Lactobacillus paracasei Jlus66 relieves DSS-induced ulcerative colitis in a murine model by maintaining intestinal barrier integrity, inhibiting inflammation, and improving intestinal microbiota structure.

PURPOSE: Ulcerative colitis (UC) is a serious health problem with increasing morbidity and prevalence worldwide. The pathogenesis of UC is complex, currently believed to be influenced by genetic factors, dysregulation of the host immune system, imbalance in the intestinal microbiota, and environmental factors. Currently, UC is typically managed using aminosalicylates, immunosuppressants, and biologics as adjunctive therapies, with the risk of relapse and development of drug resistance upon discontinuation. Therefore, further research into the pathogenesis of UC and exploration of potential treatment strategies are necessary to improve the quality of life for affected patients. According to previous studies, Lactobacillus paracasei Jlus66 (Jlus66) reduced inflammation and may help prevent or treat UC. METHODS: We used dextran sulfate sodium (DSS) to induce a mouse model of UC to assess the effect of Jlus66 on the progression of colitis. During the experiment, we monitored mouse body weight, food and water consumption, as well as rectal bleeding. Hematoxylin-eosin staining was performed to assess intestinal pathological damage. Protein imprinting and immunohistochemical methods were used to evaluate the protein levels of nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and tight junction (TJ) proteins in intestinal tissues. Fecal microbiota was analyzed based on partial 16S rRNA gene sequencing. RESULTS: Jlus66 supplementation reduced the degree of colon tissue damage, such as colon shortening, fecal occult blood, colon epithelial damage, and weight loss. Supplementation with Jlus66 reduced DSS-induced upregulation of cytokine levels such as TNF-α, IL-1ß, and IL-6 (p < 0.05). The NF-κB pathway and MAPK pathway were inhibited, and the expression of TJ proteins (ZO-1, Occludin, and Claudin-3) was upregulated. 16S rRNA sequencing of mouse cecal contents showed that Jlus66 effectively regulated the structure of the intestinal biota. CONCLUSION: In conclusion, these data indicate that Jlus66 can alter the intestinal biota and slow the progression of UC, providing new insights into potential therapeutic strategies for UC.

Improving the Prognostic Evaluation Precision of Hospital Outcomes for Heart Failure Using Admission Notes and Clinical Tabular Data: Multimodal Deep Learning Model.

BACKGROUND: Clinical notes contain contextualized information beyond structured data related to patients' past and current health status. OBJECTIVE: This study aimed to design a multimodal deep learning approach to improve the evaluation precision of hospital outcomes for heart failure (HF) using admission clinical notes and easily collected tabular data. METHODS: Data for the development and validation of the multimodal model were retrospectively derived from 3 open-access US databases, including the Medical Information Mart for Intensive Care III v1.4 (MIMIC-III) and MIMIC-IV v1.0, collected from a teaching hospital from 2001 to 2019, and the eICU Collaborative Research Database v1.2, collected from 208 hospitals from 2014 to 2015. The study cohorts consisted of all patients with critical HF. The clinical notes, including chief complaint, history of present illness, physical examination, medical history, and admission medication, as well as clinical variables recorded in electronic health records, were analyzed. We developed a deep learning mortality prediction model for in-hospital patients, which underwent complete internal, prospective, and external evaluation. The Integrated Gradients and SHapley Additive exPlanations (SHAP) methods were used to analyze the importance of risk factors. RESULTS: The study included 9989 (16.4%) patients in the development set, 2497 (14.1%) patients in the internal validation set, 1896 (18.3%) in the prospective validation set, and 7432 (15%) patients in the external validation set. The area under the receiver operating characteristic curve of the models was 0.838 (95% CI 0.827-0.851), 0.849 (95% CI 0.841-0.856), and 0.767 (95% CI 0.762-0.772), for the internal, prospective, and external validation sets, respectively. The area under the receiver operating characteristic curve of the multimodal model outperformed that of the unimodal models in all test sets, and tabular data contributed to higher discrimination. The medical history and physical examination were more useful than other factors in early assessments. CONCLUSIONS: The multimodal deep learning model for combining admission notes and clinical tabular data showed promising efficacy as a potentially novel method in evaluating the risk of mortality in patients with HF, providing more accurate and timely decision support.

