To investigate the changes in peripheral blood immune cells before and after the onset of septic shock in patients with malignant tumors, and to analyze the relationship between these immune cells and patient prognosis.

Objective To analyze the clinical and therapeutic characteristics of Epstein-Barr virus (EBV)-negative posttransplant lymphoproliferative disease (PTLD) with diffuse large B-cell lymphoma (DLBCL) in the context of specific cases and literature. Methods A case of EBV-negative DLBCL (GCB type) after kidney transplantation is reported. The patient was a 45-year-old male who underwent living-related kidney transplantation in 2016 and has been receiving triple immunosuppressive therapy with tacrolimus, mycophenolate mofetil and methylprednisolone since then. In 2024, the patient presented with intermittent fever, night sweats and gastrointestinal symptoms. The diagnosis was confirmed by endoscopic pathology, immunohistochemical staining and positron emission tomography/computed tomography. The R-CDOP regimen (rituximab + cyclophosphamide + liposomal doxorubicin + vincristine + dexamethasone) was used for treatment. Results The patient was diagnosed with EBV-negative DLBCL (GCB type, Ann Arbor stage Ⅳ B). After 4 cycles of R-CDOP chemotherapy, the efficacy assessment was partial remission, and the transplant kidney function remained stable. Conclusions For EBV-negative PTLD after kidney transplantation, it is necessary to break through the "virus-dependent" diagnostic thinking. In clinical practice, the focus should be on protecting the transplant kidney, and individualized treatment plans should be developed for patients.

Objective: With the development of global nuclear power, the discharge of tritium during nuclear power plant operation has raised concerns. This study provides basic data support for the assessment of tritium radioactivity levels in sea-water and seafood around nuclear power plants. Methods: This study selected the coastal waters near a nuclear power plant in China as the research area. A total of 15 surface seawater samples and three types of marine organisms (laver, oyster, and mullet) were collected to measure and analyze the tritium activity concentrations in seawater and marine organisms. Results: The tritium activity concentrations in seawater ranged from 1.54 to 3.55 Bq/L, with an average of 2.25 ± 0.70 Bq/L.In marine organisms, the tritium activity concentrations ranged from 1.1 to 1.6 Bq/L. The total dose rates of tritium to mullet and oyster were 6.93 × 10−7 μGy/h and 5.39 × 10−7 μGy/h, respectively. Conclusion Compared with tritium activity concentrations in adjacent waters, those in seawater near this nuclear power plant showed no significant increases, and the tritium content in marine organisms remained within normal ranges. The radiation doses of tritium in mullet and oyster did not pose a radiation hazard to these two organisms.

Objective Magnetic resonance angiography(MRA)offers a non-invasive and radiation-free advantage in detecting and diagnosing intracranial artery stenosis;however,it is associated with high equipment costs.Transcranial color-coded Duplex ultrasound(TCCD)combined with contrast-enhanced ultrasound(CEUS)presents advantages such as non-invasiveness,real-time dynamic monitoring,and low cost.Nevertheless,there were no reports comparing the sensitivity,specificity,diagnostic agreement with MRA,or health economic evaluation of TCCD combined with CEUS for detecting major intracranial artery stenosis.Methods From April 2023 to August 2024,a total of 55 patients suspected of having intracranial artery stenosis or occlusion were recruited at Beijing Tiantan Hospital,Capital Medical University.Both TCCD combined with CEUS and MRA were performed to evaluate the degree of stenosis in the terminal segment of the internal carotid artery,M1 and M2 segments of the middle cerebral artery,A1 and A2 segments of the anterior cerebral artery,P1 and P2 segments of the posterior cerebral artery,and the V4 segment of the vertebral artery.Intracranial artery stenosis was categorized into three groups:normal/mild,moderate,and severe/occlusion.Sensitivity,specificity,and consistency between the two methods were calculated.The Wilcoxon signed-rank test was used to compare the differences in examination costs and diagnostic time.Results Fifty-five high-risk patients(110 cerebral hemispheres in total)with suspected cerebrovascular stenosis were included(median age:46 years;69.0%male).TCCD combined with CEUS and MRA were performed simultaneously.TCCD combined with CEUS showed high sensitivity and specificity in diagnosing intracranial artery stenosis,with good consistency compared to MRA.The highest diagnostic consistency was observed in the M2 segment(Kappa=0.704)and A2 segment(Kappa=0.650),while the M1 segment showed moderate consistency(Kappa=0.569).The average cost of TCCD combined with CEUS was 240 CNY with a diagnostic duration of 21 min,compared to 722 CNY and 287 min for MRA(P<0.001,effect sizer=0.89-0.91).Conclusion Compared to MRA,TCCD combined with CEUS demonstrates higher consistency in screening for stenosis in the M2 segment of the middle cerebral artery and the A2 segment of the anterior cerebral artery.It is also more cost-effective.However,MRA has advantages in assessing deep intracranial vessels.A synergistic use of both methods can optimize the allocation of diagnostic resources for intracranial artery stenosis.It is recommended that primary healthcare institutions adopt TCCD as the initial screening tool,and,with standardized training and technical upgrades,combine it with CEUS.Complex cases should be referred for detailed evaluation by using MRA.

