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Abstract Background and purpose Ir192 vaginal brachytherapy (IBT) is commonly used for patients with postoperative endometrial cancer (EC). We devised a novel multichannel vaginal applicator that could be equipped with an electronic brachytherapy (EBT) device. We aimed to explore the differences in physical parameters between the EBT and IBT. Materials and methods This retrospective study included 20 EC patients who received adjuvant IBT from March 1, 2023, to May 1, 2023. Multichannel vaginal cylinders were used, and three-dimensional plans were generated. We designed an electronic multichannel vaginal applicator model and simulated a three-dimensional EBT plan. In order to ensure comparability, D90 of the CTV for the EBT plan was normalized to be equivalent to that of the IBT plan for the same patient. Results Twenty EBT plans were compared with 20 IBT plans. Results showed, the mean D90 value of clinical target volume (CTV) was 536.1 cGy for both treatment plans. For the mean dose of CTV, the EBT was significantly greater (738.3 vs. 684.3 cGy, p = 0.000). There was no significant difference in CTV coverage between the EBT and IBT plans. For high-dose areas (V200% and V150%), the EBTs were significantly greater. There were no significant differences in the maximum doses to the vaginal mucosa between the EBT and IBT, whether at the apex or in the middle segment. For the bladder and rectum, both the low-dose area and high-dose area were significantly lower in the EBT plans. For the conformity index, there was no significant difference between the EBT and IBT plans. For the dose homogeneity index, the EBT value was lower. Conclusion In conclusion, under the premise of a three-dimensional brachytherapy plan, for patients receiving multichannel vaginal applicator brachytherapy, compared with IBT, EBT could reduce the dose to the surrounding organs at risk while maintaining the dose in the target area.

Background Bronchial asthma (asthma) is the most common chronic respiratory disease in childhood, with long disease course and repeated attacks, which affecting the development and life quality of children. As the main providers of primary healthcare, general practitioners play important role in the early diagnosis and grading management of childhood asthma. Understanding their level of prevention and treatment services for this disease can provide suggestions for improving the quality of primary care childhood asthma prevention and treatment services. Objective To investigate the service level of primary general practitioners in the prevention and treatment of childhood asthma, and the influencing factors on the service level. Methods From April to July 2022, 22 districts (counties) were randomly selected from the 38 districts (counties) in Chongqing Municipality, and conducted a questionnaire survey on primary general practitioners in the sampling. The questionnaire was designed by the research team based on relevant guidelines and literatures, and formed through two rounds of expert consultation and pre-investigation, including four dimensions of knowledge, attitude, behavior and self-evaluation. We investigated the knowledge, attitude, behavior and self-evaluation of primary general practitioners regarding the prevention and treatment of childhood asthma and analyzed the influencing factors. Results A total of 234 general practitioners participated in the questionnaire survey. The knowledge score of general practitioners on the prevention and treatment of childhood asthma was (6.03±2.04) , with a pass rate of 44.9%; the attitude score was (49.42±4.94) , with a pass rate of 100.0%; the behavior score was (30.55±6.66) , with a pass rate of 87.2%; and the self-evaluation score was (21.57±5.30) , with a pass rate of 85.0%. Regarding the selection of referral indications, 98.7% (231/234) of the general practitioners believed that children with moderate or severe acute asthma attack that was not significantly relieved after emergency treatment needed to be referred, and 94.0% (220/234) of the general practitioners believed that children with asthma that could not be controlled effectively after standardized treatment needed to be referred. For children with poorly controlled symptoms, 33.8% (79/234) of the general practitioners would carefully analyze the cause of poor control, and 17.5% (41/234) of the general practitioners would advise patients to follow the doctor's advice, temporarily observe the condition and make an appointment for next reexamination. 33.8% (79/234) of the general practitioners held an uncertain or opposed attitude towards the diagnosis and treatment of childhood asthma in primary medical institutions. The main influencing factors of this attitude was the lack of disease-related knowledge and learning opportunities for general practitioners, reluctance of parents to visit primary medical institutions, strained pediatric doctor-patient relationship, the small number of children suffering from asthma, and the lack of related facilities and equipment. Multiple linear regression analysis showed that professional title and training experience on childhood asthma were the influencing factors of knowledge score (P

