Diagnostic value of carbohydrate antigen 50 in biliary tract cancer: A large-scale multicenter study.

BACKGROUND: To date, carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) have been widely used for the screening, diagnosis and prediction of biliary tract cancer (BTC) patients. However, few studies with large sample sizes of carbohydrate antigen 50 (CA50) were reported in BTC patients. METHODS: A total of 1121 patients from the Liver Cancer Clin-Bio Databank of Anhui Hepatobiliary Surgery Union between January 2017 and December 2022 were included in this study (673 in the training cohort and 448 in the validation cohort): among them, 458 with BTC, 178 with hepatocellular carcinoma (HCC), 23 with combined hepatocellular-cholangiocarcinoma, and 462 with nontumor patients. Receiver operating characteristic (ROC) curves and decision curve analysis (DCA) were used to evaluate the diagnostic efficacy and clinical usefulness. RESULTS: ROC curves obtained by combining CA50, CA19-9, and AFP showed that the AUC value of the diagnostic MODEL 1 was 0.885 (95% CI 0.856-0.885, specificity 70.3%, and sensitivity 84.0%) in the training cohort and 0.879 (0.841-0.917, 76.7%, and 84.3%) in the validation cohort. In addition, comparing iCCA and HCC (235 in the training cohort, 157 in the validation cohort), the AUC values of the diagnostic MODEL 2 were 0.893 (95% CI 0.853-0.933, specificity 96%, and sensitivity 68.6%) in the training cohort and 0.872 (95% CI 0.818-0.927, 94.2%, and 64.6%) in the validation cohort. CONCLUSION: The model combining CA50, CA19-9, and AFP not only has good diagnostic value for BTC but also has good diagnostic value for distinguishing iCCA and HCC.

[Interaction between central nervous system and immune system after ischemic stroke and its therapeutic significance of traditional Chinese medicine].

Ischemic stroke is divided into acute phase, subacute phase, and recovery phase, with different pathological and physiological characteristics manifested at each stage. Among them, immune and inflammatory reactions persist for several days and weeks after ischemia. Ischemic stroke not only triggers local inflammation in damaged brain regions but also induces a disorder in the immune system, thereby promoting neuroinflammation and exacerbating brain damage. Therefore, conducting an in-depth analysis of the interaction between the central nervous system and the immune system after ischemic stroke, intervening in the main factors of the interaction between them, blocking pathological cascades, and thereby reducing brain inflammation have become the treatment strategies for ischemic stroke. This study summarizes and sorts out the interaction pathways between the central nervous system and the immune system. The impact of the central nervous system on the immune system can be analyzed from the perspective of the autonomic nervous system, the hypothalamic-pituitary-adrenal axis(HPA), and local inflammatory stimulation. The impact of the immune system on the central nervous system can be analyzed from the dynamic changes of immune cells. At the same time, the relevant progress in the prevention and treatment of traditional Chinese medicine(TCM) is summarized, so as to provide new insights for the analysis of complex mechanisms of TCM in preventing and treating ischemic stroke.

UBE2O reduces the effectiveness of interferon-α via degradation of IFIT3 in hepatocellular carcinoma.

Interferon (IFN) exerts its effects through interferon-stimulated genes (ISGs), but its efficacy is limited by interferon resistance, which can be caused by the ubiquitination of key proteins. UBE2O was initially identified as a promising therapeutic target based on data from the TCGA and iUUCD 2.0 databases. Through the inhibition of UBE2O, interferon α/ß signaling and overall interferon signaling were activated. Integrating data from proteomic, mass spectrometry, and survival analyses led to the identification of IFIT3, a mediator of interferon signaling, as a ubiquitination substrate of UBE2O. The results of in vitro and in vivo experiments demonstrated that the knockdown of UBE2O can enhance the efficacy of interferon-α by upregulating IFIT3 expression. K236 was identified as a ubiquitination site in IFIT3, and the results of rescue experiments confirmed that the effect of UBE2O on interferon-α sensitivity is dependent on IFIT3 activity. ATO treatment inhibited UBE2O and increased IFIT3 expression, thereby increasing the effectiveness of interferon-α. In conclusion, these findings suggest that UBE2O worsens the therapeutic effect of interferon-α by targeting IFIT3 for ubiquitination and degradation.