Remodeling the immune microenvironment for gastric cancer therapy through antagonism of prostaglandin E2 receptor 4.

Gastric cancer is highly prevalent among digestive tract tumors. Due to the intricate nature of the gastric cancer immune microenvironment, there is currently no effective treatment available for advanced gastric cancer. However, there is promising potential for immunotherapy targeting the prostaglandin E2 receptor subtype 4 (EP4) in gastric cancer. In our previous study, we identified a novel small molecule EP4 receptor antagonist called YY001. Treatment with YY001 alone demonstrated a significant reduction in gastric cancer growth and inhibited tumor metastasis to the lungs in a mouse model. Furthermore, administration of YY001 stimulated a robust immune response within the tumor microenvironment, characterized by increased infiltration of antigen-presenting cells, T cells, and M1 macrophages. Additionally, our research revealed that YY001 exhibited remarkable synergistic effects when combined with the PD-1 antibody and the clinically targeted drug apatinib, rather than fluorouracil. These findings suggest that YY001 holds great promise as a potential therapeutic strategy for gastric cancer, whether used as a standalone treatment or in combination with other drugs.

Protective effect of synbiotic combination of Lactobacillus plantarum SC-5 and olive oil extract tyrosol in a murine model of ulcerative colitis.

BACKGROUND: Ulcerative colitisis (UC) classified as a form of inflammatory bowel diseases (IBD) characterized by chronic, nonspecific, and recurrent symptoms with a poor prognosis. Common clinical manifestations of UC include diarrhea, fecal bleeding, and abdominal pain. Even though anti-inflammatory drugs can help alleviate symptoms of IBD, their long-term use is limited due to potential side effects. Therefore, alternative approaches for the treatment and prevention of inflammation in UC are crucial. METHODS: This study investigated the synergistic mechanism of Lactobacillus plantarum SC-5 (SC-5) and tyrosol (TY) combination (TS) in murine colitis, specifically exploring their regulatory activity on the dextran sulfate sodium (DSS)-induced inflammatory pathways (NF-κB and MAPK) and key molecular targets (tight junction protein). The effectiveness of 1 week of treatment with SC-5, TY, or TS was evaluated in a DSS-induced colitis mice model by assessing colitis morbidity and colonic mucosal injury (n = 9). To validate these findings, fecal microbiota transplantation (FMT) was performed by inoculating DSS-treated mice with the microbiota of TS-administered mice (n = 9). RESULTS: The results demonstrated that all three treatments effectively reduced colitis morbidity and protected against DSS-induced UC. The combination treatment, TS, exhibited inhibitory effects on the DSS-induced activation of mitogen-activated protein kinase (MAPK) and negatively regulated NF-κB. Furthermore, TS maintained the integrity of the tight junction (TJ) structure by regulating the expression of zona-occludin-1 (ZO-1), Occludin, and Claudin-3 (p < 0.05). Analysis of the intestinal microbiota revealed significant differences, including a decrease in Proteus and an increase in Lactobacillus, Bifidobacterium, and Akkermansia, which supported the protective effect of TS (p < 0.05). An increase in the number of Aspergillus bacteria can cause inflammation in the intestines and lead to the formation of ulcers. Bifidobacterium and Lactobacillus can regulate the micro-ecological balance of the intestinal tract, replenish normal physiological bacteria and inhibit harmful intestinal bacteria, which can alleviate the symptoms of UC. The relative abundance of Akkermansia has been shown to be negatively associated with IBD. The FMT group exhibited alleviated colitis, excellent anti-inflammatory effects, improved colonic barrier integrity, and enrichment of bacteria such as Akkermansia (p < 0.05). These results further supported the gut microbiota-dependent mechanism of TS in ameliorating colonic inflammation. CONCLUSION: In conclusion, the TS demonstrated a remission of colitis and amelioration of colonic inflammation in a gut microbiota-dependent manner. The findings suggest that TS could be a potential natural medicine for the protection of UC health. The above results suggest that TS can be used as a potential therapeutic agent for the clinical regulation of UC.

