Search

ObjectiveAcute aneurysmal rupture can be treated with endovascular therapy or surgical clipping. For patients with concurrent acute hydrocephalus, the placement of an external ventricular drainage (EVD) is required. This study aims to investigate the impact of pre-treatment EVD placement on rebleeding in ruptured aneurysms and to examine the influence of dual antiplatelet therapy and the sequencing of dual antiplatelet therapy with EVD placement on EVD-related hematomas.MethodsWe reviewed the clinical data of 83 patients with ruptured aneurysms who underwent EVD placement from a total of 606 aneurysm patients consecutively admitted between January 2018 and January 2023. The analysis focused on the impact of pre-treatment EVD placement on aneurysmal rebleeding and the effect of dual antiplatelet therapy and its sequencing with EVD placement on EVD-related hematomas.ResultsAmong the 503 patients with ruptured aneurysms, 83 required EVD placement. EVD was placed before aneurysm treatment in 63 patients and after treatment in 20 patients. The number of aneurysmal rebleeding cases in the pre-treatment EVD group and non-EVD group was 1 (1.6%) and 20 (4.8%), respectively (p = 0.406). 31 patients (37.3%) underwent stent-assisted embolization or flow diversion requiring dual antiplatelet therapy, while 52 patients (62.7%) underwent simple embolization or surgical clipping without antiplatelet therapy. EVD-related hematomas occurred in 14 patients (16.9%), with 10 cases (32.3%) in those receiving dual antiplatelet therapy and 4 cases (7.7%) in those not receiving antiplatelet therapy (p = 0.01). Among 16 patients who had EVD placed before dual antiplatelet therapy, 4 (25%) developed EVD-related hematomas. Of the 15 patients who had EVD placed after dual antiplatelet therapy, 6 (40%) developed EVD-related hematomas (p = 0.458).ConclusionIn patients with aneurysmal subarachnoid hemorrhage (aSAH) and acute hydrocephalus, the placement of EVD before aneurysm treatment does not increase the risk of rebleeding. However, dual antiplatelet therapy increases the risk of EVD-related hematoma, and the sequence of EVD placement relative to dual antiplatelet therapy does not appear to significantly affect the outcome of EVD-related hematoma.

Introduction: Epidemiological evidence over the last few decades has consistently shown that exposure to endocrine-disrupting chemicals (EDCs) is associated with adverse reproductive health outcomes, including male and female infertility, poor-pregnancy outcomes, and increased risk of diseases in childhood and beyond. To investigate the effects of EDCs and lifestyle on all aspects of reproduction (including early oocyte development, fertilization, embryo development, embryo implantation, abortion, and preterm birth).Methods: We performed this cohort study on patients receiving in vitro fertilization (IVF) treatment. Biological samples including urine, serum, follicular fluid, semen, fetal tissue, decidua, and placenta, were obtained.Results: By studying the correlations between reproductive outcomes and environmental pollutant exposure and lifestyle, we determined the toxicological mechanisms and health effects of EDCs on female reproductive health. We found that higher concentrations of per- and polyfluoroalkyl substances were correlated with polycystic ovary syndrome (PCOS). Using specific biomarkers, we also detected the concentrations of organophosphorus flame retardants (OPFRs) in urine and found that OPFRs may disrupt hormone homeostasis.Discussion: All of these results reveal EDCs may disrupt female reproduction.

This paper introduces a new green decomposition model of carbon productivity that aims to further analyze the regional differences in carbon productivity and its interaction with regional industrial performance. We combine desired outputs and undesired outputs orientation, and multiple factor inputs to derive a new green decomposition theorem, establish a new green decomposition model of carbon productivity, and obtain nine effects of regional carbon productivity differences. Empirical analysis is conducted using input-output data from 29 provinces and 15 industries in China, comparing the differences in carbon productivity from both the provincial and industry perspectives and exploring the mechanism of action. This paper provides theoretical basis and empirical evidence for regional carbon productivity enhancement and economic and industrial optimization from the perspective of multi-factor inputs, as well as policy insights for regional low-carbon transition development.

Currently kiwifruit picking process mainly leverages manual labor, which has low productivity and high labor intensity, meanwhile, the existing kiwifruit picking machinery also has low picking efficiency and easily damages fruits. In this regard, a kiwifruit picking robot suitable for orchard operations was developed in this paper for kiwifruit grown in orchard trellis style. First, based on the analysis of kiwifruit growth pattern and cultivation parameters, the expected design requirements and objectives of a kiwifruit picking robot were proposed, and the expected workflow of the robot in the kiwifruit orchard environment was given, which in turn led to a multi-fruit envelope-cutting kiwifruit picking robot was designed. Then, the D-H method was used to establish the kinematic Equations of the kiwifruit-picking robot, the forward and inverse kinematic calculations were carried out, and the Monte Carlo method was used to analyze the workspace of the robot. By planning the trajectory of the robotic arm and calculating critical nodes in the picking path, the scheme of trajectory planning of the robot was given, and MATLAB software was applied to simulate the motion trajectory as well as to verify the feasibility of the trajectory planning scheme and the picking strategy. Finally, a kiwifruit picking test bed was set up to conduct picking tests in the form of fruit clusters. The results show that the average time to pick each cluster of fruit was 9.7s, the picking success rate was 88.0%, and the picking damage rate was 7.3%. All the indicators met the requirements of the expected design of the kiwifruit-picking robot.

The complex and variable oceanic environment challenges channel modeling of Underwater Wireless Optical Communication (UWOC) systems. Most of the classical modeling methods focus mainly on the water environment and ignore the effect of communication equipment on signal transmission, thus making it difficult to model the UWOC channel’s complicated characteristics comprehensively. In this work, a UWOC channel emulator based on Deep Convolutional Conditional Generative Adversarial Networks is established and verified to address the challenge, which can effectively learn the characteristics of channel response and generate emulated signals with randomness like a real UWOC system in a practical application environment. Compared with the approaches based on multi-layer perceptron and convolutional neural network, the experimental results of the proposed method indicate outstanding performances in time domain, frequency domain and universality with different turbidity levels, respectively. This approach provides a new idea for applying deep learning techniques to the field of UWOC channel modeling.

BackgroundMalaria remains a severe life-threatening disease caused by plasmodium parasites. Microscopy is widely used for malaria diagnosis. However, it relies heavily on the skills and experience of inspectors. Due to low-level medical services and the lack of skilled inspectors, misdiagnoses are frequently made in some areas.MethodsIn recent years, many successful applications of CNN models have been reported. Unlike images in the ImageNet, the image of plasmodium only has a tiny defect area with a large amount of information. In addition, the dataset is extremely unbalanced: the number of positive samples is much less than that of negative samples. This paper proposes a classification network by combining attention mechanism and ResNeSt for plasmodium detection and using self-supervised learning to pre-train the network. First, the positive samples were adopted to pre-train the network. Then, attention modules were taken to highlight the feature area. To support current and future research, we also constructed a plasmodium dataset with Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, and Plasmodium malaria and non-Plasmodium. Through self-supervised learning, a large amount of unlabeled data is used to mine the representational features, thus improving the feature extraction capability of the model and achieving higher accuracy, while saving the physician’s labeling time and improving the classification accuracy.ResultsThe experiments show that our model exhibits an excellent performance and that the test accuracy, sensitivity, and specificity attain 97.8%, 96.5%, and 98.9%, respectively.ConclusionThe AI classification method proposed in this paper can effectively assist clinicians in the diagnosis and provide a basis for the automatic detection of malaria parasites in the future.

