Search

Abstract Background/aims To investigate the clinical situation, treatment methods, and clinical predictors of surgical intervention in children with magnetic foreign bodies in the digestive tract. Materials and methods From January 2019 to June 2022, we retrospectively analyzed the clinical data of 72 children who ingested magnetic foreign bodies inadvertently in our hospital, including their general information, admissions, clinical manifestations, and treatment methods, as well as pertinent literature and statistical data. Following software processing, univariate and multivariate logistic regression analyses were conducted to determine the independent risk factors of this study. Results In this study, 16 patients (22.2%) were discharged smoothly following conservative treatment and 19 patients (26.4%) were cured by gastroscopy. The remaining 37 patients (51.4%) were underwent surgery, in which 26 cases developed gastrointestinal perforation. There were statistical differences between surgery group and non- surgery group in the days of eating by mistake, clinical manifestations (nausea and vomiting, intermittent abdominal pain, abdominal muscle tension) and movement trajectory by every 24-h radiograph (P

ObjectiveDiabetic kidney disease (DKD) has been reported as a main microvascular complication of diabetes mellitus. Although renal biopsy is capable of distinguishing DKD from Non Diabetic kidney disease(NDKD), no gold standard has been validated to assess the development of DKD.This study aimed to build an auxiliary diagnosis model for type 2 Diabetic kidney disease (T2DKD) based on machine learning algorithms.MethodsClinical data on 3624 individuals with type 2 diabetes (T2DM) was gathered from January 1, 2019 to December 31, 2019 using a multi-center retrospective database. The data fell into a training set and a validation set at random at a ratio of 8:2. To identify critical clinical variables, the absolute shrinkage and selection operator with the lowest number was employed. Fifteen machine learning models were built to support the diagnosis of T2DKD, and the optimal model was selected in accordance with the area under the receiver operating characteristic curve (AUC) and accuracy. The model was improved with the use of Bayesian Optimization methods. The Shapley Additive explanations (SHAP) approach was used to illustrate prediction findings.ResultsDKD was diagnosed in 1856 (51.2 percent) of the 3624 individuals within the final cohort. As revealed by the SHAP findings, the Categorical Boosting (CatBoost) model achieved the optimal performance 1in the prediction of the risk of T2DKD, with an AUC of 0.86 based on the top 38 characteristics. The SHAP findings suggested that a simplified CatBoost model with an AUC of 0.84 was built in accordance with the top 12 characteristics. The more basic model features consisted of systolic blood pressure (SBP), creatinine (CREA), length of stay (LOS), thrombin time (TT), Age, prothrombin time (PT), platelet large cell ratio (P-LCR), albumin (ALB), glucose (GLU), fibrinogen (FIB-C), red blood cell distribution width-standard deviation (RDW-SD), as well as hemoglobin A1C(HbA1C).ConclusionA machine learning-based model for the prediction of the risk of developing T2DKD was built, and its effectiveness was verified. The CatBoost model can contribute to the diagnosis of T2DKD. Clinicians could gain more insights into the outcomes if the ML model is made interpretable.

Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a check point protein expressed on the surface of T cells and plays a central role in regulating the immune response. In recent years, CTLA-4 has become a popular target for cancer immunotherapy in which blocking CTLA-4 can restore T-cell function and enhance the immune response against cancer. Currently, there are many CTLA-4 inhibitors in a variety of modalities, including cell therapies, which are being developed in both preclinical and clinical stages to further harness the potential of the target for the treatment of certain types of cancer. In drug discovery research, measuring the level of CTLA-4 in T cells is important for drug discovery and development because it provides key information for quantitative assessment of the pharmacodynamics, efficacy, and safety of the CTLA-4-based therapies. However, to our best knowledge, there is still no report of a sensitive, specific, accurate, and reliable assay for CTLA-4 measurement. In this work, an LC/MS-based method was developed to measure CTLA-4 in human T cells. The assay demonstrated high specificity with an LLOQ of 5 copies of CTLA-4 per cell when using 2.5 million T cells for analysis. As shown in the work, the assay was successfully used to measure CTLA-4 levels in subtype T-cell samples from individual healthy subjects. The assay could be applied in supporting the studies of CTLA-4-based cancer therapies.