Non-darcy seepage through layered porous media is common in soil-groundwater systems under the influence of human activities. The effect of average particle size and coarse-fine particle interface on the characteristics of non-Darcy porous flow through layered porous media was investigated from the relation between hydraulic gradient and flow velocity, non-Darcy seepage parameters, and critical Reynolds number. The results show that when water flows through layered porous media, the coarse-fine particle interface has an important effect on the characteristics of non-Darcy flow. The critical Reynolds number, which is used to judge the transition from Darcy flow to non-Darcy flow, decreases with the increase of the average particle size in monolayer porous media, but increases with the increase of the average particle size and the decrease of the coarse/fine particle size ratio when water flows through layered porous media. The critical Reynolds number of single-layer porous media is lower than that of the double-layer porous media with the same corresponding particle size due to the coarse-fine particle interface. By introducing the nonlinear component index E, it is found that the coarse/fine particle interface has a certain inhibitory effect on the hydrodynamic inertia force component, and the inhibitory effect degree is negatively correlated with the difference in size of the coarse and fine particles. The results in this study have a good guiding significance for studying non-Darcy seepage through layered rock and soil.

Abstract Background Our study aims to explore the relationship, shared gene signature, and the underlying mechanisms that connect rheumatoid arthritis (RA) to colorectal cancer (CRC). Methods Mendelian randomization (MR) analysis was conducted to assess the causality between RA and CRC. Summary statistic data-based Mendelian randomization (SMR) leveraging eQTL data was employed to identify the CRC-related causal genes. Integrated analyses of single-cell RNA sequencing and bulk RNA sequencing were employed to comprehensively investigate the shared gene signature and potential mechanisms underlying the pathogenesis of both RA and CRC. Predictive analysis of the shared hub gene in CRC immunotherapy response was performed. Pan-cancer analyses were conducted to explore the potential role of MYO9A in 33 types of human tumors. Results MR analysis suggested that RA might be associated with a slight increased risk of CRC (Odds Ratio = 1.04, 95% Confidence Interval = 1.01–1.07, P = 0.005). SMR analysis combining transcriptome analyses identified MYO9A as a causal gene in CRC and a shared gene signature in both RA and CRC. MYO9A may contribute to tumor suppression, while downregulation of MYO9A may impact CRC tumorigenesis by disrupting epithelial polarity and architecture, resulting in a worse prognosis in CRC. Additionally, MYO9A shows promise as a powerful predictive biomarker for cancer prognosis and immunotherapy response in CRC. Pan-cancer analyses demonstrated MYO9A may have a protective role in the occurrence and progression of various human cancers. Conclusion RA might be associated with a slight increased risk of CRC. MYO9A is a shared gene signature and a potential immune-related therapeutic target for both CRC and RA. Targeting the MYO9A-mediated loss of polarity and epithelial architecture could be a novel therapeutic approach for CRC.

Abstract With triboelectric nanogenerators (TENGs) introduced in 2012, they have emerged in the fields of flexible wearable electronics, portable energy, Internet of Things (IoTs), and biomedicine by virtue of their lightweight, high‐energy conversion, low cost, and material selectivity. However, as the application areas of TENGs increase, ambient humidity and human movement generate sweat and moisture that can lead to a decrease in output, so exploring how TENGs operate in high humidity environments is critical to their long‐term development. In this paper, different strategies are introduced to enhance TENGs in high humidity environments, such as encapsulation, construction of hydrophobic/superhydrophobic surfaces, and hydrogen bonding enhancement, and discuss the applications of humidity‐resistant TENGs in fields such as self‐powered sensors, energy harvesters, and motions, and so forth. Finally, we explore the future directions and routes for the development of humidity‐resistant TENGs.