Non-infectious chronic diseases, especially inflammatory bowel diseases (IBDs), hypertension, and diabetes mellitus, are characterized by a prolonged and multisystemic course, and their incidence increases annually, usually causing serious economic burden and psychological stress for patients. Therefore, these diseases deserve scientific and consistent disease management. In addition, the lack of a comprehensive “early disease clues tracking—personalized treatment system—follow-up” model in hospitals also exacerbates this dilemma. Based on these facts, we propose an individualized prediction management system for IBDs based on chronic diseases, focusing on the established IBDs-related prediction models and summarizing their advantages and disadvantages. We call on researchers to pay attention to the integration of models with clinical practice and the continuous correction of models to achieve truly individualized medical treatment for chronic diseases, thus providing substantial value for the rapid diagnosis and adequate treatment of chronic diseases such as IBDs, which follow the “relapse-remission” disease model, and realizing long-term drug use and precise disease management for patients. The goal is to achieve a new level of chronic disease management by scientifically improving long-term medication, precise disease management, and individualized medical treatment, effectively prolonging the remission period and reducing morbidity and disability rates.

PurposeTo explore the changes of bacterial flora in anophthalmic patients wearing ocular prosthesis (OP) and the microbiome diversity in conditions of different OP materials.MethodsA cross-sectional clinical study was conducted, involving 19 OP patients and 23 healthy subjects. Samples were collected from the upper, lower palpebral, caruncle, and fornix conjunctiva. 16S rRNA sequencing was applied to identify the bacterial flora in the samples. The eye comfort of each OP patient was determined by a questionnaire. In addition, demographics information of each participant was also collected.ResultsThe diversity and richness of ocular flora in OP patients were significantly higher than that in healthy subjects. The results of flora species analysis also indicated that in OP patients, pathogenic microorganisms such as Escherichia Shigella and Fusobacterium increased significantly, while the resident flora of Lactobacillus and Lactococcus decreased significantly. Within the self-comparison of OP patients, compared with Polymethyl Methacrylate (PMMA), prosthetic material of glass will lead to the increased colonization of opportunistic pathogens such as Alcaligenes, Dermabacter and Spirochaetes, while gender and age have no significant impact on ocular flora.ConclusionsThe ocular flora of OP patients was significantly different from that of healthy people. Abundant colonization of pathogenic microorganisms may have an important potential relationship with eye discomfort and eye diseases of OP patients. PMMA, as an artificial eye material, demonstrated potential advantages in reducing the colonization of opportunistic pathogens.

As the core carrier and organizational bodies of the regional industrial space, the study of the location of industrial enterprises and the formation of their economic location is related to the rational development of regional industries, the coordination of humans and the environment, and the effective allocation of resources. Taking Chongqing, one of the six old industrial bases in China, as an example, this study analyzed the spatial distribution characteristics, economic location characteristics, and formation laws of industrial enterprises based on the Points of interest data (POI), and investigation data. The results showed that industrial enterprises in Chongqing show obvious spatial clustering characteristics. About 93.50%, 60.34%, 96.67%, 97.57%, 73.57%, 64.83% of industrial enterprises were distributed within the spatial range of 10 Km from the motorways, national highways, provincial highways, county highways, main streams of rivers and central towns, and 93.48% of industrial enterprises were distributed at an altitude of 800 m or less. In order to further reveale the economic location characteristics of industrial enterprises in Chongqing, this study further quantified the spatial differentiation law of industrial economic location based on Geographically weighted regression (GWR). The results showed that factors such as the Distance to National Highways (DNH), Distance to County Highways (DCH), Distance to Central Towns (DCC), Distance to River systems (DR), and Population Density (POP) had significant positive impacts on the formation of economic locations of industrial enterprises, while the Distance to Motorway (DMW) exerted a certain negative influence, but the effectiveness sees strong spatial heterogeneity according to the type of industry and the actual regional industrial development, with factors such as transportation accessibility, environment, and labor force playing a moderating role.

Preeclampsia (PE) is a severe placenta-related pregnancy disease that has been associated with maternal systemic inflammation and immune system disorders. However, the distribution and functional changes in immune cells of the maternal–placental interface have not been well characterized. Herein, cytometry by time-of-flight mass spectrometry (CyTOF) was used to investigate the immune atlas at the decidua, which was obtained from four PE patients and four healthy controls. Six superclusters were identified, namely, T cells, B cells, natural killer (NK) cells, monocytes, granulocytes, and others. B cells were significantly decreased in the PE group, among which the reduction in CD27+CD38+ regulatory B cell (Breg)-like cells may stimulate immune activation in PE. The significantly increased migration of B cells could be linked to the significantly overexpressed chemokine C-X-C receptor 5 (CXCR5) in the PE group, which may result in the production of excessive autoantibodies and the pathogenesis of PE. A subset of T cells, CD11c+CD8+ T cells, was significantly decreased in PE and might lead to sustained immune activation in PE patients. NK cells were ultimately separated into four subsets. The significant reduction in a novel subset of NK cells (CD56-CD49a-CD38+) in PE might have led to the failure to suppress inflammation at the maternal–fetal interface during PE progression. Moreover, the expression levels of functional markers were significantly altered in the PE group, which also inferred that shifts in the decidual immune state contributed to the development of PE and might serve as potential treatment targets. This is a worthy attempt to elaborate the differences in the phenotype and function of CD45+ immune cells in the decidua between PE and healthy pregnancies by CyTOF, which contributes to understand the pathogenesis of PE, and the altered cell subsets and markers may inspire the immune modulatory therapy for PE.

Studies have shown that letrozole cotreatment can improve clinical outcomes in high and poor responders in GnRH-antagonist protocol. However, whether letrozole is also beneficial to normal responders is not known. To investigate the clinical value of letrozole cotreatment during ovarian stimulation in vitro fertilization for normal ovarian reserve patients who were treated with the GnRH antagonist protocol, we conducted a retrospective study that based data from 1 January to 31 December 2017 for all IVF–ICSI GnRH-antagonist protocols. A total of 252 women who aged 6 were included in the analysis (96 in the letrozole group and 156 in the no-letrozole group). The cumulative live-birth rate was calculated as the first live birth achieved after all cycles having an embryo transfer (cycles using fresh embryos and frozen–thawed embryos) among both groups. The initial gonadotropin (Gn) dosage and total Gn dosage were significantly lower and the number of days of Gn treatment was significantly fewer in the letrozole group than the non-letrozole group (p < 0.05). There were also significant between-group differences in luteinizing hormone, estradiol, and progesterone concentrations; and the number of metaphase II oocytes on the day of human chorionic gonadotropin treatment (p < 0.05). There was a significant difference in the implantation rate between the two groups that the letrozole group higher than the non-letrozole group (39.79 vs. 27.96%, p = 0.006), but there was no significant difference in the cumulative live-birth rate. The combination of letrozole with a GnRH antagonist may have no effect on the clinical pregnancy rate or cumulative live-birth rate in patients with a normal ovarian reserve. However, letrozole may increase the rate of embryo implantation and may reduce the requirement for exogenous gonadotrophins and, consequently, the cost of an IVF treatment cycle. In addition, the decreased estradiol level in the ovarian simulation by letrozole supports letrozole can be a safe solution for fertility preservation in estrogen-related cancer patients.