Abstract Porcine circovirus type 3 (PCV3) is a novel circovirus identified in sows with PDNS-like clinical signs and reproductive failure. The capsid protein (CAP) of PCV3 is expected to be an effective vaccine candidate. Here, we expressed the original capsid protein, truncated capsid protein without anterior highly repetitive arginine (ΔCAP) and their codon-optimized counterparts in E. coli. These results showed that lots of repeated arginine could severely lower the expression of PCV3 capsid protein in E. coli. At the same time, the recombined truncated PCV3 capsid protein forms typic virions. The efficient expression of capsid protein is expected to serve the development of PCV3 vaccines and other studies of PCV3 capsid protein.

Smart government is an important means of optimizing government management, improving the government decision-making capacity, and pushing forward the public service. When the smart government process applies, the dire straits of collaborative governance among the different participants could not be ignored usually caused by maximizing their profits. Based on the current research, this paper introduces the blockchain technology into the smart government system and establishes a smart government platform architecture. Meanwhile, to analyse the evolutionary and stable strategies of the three parties under the blockchain technology, the evolutionary game model including functional departments, local governments, and end users as the main players is established on account of the bounded rationality. By examining the “blockchain + government service” in Beijing with the systemic dynamics theory, this paper changes the influencing factors simulated by changing the parameter assignment, to determine the evolutionary stable equilibrium under different external conditions. The results show that local government supervision plays a leading role in the process of collaborative governance of smart government based on blockchain technology; meanwhile, effective cost control is a key factor affecting the evolutionary stability strategy (ESS). Besides, the “decentralized” structure, “distrust” architecture, and “precision” mechanism of the blockchain are verified for the effect of the evolution process. Among them, precision service and flat management improve the possibility of collaborative governance, but the impact of the trust mechanism is not obvious. Therefore, the collaborative governance model of smart government based on blockchain technology is loaded with far-reaching significance for promoting the modernization of China’s governance capacity and governance system.

Eucalyptus regnans was subjected to thermal treatment. The samples were placed in superheated vapors at 120, 130, 140, 150, 160, 170, 180, 190, and 200 °C at ambient pressure to determine the effect of heat treatment on the physical-mechanical properties of Eucalyptus regnans. The results showed that heat treatment played an important role in the impact toughness, nail-holding ability, surface hardness, bending strength, and bending modulus of elasticity of E. regnans. The nail-holding ability, surface hardness, bending strength, and bending modulus of elasticity of E. regnans treated at 120 and 130 °C increased related to untreated wood, but decreased at 140 to 200 °C. The impact toughness decreased after heat treatment from 120 to 200 °C, while the bending modulus of elasticity increased. Consequently, heating at 120 and 130 °C was found to be more suitable to ensure sufficient strength.

Background: Photodynamic therapy (PDT) is a new treatment for esophageal cancer which has been shown to be effective in the elimination of tumor. However, PDT could induce the activation of nuclear factor-kappa B (NF-κB) in many photosensitizers based PDT, which plays a negative role in PDT. In addition, our previous results have shown that dihydroartemisinin (DHA), which was the most potent one of artemisinin derivatives, has anticancer activity in esophageal cancer cells. Methods: Cell viability was determined by MTT analysis, and apoptosis was evaluated by flow cytometry. Nuclear extract was obtained for determining NF-κB DNA-binding activity, while total protein extract obtained for downstream gene expression by western blot. Results: We demonstrated DHA enhanced PDT-induced growth inhibition and apoptosis in both human esophageal cancer cell lines Eca109 and Ec9706 in vitro. The mechanism was at least partially due to DHA deactivated PDT-induced NF-κB activation, so as to decrease tremendously the expression of its target gene Bcl-2. Conclusion: Our results demonstrate that DHA augments PDT-induced growth inhibition and apoptosis in esophageal cancer cells, and that inactivation of NF-κB activity is a potential mechanism by which DHA sensitizes esophageal cancer cells to PDT-induced growth inhibition and apoptosis.