In modern society, sugary foods have become an integral part of many people′s lives. However, excessive sugar consumption has adverse effects on both overall health and oral health, serving as a contributing factor to the global increasing incidence in oral diseases, cardiovascular diseases, cancers, obesity, and diabetes. In response to the health risks related to high-sugar diets, the World Health Organization (WHO) and World Dental Federation (FDI) have proposed initiatives and recommendations, with various governments implementing different policies and strategies to reduce sugar intake. Chinese government has also taken proactive measures. The "Healthy China Action (2019-2030)" initiative introduced by the State Council in 2019 established a crucial benchmark in limiting the average daily intake of added sugar to 25 g per person forward to 2030. Experts from Chinese Center for Disease Control and Prevention and the field of oral health have meticulously examined the impacts of sugar reduction on oral health, as well as strategies, methods, and practical considerations related to reducing sugar intake through several meeting and wrote the "Expert consensus: reducing free-sugar for caries prevention", which was subsequently reviewed and revised based on the feedback from multiple stakeholders. They have conducted thorough analyses of global trends in sugar reduction and best practices to provide valuable insights to China for crafting effective policies and strategies on sugar reduction. This consensus mainly includes the classification of free sugars, the latest scientific evidence on dental caries, recommendations from WHO on sugar-sweetened beverage taxes, nutrition labeling, advertising, food reform, adjusting supply systems, education, and promotion strategies, as well as sugar reduction actions taken by various governments around the world. Combining the actual situation in China, policy recommendations and authoritative popular science knowledge on sugar reduction for caries prevention to public are proposed to advocate for experts in multiple fields to focus on sugar reduction for caries prevention, promote the work process, and provide the scientific basis for oral health educators.

Objective To investigate the influencing factors for the short-term prognosis of patients with alcohol-related liver diseases-acute-on-chronic liver failure(ALD-ACLF)comorbid with infection.Methods A total of 89 ALD-ACLF patients with infection who were admitted to the Fifth Medical Center of PLA General Hospital from January 2019 to December 2021 were enrolled as subjects,and related clinical data were collected at baseline(time of patient enrollment).According to the 28-day survival status of patients,they were divided into survival group with 53 patients and death group with 36 patients,and baseline clinical data were compared between the two groups.The t-test was used for comparison of normally distributed continuous data between groups,and the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between groups;the chi-square test was used for comparison of categorical data between groups.A non-conditional Logistic regression analysis was used to perform the multivariate analysis.The Z-test was used for comparison of the area under the ROC curve(AUC),and the diagnostic value of the model was assessed.Results Compared with the survival group,the death group had significantly higher hemoglobin(t=-2.397,P=0.019),alanine aminotransferase(Z=-3.437,P=0.001),gamma-glutamyl transpeptidase(Z=-2.617,P=0.009),creatinine(Z=-3.938,P<0.001),blood urea nitrogen(Z=-3.423,P=0.001),NH3(Z=-4.406,P<0.001),international normalized ratio(Z=-3.428,P=0.001),C-reactive protein(Z=-2.128,P=0.033),procalcitonin(Z=-2.441,P=0.015),Model for End-Stage Liver Disease(MELD)score(t=-4.817,P<0.001),incidence rate of acute kidney injury(χ2=21.602,P<0.001),incidence rate of pulmonary infection(χ2=4.866,P=0.027),and incidence rate of shock(χ2=16.285,P<0.001),as well as significantly lower albumin(Z=-2.473,P=0.013)and incidence rate of abdominal infection(χ2=5.897,P=0.015).The multivariate analysis showed that NH3(odds ratio[OR]=1.027,95%confidence interval[CI]:1.006-1.049,P=0.012),MELD score(OR=1.103,95%CI:1.011-1.203,P=0.027],and the incidence rate of shock(OR=6.326,95%CI:1.533-26.101,P=0.011)were independent risk factors for 28-day mortality in ALD-ACLF patients comorbid with infection.Based on these factors,a predictive model was established as Y=0.027×NH3+0.098×MELD score+1.845×shock-4.111.The ROC curve analysis showed that the new model had an AUC of 0.861,a sensitivity of 77.78%,and a specificity of 88.68%,while MELD score had an AUC of 0.776,a sensitivity of 77.78%,and a specificity of 67.92%,suggesting that the new model had a significantly higher diagnostic value than MELD score(Z=2.136,P=0.032 6).Conclusion ALD-ACLF patients with infection tend to have a poor short-term prognosis,and MELD score,NH3,and shock are influencing factors for the short-term prognosis of such patients.The combination of these three factors has a high value in predicting short-term prognosis.