As the basic pathological changes of diabetic retinopathy (DR), the destruction of the blood-retina barrier (BRB) and vascular leakage have attracted extensive attention. Without timely intervention, BRB damage will eventually lead to serious visual impairment. However, due to the delicate structure and complex function of the BRB, the mechanism underlying damage to the BRB in DR has not been fully clarified. Here, we used single-cell RNA sequencing (RNA-seq) technology to analyze 35,910 cells from the retina of healthy and streptozotocin (STZ)-induced diabetic rats, focusing on the degeneration of the main cells constituting the rat BRB in DR and the new definition of two subpopulations of Müller cells at the cell level, Ctxn3+Müller and Ctxn3−Müller cells. We analyzed the characteristics and significant differences between the two groups of Müller cells and emphasized the importance of the Ctxn3+Müller subgroup in diseases. In endothelial cells, we found possible mechanisms of self-protection and adhesion and recruitment to pericytes. In addition, we constructed a communication network between endothelial cells, pericytes, and Müller subsets and clarified the complex regulatory relationship between cells. In summary, we constructed an atlas of the iBRB in the early stage of DR and elucidate the degeneration of its constituent cells and Müller cells and the regulatory relationship between them, providing a series of potential targets for the early treatment of DR.

ObjectivesThis study aimed to explore the effect of maternal iodine status on the brain development of offspring in rats. Since in human studies, the interference of environmental factors and other nutrients cannot be removed.Materials and methodsA total of 48 female Wistar rats were randomly divided into four groups: low iodine (LI), normal iodine (NI), 10-fold high iodine (10HI), and 50-fold high iodine (50HI). The rats were killed on the 15th day of pregnancy and lactation after collecting 24-h urine. The iodine concentration in 24-h urine, blood, and placenta of pregnant rats, and 24-h urine, milk, blood, and mammary glands of lactating rats was determined by inductively coupled plasma mass spectrometry. The thyroid hormone of pregnant and lactating rats was detected by chemiluminescence. The offspring were subjected to the Morris water maze on the 10th day after birth. Serum was collected to detect the thyroid hormone of offspring. The protein expression of neuroendocrine-specific protein (NSP)-A and brain-derived neurotrophic factor (BDNF) in the offspring brain were studied.ResultsIodine storage in the placenta during pregnancy and mammary glands during lactation was positively correlated with iodine intake, and iodine storage in the placenta and mammary glands in the 50HI group was significantly higher than that in the NI group (P = 0.045 and P = 0.040). Compared with the NI group, the offspring thyroid-stimulating hormone (TSH) level was significantly higher in the 10HI group (P = 0.046), and the FT4 level was significantly lower in the 50HI group (P = 0.032). The Morris water maze showed that LI and 50HI groups required longer time and distance to find the platform than the NI group (P < 0.001). The platform crossing numbers in the LI and 50HI groups decreased significantly (P < 0.001). The expression of NSP-A in offspring brain was lower in the 10HI and 50HI groups than in the NI group (P = 0.026 and P = 0,008). BDNF expression levels were significantly lower in the LI, 10HI, and 50HI groups than in the NI group (P < 0.001).ConclusionMaternal iodine intake affects iodine storage in the placenta and lactating mammary gland, which in turn affects thyroid function and BDNF and NSP-A expression in the offspring.

Background: The cure rates of Helicobacter pylori (H. pylori) treatment using a proton pump inhibitor (PPI) are gradually decreasing due to antibiotic resistance, poor compliance, high gastric acidity, and cytochrome P450 2C19 (CYP2C19) polymorphism, and the effects of PPI depend on metabolic enzymes, cytochrome P450 enzymes. The aim of this meta-analysis was to determine whether CYP2C19 polymorphisms affect H. pylori cure rates in patients treated with different proton pump inhibitors (PPIs) according to stratified analysis.Materials and methods: The literature was searched with the key words “H. pylori” and “CYP2C19” in PubMed, CNKI, and Wanfang up to 31 May 2022, and the studies were limited to clinical observational or randomized controlled trials (RCTs). Finally, seven RCTs and 29 clinical observational studies met the inclusion criteria and were used for the meta-analysis via STATA version 16.Results: The cure rates were significantly different between genotypes of homozygous extensive metabolizers (EM) and poor metabolizers (PM) (OR = 0.58, 95% CI: 0.47–0.71) and between EM and heterozygous extensive metabolizers (IM) (OR = 0.71, 95% CI: 0.59–0.86), but not between IM and PM. Moreover, there was a significantly lower H. pylori cure rate in EM subjects than that in IM subjects when treated with omeprazole (66.4% vs. 84.1%), lansoprazole (76.1% vs. 85.6%), but not rabeprazole, esomeprazole, or pantoprazole. In addition, there was a significantly lower H. pylori cure rate in EM subjects than that in IM subjects when treated with a PPIs for 7 days (77.4% vs. 82.1%), but not 14 days (85.4% vs. 90.0%).Conclusion: Carriers of CYP2C19 loss-of-function variant alleles (IM and PM) exhibit a significantly greater cure rate of H. pylori than noncarriers (EM) regardless of other factors (84.7% vs. 79.2%). In addition, pantoprazole- and rabeprazole-based quadruple therapy for H. pylori treatment is less dependent on the CYP2C19 genotype and should be prioritized in Asian populations with H. pylori.

Jiangtang Sanhao formula (JTSHF), one of the prescriptions for treating the patients with diabetes mellitus (DM) in traditional Chinese medicine clinic, has been demonstrated to effectively ameliorate the clinical symptoms of diabetic patients with overweight or hyperlipidemia. The preliminary studies demonstrated that JTSHF may enhance insulin sensitivity and improve glycolipid metabolism in obese mice. However, the action mechanism of JTSHF on skeletal muscles in diabetic mice remains unclear. To this end, high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic mice were subjected to JTSHF intervention. The results revealed that JTSHF granules could reduce food and water intake, decrease body fat mass, and improve glucose tolerance, lipid metabolism, and insulin sensitivity in the skeletal muscles of diabetic mice. These effects may be linked to the stimulation of GLUT4 expression and translocation via regulating AMPKα/SIRT1/PGC-1α signaling pathway. The results may offer a novel explanation of JTSHF to prevent against diabetes and IR-related metabolic diseases.

Subject: Perioperative regulation of coagulation function through heparin in patients undergoing cardiac surgery with cardiopulmonary bypass is an important part of performing cardiac surgery, and postoperative bleeding due to abnormal coagulation function caused by differences in heparin sensitivity in different individuals is an independent risk factor for postoperative complications and death.Method: Using an online database, 10 miRNAs interacting with AT-III and FX genes were predicted. Patients were divided into three groups according to the difference in activated clotting time (ACT) after the first dose of heparin (2.5 mg kg−1): group A: hyposensitive group (ACT < 480 s); group B: sensitive group (480 s ≤ ACT ≤ 760 s); and group C: hypersensitive group (ACT > 760 s). Perioperative and 24 h postoperative blood loss and other clinical data of patients in the three groups were recorded. Blood samples were collected before surgery, and RT-PCR was used to detect the levels of AT-III and FX gene mRNA and the levels of predicted 10 miRNAs.Result: Heparin sensitivity was positively correlated with AT-III mRNA levels and negatively correlated with FX gene mRNA levels in the three groups, and the blood loss in group B was significantly lower than that in groups A and C, which was statistically significant (p < 0.05). miR-3064-5p and miR-4745-5p expression levels were significantly different among group A, group B, and group C (p < 0.05) and were closely correlated with AT-III and FX gene mRNA expression levels, respectively.Conclusion: Differences in heparin sensitivity in patients undergoing cardiac surgery were associated with the mRNA expression of AT-III and FX genes, and the expression levels of miR-3064-5p and miR-4745-5p were found to be closely related to the AT-III and FX gene mRNA, respectively, indicating that miR-3064-5p and miR-4745-5p affect the differences in heparin sensitivity among different individuals by regulating the mRNA expression levels of AT-III and FX genes.Clinical Trial Registration:http://www.chictr.org.cn/abouten.aspx, identifier registration number: ChiCTR-2100047348

