Follicular CD8+ T cells promote immunoglobulin production and demyelination in multiple sclerosis and a murine model.

Emerging evidence underscores the importance of CD8+ T cells in the pathogenesis of multiple sclerosis (MS), but the precise mechanisms remain ambiguous. This study intends to elucidate the involvement of a novel subset of follicular CD8+ T cells (CD8+CXCR5+ T) in MS and an experimental autoimmune encephalomyelitis (EAE) murine model. The expansion of CD8+CXCR5+ T cells was observed in both MS patients and EAE mice during the acute phase. In relapsing MS patients, higher frequencies of circulating CD8+CXCR5+ T cells were positively correlated with new gadolinium-enhancement lesions in the central nervous system (CNS). In EAE mice, frequencies of CD8+CXCR5+ T cells were also positively correlated with clinical scores. These cells were found to infiltrate into ectopic lymphoid-like structures in the spinal cords during the peak of the disease. Furthermore, CD8+CXCR5+ T cells, exhibiting high expression levels of ICOS, CD40L, IL-21, and IL-6, were shown to facilitate B cell activation and differentiation through a synergistic interaction between CD40L and IL-21. Transferring CD8+CXCR5+ T cells into naïve mice confirmed their ability to enhance the production of anti-MOG35-55 antibodies and contribute to the disease progression. Consequently, CD8+CXCR5+ T cells may play a role in CNS demyelination through heightening humoral immune responses.

Effects of light qualities on growth and physiological-biochemical traits of Scutellaria baicalensis.

Canopy spectral composition significantly affects growth and functional traits of understory plants. In this study, we explored the optimal light condition suitable for enhancing Scutellaria baicalensis's yield and quality, aiming to provide scientific reference for the exploitation and utilization of medicinal plant resources in the understory of forests. We measured the responses of growth, morphology, biomass allocation, physiological traits, and secon-dary metabolites of S. baicalensis to different light qualities. S. baicalensis was cultured under five LED-light treatments including full spectrum light (control), ultraviolet-A (UV-A) radiation, blue, green, and red light. Results showed that UV-A significantly reduced plant height, base diameter, leaf thickness, leaf area ratio, and biomass of each organ. Red light significantly reduced base diameter, biomass, effective quantum yield of photosystem Ⅱ (ФPSⅡ), and total flavonoid concentration. Under blue light, root length and total biomass of S. baicalensis significantly increased by 48.0% and 10.8%, respectively, while leaf number and chlorophyll content significantly decreased by 20.0% and 31.6%, respectively. The other physiological and biochemical traits were consistent with their responses in control. Our results suggested that blue light promoted photosynthesis, biomass accumulation, and secondary metabolite synthesis of S. baicalensis, while red light and UV-A radiation negatively affected physiological and biochemical metabolic processes. Therefore, the ratio of blue light could be appropriately increased to improve the yield and quality of S. baicalensis.

Cardiovascular safety of febuxostat versus allopurinol among the Asian patients with or without gout: A systematic review and meta-analysis.

The cardiovascular (CV) safety of febuxostat compared to allopurinol for the treatment of hyperuricemia among Asian patients is uncertain. In this study, we conducted a systematic review and meta-analysis to compare the CV safety profiles of febuxostat with allopurinol in Asian patients with hyperuricemia. A total of 13 studies were included. On the basis of the pooled results of cohort studies, febuxostat users were at a significantly higher risk for acute coronary syndrome (ACS; hazard ratio [HR]: 1.06, 95% confidence interval [CI]: 1.03-1.09, p < 0.01), atrial fibrillation (HR: 1.19, 95% CI: 1.05-1.35, p < 0.01) than allopurinol users, whereas no significant difference between febuxostat and allopurinol existed for urgent coronary revascularization (HR: 1.07, 95% CI: 0.98-1.16, p = 0.13), and stroke (HR: 0.96, 95% CI: 0.91-1.01, p = 0.13). Nevertheless, that difference in results of acute decompensated heart failure (ADHF; HR: 0.73, 95% CI: 0.35-1.53, p = 0.40) and all-cause death (HR = 0.86, 95% CI: 0.49-1.51, p = 0.60) was not significant based on randomized controlled trials. In the Chinese subgroup, febuxostat could increase the risk of ADHF (HR: 1.22, 95% CI: 1.01-1.48, p < 0.05), CV death (HR: 1.25, 95% CI: 1.03-1.50, p < 0.05), and all-cause mortality (HR: 1.07, 95% CI: 1.01-1.14, p < 0.05) compared to allopurinol. In conclusion, the use of febuxostat, compared with allopurinol among Asian patients, was associated with a significantly increased risk of adverse CV events.