The Inhibitory Effect of Early Pregnancy Factor on Red Meat Neu5Gc-Mediated Antibody Production in CMAH-/- Mice.

The meat derived from mammals such as cows, sheep, and pigs is commonly referred to as red meat. Recent studies have shown that consuming red meat can activate the immune system, produce antibodies, and subsequently develop into tumors and cancer. This is due to the presence of a potential carcinogenic compound in red meat called N-ethanol neuraminic acid (Neu5Gc). Neu5Gc is a common sialic monosaccharide in mammals, synthesized from N-acetylneuraminic acid (Neu5Ac) in the body and typically present in most mammals. However, due to the lack of the CMAH gene encoding the cytidine 5'-monophosphate Neu5Ac hydroxylase, humans are unable to synthesize Neu5Gc. Compared to primates such as mice or chimpanzees, the specific loss of Neu5Gc expression in humans is attributed to fixed genome mutations in CMAH. Although Neu5Gc cannot be produced, it can be introduced from specific dietary sources such as red meat and milk, so it is necessary to use mice or chimpanzees that knock out the CMAH gene instead of humans as experimental models. Further research has shown that early pregnancy factor (EPF) has the ability to regulate CD4+T cell-dependent immune responses. In this study, we established a simulated human animal model using C57/BL6 mice with CMAH gene knockout and analyzed the inhibitory effect of EPF on red meat Neu5Gc-induced CMAH-/- C57/BL6 mouse antibody production and chronic inflammation development. The results showed that the intervention of EPF reduced slow weight gain and shortened colon length in mice. In addition, EPF treatment significantly reduced the levels of anti Neu5Gc antibodies in the body, as well as the inflammatory factors IL-6 and IL-1ß, TNF-α and the activity of MPO. In addition, it also alleviated damage to liver and intestinal tissues and reduced the content of CD4 cells and the expression of B cell activation molecules CD80 and CD86 in mice. In summary, EPF effectively inhibited Neu5Gc-induced antibody production, reduced inflammation levels in mice, and alleviated Neu5Gc-induced inflammation. This will provide a new re-search concept and potential approach for developing immunosuppressants to address safety issues related to long-term consumption of red meat.

Characterization of an Aptamer Targeting Neu5Gc, as an Endogenous Pathogenic Factor Derived from Red Meat.

N-glycolylneuraminic acid (Neu5Gc), a sialic acid predominantly found in the non-neurohumoral fluids of hind-mouthed animals, is incapable of synthesizing Neu5Gc due to a deletion in the CMAH exon of the gene encoding human CMP-Neu5Gc hydroxylase. But consumption of animal-derived foods that contain Neu5Gc, such as red meat, can instigate an immune response in humans, as Neu5Gc is recognized as a foreign substance by the human immune system. This recognition leads to the production of anti-Neu5Gc antibodies, subsequently resulting in chronic inflammation. When Neu5Gc is consumed excessively or frequently, it may contribute to the development of heart disease and cancer. This makes Neu5Gc, an endogenous pathogenic factor derived from red meat, a new hot topic in red meat safety research. In this study, aptamers obtained by the magnetic bead SELEX technique were subjected to homology and secondary structure prediction analysis as well as affinity determination. The result indicated that the aptamer 2B.N2A9 exhibited a robust binding affinity, with an affinity constant (Ka) of 1.87 × 108 L/mol. This aptamer demonstrated optimal binding specificity within a pH range of 5.4 to 7.4. Molecular docking analysis further revealed that aptamer 2B.N2A9 formed stable binding interactions with the target Neu5Gc at specific sites, namely G-14, C-15, G-13, G-58, G-60, and C-59. An Enzyme-Linked Oligonucleotide Sorbent Assay (ELOSA) methodology was established to detect the endogenous pathogenic factor Neu5Gc present in red meat. This method demonstrated a limit of detection (LOD) of 0.71 ng/mL, along with an average recovery rate of 92.23%. The aptamer obtained in this study exhibited favorable binding properties to Neu5Gc. The assay was relatively convenient and demonstrated good sensitivity. Further investigation into the distribution of Neu5Gc in various red meats is of public health significance and scientific potential. A practical detection method should be provided to guide red meat diets and ensure the nutrition and safety of meat products.