BackgroundAccumulating evidence shows that m6A regulates oncogene and tumor suppressor gene expression, thus playing a dual role in cancer. Likewise, there is a close relationship between the immune system and tumor development and progression. However, for glioblastoma, m6A-associated immunological markers remain to be identified.MethodsWe obtained gene expression, mutation, and clinical data on glioblastoma from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. Next, we performed univariate COX–least absolute shrinkage and selection operator (LASSO)–multivariate COX regression analyses to establish a prognostic gene signature and develop a corresponding dynamic nomogram application. We then carried out a clustering analysis twice to categorize all samples according to their m6A-regulating and m6A-associated immune gene expression levels (high, medium, and low) and calculated their m6A score. Finally, we performed quantitative reverse transcription-polymerase chain reaction, cell counting kit-8, cell stemness detection, cell migration, and apoptosis detection in vitro assays to determine the biological role of CD81 in glioblastoma cells.ResultsOur glioblastoma risk score model had extremely high prediction efficacy, with the area under the receiver operating characteristic curve reaching 0.9. The web version of the dynamic nomogram application allows rapid and accurate calculation of patients’ survival odds. Survival curves and Sankey diagrams indicated that the high-m6A score group corresponded to the groups expressing medium and low m6A-regulating gene levels and high m6A-associated prognostic immune gene levels. Moreover, these groups displayed lower survival rates and higher immune infiltration. Based on the gene set enrichment analysis, the pathophysiological mechanism may be related to the activation of the immunosuppressive function and related signaling pathways. Moreover, the risk score model allowed us to perform immunotherapy benefit assessment. Finally, silencing CD81 in vitro significantly suppressed proliferation, stemness, and migration and facilitated apoptosis in glioblastoma cells.ConclusionWe developed an accurate and efficient prognostic model. Furthermore, the correlation analysis of different stratification methods with tumor microenvironment provided a basis for further pathophysiological mechanism exploration. Finally, CD81 may serve as a diagnostic and prognostic biomarker in glioblastoma.

N6-methylandrostenedione (m6A) methylation plays a very important role in the development of malignant tumors. The immune system is the key point in the progression of tumors, particularly in terms of tumor treatment and drug resistance. Tumor immunotherapy has now become a hot spot and a new approach for tumor treatment. However, as far as the stomach adenocarcinoma (STAD) is concerned, the in-depth research is still a gap in the m6A-associated immune markers. The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases is extremely important for our research, where we obtained gene mutation, gene expression data and relevant clinical information of STAD patients. Firstly, the samples from GEO were used as external validation groups, while the TCGA samples were divided into a training group and an internal validation group randomly. Using the way of Single factor COX-LASSO- and multi-factor Cox to construct the prognostic model. Then, all samples were subjected to cluster analysis to generate high and low expression groups of immune gene. Meanwhile, we also collected the correlation between these types and tumor microenvironment. On this basis, a web version of the dynamic nomogram APP was developed. In addition, we performed microenvironmental correlation, copy number variation and mutation analyses for model genes. The prognostic model for STAD developed here demonstrated a very strong predictive ability. The results of cluster analysis manifested that the immune gene low expression group had lower survival rate and higher degree of immune infiltration. Therefore, the immune gene low expression group was associated with lower survival rates and a higher degree of immune infiltration. Gene set enrichment analysis suggested that the potential mechanism might be related to the activation of immunosuppressive functions and multiple signaling pathways. Correspondingly, the web version of the dynamic nomogram APP produced by the DynNom package has successfully achieved rapid and accurate calculation of patient survival rates. Finally, the multi-omics analysis of model genes further enriched the research content. Interference of RAB19 was confirmed to facilitate migration of STAD cells in vitro, while its overexpression inhibited these features. The prognostic model for STAD constructed in this study is accurate and efficient based on multi-omics analysis and experimental validation. Additionally, the results of the correlation analysis between the tumor microenvironment and m6Ascore are the basics of further exploration of the pathophysiological mechanism in STAD.

Background and AimsWe aim to develop a diagnostic tool for pathological-image classification using transfer learning that can be applied to diverse tumor types.MethodsMicroscopic images of liver tissue with and without hepatocellular carcinoma (HCC) were used to train and validate the classification framework based on a convolutional neural network. To evaluate the universal classification performance of the artificial intelligence (AI) framework, histological images from colorectal tissue and the breast were collected. Images for the training and validation sets were obtained from the Xiamen Hospital of Traditional Chinese Medicine, and those for the test set were collected from Zhongshan Hospital Xiamen University. The accuracy, sensitivity, and specificity values for the proposed framework were reported and compared with those of human image interpretation.ResultsIn the human–machine comparisons, the sensitivity, and specificity for the AI algorithm were 98.0, and 99.0%, whereas for the human experts, the sensitivity ranged between 86.0 and 97.0%, while the specificity ranged between 91.0 and 100%. Based on transfer learning, the accuracies of the AI framework in classifying colorectal carcinoma and breast invasive ductal carcinoma were 96.8 and 96.0%, respectively.ConclusionThe performance of the proposed AI framework in classifying histological images with HCC was comparable to the classification performance achieved by human experts, indicating that extending the proposed AI’s application to diagnoses and treatment recommendations is a promising area for future investigation.

Background: Stomach adenocarcinoma (STAD) is one of the most common tumors. Tumor mutation burden (TMB) has been linked to immunotherapy response. We wanted to see if there was any link between TMB and cancer prognosis.Methods: The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases were used to obtain mutation data, gene expression profiles, and clinical data. We looked at the differences in gene expression and immune markers between low and high TMB groups, built an immune prognostic model, and created a dynamic nomograph App that may be used in the clinic. Simultaneously, We ran the immunotherapy prediction and model comparison at the same time. Finally, model gene mutation and copy number variation (CNV) were displayed. The cellular functional experiments were used to investigate the potential role of GLP2R in gastric cancer.Results: Firstly, basic mutation information and differences in immune infiltration in STAD are revealed. Secondly, the prognostic model developed by us has good accuracy, and the corresponding dynamic nomograph Apps online and immunotherapy prediction facilitate clinical transformation. Furthermore, GLP2R knockdown significantly inhibited the proliferation, migration of gastric cancer cells in vitro.Conclusion: Our findings imply that TMB plays a significant role in the prognosis of STAD patients from a biological perspective. GLP2R may serve as a potential target for gastric cancer.

Colletotrichum fructicola infects pear leaves, resulting in two major symptoms: tiny black spots (TS) followed by severe early defoliation and big necrotic lesions (BnL) without apparent damage depending on the pathotypes. How the same fungal species causes different symptoms remains unclear. To understand the molecular mechanism underlying the resulting diseases and the diverse symptoms, two C. fructicola pathogenetic strains (PAFQ31 and PAFQ32 responsible for TS and BnL symptoms, respectively) were inoculated on Pyrus pyrifolia leaves and subjected to transcriptome sequencing at the quiescent stage (QS) and necrotrophic stage (NS), respectively. In planta, the genes involved in the salicylic acid (SA) signaling pathway were upregulated at the NS caused by the infection of each strain. In contrast, the ethylene (ET), abscisic acid (ABA), and jasmonic acid (JA) signaling pathways were specifically related to the TS symptoms caused by the infection of strain PAFQ31, corresponding to the yellowish and early defoliation symptoms triggered by the strain infection. Correspondingly, SA was accumulated in similar levels in the leaves infected by each strain at NS, but JA was significantly higher in the PAFQ31-infected as measured using high-performance liquid chromatography. Weighted gene co-expression network analysis also reveals specific genes, pathways, phytohormones, and transcription factors (TFs) associated with the PAFQ31-associated early defoliation. Taken together, these data suggest that specific metabolic pathways were regulated in P. pyrifolia in response to the infection of two C. fructicola pathotypes resulting in the diverse symptoms: JA, ET, and ABA accumulated in the PAFQ31-infected leaves, which negatively affected the chlorophyll metabolism and photosynthesis pathways while positively affecting the expression of senescence-associated TFs and genes, resulted in leaf yellowing and defoliation; whereas SA inhibited JA-induced gene expression in the PAFQ32-infected leaves, which led to hypersensitive response-like reaction and BnL symptoms.