Background Acute Stanford Type A Aortic Dissection (ATAAD) is a critical medical emergency characterized by significant morbidity and mortality. This study aims to identify specific gene expression patterns and RNA modification associated with ATAAD. Methods The GSE153434 dataset was obtained from the Gene Expression Omnibus (GEO) database. Differential expression analysis was conducted to identify differential expression genes (DEGs) associated with ATAAD. To validate the involvement of RNA modification in ATAAD, RNA modification-related genes (M6A, M1A, M5C, APA, A-to-I) were acquired from GeneCards, following by Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. A gene prediction signature consisting of key genes was established, and Real-time PCR was used to validate the gene expression in clinical samples. The patients were then divided into high and low-risk groups, and subsequent enrichment analysis, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), Gene Set Variation Analysis (GSVA), and assessments of immune infiltration. A co-expression network analysis (WGCNA) was performed to explore gene-phenotype relationships and identify key genes. Results A total of 45 RNA modification genes were acquired. Six gene signatures (YTHDC1, WTAP, CFI, ADARB1, ADARB2, TET3) were developed for ATAAD diagnosis and risk stratification. Enrichment analysis suggested the potential involvement of inflammation and extracellular matrix pathways in the progression of ATAAD. The incorporation of pertinent genes from the GSE147026 dataset into the six-gene signature further validated the model's effectiveness. A significant upregulation in WTAP, ADARB2, and TET3 expression, whereas YTHDC1 exhibited a noteworthy downregulation in the ATAAD group. Conclusion Six-gene signature could serve as an efficient model for predicting the diagnosis of ATAAD. [ABSTRACT FROM AUTHOR]

ContextHigh progesterone levels in the follicular stage interfere with the implantation window, causing infertility in women with 17-hydroxylase/17,20-lyase deficiency (17OHD). Dexamethasone can restore cortisol deficiency and suppress inappropriate mineralocorticoid secretion to control hypertension in 17OHD patients, but poses risks to the foetus if administered during pregnancy.ObjectiveWe prospectively explored a rational glucocorticoid use protocol for assistive reproduction in a woman with non-classic 17OHD that reduced glucocorticoid side effects.MethodIn this study, the treatment protocol for this 17OHD patient included the following steps. First, the appropriate type and dose of glucocorticoid for endogenous progesterone suppression was determined. Then, glucocorticoid was discontinued to increase endogenous progesterone levels for ovarian stimulation. Next, dexamethasone plus GnRHa were used to reduce progesterone levels in frozen embryos for transfer. Once pregnancy was confirmed, dexamethasone was discontinued until delivery.ResultsDexamethasone, but not hydrocortisone, reduced progesterone levels in the 17OHD woman. After endogenous progesterone-primed ovarian stimulation, 11 oocytes were retrieved. Seven oocytes were 2PN fertilised and four day-3 and two day-5 embryos were cryopreserved. After administering dexamethasone plus gonadotropin-releasing hormone agonist (GnRHa) to reduce progesterone levels to normal, hormone replacement therapy was administered until the endometrial width reached 9 mm. Exogenous progesterone (60 mg/day) was used for endometrial preparation. Two thawed embryos were transferred on day 4. Dexamethasone was continued until pregnancy confirmation on the 13th day post-transfer. Two healthy boys, weighing 2100 and 2000 g, were delivered at 36 weeks’ gestation.ConclusionRational use of dexamethasone synchronised embryonic development with the endometrial implantation window, while not using in post-implantation avoided its side effects and promoted healthy live births in women non-classic 17OHD undergoing in vitro fertilisation.

