT devices.

ABSTRACT: Objectives: Overuse and misuse of antibiotics are major factors in the development of antibiotic resistance in primary care institutions of rural China. In this study, the effectiveness of a Health Information System-based, automatic, and confidential antibiotic feedback intervention was evaluated. Methods: A randomized, cross-over, cluster-controlled trial was conducted in primary care institutions. All institutions were randomly divided into two groups and given either a three-month intervention followed by a three-month period without any intervention or vice versa. The intervention consisted of three feedback measures: a real-time pop-up warning message of inappropriate antibiotic prescriptions on the prescribing physician's computer screen, a 10-day antibiotic prescription summary, and distribution of educational manuals. The primary outcome was the 10-day inappropriate antibiotic prescription rate. Results: There were no significant differences in inappropriate antibiotic prescription rates (69.1% vs. 72.0%) between two groups at baseline (P = 0.072). After three months (cross-over point), inappropriate antibiotic prescription rates decreased significantly faster in group A (12.3%, P < 0.001) compared to group B (4.4%, P < 0.001). At the end point, the inappropriate antibiotic prescription rates decreased in group B (15.1%, P < 0.001) while the rates increased in group A (7.2%, P < 0.001). The characteristics of physicians did not significantly affect the rate of antibiotic or inappropriate antibiotic prescription rates. Conclusion: A Health Information System-based, real-time pop-up warnings, a 10-day prescription summary, and the distribution of educational manuals, can effectively reduce the rates of antibiotic and inappropriate antibiotic prescriptions.

PurposeTo analyze the causal relationship between 486 human serum metabolites and the active tuberculosis (ATB) in European population.MethodsIn this study, the causal relationship between human serum metabolites and the ATB was analyzed by integrating the genome-wide association study (GWAS). The 486 human serum metabolites were used as the exposure variable, three different ATB GWAS databases in the European population were set as outcome variables, and single nucleotide polymorphisms were used as instrumental variables for Mendelian Randomization. The inverse variance weighting was estimated causality, the MR-Egger intercept to estimate horizontal pleiotropy, and the combined effects of metabolites were also considered in the meta-analysis. Furthermore, the web-based MetaboAnalyst 6.0 was engaged for enrichment pathway analysis, while R (version 4.3.2) software and Review Manager 5.3 were employed for statistical analysis.ResultsA total of 21, 17, and 19 metabolites strongly associated with ATB were found in the three databases after preliminary screening (P < 0.05). The intersecting metabolites across these databases included tryptophan, betaine, 1-linoleoylglycerol (1-monolinolein) (1-LG), 1-eicosatrienoylglycerophosphocholine, and oleoylcarnitine. Among them, betaine (I2 = 24%, P = 0.27) and 1-LG (I2 = 0%, P = 0.62) showed the lowest heterogeneity among the different ATB databases. In addition, the metabolic pathways of phosphatidylethanolamine biosynthesis (P = 0.0068), methionine metabolism (P = 0.0089), betaine metabolism (P = 0.0205) and oxidation of branched-chain fatty acids (P = 0.0309) were also associated with ATB.ConclusionBetaine and 1-LG may be biomarkers or auxiliary diagnostic tools for ATB. They may provide new guidance for medical practice in the early diagnosis and surveillance of ATB. In addition, by interfering with phosphatidylethanolamine biosynthesis, methionine metabolism, betaine metabolism, oxidation of branched-chain fatty acids, and other pathways, it is helpful to develop new anti-tuberculosis drugs and explore the virulence or pathogenesis of ATB at a deeper level, providing an effective reference for future studies.

The broad-banded velvetchin Hapalogenys analis is an economically and scientifically important global temperate and tropical nearshore marine fish. To understand the genetic evolution mechanism of H. analis, simplified genome sequencing analysis was conducted on 82 samples of H. analis from three populations (Akashi, Zhoushan, and Shantou) in the northwestern Pacific Ocean using double-digest restriction site-associated DNA sequencing. Genetic characteristics were identified using single-nucleotide polymorphism loci, and a small fragment library (250–450 bp long) was constructed for double-end sequencing. Single-nucleotide polymorphisms (SNPs) were detected using Stacks software and analyzed. The phylogenetic tree was constructed to analyze the population structure characteristics and the genetic evolutionary relationships between individuals in different regions at the genetic level. The sequencing library constructed for 82 samples of H. analis using double-digest restriction site-associated DNA sequencing possessed an average of 7,931,195 sequencing sequences and an average of 1,141,560,806 bases in the 82 samples. A total of 3,204,106 SNP loci were obtained from the three populations of H. analis, indicating rich genetic diversity. The transition to transversion ratio of SNPs was >1.5, indicating transformational reversal bias in H. analis. The observed heterozygosity of the various populations was 0.186–0.199, with an expected heterozygosity of 0.253–0.268. High diversity in all three populations was detected using nucleotide diversity analysis. AS and ZS had the highest degree of differentiation. The H. analis samples shared two gene libraries; some populations were closely related, whereas others had a distant genetic relationship. The results of genetic statistics, genetic differentiation, population structure, principal component, phylogenetic, and genetic relationship analyses supported independent clustering of the AS population, which can be used as a new genetic resource for conserving H. analis. These results provide a reference basis for comparative genomics studies of H. analis and rational utilization of Hapalogenys resources.