This is a retrospective cohort study included 1021 patients underwent a flexible GnRH antagonist IVF protocol from January 2017 to December 2017 to explore the effect of a premature rise in luteinizing hormone (LH) level on the cumulative live birth rate. All patients included received the first ovarian stimulation and finished a follow-up for 3 years. A premature rise in LH was defined as an LH level >10 IU/L or >50% rise from baseline during ovarian stimulation. The cumulative live birth rate was calculated as the number of women who achieved a live birth divided by the total number of women who had either delivered a baby or had used up all their embryos received from the first stimulated cycle. In the advanced patients (≥37 years), the cumulative live birth rate was reduced in patients with a premature rise of LH (β: 0.20; 95% CI: 0.05–0.88; p=0.03), compared to patients (≥37 years) without the premature LH rise. The incidence of premature LH rise is associated with decreased rates of cumulative live birth rate in patients of advanced age (≥37 years) and aggravated the reduced potential of embryos produced by the advanced age, not the number of embryos.

PurposeImmunotherapy for gastrointestinal stromal tumors (GISTs) remains a clinical challenge. The present study aimed to explore the clinical and prognostic significance of immune cell infiltration and PD-L1 expression in GISTs.MethodsA total of 507 clinical tissue specimens of primary GISTs were collected for immunohistochemical analysis of immune cell infiltration and PD-L1 expression. Influencing factors of survival were evaluated by Kaplan–Meier analysis. Univariate and multivariate analyses were performed using the Cox regression model.ResultsThere were significant differences in sex, tumor location, size, mitotic index, NIH risk grade, and cell morphology between different gene mutation types of GISTs. Immune cell infiltration in GISTs mainly involved macrophages and T cells. PD-1 was expressed in 48.5% of the tissue specimens, and PD-L1 expression was detected in 46.0% of the samples. PD-L1 expression was negatively correlated with the tumor size and mitotic index but positively correlated with the number of CD8+ T cells. There were significant differences in the number of CD8+ T cells between different gene mutation types. Wild type-mutant GISTs were enriched with CD8+ T cells as compared with KIT- and PDGFRA-mutant GISTs. The number of CD8+ T cells was higher in non-gastric GISTs. PD-L1 and CD8+ T cells were independent predictors for better relapse-free survival of GISTs.ConclusionsPD-L1 expression is a predictive biomarker for better prognosis of GISTs. Non-gastric GIST patients with wild-type mutations may be the beneficiaries of PD-1/PD-L1 inhibitors.

Significance: Perifoveal exudative vascular anomalous complex (PEVAC) is a unique clinical lesion. It manifests as isolated lesions and is easily misdiagnosed. Thus far, few PEVAC case reports have been published. PEVAC is typically inconsistent with other reported macular lesions.Purpose: To report our 24-month follow-up experience on the treatment of PEVAC with a micropulse laser (MPL).Case Report: A 56-year-old Chinese woman with no history of other diseases complained of decreased vision in her left eye that had persisted for more than 1 year. Comprehensive ophthalmic examinations were performed, including a vision test, slit lamp fundus exam, optical coherence tomography (OCT), optical coherence tomography angiography (OCT-A), fluorescein fundus angiography (FFA) and indocyanine green angiography (ICGA). Intravitreal injection of ranibizumab was ineffective, and bleeding, exudation and visual acuity were not improved. After two rounds of micropulse laser (MPL) treatment, the patient was followed up, and the prognosis was good.Conclusion: PEVAC is very rare, and early diagnosis is important, as the lesions readily cause irreversible damage. Our results indicate that an MPL can be used as an alternative treatment for PEVAC patients.

Methionine (Met) is the first limiting amino acid in broiler diets, but its unclear physiological effects hamper its effective use in the poultry production industry. This study assessed the effect of a Met-deficient (MD) diet on chicken liver and kidney health, exploring the associated mechanisms of antioxidant capacity and ileum mucosal immunity. Seventy-two broilers were administered either the control diet (0.46% Met in starter diet, 0.36% Met in grower diet) or the MD diet (0.22% Met in starter diet, 0.24% Met in grower diet). Liver and kidney samples were collected every 14 days for anatomical, histological, and ultrastructural analyses, accompanied by oxidative stress assessment. Meanwhile, T- and B-lymphocyte abundance and essential cytokine gene expression were measured in the ileum, the center of the gut–liver–kidney axis. Signs of kidney and liver injury were observed morphologically in the MD group at 42 days of age. Furthermore, aspartate aminotransferase, alanine aminotransferase, creatinine, and uric acid levels were decreased in the MD group compared with the control group, accompanied by decreased superoxide dismutase activity, increased malondialdehyde content, decreased numbers of T and B lymphocytes, and decreased cytokine expression in the ileum, such as IL-2, IL-6, LITAF, and IFN-γ. These results suggest that MD can induce kidney and liver injury, and the injury pathway might be related to oxidative stress and intestinal immunosuppression.

BackgroundProstate cancer (PCa) is an immune-responsive disease. The current study sought to explore a robust immune-related prognostic gene signature for PCa.MethodsData were retrieved from the tumor Genome Atlas (TCGA) database and GSE46602 database for performing the least absolute shrinkage and selection operator (LASSO) cox regression model analysis. Immune related genes (IRGs) data were retrieved from ImmPort database.ResultsThe weighted gene co-expression network analysis (WGCNA) showed that nine functional modules are correlated with the biochemical recurrence of PCa, including 259 IRGs. Univariate regression analysis and survival analysis identified 35 IRGs correlated with the prognosis of PCa. LASSO Cox regression model analysis was used to construct a risk prognosis model comprising 18 IRGs. Multivariate regression analysis showed that risk score was an independent predictor of the prognosis of PCa. A nomogram comprising a combination of this model and other clinical features showed good prediction accuracy in predicting the prognosis of PCa. Further analysis showed that different risk groups harbored different gene mutations, differential transcriptome expression and different immune infiltration levels. Patients in the high-risk group exhibited more gene mutations compared with those in the low-risk group. Patients in the high-risk groups showed high-frequency mutations in TP53. Immune infiltration analysis showed that M2 macrophages were significantly enriched in the high-risk group implying that it affected prognosis of PCa patients. In addition, immunostimulatory genes were differentially expressed in the high-risk group compared with the low-risk group. BIRC5, as an immune-related gene in the prediction model, was up-regulated in 87.5% of prostate cancer tissues. Knockdown of BIRC5 can inhibit cell proliferation and migration.ConclusionIn summary, a risk prognosis model based on IGRs was developed. A nomogram comprising a combination of this model and other clinical features showed good accuracy in predicting the prognosis of PCa. This model provides a basis for personalized treatment of PCa and can help clinicians in making effective treatment decisions.