Background: Green tea, mulberry leaf and corn silk are traditional herbs used in the prevention and treatment of diabetes in China for a long time, but their synergistic hypoglycemic effects and mechanisms remain unclear. Methods: The effective components of green tea, mulberry leaf and corn silk were extracted and enriched. Mixture design of experiments was used to study the influences of different combinations on the cell viability and glucose uptake level of L6 myoblasts, so as to determine the optimal synergistic hypoglycemic combination. The possible hypoglycemic mechanism of the optimal synergistic combination was explored by cytotoxicity assay, glucose uptake assay, and western blot. Results: Three polyphenol enrichment fractions of the herbs, 30% ethanol elution fraction of green tea (GT), 50% ethanol elution fraction of mulberry leaf (ML) and 60% ethanol elution fraction of corn silk (CS) were obtained. The antioxidant activities of GT-30%, ML-50% and CS-60% were superior to those of crude extracts, and showed strong potential in a-amylase and a-glucosidase inhibition activities. The optimal synergistic combination of crude extracts G7 (crude extract of green tea:crude extract of mulberry leaf:crude extract of corn silk = 1:5:3), polyphenol enrichment fractions R3 (GT-30%:ML-50%:CS-60% = 1:7:1) and monomers X2 (epigallocatechin gallate:morusin:formononetin = 3:1:2) were selected, respectively. G7, R3, and X2 showed promoting effects on the cell viability and glucose uptake of L6 myoblasts within the detected concentration range. In addition, G7, R3, and X2 could increase the expression levels of p-PI3K/PI3K and p-Akt/Akt in L6 myoblasts, and promote the translocation of Glut4, but G7 and R3 showed more significant effects. Conclusion: The synergistic hypoglycemic effects of green tea, mulberry leaf and corn silk had the characteristics of multiple-components and multiple-targets with p-PI3K/PI3K, p-Akt/Akt and the translocation of Glut4 signal pathways involved. The three traditional herbs might have the potential to be combined used for the prevention and treatment of diabetes based on the synergistic hypoglycemic effects. [ABSTRACT FROM AUTHOR]

Acidosis is a hallmark of ischemic stroke and a promising neuroprotective target for preventing neuronal injury. Previously, genetic manipulations showed that blockade of acid-sensing ion channel 1a (ASIC1a)-mediated acidotoxicity could dramatically alleviate the volume of brain infarct and restore neurological function after cerebral ischemia. However, few pharmacological candidates have been identified to exhibit efficacy on ischemic stroke through inhibition of ASIC1a. In this work, we examined the ability of a toxin-inspired compound 5b (C5b), previously found to effectively inhibit ASIC1a in vitro, to exert protective effects in animal models of ischemic stroke in vivo. We found that C5b exerts significant neuroprotective effects not only in acid-induced neuronal death in vitro but also ischemic brain injury in vivo, suggesting that ASIC1a is a druggable target for therapeutic development. More importantly, C5b is able to cross the blood brain barrier and significantly reduce brain infarct volume when administered intravenously in the ischemic animal model, highlighting its systemic availability for therapies against neurodegeneration due to acidotoxicity. Together, our data demonstrate that C5b is a promising lead compound for neuroprotection through inhibiting ASIC1a, which warrants further translational studies.

Background/purpose: Previous epidemiological studies have associated interstitial lung disease (ILD) with rheumatoid arthritis (RA), yet the causality of this relationship remains uncertain. This study aimed to investigate the genetic causal link between ILD and RA. Methods: Genome-wide association study (GWAS) statistics for ILD and RA were collected from public datasets. Relevant single-nucleotide polymorphisms (SNPs) were selected by executing quality control steps from the GWAS summary results. A two-sample bidirectional Mendelian randomization (MR) analysis was performed to assess the causal relationship between the two conditions. The MR analysis primarily used the inverse variance weighting (IVW), weighted median (WM), and MR-Egger regression methods. Sensitivity analyses, including MR-Egger, leave-one-out, and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO), were conducted to evaluate the heterogeneity and pleiotropy. Replication analyses using Asian datasets were also conducted to enhance the robustness of our findings. Results: In the European population, RA was found to increase the risk of ILD by 9.6% (OR: 1.096, 95% CI: 1.023-1.174, p = 0.009). Conversely, ILD was associated with a 12.8% increased risk of RA (OR: 1.128, 95% CI: 1.013-1.256, p = 0.029). Replication analyses from Asian GWAS further supported these findings, particularly the increased risk of ILD attributable to RA (OR: 1.33, 95% CI: 1.18-1.49, p-value <0.001). Conclusion: Our findings underscore the clinical importance of screening for ILD in RA patients and suggest that effective management of RA could significantly benefit ILD patients. The potential applicability of novel RA treatments to ILD warrants further exploration. Additionally, racial disparities in the manifestation of these diseases should not be overlooked, as they may offer new perspectives for targeted therapies in diverse populations. [ABSTRACT FROM AUTHOR]