Dual-energy CT-based radiomics in predicting EGFR mutation status non-invasively in lung adenocarcinoma.

Objectives: Patients with epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma (LUAD) can benefit from individualized targeted therapy. This study aims to develop, compare, analyse prediction models based on dual-energy spectral computed tomography (DESCT) and CT-based radiomic features to non-invasively predict EGFR mutation status in LUAD. Materials and methods: Patients with LUAD (n = 175), including 111 patients with and 64 patients without EGFR mutations, were enrolled in the current study. All patients were randomly divided into a training dataset (122 cases) and validation dataset (53 cases) at a ratio of 7:3. After extracting CT-based radiomic, DESCT and clinical features, we built seven prediction models and a nomogram of the best prediction. Receiver operating characteristic (ROC) curves and the mean area under the curve (AUC) values were used for comparisons among the models to obtain the best prediction model for predicting EGFR mutations. Results: The best distinguishing ability is the combined model incorporating radiomic, DESCT and clinical features for predicting the EGFR mutation status with an AUC of 0.86 (95 % CI: 0.79-0.92) in the training group and an AUC value of 0.83 (95 % CI: 0.73, 0.96) in the validation group. Conclusions: Our study provides a predictive nomogram non-invasively with a combination of CT-based radiomic, DESCT and clinical features, which can provide image-based biological information for targeted therapy of LUAD with EGFR mutations.

Safety and efficacy of percutaneous electrocoagulation haemostasis in the treatment of grade IV haemorrhagic cystitis after allogeneic haematopoietic stem cell transplantation in children: a retrospective analysis.

BACKGROUND: To investigate the efficacy and safety of endoscopic electrocoagulation haemostasis via a percutaneous transhepatic approach for the treatment of grade IV haemorrhagic cystitis (HC) after allogeneic haematopoietic stem cell transplantation (allo-HSCT) in children. METHODS: The clinical data of 14 children with severe HC, who were admitted to Hebei Yanda Hospital between July 2017 and January 2020, were analysed retrospectively. There were nine males and five females, with an average age of 8.6 years (range: 3 to 13 years). After an average of 39.6 (7 to 96) days of conservative treatment in the hospital's haematology department, the bladders of all patients were filled with blood clots. A small 2-cm incision was made in the suprapubic area to enter the bladder and quickly clear the blood clots, and a percutaneous transhepatic approach to electrocoagulation and haemostasis was performed. RESULTS: In the 14 children, a total of 16 operations were performed, with an average operation time of 97.1 (31 to 150) min, an average blood clot of 128.1 (80 to 460) mL and an average intraoperative blood loss of 31.9 (20 to 50) mL. There were three cases of postoperative bladder spasm remission after conservative treatment. During the follow-up period of 1 to 31 months, one patient improved after one operation, 11 patients were cured after one operation, and two patients were cured after recurrent haemostasis by secondary electrocoagulation, four of whom died of postoperative non-surgical blood-related diseases and severe lung infections. CONCLUSION: Percutaneous electrocoagulation haemostasis can quickly remove blood clots in the bladders of children after allo-HSCT with grade IV HC. It is a safe and effective minimally invasive treatment.