Diabetic kidney disease (DKD) stands as the predominant cause of chronic kidney disease (CKD) on a global scale, with its incidence witnessing a consistent annual rise, thereby imposing a substantial burden on public health. The pathogenesis of DKD is primarily rooted in metabolic disorders and inflammation. Recent years have seen a surge in studies highlighting the regulatory impact of energy metabolism on innate immunity, forging a significant area of research interest. Within this context, fibroblast growth factor 21 (FGF21), recognized as an energy metabolism regulator, assumes a pivotal role. Beyond its role in maintaining glucose and lipid metabolism homeostasis, FGF21 exerts regulatory influence on innate immunity, concurrently inhibiting inflammation and fibrosis. Serving as a nexus between energy metabolism and innate immunity, FGF21 has evolved into a therapeutic target for diabetes, nonalcoholic steatohepatitis, and cardiovascular diseases. While the relationship between FGF21 and DKD has garnered increased attention in recent studies, a comprehensive exploration of this association has yet to be systematically addressed. This paper seeks to fill this gap by summarizing the mechanisms through which FGF21 operates in DKD, encompassing facets of energy metabolism and innate immunity. Additionally, we aim to assess the diagnostic and prognostic value of FGF21 in DKD and explore its potential role as a treatment modality for the condition.

ABSTRACTAs a hallmark of COVID-19 progression, lymphopenia alongside its subtle immune disturbance has been widely reported, but yet to be thoroughly elucidated. Aiming at exploring clinical immune biomarkers with accessibility in the current and acute omicron epidemic abrupted in China post-control era, we design a real-world prospective observation cohort in Peking Union Medical College Hospital to describe immunological, haematological profiles inducing lymphocyte subsets related to SARS-CoV-2 infection. In this COVID-19 cohort, we enrolled 17 mild/moderate (M/M), 24 severe (S) and 25 critical (C) patients. The dynamics of lymphocytes of COVID-19 demonstrated that the sharp decline of NK, CD8+, and CD4+ T cell counts was the main contributor to lymphopenia in the S/C group, compared to the M/M group. Expressions of activation marker CD38 and proliferation marker Ki-67 both in CD8+ T and NK cells were significantly higher in all COVID-19 patients than that in healthy donors, independent of disease severity. The subsequent analysis showed in contrast to the M/M group, NK and CD8+ T cell counts remained low-level after therapy in the S/C group. CD38 and Ki-67 expressions in NK and CD8+ T cells still stay at a high level, despite active treatment. Targeting relatively elderly patients with SARS-CoV-2 infection, severe COVID-19 features the unreversible reduction of NK and CD8+ T cells with persistent activation and proliferation, which assist clinicians in early recognizing and saving severe or critical COVID-19 patients. Given that immunophenotype, the new immunotherapy improving NK and CD8+ T lymphocyte antiviral efficiency should be considered.

In order to solve the problem of determining the width of coal pillar and surrounding rock control in gob-side entry driving with soft and broken composite roof, in view of the deformation and damage characteristics of soft and broken composite roof in gob-side entry driving of 21210 working face of a mine, the width of narrow coal pillar is comprehensively determined to be 7 m by means of theoretical analysis, numerical simulation and engineering practice, and the corresponding surrounding rock control countermeasures and technologies are proposed. The results show that: the width of the internal stress field is 11.8 m, the failure width of the coal pillar near the goaf side and the roadway side is 2.5 m and 1.8 m respectively, and the reasonable width range of the narrow coal pillar is 5.6-7.3 m; when the coal pillar size is 7-11 m, the plastic zone of the surrounding rock of the roadway roof decreases, and the range of the elastic core zone expands, which is conducive to the anchoring of the anchor cable in the composite roof; 7 m coal pillar and the combined support technology of “high-strength bolt (cable) channel steel truss mesh + roof grouting” can effectively control the surrounding rock in gob-side entry driving with soft and broken composite roof.

Background Migraine underdiagnosis and undertreatment are so widespread, that hence is essential to diagnose migraine sufferers in nonclinical settings. A systematic review of validation studies on migraine diagnostic tools applicable to nonclinical settings can help researchers and practitioners in tool selection decisions. Objective To systematically review and critically assess published validation studies on migraine diagnostic tools for use in nonclinical settings, as well as to describe their diagnostic performance. Methods A multidisciplinary workgroup followed transparent and systematic procedures to collaborate on this work. PubMed, Medline, and Web of Science were searched for studies up to January 17, 2022. The QUADAS-2 was employed to assess methodological quality, and the quality thresholds adopted by the Global Burden Disease study were used to tail signaling questions. Results From 7,214 articles identified, a total of 27 studies examining 19 tools were eligible for inclusion. There has been no high-quality evidence to support any tool for use of migraine diagnosis in nonclinical settings. The diagnostic accuracy of the ID-migraine, structured headache and HARDSHIP questionnaires have been supported by moderate-quality evidence, with sensitivity and specificity above 70%. Of them, the HARDSHIP questionnaire has been the most extensively validated. The remaining 16 tools have provided poor-quality evidence for migraine diagnosis in nonclinical populations. Conclusions Up till now, the HARDSHIP questionnaire is the optimal choice for diagnosing migraine in nonclinical settings, with satisfactory diagnostic accuracy supported by moderate methodological quality. This work reveals the crucial next step, which is further high-quality validation studies in diverse nonclinical population groups.

Abstract Background Inappropriate use of antibiotics in children is common in many countries. The purpose of the study was to explore patterns of antibiotic prescribing in children’s outpatient clinics in primary care institutions in a province of southwest China. Methods We obtained electronic prescription data from 75 primary care institutions in Guizhou province in 2020. The classification of incorrect spectrum of antibiotics, unnecessary use and combined use of antibiotics was based on the Guiding Principle of Clinical Use of Antibiotics (2015, China) and guidelines from the USA Centers for Disease Control and Prevention. Potential risk factors for inappropriate use of antibiotics were identified using bivariate analyses. The generalized estimation equation was used to identify independent predictors of inappropriate use of antibiotics. Results A total of 158,267 antibiotic prescriptions were retrieved. Acute upper respiratory tract infections were the most common diseases, accounting for 74.9% of all prescriptions. The main antibiotic group used was penicillins (63.7%), followed by cephalosporins (18.8%). Of 137,284 visits, 18.3% of antibiotic prescriptions were appropriate and the percentage of unnecessary use, incorrect spectrum of antibiotics and combined use of antibiotics was 76.9, 2.4 and 2.4%, respectively. Physicians with lower professional titles and more than 40 years of work duration were relatively more likely to prescribe inappropriate antibiotics. Conclusion The inappropriate use of antibiotics in children is still prominent in primary care institutions of southwest China. The education and training of physicians and caregivers in these institutions should be strengthened.