Clinical studies have shown that epileptic seizures worsen Alzheimer’s disease (AD) pathology and related cognitive deficits; however, the underlying mechanism is unclear. To assess the effects of seizures on the progression of AD, chronic temporal lobe epilepsy was induced in five familial AD mutation (5×FAD) mice by kindling with the chemoconvulsant pentylenetetrazole (PTZ) at 3–3.5 months of age. The amyloidogenic pathway, tauopathy, synaptic damage, neuronal death, neurological inflammatory response and associated kinase signaling pathway dysregulation were examined at 9 months of age. We found that APP, p-APP, BACE1, Aβ and kinase-associated p-tau levels were elevated after PTZ kindling in 5×FAD mice. In addition, PTZ kindling exacerbated hippocampal synaptic damage and neuronal cell death, as determined by scanning electron microscopy and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining, respectively. Finally, the levels of the neuroinflammation markers GFAP and Iba1, as well as the inflammatory cytokine IL-1β, were increased after PTZ insult. PTZ kindling profoundly exacerbated extracellular regulated kinase (ERK)-death-associated protein kinase (DAPK) signaling pathway overactivation, and acute ERK inhibitor treatment downregulated Aβ production and p-APP and p-tau levels in epileptic 5×FAD mice. In addition, long-term use of the antiseizure drug carbamazepine (CBZ) alleviated seizure-induced accelerated amyloid and tau pathology and ERK-DAPK overactivation in 5×FAD mice. Collectively, these results demonstrate that seizure-induced increases in AD-like neuropathology in 5×FAD mice are partially regulated by the ERK-DAPK pathway, suggesting that the ERK-DAPK axis could be a new therapeutic target for the treatment of AD patients with comorbid seizures.

ABSTRACT: Brevibacillus laterosporus S62-9 has been shown to improve broiler growth performance and immunity. In the present study, we aimed to evaluate the effects of B. laterosporus S62-9 on the immunity and lipid metabolism of broilers by means of transcriptomic analysis. A total of 160 1-day-old broilers were randomly allocated to a S62-9 group, the diet of which was supplemented with 106 CFU/g B. laterosporus S62-9 daily, and a control group, which was not. After 42 d of feeding, the broilers in the S62-9 group had higher body mass (7.2%) and feed conversion ratio (5.19%) than the control group. Supplementation with B. laterosporus S62-9 resulted in lower serum total cholesterol and low-density lipoprotein-cholesterol concentrations and higher high-density lipoprotein-cholesterol concentrations. An analysis of the fatty acid composition of the broiler's thigh muscles revealed that the proportions of the unsaturated fatty acids myristoleic acid (C14:1) and arachidonic acid (C20:1) were higher for birds in the S62-9 group. Transcriptomic analysis also showed an upregulation of immunity-related genes in the S62-9 group. Gene Ontology functional enrichment analysis showed that the mitogen-activated protein kinase pathway was enriched in the liver, the defense response was enriched in the duodenum, and immunoglobulin-related entries were enriched in the jejunum of the S62-9 group. Furthermore, the expression of key genes involved in unsaturated fatty acid synthesis (SCD, encoding stearoyl-CoA desaturase) and fatty acid metabolism (HACD2, encoding 3-hydroxyacyl-CoA dehydratase 2) was upregulated in the liver, and the expression of genes associated with fat biosynthesis and accumulation, such as PLIN1, encoding perilipin 1, and FABP4, encoding fatty acid binding protein 4, was upregulated in the ileum of the birds in the S62-9 group. In summary, supplementation with B. laterosporus S62-9 could improve immune defense and the fatty acid metabolism of broiler chickens, thereby enhancing their disease resistance and promoting growth and development.