IGF2BP2 promotes colorectal cancer progression by upregulating the expression of TFRC and enhancing iron metabolism.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive system, ranking third for morbidity and mortality worldwide. At present, no effective control method is available for this cancer type. In tumor cells, especially iron metabolization, is necessary for its growth and proliferation. High levels of iron are an important feature to maintain tumor growth; however, the overall mechanism remains unclear. METHODS: We used western blotting, immunohistochemistry (IHC) and real-time quantitative PCR to analyze the expression of IGF2BP2 in cell lines and tissues. Further, RNA-sequencing, RNA immunoprecipitation and methylated RNA immunoprecipitation experiments explored the specific binding of target genes. Moreover, the RNA stability assay was performed to determine the half-life of genes downstream of IGF2BP2. In addition, the Cell Counting Kit-8, colony formation assay, 5-ethynyl-2'-deoxyuridine assay and flow cytometry were used to evaluate the effects of IGF2BP2 on proliferation and iron metabolism. Lastly, the role of IGF2BP2 in promoting CRC growth was demonstrated in animal models. RESULTS: We observed that IGF2BP2 is associated with iron homeostasis and that TFRC is a downstream target of IGF2BP2. Further, overexpression of TFRC can rescue the growth of IGF2BP2-knockdown CRC cells. Mechanistically, we determined that IGF2BP2 regulates TFRC methylation via METTL4, thereby regulating iron metabolism and promoting CRC growth. Furthermore, using animal models, we observed that IGF2BP2 promotes CRC growth. CONCLUSION: IGF2BP2 regulates TFRC mRNA methylation via METTL4, thereby regulating iron metabolism and promoting CRC growth. Our study highlights the key roles of IGF2BP2 in CRC carcinogenesis and the iron transport pathways.

Machine learning for identifying benign and malignant of thyroid tumors: A retrospective study of 2,423 patients.

Thyroid tumors, one of the common tumors in the endocrine system, while the discrimination between benign and malignant thyroid tumors remains insufficient. The aim of this study is to construct a diagnostic model of benign and malignant thyroid tumors, in order to provide an emerging auxiliary diagnostic method for patients with thyroid tumors. The patients were selected from the Chongqing General Hospital (Chongqing, China) from July 2020 to September 2021. And peripheral blood, BRAFV600E gene, and demographic indicators were selected, including sex, age, BRAFV600E gene, lymphocyte count (Lymph#), neutrophil count (Neu#), neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), red blood cell distribution width (RDW), platelets count (PLT), red blood cell distribution width-coefficient of variation (RDW-CV), alkaline phosphatase (ALP), and parathyroid hormone (PTH). First, feature selection was executed by univariate analysis combined with least absolute shrinkage and selection operator (LASSO) analysis. Afterward, we used machine learning algorithms to establish three types of models. The first model contains all predictors, the second model contains indicators after feature selection, and the third model contains patient peripheral blood indicators. The four machine learning algorithms include extreme gradient boosting (XGBoost), random forest (RF), light gradient boosting machine (LightGBM), and adaptive boosting (AdaBoost) which were used to build predictive models. A grid search algorithm was used to find the optimal parameters of the machine learning algorithms. A series of indicators, such as the area under the curve (AUC), were intended to determine the model performance. A total of 2,042 patients met the criteria and were enrolled in this study, and 12 variables were included. Sex, age, Lymph#, PLR, RDW, and BRAFV600E were identified as statistically significant indicators by univariate and LASSO analysis. Among the model we constructed, RF, XGBoost, LightGBM and AdaBoost with the AUC of 0.874 (95% CI, 0.841-0.906), 0.868 (95% CI, 0.834-0.901), 0.861 (95% CI, 0.826-0.895), and 0.837 (95% CI, 0.802-0.873) in the first model. With the AUC of 0.853 (95% CI, 0.818-0.888), 0.853 (95% CI, 0.818-0.889), 0.837 (95% CI, 0.800-0.873), and 0.832 (95% CI, 0.797-0.867) in the second model. With the AUC of 0.698 (95% CI, 0.651-0.745), 0.688 (95% CI, 0.639-0.736), 0.693 (95% CI, 0.645-0.741), and 0.666 (95% CI, 0.618-0.714) in the third model. Compared with the existing models, our study proposes a model incorporating novel biomarkers which could be a powerful and promising tool for predicting benign and malignant thyroid tumors.