Pleurisy and pleural effusion caused by Brucella infection are rare. However, clinicians lack an understanding of these possibilities, and the underlying disorder is easy to misdiagnose. We report a 52-year-old male farmer who was admitted to hospital with a fever, chest pain, and shortness of breath. Closed chest drainage was performed by thoracocentesis, and the concentration of adenosine deaminase (ADA) in the pleural fluid was >45 U/L. Mononuclear cells in the pleural fluid accounted for 90% of the cells, and pathology indicated a large number of lymphocytes. The clinical diagnosis was tuberculosis with tuberculous pleurisy. However, subsequent pleural fluid culture results did not support tuberculous pleurisy. The results of pleural fluid culture indicated Brucella , and the results of Brucella tiger red plate agglutination indicated a titer of 1:400 (+++). The final diagnosis was brucellosis with pneumonia and pleurisy. After 12 weeks of oral treatment, the patient underwent follow-up chest radiographs. Radiography indicated complete resolution of the hydrothorax and pneumonia, and the patient reported no discomfort. The short-term curative effect was excellent. Pleurisy associated with brucellosis should be considered a differential for pleurisy in regions where brucellosis is endemic, to minimize the risk of misdiagnosis.

We report first-time reverberation-mapping results for 14 active galactic nuclei (AGNs) from the ongoing Monitoring AGNs with H β Asymmetry campaign (MAHA). These results utilize optical spectra obtained with the Long Slit Spectrograph on the Wyoming Infrared 2.3 m Telescope between 2017 November and 2023 May. MAHA combines long-duration monitoring with high cadence. We report results from multiple observing seasons for nine of the 14 objects. These results include H β time lags, supermassive black hole masses, and velocity-resolved time lags. The velocity-resolved lags allow us to investigate the kinematics of the broad-line region.

Carbon nanotubes (CNTs) have rapidly received increasing attention and great interest as potential materials for energy storage and catalyst fields, which is due to their unique physicochemical and electrical properties. With continuous improvements in fabrication routes, CNTs have been modified with various types of materials, opening up new perspectives for research and state-of-the-art technologies. Amorphous CNTs (aCNTs) are carbon nanostructures that are distinctively different from their well-ordered counterparts, such as single-walled and multi-walled carbon nanotubes (SWCNTs and MWCNTs, respectively), while the atoms in aCNTs are grouped in a disordered, crystalline/non-crystalline manner. Owing to their unique structure and properties, aCNTs are attractive for energy storage, catalysis, and aerospace applications. In this review, we provide an overview of the synthetic routes of aCNTs, which include chemical vapor deposition, catalytic pyrolysis, and arc discharge. Detailed morphologies of aCNTs and the systematic elucidation of tunable properties are also summarized. Finally, we discuss the future perspectives as well as associated challenges of aCNTs. With this review, we aim to encourage further research for the widespread use of aCNTs in industry.

For triple-frequency radar, the attenuation attributed to atmospheric gases and stratiform clouds is diverse due to different snowfall microphysical properties, particularly in regions far from the radar. When using triple-frequency ground-based radar measurements, evaluating the attenuation of the three radars at different heights is common to derive attenuation-corrected effective reflectivity. Therefore, this study proposes a novel quality-controlled approach to identify radar attenuation due to gases and stratiform clouds that can be neglected due to varying snowfall microphysical properties and assess attenuation along the radar observation path. The key issue lies in the lack of information about vertical hydrometeor and cloud distribution. Therefore, European Centre for Medium-Range Weather Forecasts (ECMWF) reanalysis data are employed. The Self-Similar-Rayleigh-Gans Approximation (SSRGA) for the nonspherical scattering model in the Passive and Active Microwave TRAnsfer model 2 (PAMTRA2) is compared and analyzed against other scattering models to obtain the optimal triple-frequency radar attenuation correction strategies for stratiform cloud meteorological conditions with varying snowfall microphysical properties. This methodology paves the way for understanding differential attenuation attributed to gas and stratiform clouds with snowfall microphysical properties. Simultaneously, the bin-by-bin approximation method is used to perform the attenuation correction. The two-way attenuation correction increased up to 4.71 dB for heights above 6 km, remaining minimal for regions with heights below 6 km. These values, attributable to gases and stratiform clouds’ two-way attenuation, are nonnegligible, especially at distances far from the W-band radar at heights above 6 km. Both values are relatively small for the X- and Ka-band radars and can be neglected for the varying snowfall microphysical properties. The attenuation correction of triple-frequency radar reflectivity is validated using the cross-calibration and dual-frequency reflectivity ratios. The results show that the method is valid and feasible.