Diagnosis based on electromagnetic navigational bronchoscopy-guided biopsied peripheral lung lesions in a 10-year-old girl: A case report.

BACKGROUND: Electromagnetic navigational bronchoscopy (ENB) is an emerging diagnostic tool that enables practitioners to biopsy peripheral lung tissues that were previously only accessible under computed tomography (CT) guidance. However, few studies have investigated ENB use in children. Here, we report a case of a 10-year-old girl with peripheral lung lesions who complained of a 7-d persistent fever. She was diagnosed with Streptococcus parasanguinis infection based on findings obtained using ENB-guided transbronchial lung biopsy (TBLB). CASE SUMMARY: A 10-year-old girl presented with constitutional symptoms of cough and fever of 7 days' duration. Chest CT scans detected peripheral lung lesions and no endobronchial lesions. TBLB performed under the guidance of an ENB Lungpro navigation system was safe, well-tolerated, and effective for biopsying peripheral lung lesions. Examination of biopsied samples indicated the patient had a pulmonary Streptococcus parasanguinis infection, which was treated with antibiotics instead of more invasive treatment interventions. The patient's symptoms resolved after she received a 3-wk course of oral linezolid. Comparisons of pre-treatment and post-treatment CT scans revealed absorption of some lung lesions within 7 mo of hospital discharge. CONCLUSION: ENB-guided TBLB biopsying of peripheral lung lesions in this child is a safe, well-tolerated, and effective alternative to conventional interventions.

Clinical efficacy of avatrombopag and recombinant human thrombopoietin in the treatment of chronic liver disease-associated severe thrombocytopenia: A real-world study.

Purpose: To investigate the clinical efficacy of avatrombopag, an oral thrombopoietin receptor agonist, versus subcutaneous recombinant human thrombopoietin (rh-TPO) in the treatment of severe thrombocytopenia (TCP) associated with chronic liver disease (CLD). Methods: Clinical data of 250 patients with severe TCP associated with CLD were collected in a single hospital from January 2019 to January 2022. The main parameters measured were the therapeutic response rate, changes in platelets (PLTs), and adverse events. Propensity score matching (PSM) was used to avoid possible selection bias. Results: After PSM, a total of 154 patients were enrolled in the study: 77 in the avatrombopag group and 77 in the rh-TPO group. There was no statistically significant difference between the two groups in the effect of increasing the PLT count (Waldχ 2 = 1.659, p = 0.198; Waldχ 2 = 0.220, p = 0.639). In addition, no interaction between time and different medications was found (Waldχ 2 = 0.540, p = 0.910; Waldχ 2 = 1.273, p = 0.736). Interestingly, in the subgroup analysis, both before and after PSM, avatrombopag showed better clinical efficacy than rh-TPO in the treatment of TCP associated with CLD in Child‒Pugh Class A (88.89% vs. 63.41%, p =0.003; 81.33% vs. 61.76%, p = 0.043). Fewer patients reported dizziness in the avatrombopag group than in the rh-TPO group both before and after PSM (7.8% vs. 25.0%; 7.8% vs. 24.7%, p < 0.05). Conclusion: Both before and after PSM, avatrombopag showed better clinical efficacy than rh-TPO in the treatment of TCP associated with CLD in Child‒Pugh Class A and showed a lower incidence of dizziness in all patients.

Sirtuins as novel targets in the pathogenesis of airway inflammation in bronchial asthma.