The retina is composed of 11 types of cells, including neurons, glial cells and vascular bed cells. It contains five types of neurons, each with specific physiological, morphological, and molecular definitions. Currently, single-cell RNA sequencing (sRNA-seq) is emerging as one of the most powerful tools to reveal the complexity of the retina. The continuous discovery of retina-related gene targets plays an important role in helping us understand the nature of diseases. The revelation of new cell subpopulations can focus the occurrence and development of diseases on specific biological activities of specific cells. In addition, sRNA-seq performs high-throughput sequencing analysis of epigenetics, transcriptome and genome at the single-cell level, with the advantages of high-throughput and high-resolution. In this paper, we systematically review the development history of sRNA-seq technology, and summarize the new subtypes of retinal cells and some specific gene markers discovered by this technology. The progress in the diagnosis of retinal related diseases is also discussed.

“Dual triggering” for final oocyte maturation using a combination of a gonadotropin-releasing hormone agonist (GnRHa) and human chorionic gonadotropin (hCG) can improve clinical outcomes in high responders during in vitro fertilization–intracytoplasmic sperm injection (IVF–ICSI) GnRH-antagonist cycles. However, whether this dual trigger is also beneficial to normal responders is not known. We retrospectively analyzed the data generated from 469 normal responders from 1 January to 31 December 2017. The final oocyte maturation was undertaken with a dual trigger with a GnRHa combined with hCG (n = 270) or hCG alone (n = 199). Patients were followed up for 3 years. The cumulative live-birth rate was calculated as the first live birth achieved after all cycles having an embryo transfer (cycles using fresh embryos and frozen–thawed embryos) among both groups. Women in the dual-trigger group achieved a slightly higher number of oocytes retrieved (11.24 vs. 10.24), higher number of two-pronuclear (2PN) embryos (8.37 vs. 7.67) and a higher number of embryos available (4.45 vs. 4.03). However, the cumulative live-birth rate and the all-inclusive success rate for assisted reproductive technology was similar between the two groups (54.07 vs. 59.30%). We showed that a dual trigger was not superior to a hCG-alone trigger for normal responders in GnRH-antagonist cycles in terms of the cumulative live-birth rate.

Background: Hypoxia is a common phenomenon in solid tumors, which plays an important role in tumor proliferation, apoptosis, angiogenesis, invasion and metastasis, energy metabolism and chemoradiotherapy resistance. However, comprehensive analysis of hypoxia markers in colorectal adenocarcinoma (COAD) is still lacking. And there is a need for mechanism exploration and clinical application.Methods: The gene expression, mutation and clinical data of COAD were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, respectively. Tumor samples from TCGA were randomly divided into the training and internal validation groups, while tumor samples from GEO were used as the external validation group. Univariate COX—LASSO—multivariate COX method was applied to construct the prognostic model. We clustered all TCGA tumor samples into high, medium and low hypoxia groups, evaluated the correlation between hypoxia degree and immunoactivity, and explored the combined effect of mutation for common target genes and model riskscore on survival in COAD patients. Finally, we developed a dynamic nomograph App online for direct clinical application and carried out multiple validations of the prognostic model.Results: Our hypoxia-related prognostic model for COAD patients is accurate and has been successfully validated internally and externally. Single Sample Gene Set Enrichment Analysis (ssGSEA) and Gene Set Enrichment Analysis (GSEA) results suggest that for COAD patients with higher hypoxia, the stronger the associated immunosuppressive activity, providing a possible mechanism for the lower survival rate. Finally, the dynamic nomograph App online enhances the clinical translational significance of the study.Conclusion: In this study, an accurate prognostic model for COAD patients was established and validated. In addition, our innovative findings include correlations between hypoxia levels and immune activity, as well as an in-depth exploration of common target gene mutations.

High glucose represents a good environment for bacterial growth on the skin, on the ocular surface (OS) and in the tears of type 2 diabetes mellitus (T2DM) patients, affecting the conjunctival bacterial community. This study aimed to investigate the OS bacterial flora of T2DM patients and healthy subjects using 16S rRNA sequencing-based bacterial identification. Among 23 healthy subjects (CON) and 31 T2DM patients, 54 eyes were examined to investigate the OS bacterial community. Factors potentially affecting the microbial growth were controlled. Results showed the OS microbiota presented higher diversity in the T2DM group than in the CON group. Bioinformatic analysis showed a lower abundance of Proteobacteria and a higher abundance of Bacteroidetes at the phyla level as well as a significantly increased abundance of Acinetobacter and Pseudomonas at the genus level in the T2DM group. The difference in OS microbiota at taxonomic level was associated with Ocular Surface Disease Index and course of T2DM. These findings indicate the OS flora in T2DM patients is significantly different from that in healthy subjects, which may be closely associated with OS discomfort and course of T2DM.

Purpose: The present study is aimed to explore whether the aqueous extract of Mori Folium (MF) exhibits bone protective effect by regulating calcium and redox homeostasis in diabetic rats, and to identify the signaling pathways involved in this process.Methods: Diabetic rats were established using high-sugar and high-fat diet and streptozotocin (STZ) (30 mg/kg for 3 consecutive days). The serum levels of osteocalcin (OC), insulin-like growth factor-1 (IGF-1), tartrate-resistant acid phosphatase (TRAP), phosphorus (P), calcium (Ca), 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], parathormone (PTH), advanced glycation end products (AGEs), superoxide dismutase (SOD), and malondialdehyde (MDA), total antioxidant capacity (TAC), 8-hydroxy-2′-deoxyguanosine (8-OH-dG), and interleukin 6 (IL-6) were determined by ELISA or biochemical assays. Histopathological alterations in the femurs were evaluated by the stainings of hematoxylin-eosin (H&E) and alizarin red S. In addition, femoral strength was detected by a three-point bending assay, bone microstructure was detected with micro-computer tomography. Bone material properties were examined by Fourier-transform infrared spectroscopy. Furthermore, the expressions of IGF-1, runt-related transcription factor 2 (Runx2), osteoprotegerin (OPG), receptor activator of nuclear factor kappa-B ligand (RANKL), cathepsin K, AGEs, receptor of advanced glycation end products (RAGE), NADPH oxidase 4 (Nox4), and nuclear factor kappa-B (NF-κB) in the femurs and tibias, and the alterations in the levels of calcium-binding protein-28k (CaBP-28k), transient receptor potential V6 (TRPV6), and vitamin D receptor (VDR) in the kidneys and duodenums were determined by western blot and immunohistochemical analysis.Results: Treatment of diabetic rats with MF aqueous extract induces an increase in the levels of OC and IGF-1 as well as a decrease in TRAP level in serum. MF treatment also upregulates the expression of OPG, downregulates the expressions of AGEs, RAGE, Nox4, NF-κB, and RANKL, which leads to improve bone microstructure and strength exhibited by an increase in cortical area ratio, cortical thickness, and trabecular area ratio as well as ultimate load, elastic modulus, and bending stress in the femurs and tibias of diabetic rats. In addition, MF aqueous extract preserves bone material properties by decreasing the ratio of fatty acid/collagen and increasing the ratio of mineral/matrix in the femurs of diabetic rats. Moreover, MF treatment increases the levels of P, Ca, and 1,25(OH)2D3, and decreases the level of PTH in the serum, as well as upregulates the expressions of TRPV6 and VDR in the duodenums and CaBP-28k in the kidneys of diabetic rats. Additionally, MF has ability of rebuilding redox homeostasis and eliminating inflammatory stress by increasing the levels of SOD and TAC as well as decreasing the levels of IL-6, AGEs, MDA, and 8-OH-dG.Conclusions: MF treatment may improve bone quality through maintenance of calcium homeostasis via regulating the PTH/VDR/CaBP signaling, and elimination of oxidative stress via regulating the AGEs/RAGE/Nox4/NF-κB signaling. These results may suggest the potential of MF in preventing the development of diabetic osteoporosis.