In this work, an oxidized g-C3N4 film was successfully synthesized using a two-step acid treatment and electrophoretic deposition method. The delocalized π-system of the oxidized g-C3N4 film was extended via an annealing treatment. We investigated the influence of hydrogen bonding reversibility and the oxidation treatment of g-C3N4 on the photoelectrochemical property and photocathodic protection for 304 stainless steel (304 SS). The resulting oxidized g-C3N4 photoelectrode with an extended π-system presents a remarkably enhanced photogenerated electron transfer capability from the photoelectrode to 304 SS (photoinduced OCP negative shift of −0.55 VAgCl) compared with oxidized g-C3N4 and protonated g-C3N4. The oxidation of g-C3N4 facilitates the formation of a porous structure and the introduction of abundant oxygen functional groups, which could promote the effective separation and transport of photogenerated electron–hole pairs. The hydrogen bonding reversibility contributes to the extension of the delocalized π-conjugation system, which could enhance light absorption efficiency. Meanwhile, the annealing treatment is beneficial for prolonging the lifetime of photoelectrons, which could reduce the recombination rate of charge carriers. In addition, to understand how the oxidation treatment and annealing treatment affect the charge transfer behavior, the electronic band structure was investigated, and we found that the oxidized g-C3N4 film with an extended π-system possesses a more negative conduction band position, which could reduce the energy barrier of the photogenerated electron transfer.

In this work, a TiO2/In2S3 heterojunction film was successfully synthesized using a one-step hydrothermal method and applied in the photocathodic protection (PCP) of 304SS. The octahedral In2S3 and In2S3@TiO2 nanoparticles combined and coexisted with each other, with In2S3 quantum dots growing on the surface of TiO2 to form In2S3@TiO2 with a wrapping structure. The composite photoelectrode, which includes TiO2 with a mixed crystalline phase and In2S3, exhibited significantly enhanced PCP performance for 304SS compared with pure In2S3 and TiO2. The In2S3@TiO2/In2S3 composites with 0.3 g of P25 titanium dioxide (P25) showed the best protection performance, resulting in a cathodic shift of its OCP coupled with 304SS to −0.664 VAgCl. The electron transfer tracking results demonstrate that In2S3@TiO2/In2S3 forms a Z-scheme heterojunction structure. The enhanced PCP performance could be attributed to the synergistic effect of the mixed crystalline phase and the Z-scheme heterojunction system. The mixed crystalline phase of TiO2 provides more electrons, and these electrons are gathered at higher energy potentials in the Z-scheme system. Additionally, the built-in electric field further promotes the more effective electrons transfer from photoelectrode to the protected metals, thus, leading to enhanced photoelectrochemical cathodic protection of 304SS.

Effectively regulating and promoting the charge separation and transfer of photoanodes is a key and challenging aspect of photoelectrochemical (PEC) water oxidation. Herein, a Ti-doped hematite photoanode with a CoFe-LDH cocatalyst loaded on the surface was prepared through a series of processes, including hydrothermal treatment, annealing and electrodeposition. The prepared CoFe-LDH/Ti:α-Fe2O3 photoanode exhibited an outstanding photocurrent density of 3.06 mA/cm2 at 1.23 VRHE, which is five times higher than that of α-Fe2O3 alone. CoFe-LDH modification and Ti doping on hematite can boost the surface charge transfer efficiency, which is mainly attributed to the interface interaction between CoFe-LDH and Ti:α-Fe2O3. Furthermore, we investigated the role of Ti doping in enhancing the PEC performance of CoFe-LDH/Ti:α-Fe2O3. A series of characterizations and theoretical calculations revealed that, in addition to improving the electronic conductivity of the bulk material, Ti doping also further enhances the interface coupling of CoFe-LDH/α-Fe2O3 and finely regulates the interfacial electronic structure. These changes promote the rapid extraction of holes from hematite and facilitate charge separation and transfer. The informative findings presented in this work provide valuable insights for the design and construction of hematite photoanodes, offering guidance for achieving excellent performance in photoelectrochemical (PEC) water oxidation.

In this study, a hematite photoanode with a CoFe-ADH co-catalyst loaded on the surface was successfully prepared through hydrothermal treatment, annealing, and electrodeposition. We investigated the influence of the deposition time and Co/Fe molar ratio for CoFe-ADH on the performance of α-Fe2O3 in photoelectrochemical (PEC) water oxidation. With an optimized condition of CoFe-ADH, the prepared CoFe-ADH/α-Fe2O3 photoanode exhibited a high photocurrent density of 1.58 mA/cm2 at 1.23 VRHE, which is about 2.5 times as high as that of α-Fe2O3. A series of characterization results and detailed mechanism studies reveal that surface modification of hematite by introducing CoFe-ADH can boost the surface charge transfer efficiency, which can be attributed to the good optical transparency, the amorphous structure of CoFe-ADH, and the synergism of Co and Fe in CoFe-ADH. The good optical transparency contributes to decreasing the loss of light absorption by the photoanodes; the amorphous structure could prevent the formation of grain boundaries and provide more active catalytic sites for PEC water oxidation; and the synergism of Co and Fe in CoFe-ADH enhances photogenerated carriers effective separation and the hole’s injection. This work provides valuable insights into the influence of bimetallic co-catalysts on the PEC performance of photoanodes, offering guidance for photoanodes to achieve excellent performance.

[INLINE:1] Acupuncture is a medical treatment that has been widely practiced in China for over 3000 years, yet the neural mechanisms of acupuncture are not fully understood. We hypothesized that neurons and astrocytes act independently and synergistically under acupuncture stimulation. To investigate this, we used two-photon in vivo calcium recording to observe the effects of acupuncture stimulation at ST36 (Zusanli) in mice. Acupuncture stimulation in peripheral acupoints potentiated calcium signals of pyramidal neurons and astrocytes in the somatosensory cortex and resulted in late-onset calcium transients in astrocytes. Chemogenetic inhibition of neurons augmented the astrocytic activity. These findings suggest that acupuncture activates neuronal and astrocytic activity in the somatosensory cortex and provide evidence for the involvement of both neurons and astrocytes in acupuncture treatment.