Objective: Glucocorticoid-induced osteoporosis (GIOP) represents a major complication arising from the long-term use of glucocorticoids, which are widely prescribed for various inflammatory and autoimmune conditions. Despite its prevalence, the current therapeutic options for GIOP are limited in terms of efficacy, safety profiles, and patient compliance. The Modified Danggui Buxue Decoction (DGBXD), a traditional Chinese herbal formulation, has shown promise in preliminary studies for its potential osteoprotective effects. The present study aimed to explore the mechanistic underpinnings of DGBXD's action on GIOP using network pharmacology and molecular docking approaches, bridging traditional medicine with modern pharmacological insights. Method: Network pharmacology is applied to screen drug-active compounds and potential core target proteins for disease treatment and to explore the drugs’ therapeutic mechanisms. Result: Altogether, 78 DGBXD active compounds and 223 DGBXD-related, 146 component-disease common, and 2168 GIOP-associated target genes were obtained. The PPI network had 43 nodes and 462 edges, and a total of 10 core target genes, including TP53, JUN and MAPK3, were identified. The results of the GO enrichment analysis implied that DGBXD might participate in biological activities, including responses to oxidative stress and nutrient levels. The outcomes of the KEGG pathway enrichment analysis showed that DGBXD may treat GIOP through TNF, IL-17, and phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathways. Based on to the molecular docking results, biologically active compounds (beta-carotene, formononetin, luteolin, and isorhamnetin) exhibited good binding to AKT1 and ESR1. Conclusion: DGBXD may aid in GIOP treatment by modulating multiple therapeutic targets and signaling pathways.

Recurrent spontaneous abortion refers to the occurrence of two or more spontaneous abortions before or during the early stages of pregnancy. The immune system plays a crucial role in the maintenance of pregnancy and embryo implantation. Various immune cells, cytokines, and immune regulatory pathways are involved in the complex immune balance required for a stable pregnancy. Studies suggest that immune abnormalities may be associated with some recurrent spontaneous abortion cases, particularly those involving the dysregulation of immune cell function, autoimmune responses, and placental immunity. In terms of treatment, interventions targeting immune mechanisms are crucial. Various therapeutic approaches, including immunomodulatory drugs, immunoadsorption therapies, and immunocellular therapies, are continually being researched and developed. These approaches aim to restore the immune balance, enhance the success rate of pregnancies, and provide more effective treatment options for patients with recurrent spontaneous abortion.

IntroductionHuman cytomegalovirus (HCMV) is the most common viral infection seen in newborns. The major route of transmission for acquired human cytomegalovirus infection is breast milk from mothers who are HCMV seropositive to the infants. Thus, a rapid, economical, and simple method to perform HCMV test in breast milk is crucial and necessary for preventing acquired HCMV infection, especially in underdeveloped regions with limited laboratory resources.MethodsIn this study, an effective technique for the detection of HCMV was constructed by combining multienzyme isothermal rapid amplification (MIRA) and lateral flow chromatography strip (LFD). Primers for the conserved HCMV sequence UL83 were utilized for MIRA-LFD testing.ResultsOur results showed that the entire MIRA reaction could be completed in 12 minutes at 37°C, and LFD outcomes could be observed visibly after 10 minutes. The detection sensitivity of this method reached 50 copy/μl. Samples of breast milk were examined to compare MIRA-LFD and conventional qPCR. The accuracy of MIRA-LFD was 100%.DiscussionThe straightforward, rapid, economic features of the test can provide the significant advantages for the prevention of breast milk-acquired cytomegalovirus infection, particularly in resource-limited locations with high seroprevalence of cytomegalovirus.