Sirtuins are NAD-dependent class III histone deacetylase, which modulate the epigenetic changes to influence the functions in normal and diseased conditions. Preclinical studies have described an increase in the levels of sirtuin 2 and decrease in the levels of sirtuin 6 in the lungs. Sirtuin 2 exerts proinflammatory actions and hence, its blockers reduce the airway inflammation and symptoms of asthma. On the other hand, sirtuin 6 is anti-inflammatory and its activators produce beneficial actions in asthma. The beneficial effects of sirtuin 6 have been attributed to decrease in acetylation of transcriptional factor GATA3 in the T cells, which is associated with decrease in the TH2 immune response. However, there seems to be dual role of sirtuin 1 in airway inflammation as its proinflammatory as well as anti-inflammatory actions have been described in asthma. The anti-inflammatory actions of sirtuin 1 have been attributed to decrease in acetylation of GATA3 and inhibition of Akt/NF-kappaB signaling. On the other hand, proinflammatory actions of sirtuin 1 have been attributed to increase in the expression of HIF-1α and VEGF along with repression of PPAR-γ activity. The present review discusses the role of different sirtuins in the pathogenesis of bronchial asthma. Moreover, it also discusses sirtuin-triggered signaling pathways that may contribute in modulating the disease state of bronchial asthma.

Lutein protects against ß-amyloid peptide-induced oxidative stress in cerebrovascular endothelial cells through modulation of Nrf-2 and NF-κb.

In the present study, we determined the protective role of lutein against Aß 25-35 peptide-induced oxidative stress and apoptosis in bEND.3 cells. Cell viability was determined through MTT assay. Reactive oxygen species, lipid peroxides, and antioxidant enzyme activities were evaluated to analyze the oxidative stress status. NF-κB and Nrf-2 downstream target protein expressions were determined through western blot. Apoptosis was analyzed through caspase activities and subG1 accumulation. The results showed that Aß 25-35 significantly increased (p < 0.001) oxidative stress biomarkers. Aß 25-35 significantly up-regulated NF-κB nuclear expression and down-regulated Nrf-2 levels and HO-1 and, NQO-1 expressions. Aß 25-35 induced apoptosis through decreasing mitochondrial membrane potential and increasing caspase 9 and 3 activities. Lutein pre-treatment significantly (p < 0.001) improved cell viability and decreased ROS levels (p < 0.001) and lipid peroxidation (p < 0.01). Lutein prevented Aß 25-35-induced NF-κB nuclear expressions and up-regulated Nrf-2 expressions. Further, lutein also improved mitochondrial membrane potential and down-regulated caspase activities and subG1 accumulation. The present study shows the protective role of lutein against Aß 25-35-induced toxicity by modulating Nrf-2 and NF-κB expressions in cerebrovascular endothelial cells.

[Early predictors of necrotizing pneumonia in children].

OBJECTIVE: To investigate the early predictors of necrotizing pneumonia in children. METHODS: The clinical data of 43 children with necrotizing pneumonia and 83 children with lobar pneumonia were retrospectively analyzed. Sex, age, the number of days with fever, laboratory examination results, and bronchoscopic findings were compared between the two groups. The multiple logistic regression analysis was used to identify the early predictors of necrotizing pneumonia. RESULTS: The necrotizing pneumonia group had a higher percentage of girls than the lobar pneumonia group (P<0.05). Compared with the lobar pneumonia group, the necrotizing pneumonia group had a larger number of days with fever, a higher peripheral blood white blood cell count (WBC), a higher percentage of neutrophils (NE%), and higher serum levels of high-sensitivity C-reactive protein (hs-CRP), albumin (Alb), and lactate dehydrogenase (LDH) (P<0.05). The necrotizing pneumonia group also had higher percentages of children with a large amount of sputum bolt under a bronchoscope which needed to be removed with biopsy forceps and children with rice-water-like bronchoalveolar lavage fluid (P<0.05). The multiple logistic regression analysis showed that being a female, the presence of sputum bolt under a bronchoscope which needed to be removed with biopsy forceps, the number of days with fever, WBC, hs-CRP, and LDH were independent predictors of necrotizing pneumonia. The receiver operating characteristic curve analysis showed that the cut-off values of the latter 4 predictors were 18.5 d, 15.1×10(9)/L, 121.5 mg/L, and 353.5 U/L, respectively. CONCLUSIONS: Increased WBC (≥15.1×10(9)/L), increased hs-CRP (≥121.5 mg/L), increased serum LDH (≥353.5 U/L), and the presence of sputum bolt under a bronchoscope which needs to be removed with biopsy forceps and rice-water-like bronchoalveolar lavage fluid may be the early predictors of necrotizing pneumonia in children.