Dysregulated alternative splicing (AS) plays critical roles in driving cancer progression, and the underlying mechanisms remain largely unknown. Here, we demonstrated that PHF5A, a component of U2 small nuclear ribonucleoproteins, was frequently upregulated in colorectal cancer (CRC) samples and associated with poor prognosis. PHF5A promoted proliferation and metastasis of CRC cells in vitro and in vivo. Transcriptomic analysis identified PHF5A-regulated AS targets and pathways. Particularly, PHF5A induced TEAD2 exon 2 inclusion to activate YAP signaling, and interference of TEAD2-L partially reversed the PHF5A-mediated tumor progression. Pharmacological inhibition of PHF5A using pladienolide B had potent antitumor activity. Collectively, these data revealed the oncogenic role of PHF5A in CRC through regulating AS and established PHF5A as potential therapeutic target.

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (COVID-19) have a substantial burden on health-care systems around the world. This is a randomized parallel controlled trial for assessment of the immunogenicity and safety of an inactivated SARS-CoV-2 vaccine, aiming to determine an appropriate vaccination interval of the vaccine for high-risk occupational population. Methods In an ongoing randomized, parallel, controlled phase IV trial between January and May 2021 in Taiyuan City, Shanxi Province, China, we randomly assigned the airport ground staff and public security officers aged 18 to 59 years to receive two doses of inactivated SARS-CoV-2 vaccine at 14 days, 21 days, or 28 days. The serum neutralizing antibody to live SARS-CoV-2 was performed at baseline and 28 days after immunization. Long-term data are being collected. The primary immunogenicity endpoints were neutralization antibody seroconversion and geometric mean titer (GMT) at 28 days after the second dose. Analysis of variance (ANOVA), chi-square, and logistic regression analysis were used for data analysis. Results A total of 809 participants underwent randomization and received two doses of injections: 270, 270, 269 in the 0–14, 0–21, and 0–28 vaccination group, respectively. By day 28 after the second injection, SARS-CoV-2 neutralizing antibody of GMT was 98.4 (95% CI: 88.4–108.4) in the 0–14 group, which was significantly lower compared with 134.4 (95% CI: 123.1–145.7) in the 0–21 group (P

Abstract Granuloma polyangiitis (GPA) is a necrotizing granulomatous inflammation, which is a systemic autoimmune disease that mainly affects the upper respiratory tract, lungs, and kidneys. Clinically, the clinical manifestations of GPA vary greatly, and it is extremely easy to be misdiagnosed. We report a 60‐year‐old man with granulomatous polyangiitis with dysuria and parotid gland enlargement as the first symptom. As the condition worsened, he gradually developed symptoms in multiple systems such as persistent high fever, nosebleeds, hemoptysis, skin rash, and multiple cavities in the lungs. Due to high fever, hemoptysis, and the gradual expansion of lung cavities, the suspected hematogenous lung abscess was not well controlled and transferred to the respiratory department. The manifestation of involvement was finally confirmed by skin biopsy. Biopsy was performed on the skin of the lower extremities with a dark red rash with multiple microprojections. Pathology indicated neutrophilic infiltration and necrosis of small vessel walls, and granuloma formation. Blood anti‐protease 3 antibody (PR3) was positive Monotherapy with prednisone. Body temperature gradually returned to normal; hemoptysis and nasal bleeding disappeared; parotid gland enlargement and dysuria relieved, and lung cavities gradually reduced. When anti‐infective treatment is ineffective, we should consider the presence of some non‐infectious diseases, especially when multiple systems are involved; biopsy should be performed as soon as possible. Granulomatous polyangiitis has various manifestations. Parotid glands and prostate may also be the first organs involved, not limited to common targets such as the respiratory tract and kidneys.

BackgroundInappropriate use of glucocorticoids in primary care institutions is serious. It not only causes economic burden, but leads to many adverse reactions. The purpose of this study is to explore systemic glucocorticoid prescription pattern and factors of inappropriate use in primary care institutions.MethodsThis is a retrospective study. Systemic glucocorticoids prescribed in 58 primary care institutions in Guizhou province of Southwest China in 2020 were selected from the Health Information System. All prescriptions were classified as appropriate or inappropriate use. Inappropriate use was classified into the following two categories: (a) Inappropriate indications; (b) Inappropriate selection of glucocorticoids. Multivariate analysis was used to explore the factors associated with inappropriate use of systemic glucocorticoids.ResultsA total of 63,315 glucocorticoid prescriptions were included in the analysis. Diseases of the respiratory system (60.8%) and diseases of the skin and subcutaneous tissue (23.1%) were the most common indications for use. Injections (89.8%) predominated and dexamethasone (86.5%) was the most prescribed glucocorticoid. 68.2% of all prescriptions were inappropriate. Compared to physicians with a college degree, physicians with a junior college (OR: 1.12, 95% CI: 1.08–1.17) and technical secondary education (OR: 1.12, 95% CI:1.05–1.19) were more likely to prescribe glucocorticoids inappropriately as were attending physicians (OR: 1.12, 95% CI: 1.01–1.25) and resident physicians (OR: 1.31, 95% CI: 1.15–1.48) compared to associate chief physicians. The risk of inappropriate glucocorticoid use was highest in patients 65 years of age and older (OR: 6.00, 95% CI: 5.62–6.40). In contrast, prescriptions given by injection were more likely to be used inappropriately than those given orally (OR: 0.44, 95% CI: 0.41–0.46).ConclusionInappropriate use of systemic glucocorticoids without appropriate indications was extremely prominent in primary care institutions of Guizhou Province, especially in diseases of the respiratory system and among the elderly. The risk of inappropriate glucocorticoid use was highest in patients 65 years of age and older. It is important to note that physicians younger than 33, with more than 40 years of service, and attending or residents were more likely to inappropriately prescribe glucocorticoids.