CircNOP14 increases the radiosensitivity of hepatocellular carcinoma via inhibition of Ku70-dependent DNA damage repair.

Circular RNAs (circRNAs) are profoundly affected in hepatocellular carcinoma (HCC) through various pathways. However, the role of circRNAs in the radiosensitivity of HCC cells is yet to be explored. In this study, we identified a circRNA-hsa_circ_0006737 (circNOP14) involved in the radiosensitivity of HCC. We found that circNOP14 increased the radiosensitivity of HCC cells both in vitro and in vivo. Notably, using a circRNA pulldown assay and RNA-binding protein immunoprecipitation, we identified Ku70 as a novel and robust interacting protein of circNOP14. Mechanistically, circNOP14 interacts with Ku70 and prevents its nuclear translocation, thereby increasing irradiation-induced DNA damage. Therefore, our findings may provide a predictive indicator and intervention option for 125I brachytherapy or external radiotherapy in HCC.

The targeting of DAPK1 with miR-190a-3p promotes autophagy in trophoblast cells.

Pre-eclampsia (PE) is a dangerous pathological status that occurs during pregnancy and is a leading reason for both maternal and fetal death. Autophagy is necessary for cellular survival in the face of environmental stress as well as cellular homeostasis and energy management. Aberrant microRNA (miRNA) expression is crucial in the pathophysiology of PE. Although studies have shown that miRNA (miR)-190a-3p function is tissue-specific, the precise involvement of miR-190a-3p in PE has yet to be determined. We discovered that miR-190a-3p was significantly lower and death-associated protein kinase 1 (DAPK1) was significantly higher in PE placental tissues compared to normal tissues, which is consistent with the results in cells. The luciferase analyses demonstrated the target-regulatory relationship between miR-190a-3p and DAPK1. The inhibitory effect of miR-190a-3p on autophagy was reversed by co-transfection of si-DAPK1 and miR-190a-3p inhibitors. Thus, our data indicate that the hypoxia-dependent miR-190a-3p/DAPK1 regulatory pathway is implicated in the development and progression of PE by promoting autophagy in trophoblast cells.

WB518, a novel STAT3 inhibitor, effectively alleviates IMQ and TPA-induced animal psoriasis by inhibiting STAT3 phosphorylation and Keratin 17.

OBJECTIVES: Psoriasis is a prevalent chronic inflammatory skin disease in humans that is characterized by frequent relapses and challenging to cure. WB518 is a novel small molecule compound with an undisclosed structure. Therefore, our study aimed to investigate the therapeutic potential of WB518 in vitro and in vivo for the treatment of psoriasis, specifically targeting the abnormal proliferation, aberrant differentiation of epidermal keratinocytes, and pathogenic inflammatory response. MATERIALS AND METHODS: We employed dual luciferase reporter assay to screen compounds capable of inhibiting STAT3 gene transcription. Flow cytometry was utilized to analyze CD3-positive cells. Protein and mRNA levels were assessed through Western blotting, immunofluorescence, immunohistochemistry, and real-time PCR. Cell viability was measured using the MTS assay, while in vivo models of psoriasis induced by IMQ and TPA were employed to study the anti-psoriasis effect of WB518. RESULTS: WB518 was found to significantly reduce the mRNA and protein levels of Keratin 17 (K17) in HaCaT cells by inhibiting the phosphorylation of STAT3 Tyr705 (Y705). In the IMQ and TPA-induced psoriasis mouse model, WB518 effectively improved scaling, epidermal hyperplasia, and inflammation. WB518 also suppressed the expression of inflammatory cytokines, such as interleukin (IL)-1ß, IL-6, IL-17, and IL-23. Furthermore, WB518 decreased the proportion of CD3-positive cells in the psoriatic skin of mice. CONCLUSIONS: WB518 exhibits promising potential as a treatment candidate for psoriasis.