Heat shock protein 20 (Hsp20) is a small molecule heat shock protein that plays an important role in plant growth, development, and stress resistance. Little is known about the function of Hsp20 family genes in apple (Malus domestica). Here, we performed a genome-wide analysis of the apple Hsp20 gene family, and a total of 49 Hsp20s genes were identified from the apple genome. Phylogenetic analysis revealed that the 49 genes were divided into 11 subfamilies, and MdHsp18.2b, a member located in the CI branch, was selected as a representative member for functional characterization. Treatment with NaCl and Botryosphaeria dothidea (B. dothidea), the causal agent of apple ring rot disease, significantly induced MdHsp18.2b transcription level. Further analysis revealed that overexpressing MdHsp18.2b reduced the resistance to salt stress but enhanced the resistance to B. dothidea infection in apple calli. Moreover, MdHsp18.2b positively regulated anthocyanin accumulation in apple calli. Physiology assays revealed that MdHsp18.2b promoted H2O2 production, even in the absence of stress factors, which might contribute to its functions in response to NaCl and B. dothidea infection. Hsps usually function as homo- or heterooligomers, and we found that MdHsp18.2b could form a heterodimer with MdHsp17.9a and MdHsp17.5, two members from the same branch withMdHsp18.2b in the phylogenetic tree. Therefore, we identified 49 Hsp20s genes from the apple genome and found that MdHsp18.2b was involved in regulating plant resistance to salt stress and B. dothidea infection, as well as in regulating anthocyanin accumulation in apple calli. [ABSTRACT FROM AUTHOR]

Abstract In this paper, we present the application of a new method measuring Hubble parameter H(z) by using the anisotropy of luminosity distance ($$d_{L}$$ dL ) of the gravitational wave (GW) standard sirens of neutron star (NS) binary system. The method has never been put into practice so far due to the lack of the ability of detecting GW. However, LIGO’s success in detecting GW of black hole (BH) binary system merger announced the potential possibility of this new method. We apply this method to several GW detecting projects, including Advanced LIGO (aLIGO), Einstein Telescope (ET) and DECIGO, and evaluate its constraint ability on cosmological parameters of H(z). It turns out that the H(z) by aLIGO and ET is of bad accuracy, while the H(z) by DECIGO shows a good one. We simulate H(z) data at every 0.1 redshift span using the error information of H(z) by DECIGO, and put the mock data into the forecasting of cosmological parameters. Compared with the previous data and method, we get an obviously tighter constraint on cosmological parameters by mock data, and a concomitantly higher value of Figure of Merit (FoM, the reciprocal of the area enclosed by the $$2\sigma $$ 2σ confidence region). For a 3-year-observation by standard sirens of DECIGO, the FoM value is as high as 170.82. If a 10-year-observation is launched, the FoM could reach 569.42. For comparison, the FoM of 38 actual observed H(z) data (OHD) is 9.3. We also investigate the undulant universe, which shows a comparable improvement on the constraint of cosmological parameters. These improvement indicates that the new method has great potential in further cosmological constraints.