Synephrine, a natural product also known as deoxyepinephrine, exists in Rutaceae plants and is widely distributed in China. In addition to natural sources, synephrine may also be obtained by means of chemical synthesis and genetic engineering methods. In recent years, extensive studies on the biological activity of synephrine have shown that this compound has significant anti-cancer, anti-depressant, anti-Parkinson and other effects. In addition, synephrine exhibits good metabolic regulatory activity and thereby is widely used in weight loss. As a foodborne compound, synephrine has the outstanding features of low toxicity and side effects. In this review, we will elaborate the pharmacological activity and toxic side effects of synephrine, as well as its new applications in the field of biomedicine.

BackgroundDrug-induced immune hemolytic anemia (DIIHA) is a rare but potentially life-threatening drug-related complication. There are no previous reports of pemetrexed plus cisplatin as first-line chemotherapy for non-small cell lung cancer, resulting in DIIHA.Case presentationIn this report, a patient with advanced-stage lung adenocarcinoma developed severe immune hemolytic anemia 21 days after pemetrexed plus cisplatin chemotherapy. Laboratory findings showed severe hemolysis, including a rapid decrease in hemoglobin (HGB) and an elevated level of reticulocytes (Rets), indirect bilirubin (IBIL), and lactate dehydrogenase (LDH). A workup for the possibility of DIIHA was performed, including a direct antiglobulin test (DAT), a test in the presence of the soluble drug, and a drug-treated red blood cell (RBC) test. It showed a strongly positive (3+) result for anti-C3d but not for anti-immunoglobin G (IgG) in DAT. Enzyme-treated RBCs reacted weakly with the patient's serum and pemetrexed when complement was added. In addition, the patient's serum and normal sera were reactive with cisplatin-treated RBCs. However, eluates from the patient's RBCs and diluted normal sera were non-reactive with cisplatin-coated RBCs. Untreated and enzyme-treated RBCs reacted with the patient's serum in the presence of soluble cisplatin. In vitro serological tests suggested that complement-dependent pemetrexed antibodies and cisplatin-associated non-immunologic protein adsorption (NIPA) might combine to cause immune hemolytic anemia. The patient's anemia gradually recovered when pemetrexed and cisplatin were discontinued.ConclusionThis rare case demonstrated that complement-dependent pemetrexed antibodies and cisplatin-associated NIPA might occur simultaneously in a patient with DIIHA.

Halomonas bluephagenesis TD01 is one of the ideal chassis for low-cost industrial production based on “Next Generation Industrial Biotechnology,” yet the limited genetically regulatory parts such as transcriptional terminators, which are crucial for tuned regulations on gene expression, have hampered the engineering and applications of the strain. In this study, a series of intrinsic Rho-independent terminators were developed by either genome mining or rational design, and seven of them proved to exhibit higher efficiencies than the canonical strong T7 terminator, among which three terminators displayed high efficiencies over 90%. A preliminary modeling on the sequence-efficiency relationship of the terminators suggested that the poly U sequence regularity, the length and GC content of the stem, and the number and the size of hairpin loops remarkably affected the termination efficiency (TE). The rational and de novo designs of novel synthetic terminators based on the sequence-efficiency relationship and the “main contributor” engineering strategy proved to be effective, and fine-tuned polyhydroxylkanoates production was also achieved by the regulation of these native or synthetic terminators with different efficiencies. Furthermore, a perfectly positive correlation between the promoter activity and the TE was revealed in our study. The study enriches our knowledge of transcriptional termination via its sequence–strength relationship and enables the precise regulation of gene expression and PHA synthesis by intrinsic terminators, contributing to the extensive applications of H. bluephagenesis TD01 in the low-cost production of various chemicals.

With the rapid growth of the power grid load and the continuous access of impact load, the range of power system frequency fluctuation has increased sharply, rendering it difficult to meet the demand for power system frequency recovery through primary frequency modulation alone. Given this headache, an optimal control strategy for battery energy storage participating in secondary frequency regulation of the power grid is proposed in this paper based on a double-layer structure. Besides, a coordinated control framework is constructed for energy storage battery joint units engaged in automatic generation control (AGC). At the dispatching level, the power allocation principle is set to coordinate the fast and slow resources of energy storage and conventional thermal power units, and the power decoupling of the two types of frequency modulation (FM) resources is completed. At the system level, a power allocation model representing the real-time frequency modulation capability of energy storage is established to realize the division of frequency modulation responsibilities of each unit and state of charge (SOC) consistency management, and the proposed control strategy is simulated and verified to provide a reference for the energy storage battery to participate in the secondary frequency modulation design of the power grid.

The administration of mRNA-based tumour vaccines is considered a promising strategy in tumour immunotherapy, although its application against kidney renal clear cell carcinoma (KIRC) is still at its infancy stage. The purpose of this study was to identify potential antigens and to further select suitable patients for vaccination. Gene expression data and clinical information were retrieved from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. GEPIA2 was used to evaluate the prognostic value of selected antigens. The relationship of antigens presenting cell infiltration with antigen expression was evaluated by TIMER, and immune subtypes were determined using unsupervised cluster analysis. Tumour antigens LRP2 and DOCK8, which are associated with prognosis and tumour-infiltrating antigen-presenting cells, were identified in KIRC. A total of six immune subtypes were identified, and patients with immune subtype 1–4 (IS1–4) tumours had an immune ‘cold’ phenotype, a higher tumour mutation burden, and poor survival. Moreover, these immune subtypes showed significant differences in the expression of immune checkpoint and immunogenic cell death modulators. Finally, the immune landscape of KIRC revealed the immune-related cell components in individual patients. This study suggests that LRP2 and DOCK8 are potential KIRC antigens in the development of mRNA vaccines, and patients with immune subtypes IS1–4 are suitable for vaccination.