Unilateral levator avulsion increases the risk of de novo stress urinary incontinence after cystocele repair.

INTRODUCTION: Patients without concurrent baseline stress urinary incontinence (SUI) can develop de novo SUI after transvaginal mesh surgery (TVM) for cystocele repair. Surgeons should be aware of de novo SUI risk factors after TVM. METHODS: A total of 1124 women who were underwent TVM surgeries were recruited and assessed for eligibility from January 1, 2012 to April 30, 2021. All data related to patients and surgeries was collected, which included general conditions, clinical examination, surgery records, and follow-up results. Patients were divided into three groups according to follow-up results and data were compared with each group. The relative risk (RR) of de novo SUI with levator avulsion was also calculated. RESULTS: Three hundred thirty-six patients were included in this study. They were divided into no complication group (n = 249), de novo SUI group (n = 68), and other complications group (n = 19). It seemed elder or obese women had a higher risk of de novo SUI after TVM (p < 0.05). In de novo SUI group, incidence of levator avulsion before surgery were higher than the other two groups (p = 0.001). TVM can significantly change a prolapse to point Aa and Ba on POP-Q quantification system (p < 0.05). RR ratios of de novo SUI with unilateral avulsion group is 2.60 (95% confidence interval [CI] 1.39-4.87), and 2.58 (95%CI 0.82-8.15) for bilateral group. CONCLUSION: Unilateral levator avulsion, instead of bilateral levator avulsion, is a risk factor of de novo SUI after cystocele repair surgery.

Therapeutic protein PAK restrains the progression of triple negative breast cancer through degrading SREBP-1 mRNA.

Triple-negative breast cancer (TNBC) represents the most challenging subtype of breast cancer. Studies have implicated an upregulation of lipid synthesis pathways in the initiation and progression of TNBC. Targeting lipid synthesis pathways may be a promising therapeutic strategy for TNBC. Our previous study developed a therapeutic protein PAK with passive targeting and inhibiting tumor proliferation. In this study, we further substantiate the efficacy of PAK in TNBC. Transcriptome sequencing analysis revealed PAK-mediated downregulation of genes involved in fatty acid synthesis, including key genes like SREBP-1, FASN, and SCD1. RNA immunoprecipitation experiments demonstrated a significant binding affinity of PAK to SREBP-1 mRNA, facilitating its degradation process. Both in vitro and in vivo models, PAK hampered TNBC progression by downregulating lipid synthesis pathways. In conclusion, this study emphasizes that PAK inhibits the progression of TNBC by binding to and degrading SREBP-1 mRNA, revealing a new strategy for regulating lipid synthesis in the intervention of TNBC and its therapeutic significance.

A recombinase polymerase amplification-SYBR Green I assay for the rapid and visual detection of Brucella.

Brucellosis is a zoonosis caused by Brucella, which poses a great threat to human health and animal husbandry. Pathogen surveillance is an important measure to prevent brucellosis, but the traditional method is time-consuming and not suitable for field applications. In this study, a recombinase polymerase amplification-SYBR Green I (RPAS) assay was developed for the rapid and visualized detection of Brucella in the field by targeting BCSP31 gene, a conserved marker. The method was highly specific without any cross-reactivity with other common bacteria and its detection limit was 2.14 × 104 CFU/mL or g of Brucella at 40 °C for 20 min. It obviates the need for costly instrumentation and exhibits robustness towards background interference in serum, meat, and milk samples. In summary, the RPAS assay is a rapid, visually intuitive, and user-friendly detection that is highly suitable for use in resource-limited settings. Its simplicity and ease of use enable swift on-site detection of Brucella, thereby facilitating timely implementation of preventive measures.

Circular RNA circEYA3 promotes the radiation resistance of hepatocellular carcinoma via the IGF2BP2/DTX3L axis.