A novel hepta-segmented double-stranded RNA (dsRNA) virus was isolated and characterized from the strain FJ-4 of the phytopathogenic fungus Colletotrichum fructicola, and was named Colletotrichum fructicola chrysovirus 1 (CfCV1). The full-length cDNAs of dsRNA1–7 were 3620, 2801, 2687, 2437, 1750, 1536, and 1211 bp, respectively. The 5′- and 3′-untranslated regions of the seven dsRNAs share highly similar internal sequence and contain conserved sequence stretches, indicating that they have a common virus origin. The 5′-and 3′-UTRs of the seven dsRNAs were predicted to fold into stable stem-loop structures. CfCV1 contains spherical virions that are 35 nm in diameter consisting of seven segments. The largest dsRNA of CfCV1 encodes an RNA-dependent RNA polymerase (RdRp), and the second dsRNA encodes a viral capsid protein (CP). The dsRNA5 encodes a C2H2-type zinc finger protein containing an R-rich region and a G-rich region. The smallest dsRNA is a satellite-like RNA. The functions of the other proteins encoded by dsRNA3, dsRNA4, dsRNA6 are unknown. Phylogenetic analysis, based on RdRp and CP, indicated that CfCV1 is phylogenetically related to Botryosphaeria dothidea chrysovirus 1 (BdCV1), and Penicillium janczewskii chrysovirus 2 (PjCV2), a cluster of an independent cluster II group in the family Chrysoviridae. Importantly, all the seven segments of CfCV1 were transmitted successfully to other virus-free strains with an all-or-none fashion. CfCV1 exerts minor influence on the growth of C. fructicola but can confer hypovirulence to the fungal host. To our knowledge, this is the first report of a hepta-segmented tentative chrysovirus in C. fructicola.

Alzheimer’s disease (AD) is a chronic neurodegenerative disease leading to dementia, which is characterized by progressive memory loss and other cognitive dysfunctions. Recent studies have attested that noninvasive repetitive transcranial magnetic stimulation (rTMS) may help improve cognitive function in patients with AD. However, the majority of these studies have focused on the effects of high-frequency rTMS on cognitive function, and little is known about low-frequency rTMS in AD treatment. Furthermore, the potential mechanisms of rTMS on the improvement of learning and memory also remain poorly understood. In the present study, we reported that severe deficits in spatial learning and memory were observed in APP23/PS45 double transgenic mice, a well known mouse model of AD. Furthermore, these behavioral changes were accompanied by the impairment of long-term potentiation (LTP) in the CA1 region of hippocampus, a brain region vital to spatial learning and memory. More importantly, 2-week low-frequency rTMS treatment markedly reversed the impairment of spatial learning and memory as well as hippocampal CA1 LTP. In addition, low-frequency rTMS dramatically reduced amyloid-β precursor protein (APP) and its C-terminal fragments (CTFs) including C99 and C89, as well as β-site APP-cleaving enzyme 1 (BACE1) in the hippocampus. These results indicate that low-frequency rTMS noninvasively and effectively ameliorates cognitive and synaptic functions in a mouse model of AD, and the potential mechanisms may be attributed to rTMS-induced reduction in Aβ neuropathology.

Purpose: This study is designed to explore whether Fructus ligustri lucidi (FLL) exhibits antioxidant effect in ovariectomized (OVX) rats, and to identify the signaling pathway involved in this process.Methods: OVX rats were treated with FLL aqueous extract (3.5 g/kg) for 12 weeks. Serum, uteri, and tibias were harvested from the rats and the levels of total antioxidant capacity (TAC), nitric oxide (NO), malondialdehyde (MDA), 8-hydroxy-desoxyguanosine (8-OHdG), and superoxide dismutase (SOD) were determined. Changes in the levels of NF-κB-p65, phosphorylation of NF-κB-p65 (NF-κB-pp65), NF-κB inhibitor alpha (IκBα), phosphorylation of IκBα (p-IκBα), and NADPH oxidase 4 (Nox4) in uteri and tibias were determined by western blot, immunofluorescent and immunohistochemical analysis, respectively. In addition, the expression of cytochrome C (Cyto-C) and B-cell lymphoma-2 (Bcl-2) were determined in the tibias of rats. Histopathological changes in the bones were evaluated by hematoxylin-eosin staining. Bone mineral density (BMD) was determined in rat femurs by dual X-ray absorptiometry.Results: Treatment of OVX rats with FLL aqueous extract improved redox homeostasis by increasing the levels of TAC and NO as well as decreasing the levels of MDA and 8-OHdG in serum, tibias, and uteri. Further, FLL extract also downregulated the expression of Nox4, NF-κB-p65, NF-κB-pp65, and p-IκBα in the uteri and tibias. Furthermore, administration of FLL–OVX rats increased Bcl-2 expression and prevented cytoplasmic release of mitochondrial Cyto-C in the tibias. In addition, FLL treatment also improved bone microstructure and increased cortical bone thickness as well as increased BMD values in the femurs of OVX rats.Conclusions: FLL treatment may suppress oxidative stress response in OVX rats via regulating the Nox4/ROS/NF-κB signaling pathway. These results suggest the potential of using FLL as a natural antioxidant agent in preventing the development of osteoporosis.

Introduction: Off-season upsurge of respiratory syncytial virus (RSV) infection with changed characteristics and heightened clinical severity during the postCOVID-19 era are raising serious concerns. This study aimed to develop and validate a nomogram for predicting the risk of severe acute lower respiratory tract infection (SALRTI) in children hospitalized for RSV infection during the postCOVID-19 era using machine learning techniques. Methods: A multicenter retrospective study was performed in nine tertiary hospitals in Yunnan, China, enrolling children hospitalized for RSV infection at seven of the nine participating hospitals during January–December 2023 into the development dataset. Thirty-nine variables covering demographic, clinical, and laboratory characteristics were collected. Primary screening and dimension reduction of data were performed using Least Absolute Shrinkage and Selection Operator (LASSO) regression, followed by identification of independent risk factors for RSV-associated SALRTI using Logistic regression, thus finally establishing a predictive nomogram model. Performance of the nomogram was internally evaluated by receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) based on the development dataset. External validation of our model was conducted using same methods based on two independent RSV cohorts comprising pediatric RSV inpatients from another two participating hospitals between January– March 2024. Results: The development dataset included 1102 patients, 239 (21.7%) of whom developed SALRTI; while the external validation dataset included 249 patients (142 in Lincang subset and 107 in Dali subset), 58 (23.3%) of whom were diagnosed as SALRTI. Nine variables, including age, preterm birth, underlying condition, seizures, neutrophil-lymphocyte ratio (NLR), interleukin-6 (IL-6), lactate dehydrogenase (LDH), D-dimer, and co-infection, were eventually confirmed as the independent risk factors of RSV-associated SALRTI. A predictive nomogram was established via integrating these nine predictors. In both internal and external validations, ROC curves indicated that the nomogram had satisfactory discrimination ability, calibration curves demonstrated good agreement between the nomogram-predicted and observed probabilities of outcome, and DCA showed that the nomogram possessed favorable clinical application potential. Conclusion: A novel nomogram combining several common clinical and inflammatory indicators was successfully developed to predict RSV-associated SALRTI. Good performance and clinical effectiveness of this model were confirmed by internal and external validations. [ABSTRACT FROM AUTHOR]