BackgroundRetroperitoneal lymphatic malformations (LMs) are rare. Currently, the treatment of retroperitoneal LMs remains challenging. This study aimed to examine the safety and efficacy of laparoscopic-assisted sclerotherapy for retroperitoneal LMs in pediatric patients.MethodsWe retrospectively reviewed patients treated with laparoscopic-assisted sclerotherapy for retroperitoneal LMs in a single tertiary medical center between July 2020 and February 2023. Doxycycline was prepared into a solution with a concentration of 10 mg/ml for use in sclerotherapy. Demographic data, clinical features, details of management, and outcomes were collected and analyzed.ResultsA total of six patients, comprising three males and three females, were identified. The LMs were categorized into four macrocystic and two mixed-cystic types. The mean age and weight were 52.2 months (range, 11–108 months) and 20 kg (range, 12.5–27.5 kg), respectively. Three patients presented with abdominal pain or distension, while the other three patients were asymptomatic. All six patients underwent a total of eight sclerotherapy sessions. Two patients experienced intra-cystic hemorrhage and required a second sclerotherapy session. Only one patient presented with vomiting after sclerotherapy, which resolved spontaneously. Five patients met the complete response criteria, and one patient met the effective criteria. The mean reduction in lesion size was 92.3% (range, 69.9%–99.6%). No further complications or recurrence were recorded during follow-up.ConclusionLaparoscopic-assisted sclerotherapy is a safe and effective approach for treating retroperitoneal LMs. This technique is applicable for both macrocystic and mixed-cystic retroperitoneal LMs.

Abstract Lysosome, the digestive organelle in eukaryotic cells, plays an important role in the degradation and recirculation of cellular products as well as in maintaining the stability of cellular metabolic microenvironment. Surface‐enhanced Raman scattering (SERS) is a molecular fingerprint technology with high detection sensitivity and photostability, suited for revealing various intracellular molecular information by inducing endocytosis of SERS‐active nanoparticles. However, it remains challenging to selectively extract the molecular information of specific organelles (e.g., lysosomes) from a high‐dimensional spectral set. Herein, we proposed a novel paradigm by combining label‐free SERS spectroscopy with confocal fluorescence imaging to investigate the digestion behavior of lysosomes in cells. The structural similarity algorithm was innovatively introduced and exhibited its effectiveness in screening out the wavenumbers in the SERS spectral set with high correlation with the metabolic behaviors of lysosomes. With comprehensive experiments on HeLa single cells, we captured the intracellular macromolecular digestion phenomenon and discovered the changing pattern of cellular SERS spectra after starvation‐induced autophagy, and analyzed the molecular information within the lysosomes in three‐dimensional space.

Abstract White adipose tissue is not only a highly heterogeneous organ containing various cells, such as adipocytes, adipose stem and progenitor cells, and immune cells, but also an endocrine organ that is highly important for regulating metabolic and immune homeostasis. In individuals with obesity, dynamic cellular changes in adipose tissue result in phenotypic switching and adipose tissue dysfunction, including pathological expansion, WAT fibrosis, immune cell infiltration, endoplasmic reticulum stress, and ectopic lipid accumulation, ultimately leading to chronic low‐grade inflammation and insulin resistance. Recently, many distinct subpopulations of adipose tissue have been identified, providing new insights into the potential mechanisms of adipose dysfunction in individuals with obesity. Therefore, targeting white adipose tissue as a therapeutic agent for treating obesity and obesity‐related metabolic diseases is of great scientific interest. Here, we provide an overview of white adipose tissue remodeling in individuals with obesity including cellular changes and discuss the underlying regulatory mechanisms of white adipose tissue metabolic dysfunction. Currently, various studies have uncovered promising targets and strategies for obesity treatment. We also outline the potential therapeutic signaling pathways of targeting adipose tissue and summarize existing therapeutic strategies for antiobesity treatment including pharmacological approaches, lifestyle interventions, and novel therapies.

Schizophrenia, influenced by genetic and environmental factors, may involve epigenetic alterations, notably histone modifications, in its pathogenesis. This review summarizes various histone modifications including acetylation, methylation, phosphorylation, ubiquitination, serotonylation, lactylation, palmitoylation, and dopaminylation, and their implications in schizophrenia. Current research predominantly focuses on histone acetylation and methylation, though other modifications also play significant roles. These modifications are crucial in regulating transcription through chromatin remodeling, which is vital for understanding schizophrenia's development. For instance, histone acetylation enhances transcriptional efficiency by loosening chromatin, while increased histone methyltransferase activity on H3K9 and altered histone phosphorylation, which reduces DNA affinity and destabilizes chromatin structure, are significant markers of schizophrenia.