BACKGROUND: Hepatocellular carcinoma (HCC) has a high incidence and mortality rate despite various treatment options, including 125I seed implantation. However, recurrence and radiation resistance remain challenging issues. Hsa_circ_0007895 (circEYA3)-derived from exons 2-6 of EYA3-facilitates the proliferation and progression of pancreatic ductal adenocarcinoma. However, the role of circEYA3 in HCC 125I radiation resistance remains unclear. Thus, we aimed to investigate the functions and underlying molecular mechanisms of circEYA3 in HCC under 125I and X-ray irradiation conditions. METHODS: CircEYA3 was identified by RNA-seq in patients with HCC before and after 125I seed implantation treatment, followed by fluorescence in situ hybridization and RNase R assays. The radiosensitivity of HCC cell lines irradiated with 125I seeds or external irradiation were evaluated using the Cell Counting Kit 8, flow cytometry, γH2A.X immunofluorescence and comet assays. RNA pull-down and RNA immunoprecipitation assays were performed to explore the interactions between circEYA3 and IGF2BP2. DTX3L mRNA was identified by RNA-seq in PLC/PRF/5 cells with overexpressed circEYA3. The corresponding in vitro results were verified using a mouse xenograft model. RESULTS: CircEYA3 decreased the radiosensitivity of HCC cells both in vitro and in vivo. Notably, using a circRNA pulldown assay and RNA-binding protein immunoprecipitation, we identified IGF2BP2 as a novel and robust interacting protein of circEYA3. Mechanistically, circEYA3 binds to IGF2BP2 and enhances its ability to stabilize DTX3L mRNA, thereby specifically alleviating radiation-induced DNA damage in HCC cells. CONCLUSIONS: Our findings demonstrate that circEYA3 increases the radioresistance of HCC to 125I seeds and external irradiation via the IGF2BP2/DTX3L axis. Thus, circEYA3 might be a predictive indicator and intervention option for 125I brachytherapy or external radiotherapy in HCC.

An Exosome-Related Long Non-coding RNA (lncRNA)-Based Signature for Prognosis and Therapeutic Interventions in Lung Adenocarcinoma.

Background The poor prognosis of lung adenocarcinoma (LUAD) has been confirmed by a large number of studies, so it is necessary to construct a prognosis model. In addition, exosome is closely related to tumors, but there are few studies on exosome-related long non-coding RNA (lncRNA) (ExolncRNA). Methods In this study, we designed a prognostic model, exosome-related lncRNA-based signature (ExoLncSig), using ExolncRNA expression profiles of LUAD patients from The Cancer Genome Atlas (TCGA). ExolncRNAs were identified through univariate and multivariate and Lasso analyses. Subsequently, based on the ExoLncSig, gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, immune function and immunotherapy analysis, drug screening, and so on were performed. Results AC026355.2, AC108136.1, AL590428.1, and LINC01312 were examined to establish the ExoLncSig. Gene enrichment analysis identified potential prognostic markers and therapeutic targets, including human leukocyte antigen (HLA), parainflammation, chemokine receptor (CCR), antigen-presenting cell (APC) co-inhibition, cancer-associated fibroblast (CAF), and myeloid-derived suppressor cell (MDSC). Moreover, we ascertained that the high-risk subgroup exhibits heightened susceptibility to pharmaceutical agents. Conclusion Our findings indicate that ExoLncSig holds promise as a valuable prognostic marker in LUAD. Furthermore, the immunogenic properties of ExolncRNAs may pave the way for the development of a therapeutic vaccine against LUAD.

Association between depression and endometriosis using data from NHANES 2005-2006.

Studies on the association between depression and self-reported endometriosis are limited, and further studies are required to investigate this association. Data were collected from the National Health and Nutrition Examination Survey database (2005-2006). Based on the inclusion and exclusion criteria, 100 participants with self-reported endometriosis and 1295 participants without self-reported endometriosis were included, representing a total population of 64,989,430. Depression severity was assessed using the Patient Health Questionnaire 9 (PHQ9). A survey-weighted logistic regression analysis was performed to explore the association between depression and endometriosis. Subgroup analyses were conducted to explore heterogeneity. The prevalence of endometriosis was 7.17%. A significant positive association was found between the PHQ9 score and endometriosis. After adjusting for all covariates, the PHQ9 score positively correlated with endometriosis. Furthermore, compared with the participants without depression, those with moderate depression were more prone to have endometriosis both in unadjusted and fully adjusted model. However, the relationship between severe depression and endometriosis was not significant in all models (P > 0.05). Our findings highlight the influence of depression on the prevalence of self-reported endometriosis. Further studies are required to elucidate the causal relationship between depression and self-reported endometriosis.