Micronodular thymoma with lymphoid stroma: Contrast-enhanced CT features with histopathological correlation in 10 patients.

Objectives: This study aimed to evaluate and summarize the contrast-enhanced computed tomography (CECT) imaging features of micronodular thymoma with lymphoid stroma (MTWLS) based on all MTWLS patients at our institution and was the first imaging study of MTWLS worldwide. Methods: This retrospective study included 10 MTWLS patients who underwent CECT between April 2012 and November 2021. We collected and analyzed the CECT imaging features, including the location, size, shape, tumor density, classification, and CT value of the solid component. Descriptive statistical analysis was performed using the SPSS software (version 26.0; IBM). Results: Ten patients (five males [50%], five females [50%]; median age, 61.4 years; range, 54-72 years) underwent CECT. Of the 10 cases, one case was purely cystic, seven cases were cystic-solid, and two cases were purely solid. Six cases were round/oval in shape, and four cases were irregularly shaped. Excluding a purely cystic tumor with an unmeasurable degree of enhancement, two cases showed moderate enhancement, and seven cases showed significant enhancement. Among the solid or cystic-solid cases, the mean CT value of the measurable solid component on the enhanced scan was 93.9 HU. Nine masses were located adjacent to the mediastinal pleura, pericardium, or large vessels. Additionally, there were no malignant tumor signs in any patient, including penetration of the mediastinal pleura or involvement of the pericardium, pleural effusion, elevation of the diaphragm, or direct vascular invasion. Conclusion: MTWLS demonstrates certain features on CECT, such as a high rate of cystic change, significant solid component enhancement, and no malignant, invasive imaging features. These CECT features are helpful for diagnosing MTWLS.

Fat-to-muscle ratio as a predictor for dyslipidaemia in transitional-age youth.

BACKGROUND: Although dyslipidaemia may have a crucial impact on cardiovascular health in adults, there is a lack of specific data in transitional-age youth. Therefore, this study attempted to evaluate the association of dyslipidaemia with fat-to-muscle ratio (FMR), and establish FMR thresholds for diagnosing dyslipidaemia in transitional-age youth. METHODS: One thousand six hundred sixty individuals aged 16 to 24 years from the baseline of a subcohort in the Northwest China Natural Population Cohort: Ningxia Project were analysed. Anthropometric characteristics were gauged by a bioelectrical impedance analyser, and dyslipidaemia components were measured using a Beckman AU480 chemistry analyser. Additionally, this study used logistic regression to estimate the risk of dyslipidaemia based on FMR quintiles, and calculate the gender-specific ideal cut-off values of dyslipidaemia and its components by the receiver operating characteristic (ROC) curve. RESULTS: Of the 1660 participants, aged 19.06 ± 1.14 years, 558 males and 1102 females. The prevalence of dyslipidaemia was 13.4% and was significantly associated with FMR quintiles among all participants (P < 0.05). The ideal values of FMR in diagnosing dyslipidaemia were 0.2224 for males and 0.4809 for females, while males had a higher AUC than females (0.7118 vs. 0.6656). Meanwhile, high FMR values were significantly associated with adverse outcomes of dyslipidaemia, hypercholesterolemia and hypertriglyceridaemia (P < 0.05). CONCLUSIONS: The FMR was positively correlated with the prevalence of dyslipidaemia. The FMR can be used as an effective body composition index for diagnosing dyslipidaemia, especially in males, and preventive strategies should be initiated in transitional-age youth to decrease obesity-related dyslipidaemia.