BACKGROUND: Lung cancer is one of the leading causes of cancer-related mortality worldwide, with above 80% of cases be non-small cell lung cancer (NSCLC), among which lung squamous cell carcinoma (LUSC) occupies a significant proportion. Although comprehensive cancer therapies have considerably improved the overall survival of patients, patients with advanced LUSC have a poorer prognosis. Therefore, there is a need for a biomarker to predict the progress of advanced LUSC in order to improve prognosis through early diagnosis. Previous studies have shown that miRNAs are differentially expressed in lung cancer tissues and play roles as potential oncogenes or tumor suppressors. The aim of this study is to identify differentially expressed miRNAs between early-stage and advanced-stage LUSC, and to establish a set of miRNAs that can predict the progress of advanced LUSC. METHODS: Clinical data and miRNA-related data of LUSC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Bioinformatic methods were applied to analyze the data. Receiver operating characteristic (ROC) curves were plotted, and various online tools were used to predict target genes, with subsequent analysis of the potential biological mechanisms of these genes. RESULTS: A total of 58 differentially expressed miRNAs were identified between the experiment group and the control group. Seven miRNAs were selected for potential construction of a miRNA biomarker through LASSO regression, and based on the area under the curve (AUC) values of each miRNA, four of these miRNAs (miR-377-3p, miR-4779, miR-6803-5p, miR-3960) were ultimately chosen as biomarkers for predicting advanced LUSC. The AUC under the ROC curve for the combined four miRNAs was 0.865. Enrichment analysis showed that these target genes were involved in several pathways, including cancer-related pathways, mitogen-activated protein kinase (MAPK) signaling pathway, serine/threonine kinase, and tyrosine kinase signaling pathways. CONCLUSIONS The combined use of miR-377-3p, miR-4779, miR-6803-5p and miR-3960 provides a good predictive ability for the progress of advanced LUSC patients, with an AUC of 0.865.
Humans ; MicroRNAs/metabolism* ; Lung Neoplasms/metabolism* ; Biomarkers, Tumor/metabolism* ; Carcinoma, Squamous Cell/pathology* ; Gene Expression Regulation, Neoplastic ; Male ; Female ; Prognosis ; ROC Curve ; Middle Aged