Abstract Background Endometrial cancer is an invasive gynecological cancer prevalent in the world. The pathogenesis of endometrial cancer is related to multiple levels of regulation, referring to oestrogen, tumor-suppressor gene (e.g. PTEN) or microRNAs (e.g. miR-23a and miR-29b). Metapristone is a hormone-related drug, which is widely used in clinical treatment of endometrial cancer. However, the underlying regulatory mechanism of metapristone on endometrial cancer is still unclear, especially the regulatory effect on microRNAs. The aim of this study is to investigate the specific molecular mechanism of metapristone regulating microRNAs in the treatment of endometrial cancer. Methods RL95-2 cells and Ishikawa cells were used as the endometrial cancer models. MiR-492 or si-miR-492 was transfected into RL95-2 cells and Ishikawa cells to explore the role of miR-492 in endometrial cancer. The cell cancer model and mice cancer model were used to confirm the function and mechanism of metapristone affected on endometrial cancer in vitro and in vivo. Mechanically, cell proliferation was monitored using MTT assay, cell colony formation assay and EdU assay. Luciferase reporter assay was used to identify the downstream target gene of miR-492. The protein expression and RNA expression were respectively measured by western blot and qRT-PCR for cell signaling pathway research, subsequently, were verified in the mice tumor model via immunohistochemistry. Results Metapristone as a kind of hormone-related drug significantly inhibited the endometrial cancer cell growth through regulating cell apoptosis-related gene expression. Mechanically, miR-492 and its target genes Klf5 and Nrf1 were highly expressed in the endometrial cancer cell lines, which promoted cell proliferation and inhibited cell apoptosis. Metapristone decreased the expression of miR-492 and its target genes Klf5 and Nrf1, leading to endometrial cancer cell growth inhibition in vitro and in vivo. Conclusion Metapristone inhibited the endometrial cancer cell growth through regulating the cell apoptosis-related signaling pathway and decreasing the expression of miR-492 and its downstream target genes (Klf5 and Nrf1), which provided the theoretical basis in clinical treatment of endometrial cancer.

Abstract Background Endometrial carcinoma is a frequently diagnosed cancer among females. LncRNAs are reported to be associated with various cancers. Their biological roles in endometrial carcinoma progression is an emerging scientific area. LINC00665 can exert a significant role in many cancers. However, its potential function in endometrial carcinoma is still poorly known. Method qRT-PCR was carried out to test expression of LINC00665 and HMGA1. Western blot analysis was carried out to detect protein expression of HMGA1. Cell proliferation was evaluated using Cell Counting Kit-8 (CCK-8) and EdU assay. Flow cytometry assay was used to determine cell apoptosis and cell cycle. Wound healing and transwell invasion assay was carried out to test cell migration and invasion. Immunohistochemical staining and HE staining were conducted to assess Ki-67 and tumor growth respectively. Results Expression of LINC00665 in clinical endometrial carcinoma tissues and cells was obviously up-regulated. Loss of LINC00665 could repress endometrial carcinoma cell viability, induce cell apoptosis and block cell cycle in G1 phase. KLE and HHUA cell migration and invasion ability were depressed by LINC00665 shRNA. Decrease of LINC00665 suppressed endometrial carcinoma tumorigenicity in vivo. RIP assay proved that LINC00665 directly bound with HMGA1 protein. shRNA of HMGA1 obviously restrained endometrial carcinoma cell growth and cell invasion. Conclusions LINC00665 might promote endometrial carcinoma progression by positively modulating HMGA1.

Abstract. Background:. The mechanism and characteristics of early and late drug-eluting stent in-stent restenosis (DES-ISR) have not been fully clarified. Whether there are different outcomes among those patients being irrespective of their repeated treatments remain a knowledge gap. Methods:. A total of 250 patients who underwent initial stent implantation in our hospital, and then were readmitted to receive treatment for the reason of recurrent significant DES-ISR in 2016 were involved. The patients were categorized as early ISR (

Objective: Antibiotic overuse is one of the major prescription problems in rural China and a major risk factor for antibiotic resistance. Low antibiotic prescription rates can effectively reduce the risk of antibiotic resistance. We hypothesized that under a paperless, computer-based feedback system the rates of antibiotic prescriptions among primary care physicians can be reduced. Methods: A cluster randomized crossover open controlled trial was conducted in 31 hospitals. These hospitals were randomly allocated to two groups to receive the intervention for three months followed by no intervention for three months in a random sequence. The feedback intervention information, which displayed the physicians’ antibiotic prescription rates and ranking, was updated every 10 days. The primary outcome was the 10-day antibiotic prescription rate of the physicians. Results: There were 82 physicians in group 1 (intervention first followed by control) and 81 in group 2 (control first followed by intervention). Baseline comparison showed no significant difference in antibiotic prescription rate between the two groups (30.8% vs 35.2%, P-value = 0.07). At the crossover point, the relative reduction in antibiotic prescription rate was significantly higher among physicians in the intervention group than in the control group (33.1% vs 20.3%, P-value

Abstract Background Acute mountain sickness has become a heavily researched topic in recent years. However, the genetic mechanism and effects have not been elucidated. Our goal is to construct a gene co-expression network to identify the key modules and hub genes associated with high altitude hypoxia. Results The GSE46480 dataset of rapidly transported healthy adults with acute mountain sickness was selected and analyzed by weighted gene co-expression network analysis (WGCNA) to construct a co-expression network. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the data set were carried out using Database for Annotation Visualization and Integrated Discovery (DAVID), and the hub genes were selected. We found that the turquoise module was most significantly correlated with acute mountain sickness. The functional enrichment analysis showed that the turquoise module was related to the apoptotic process, protein transport, and translation processes. The metabolic pathway analysis identified hsa03010:ribosome and hsa04144:endocytosis as the most important pathways in the turquoise module. Ten top 10 hub genes (MRPL3, PSMC6, AIMP1, HAT1, DPY30, ATP5L, COX7B, UQCRB, DPM1, and COMMD6) for acute mountain sickness were identified. Conclusion One module and 10 hub genes were identified, which were related to acute mountain sickness. The reference provided by this module may help to elucidate the mechanism of acute mountain sickness. In addition, the hub genes may be used in the future as a biomarker and therapeutic target for accurate diagnosis and treatment.