Alzheimer’s disease (AD) is the most common form of dementia. Although the incidence of AD is high, the rates of diagnosis and treatment are relatively low. Moreover, effective means for the diagnosis and treatment of AD are still lacking. MicroRNAs (miRNAs, miRs) are non-coding RNAs that play regulatory roles by targeting mRNAs. The expression of miRNAs is conserved, temporal, and tissue-specific. Impairment of microRNA function is closely related to AD pathogenesis, including the beta-amyloid and tau hallmarks of AD, and there is evidence that the expression of some microRNAs differs significantly between healthy people and AD patients. These properties of miRNAs endow them with potential diagnostic and therapeutic value in the treatment of this debilitating disease. This review provides comprehensive information about the regulatory function of miRNAs in AD, as well as potential applications as diagnostic biomarkers.

Because of the large delay of DTN network,node cannot receive broadcast updating private key messages in a timely manner,thus unable to update the private key for a certain time period.Aiming at this problem,an allowing private key self-healing clustering key was management scheme.The scheme can not only accomplish the distribution of the private keys of node and update,but also can self-heal the old time private keys.Security and efficiency analysis show that the scheme is particularly suitable for large network latency,intermittent connection DTN network.

Background: To determine the efficacy of the Caulis Sargentodoxae prescription, which is an empirical formula of Chinese herbs and has definite curative effects on endometriosis. Methods: The Caulis Sargentodoxae prescription on the growth of ectopic endometria was studied with a rat endometriosis (EMS) model. The EMS model was established by autoplastic transplantation. To study the curative effects of Chinese medicine on EMS in comparison with western medicine, gestrinone and an angiogenesis inhibitor were introduced. The rats were randomly divided into seven groups: normal group, model group, ovariectomized group, gestrinone (western medicine) group, Caulis Sargentodoxae prescription (Chinese medicine) group, apatinib (inhibitor) group, and combination (Chinese medicine + inhibitor) group. After administration for 21 days, the growth inhibitory rates of ectopic endometria in the treatment groups were evaluated, and the levels of vascular endothelial growth factor (VEGF) and VEGF receptor-2 (VEGFR2) were detected by ELISA in the serum and peritoneal fluid, as well as in the ectopic endometrial tissues by real-time polymerase chain reaction and Western blotting. Results: The growth inhibitory rates of ectopic endometria in the treatment groups were significantly higher (P < 0.05). In the Caulis Sargentodoxae prescription group, the levels of angiogenesis-related factors, including VEGF and VEGFR2, were reduced in the serum and peritoneal fluid compared with the model group (P < 0.05). In addition, the positive expression of VEGF and VEGFR2 in ectopic endometria significantly decreased in the Caulis Sargentodoxae prescription group both at mRNA and protein levels. Conclusions: VEGF and VEGFR2 levels in the serum and peritoneal fluid can be used as a clinical reference for endometriotic pathogenesis and treatment, and the Caulis Sargentodoxae prescription has reliable therapeutic effects on EMS for its target-action ability to decrease angiogenesis.

Background This study was designed to investigate the clinicopathological characteristics, treatment and survival of patients with pulmonary large cell neuroendocrine carcinoma (LCNEC). Methods The Surveillance, Epidemiology and End Results database was utilized to identify patients diagnosed with pulmonary LCNEC between 2004 and 2013. Kaplan–Meier analysis was conducted to determine the overall survival (OS) and cancer-specific survival (CSS) rate. Univariate survival analysis along with log-rank test, and Cox proportional hazards model were employed to detect independent prognostic factors. Results Pulmonary LCNEC accounted for 0.58% (2972/510607) of the total number of lung and bronchus carcinoma. And a total of 1,530 eligible cases were identified, with the median follow-up time of 11 months. To be specific, the 3-, 5-year OS and CSS rates were 22.8%, 16.8% and 26.5%, 20.8% respectively. Generally, pulmonary LCNEC was commonly detected in the elderly (72.2%), males (55.9%), the upper lobe (62.0%) and advanced AJCC stage (65.5%). Multivariate analysis revealed that elderly [(≥60 and