A Functional Stent Encapsulating Radionuclide in Temperature-Memory Spiral Tubes for Malignant Stenosis of Esophageal Cancer.

Stent implantation is a commonly used palliative treatment for alleviating stenosis in advanced esophageal cancer. However, tissue proliferation induced by stent implantation and continuous tumor growth can easily lead to restenosis. Therefore, functional stents are required to relieve stenosis while inhibiting tissue proliferation and tumor growth, thereby extending the patency. Currently, no ideal functional stents are available. Here, iodine-125 (125 I) nuclides are encapsulated into a nickel-titanium alloy (NiTi) tube to develop a novel temperature-memory spiral radionuclide stent (TSRS). It has the characteristics of temperature-memory, no cold regions at the end of the stent, and a uniform spatial dose distribution. Cell-viability experiments reveal that the TSRS can reduce the proliferation of fibroblasts and tumor cells. TSRS implantation is feasible and safe, has no significant systemic radiotoxicity, and can inhibit in-stent and edge stenosis caused by stent-induced tissue proliferation in healthy rabbits. Moreover, TSRS can improve malignant stenosis and luminal patency resulting from continuous tumor growth in a VX2 esophageal cancer model. As a functional stent, the TSRS combines the excellent properties of NiTi with brachytherapy of the 125 I nuclide and will make significant contributions to the treatment of malignant esophageal stenosis.

Iodine-125 seed implantation in the treatment of malignant tumors.

Malignant tumors are major causes of morbidity and mortality in China. Despite advances in surgical, radiological, chemotherapeutic, molecular targeting, and immunotherapeutic treatments, patients with malignant tumors still have poor prognoses. Low-dose-rate brachytherapy, specifically 125I seed implantation, is beneficial because of its high local delivery dose and minimal damage to surrounding tissues. Consequently, it has gained increasing acceptance as a treatment modality for various malignant tumors. In this study, we explored the fundamental principles, clinical applications, and new technologies associated with 125I radioactive seed implantation.

DENV-2 NS1 promotes AMPK-LKB1 interaction to activate AMPK/ERK/mTOR signaling pathway to induce autophagy.

The global incidence of dengue fever has gradually increased in recent years, posing a serious threat to human health. In the absence of specific anti-dengue drugs, understanding the interaction of Dengue virus (DENV) with the host is essential for the development of effective therapeutic measures. Autophagy is often activated during DENV infection to promote viral replication, but the mechanism of how DENV's own proteins induce autophagy has not been clarified. In this study, we first preliminarily identified DENV-2 NS1 as the most likely viral protein for DENV-2-induced autophagy with the help of molecular docking techniques. Further experimental results confirmed that DENV-2 NS1 regulates DENV-2 infection of HUVEC-induced autophagy through the AMPK/ERK/mTOR signaling pathway. Mechanistically, DENV-2 NS1 mainly interacted with AMPK by means of its Wing structural domain, and NS1 bound to all three structural domains on the AMPKα subunit. Finally, the experimental results showed that DENV-2 NS1 promoted the interaction between LKB1 and AMPKα1 and thus activated AMPK by both increasing the expression of LKB1 and binding LKB1. In conclusion, the results of this study revealed that DENV-2 NS1 protein served as a platform for the interaction between AMPK and LKB1 after DENV-2 infection with HUVEC, and pulled AMPK and LKB1 together to form a complex. LKB1 to form a complex, promoting LKB1 action on the kinase structural domain of AMPKα1, which in turn promotes phosphorylation of the Thr172 site on the AMPK kinase structural domain and activates AMPK, thereby positively regulating the AMPK/ERK/mTOR signaling pathway and inducing autophagy. The present discovery improves our understanding of DENV-2-induced host autophagy and contributes to the development of anti-dengue drugs.