Antiepileptic drugs frequently cause cutaneous adverse reactions (cADRs). Numerous studies have reported associations between human leukocyte antigen (HLA) alleles and cADRs caused by single antiepileptic drug in Southern Han Chinese people. However, the relationship between the HLA allele and cADRs sequentially induced by two or more antiepileptic drugs (AEDs-induced cross-reactivity) is unclear. To explore the associations between HLA alleles and AEDs-induced cross-reactivity, we prospectively recruited patients with AEDs-induced cross-reactivity from 2009 to 2017 and performed high-resolution genotyping to detect the HLA-A, B, C, and DRB1 alleles in patients for comparison with normal controls. To verify the important genotype, we compared its presence in patients with cross-reactivity to enlarged normal controls, and its presence in patients with carbamazepine (CBZ)-induced maculopapular exanthema (MPE) to CBZ-tolerant controls. Further, the important allele was replicated by meta-analysis. Twenty-three patients with AED-induced cross-reactivity and 500 healthy individuals were enrolled from Southern China. All patients had a mild rash without mucosal or systemic involvement. The HLA-B*13:01 allele was present in 34.78% (8/23) of patients, 14.60% (73/500) of healthy individuals, and 14.5% (763/5,270) healthy individuals, revealing a significant association (8/23 vs. 73/500; P = 0.02; OR: 3.12; 95% CI: 1.28–7.62; 8/23 vs. 763/5,270; P = 0.014; OR: 3.15; 95% CI: 1.33–7.46). HLA-B*13:01 was presented numerically higher in CBZ-induced MPE than that in CBZ-tolerant individuals without statistical significance (33/145, 22.76%, vs. 28/179, 15.64%; P = 0.103). Meta-analysis revealed an association between HLA-B*13:01 and cADRs induced by single AEDs or/and non-AEDs in Chinese and Thai populations (P = 0.000). This study suggests that HLA-B*13:01 is potentially associated with AED-cADRs in general, possibly with stronger effect in cross-reactivity. Screening for HLA-B*13:01 prior to starting AEDs therapy may help to avoid cADRs. However, this association requires further analysis in a multi-center study with a larger sample size. [ABSTRACT FROM AUTHOR]

When plants are pre-exposed to stress, they can produce some stable signals and physiological reactions that may be carried forward as “stress memory”. However, there is insufficient information about plants’ stress memory responses mechanisms. Here, two tall fescue genotypes, heat-tolerant PI 574522 and heat-sensitive PI 512315, were subjected to recurring high-temperature pre-acclimation treatment. Two heat shock protein (HSP) genes, LMW-HSP and HMW-HSP, exhibited transcriptional memory for their higher transcript abundance during one or more subsequent stresses (S2, S3, S4) relative to the first stress (S1), and basal transcript levels during the recovery states (R1, R2, and R3). Activated transcriptional memory from two trainable genes could persist up to 4 days, and induce higher thermotolerance in tall fescue. This was confirmed by greater turf quality and lower electrolyte leakage. Pre-acclimation treatment inhibited the decline at steps of O-J-I-P and energy transport fluxes in active Photosystem II reaction center (PSII RC) for both tall fescue genotypes. The heat stress memory was associated with major shifts in leaf metabolite profiles. Furthermore, there was an exclusive increase in leaf organic acids (citric acid, malic acid, tris phosphoric acid, threonic acid), sugars (sucrose, glucose, idose, allose, talose, glucoheptose, tagatose, psicose), amino acids (serine, proline, pyroglutamic acid, glycine, alanine), and one fatty acid (butanoic acid) in pre-acclimated plants. These observations involved in transcriptional memory, PSII RC energy transport and metabolite profiles could provide new insights into the plant high–temperature response process. [ABSTRACT FROM AUTHOR]

BackgroundThe SARS-CoV-2 Omicron variant was reported to be linked to febrile seizures (FSs), but studies on FSs in children with Omicron infection remain relatively scarce, especially in the Chinese population. This study aimed to investigate the characteristics of children diagnosed with Omicron infection with FSs in Yunnan, China, and evaluate the potential association between FSs and Omicron infection.MethodsThis study was conducted at four hospitals in Yunnan from December 8, 2022, to January 8, 2023, and consisted of 590 pediatric subjects. According to clinical characteristics, 85, 129 and 376 subjects were divided into the FS-only, Omicron-FS, and Omicron-only groups, respectively. Demographic, clinical and laboratory data were retrospectively collected for analysis.ResultsThe incidence of FSs in children with Omicron infection was 25.5% (129/505). Older age, stronger male predominance, as well as lower proportions of prior history and family history of seizures were observed in Omicron-FS and Omicron-only groups than in FS-only group, but there were no differences in these four above-mentioned events between these two Omicron-related groups. Compared to FS-only group, Omicron-FS group also had a shorter fever-to-seizure onset duration and more frequent seizures during a single course of fever. Moreover, higher levels of IL-6, TNF-α and ferritin as well as decreased counts of leukocytes and lymphocytes were confirmed in Omicron-FS group than in FS-only and Omicron-only groups. Regarding COVID-19 vaccination status, Omicron-FS group revealed a higher proportion of unvaccinated children and a lower proportion of three-dose vaccination than Omicron-only group. As for clinical outcomes, proportions of mechanical ventilation and intensive care unit admission observed in the two Omicron-related groups were notably higher than those in FS-only group. Meanwhile, Omicron-FS group showed the longest length of hospital stay, followed by Omicron-only group and FS-only group, in order. Finally, all patients but one who died of fulminant myocarditis had been successfully discharged.ConclusionsThe incidence of FSs in children with Omicron infection was 25.5% in Yunnan. FSs might be a clinical sign deserving more attention in children with Omicron infection. Furthermore, COVID-19 vaccination is likely to provide effective protection against Omicron-related FSs in children.

Background: Peripheral biomarkers may be affected by various factors, their reliability in reflecting local cardiac inflammatory status in patients with atrial fibrillation (AF) needs further exploration. This prospective study was aimed to investigate the relationship between circulating biomarkers and local cardiac inflammation measured by epicardial adipose tissue (EAT) activity via18F-fluorodeoxyglucose (FDG) imaging in AF patients.Methods: From 2017 to 2018, 83 AF patients [43 persistent AF (PsAF) and 40 paroxysmal AF (PAF)] referred for radiofrequency catheter ablation (RFCA) were recruited. Pre- and post-RFCA blood samples were collected to measure IL-6, IL-8, IL-10, IL-18, TNF-α, Hsp27, Hsp60, Hsp70, PDGF-BB, MMP-2, MMP-9, MPO, TGF-β1, Gal-3, and sST2. Pre-RFCA FDG images were obtained to assess EAT activity. Sixty-seven patients (35 PAF and 32 PsAF) received RFCA were regularly followed for 27 (24, 29) months.Results: Higher hsCRP and IL-6 and lower TGF-β1 were demonstrated in PsAF patients compared with PAF patients. Multivariate logistic regression analysis demonstrated that Gal-3 (OR: 1.221, 95% CI: 1.024–1.456, P = 0.026) and MPO (OR: 1.002, 95% CI: 1.001–1.003, P = 0.027) were independently correlated with EAT activity. The percentage decrease of Hsp60 linearly correlated with that of EAT activity post-RFCA (Spearman rs = 0.455, P = 0.019). Seventeen patients (10 PsAF and 7 PAF) had AF recurrence, but none of the selected biomarkers were predictive of post-RFCA recurrence.Conclusion: Our findings demonstrated that in patients with AF, Gal-3 correlated with local cardiac inflammation, and Hsp60 was associated with the alleviation of cardiac inflammation after RFCA.