The health-maintaining effects of tea on the human body have been widely proven, even with the tea prepared by brewing tea leaves in cold water becoming a new choice other than hot water. In this research, quality and the antioxidant properties of the Pouchong tea infusions prepared with cold water and hot water were determined and explored their relationships under a consumer hedonic test. The results showed that the chemical components of cold tea infusions increased with increasing duration of brewing, and a maximal increment was observed during the first 2 h of brewing. All chemical components under investigation, except caffeine, were found to be higher in the cold tea infusions over 8 h as compared in the hot tea infusions. The antioxidant ability of cold tea infusion increased with increasing duration of brewing and approached the plateau after 12 hours. The chemical components showed a significantly positive correlation with the antioxidant activities (P

BackgroundThe overuse and abuse of antibiotics is a major risk factor for antibiotic resistance in primary care settings of China. In this study, the effectiveness of an automatically-presented, privacy-protecting, computer information technology (IT)-based antibiotic feedback intervention will be evaluated to determine whether it can reduce antibiotic prescribing rates and unreasonable prescribing behaviours.MethodsWe will pilot and develop a cluster-randomised, open controlled, crossover, superiority trial. A total of 320 outpatient physicians in 6 counties of Guizhou province who met the standard will be randomly divided into intervention group and control group with a primary care hospital being the unit of cluster allocation. In the intervention group, the three components of the feedback intervention included: 1. Artificial intelligence (AI)-based real-time warnings of improper antibiotic use; 2. Pop-up windows of antibiotic prescription rate ranking; 3. Distribution of educational manuals. In the control group, no form of intervention will be provided. The trial will last for 6 months and will be divided into two phases of three months each. The two groups will crossover after 3 months. The primary outcome is the 10-day antibiotic prescription rate of physicians. The secondary outcome is the rational use of antibiotic prescriptions. The acceptability and feasibility of this feedback intervention study will be evaluated using both qualitative and quantitative assessment methods.DiscussionThis study will overcome limitations of our previous study, which only focused on reducing antibiotic prescription rates. AI techniques and an educational intervention will be used in this study to effectively reduce antibiotic prescription rates and antibiotic irregularities. This study will also provide new ideas and approaches for further research in this area.Trial registrationISRCTN, ID: ISRCTN13817256. Registered on 11 January 2020.

Background: Workplace social support might have a protective function against migraine in the social context of China, as close co-worker relationships and collectivism are acknowledged as work values in Chinese society. Objectives: This paper aimed to analyse the association between migraine and workplace social support. The validity and reliability of the Chinese version of the Support scale of the Demand-Control-Support Questionnaire (DCSQ) used were also determined. Methods: Following international guidelines, this study was carried out in two stages. Stage I involved translations and pilot testing to assess content and face validity of the Chinese version of the DCSQ Support scale. Stage II was a cross-sectional survey (N = 677 bank employees) to evaluate structural validity, internal consistency and test-retest reliability of the Support scale, as well as to examine the association between workplace social support and a migraine-positive diagnosis. Results: A high level of social support in the workplace was associated with a 74% decreased likelihood of migraine (adjusted OR = 0.26, 95%CI: 0.14–0.46). Of the six aspects of workplace social support, co-worker support had the greatest protective effect (adjusted OR = 0.49, 95% CI: 0.39–0.60). The Chinese version of the DCSQ Support scale established satisfactory content and face validity (I-CVIs ≥ 0.78; S-CVIAVE ≥ 0.90). Confirmatory factor analysis verified its one-dimensional theoretical factor, with adequate internal consistency (Cronbach’s α 0.98; item-total correlations ≥ 0.80) and test-retest reliability (weighted Kappa coefficients 0.81–0.87; percentages agreement 85.23–88.92%). Conclusions: In the Chinese social context, workplace social support could protect against migraine, with the strongest benefit coming from co-workers. This study also provides a Chinese-language DCSQ Support scale as a valid and reliable instrument for measuring workplace social support.

PICALM rs3851179, one of the genes most frequently linked to susceptibility of late-onset Alzheimer’s disease (LOAD), plays a crucial role in regulating amyloid precursor protein, and amyloid β (Aβ) transcytosis. To explore the effects of PICALM and AD continuum stage on cortex thickness, CSF Aβ, and tau, 188 cognitively normal controls, 261 MCI patients, and 140 early LOAD patients were recruited, and each group was divided into rs3851179 A-carriers and GG-carriers. A full factorial ANCOVA was used to analyze the main effects and interactive effects of AD continuum stage, and PICALM. The interactive effects of AD continuum stage and PICALM on cortex thickness and CSF biomarkers were not significant. The main effect of PICALM was significant on the left postcentral cortex thickness, and the cortex thickness of A-carriers was less than that of GG-carriers. The rs3851179 A-carriers displayed higher Aβ42 levels and Aβ42/40 ratios, and lower P/T–tau ratios, compared with GG-carriers. A higher MMSE score was found in A-carriers among the LOAD patients. In conclusion, the main effects of PICALM were independent of AD continuum stage, and PICLAM rs3851179 genotypes may modulate left postcentral cortex thickness, Aβ42 level, and P/T–tau ratio. The rs3851179 A-allele may protect the cognitive function of LOAD patients.