OBJECTIVES: Neurodegenerative diseases are closely associated with myelin loss, and the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) are crucial to remyelination. However, the regulatory mechanisms involved remain incompletely understood. This study aims to investigate how astrocytes (ASTs) regulate the secretion of chitinase-3-like protein 1 (CHI3L1) via connexin 47 (Cx47)-mediated exosome signaling, and its subsequent effect on OPC proliferation. METHODS: Primary cells were isolated from postnatal day 1 Sprague-Dawley (P1SD) rats to establish 3 culture conditions: OPCs alone (Group O), OPCs in direct contact with ASTs (Group C), and OPCs cultured with AST-conditioned medium (Group A). Cellular morphology and proliferation were assessed using optical microscopy, 5-ethynyl-2'- deoxyuridine (EdU) incorporation, and flow cytometry. RNA sequencing (RNA-Seq) and bioinformatics analysis (BA) were conducted to identify differentially expressed genes (DEGs) among groups. Protein expression and cell cycle distribution were analyzed by Western blotting (WB) and flow cytometry. Exosomes were isolated and purified via differential centrifugation, characterized by nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM), and CHI3L1 expression in exosomes was verified via WB. Cx47 was silenced using small interfering RNA (siRNA) to evaluate its effect on OPC proliferation and exosome secretion. Artificial exosomes were constructed by encapsulating CHI3L1 in single unilamellar vesicles (SUVs), whose structure and size were validated by NTA and TEM. Following Cx47 knockdown, artificial exosomes were added back, and OPC proliferation was assessed via flow cytometry and EdU assay. RESULTS: Direct co-cultured with ASTs (Group C) resulted in significantly enhanced OPC proliferation compared to the Group O and Group A (P<0.05). RNA-Seq and WB analyses revealed that ASTs promote OPC proliferation and exosome secretion enriched in CHI3L1 through Cx47. Cx47 knockdown by siRNA led to significant decreases in OPC proliferation and exosome release (P<0.05). The inhibitory effect of Cx47 silencing on OPC proliferation was partially reversed by supplementation with either isolated exosomes or exogenous CHI3L1. CONCLUSIONS This study reveals a novel mechanism by which ASTs regulate OPC proliferation: Through direct contact, ASTs enhance the secretion of CHI3L1-rich exosomes via Cx47, thereby converting intercellular contact signals into secretory signals that promote OPC proliferation. As a key exosomal molecule, CHI3L1 may play an important role in neural function and remyelination and warrants further investigation.
Animals ; Exosomes/metabolism* ; Cell Proliferation ; Rats, Sprague-Dawley ; Rats ; Connexins/genetics* ; Oligodendrocyte Precursor Cells/metabolism* ; Astrocytes/metabolism* ; Chitinase-3-Like Protein 1/metabolism* ; Cells, Cultured ; Cell Differentiation

Environmental toxicants have been linked to aging and age-related diseases. The emerging evidence has shown that the enhancement of detoxification gene expression is a common transcriptome marker of long-lived mice, Drosophila melanogaster, and Caenorhabditis elegans. Meanwhile, the resistance to toxicants was increased in long-lived animals. Here, we show that farnesoid X receptor (FXR) agonist obeticholic acid (OCA), a marketed drug for the treatment of cholestasis, may extend the lifespan and healthspan both in C. elegans and chemical-induced early senescent mice. Furthermore, OCA increased the resistance of worms to toxicants and activated the expression of detoxification genes in both mice and C. elegans. The longevity effects of OCA were attenuated in Fxr ^-/- mice and Fxr homologous nhr-8 and daf-12 mutant C. elegans. In addition, metabolome analysis revealed that OCA increased the endogenous agonist levels of the pregnane X receptor (PXR), a major nuclear receptor for detoxification regulation, in the liver of mice. Together, our findings suggest that OCA has the potential to lengthen lifespan and healthspan by activating nuclear receptor-mediated detoxification functions, thus, targeting FXR may offer to promote longevity.

Disrupted bone morphogenetic protein type 2 receptor (BMPR2) signaling in endothelial cells drives pulmonary arterial hypertension (PAH). However, targeted recovery of this signaling pathway by lipid nanoparticles (LNPs) has not been explored as a therapy. Here, we employed Design of Experiments to optimize the delivery efficiency of LNPs targeting pulmonary endothelial cells developed by our laboratory, resulting in a remarkable 35-fold increase in a simplified three-component formulation without helper lipids. Administration of BMPR2 mRNA LNPs effectively reversed established PAH in two experimental rat models (monocrotaline or SU5416-hypoxia) by reversing pulmonary vascular remodeling. Specifically, BMPR2 mRNA LNPs replenished the expression of BMPR2 protein and subsequently activated downstream pathways, as confirmed by elevated levels of p-SMAD1/5/9 and ID1 proteins. The relief of pulmonary arterial occlusion was demonstrated by thinned pulmonary arterial media and decreased proportion of full muscularized vessels. Alleviation of right ventricular hypertrophy was indicated by declined Fulton index, the cross-sectional area of right ventricular cardiomyocytes as well as collagen deposition. Effective recovery of right ventricular function was evidenced by increased pulmonary artery flow acceleration time/pulmonary artery flow ejection time ratio. These findings underscore the potential of restoring BMPR2 signaling through pulmonary endothelial cell-specific LNPs for treating PAH.