[Application of brain functional connectivity and nonlinear dynamic analysis in brain function assessment for infants with controlled infantile spasm]. / 脑功能连接及非线性动力学分析在发作控制的婴儿痉挛症患儿脑功能评估中的应用.

OBJECTIVES: To investigate the role of brain functional connectivity and nonlinear dynamic analysis in brain function assessment for infants with controlled infantile spasm (IS). METHODS: A retrospective analysis was performed on 14 children with controlled IS (IS group) who were admitted to the Department of Neurology, Anhui Provincial Children's Hospital, from January 2019 to January 2023. Twelve healthy children, matched for sex and age, were enrolled as the control group. Electroencephalogram (EEG) data were analyzed for both groups to compare the features of brain network, and nonlinear dynamic indicators were calculated, including approximate entropy, sample entropy, permutation entropy, and permutation Lempel-Ziv complexity. RESULTS: Brain functional connectivity showed that compared with the control group, the IS group had an increase in the strength of functional connectivity, and there was a significant difference between the two groups in the connection strength between the Fp2 and F8 channels (P<0.05). The network stability analysis showed that the IS group had a significantly higher network stability than the control group at different time windows (P<0.05). The nonlinear dynamic analysis showed that compared with the control group, the IS group had a significantly lower sample entropy of Fz electrode (P<0.05). CONCLUSIONS: Abnormalities in brain network and sample entropy may be observed in some children with controlled IS, and it is suggested that quantitative EEG analysis parameters can serve as neurological biomarkers for evaluating brain function in children with IS.

Dry eye disease among patients infected with the SARS-CoV-2 Omicron variant: a cross-sectional study.

AIM: To investigate the incidence of dry eye disease (DED) and relevant risk factors among patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant. METHODS: This cross-sectional, observational analysis included 993 patients with corona virus disease 2019 (COVID-19) treated at the National Exhibition and Convention Center (Shanghai) Fangcang Shelter Hospital, from April 10 to May 26, 2022. Totally 944 uninfected control participants were recruited. All participants completed ocular surface disease index (OSDI) questionnaires, and DED symptoms were determined using OSDI scores. The demographic characteristics, length of hospital stay and in nasopharyngeal swabs were performed using questionnaires. SARS-CoV-2 Omicron variant infection was confirmed by nucleic acid-based detection in nasopharyngeal swabs using a 2019-nCoV nucleic acid detection kit. The risk factors for DED symptoms among patients with COVID-19 and control participants were determined by logistic regression analysis. RESULTS: Patients with COVID-19 showed a higher incidence of DED than controls (64.9% vs 55.1%, P<0.001). SARS-CoV-2 infection [odds ratios (ORs) (95%CI): 1.271 (1.038, 1.556)], use of contact lenses [ORs (95%CI): 9.350 (3.676, 23.783)], history of corneal refractive surgery [ORs (95%CI): 2.047 (1.494, 2.804)], poor sleep quality [ORs (95%CI): 2.657 (2.029, 3.480)], and video display terminal (VDT) use for more than 8h per day [ORs (95%CI): 6.348 (4.720, 8.538)] were found to be risk factors for DED symptoms in patients with COVID-19 as well as controls. For patients with COVID-19, the length of hospital stay [ORs (95%CI): 1.196 (1.134, 1.262)], use of contact lenses [ORs (95%CI): 20.423 (2.680, 155.632)], history of corneal refractive surgery [ORs (95%CI): 2.166 (1.321, 3.553)], poor sleep quality [ORs (95%CI): 3.650 (2.381, 5.597)], and VDT use for more than 8h per day [ORs (95%CI): 7.740 (4.918, 12.180)] were significant risk factors for DED symptoms. CONCLUSION: Patients with COVID-19 are more prone to develop symptomatic DED. SARS-CoV-2 infection and length of hospital stay are important risk factors for DED symptoms.