[Variation characteristics of plant electrical signal and their relationship with negative air ion under different light intensities.] / ä¸åŒå ‰ç §å¼ºåº¦ä¸‹æ¤ç‰©ç”µä¿¡å·å˜åŒ–ç‰¹å¾åŠå ¶ä¸Žç©ºæ°”è´Ÿç¦»å­çš„å ³ç³».

Negative air ion (NAI) is an essential indicator for measuring air cleanliness of a given area, with vital role in regulating psychological and physiological functions of human body. The photoelectric effect is an important source and influencing factor for the generation of NAI during photosynthesis, but the photoelectric effect is extremely weak and difficult to monitor. Plant electrical signal is an important indicator that indirectly reflects photoelectric effect. Previous studies mostly focused on the spatiotemporal variation of NAI in different forest communities and its relationship with meteorological factors. At present, there is little research on NAI and plant electrical signal. In this study, we explored the effect of different light intensities (0, 150, 300, 500, 700, 800, 1000 and 1200 µmol·m-2·s-1) on characteristics of the plant electrical signal and its relationship with negative air ion, with Pinus bungeana as the research object. The results showed that the intensity of plant electrical signal increased significantly with the increases of light intensity in the illumination range of 0-700 µmol·m-2·s-1. When light intensity reached 700 µmol·m-2·s-1, plant electrical signal activity reached the highest level, and plant was inhibited by light when light intensity increased further, with plant electrical signal activity decreased. The frequency-domain parameters (edge frequency, gravity frequency, power spectrum entropy and power spectrum peak) of plant electrical signals were significantly correlated with NAI. The correlation coefficient between edge frequency (E) and NAI was the highest, the relationship between them was NAI=30.981E+168.814 (R2=0.54), and the mean square error was 52.203. There was a significant correlation between plant electrical signals and NAI, which could characterize the change rule of NAI, and provide scientific evidence for further understanding the contribution potential and production mechanism of forest to NAI.

Circular RNA circSNX6 promotes sunitinib resistance in renal cell carcinoma through the miR-1184/GPCPD1/ lysophosphatidic acid axis.

Sunitinib resistance is a major challenge in systemic therapy for renal cell carcinoma (RCC). The role of circular RNAs (circRNAs) in regulating sunitinib resistance of RCC is largely unknown. We established sunitinib-resistant RCC cell lines in vivo. Through RNA-sequencing, we identified circSNX6, whose expression is upregulated in sunitinib-resistant cells compared with their parental cells. High circSNX6 expression was correlated with sunitinib resistance and worse oncologic outcomes in a cohort of 81 RCC patients. In vitro and in vivo experiments confirmed that circSNX6 could promote sunitinib resistance in RCC. circSNX6 acts as a molecular "sponge" to relieve the suppressive effect of microRNA (miR)-1184 on its target gene, glycerophosphocholine phosphodiesterase 1 (GPCPD1), which increases intracellular lysophosphatidic acid (LPA) levels and, ultimately, promotes sunitinib resistance in RCC cells. Our findings demonstrated that the circSNX6/miR-1184/GPCPD1 axis had a critical role in regulation of intracellular LPA levels and sunitinib resistance in RCC; they also provide a novel prognostic indicator and promising therapeutic targets.

Predictive Value of the TP53/PIK3CA/ATM Mutation Classifier for Patients With Bladder Cancer Responding to Immune Checkpoint Inhibitor Therapy.

Background: Only a proportion of patients with bladder cancer may benefit from durable response to immune checkpoint inhibitor (ICI) therapy. More precise indicators of response to immunotherapy are warranted. Our study aimed to construct a more precise classifier for predicting the benefit of immune checkpoint inhibitor therapy. Methods: This multi-cohort study examined the top 20 frequently mutated genes in five cohorts of patients with bladder cancer and developed the TP53/PIK3CA/ATM mutation classifier based on the MSKCC ICI cohort. The classifier was then validated in a validation set consisting of IMvigor210 cohort and Broad/Dana-Farber cohort. The molecular profile and immune infiltration characteristics in each subgroup as defined by this classifier were explored. Results: Among all 881 patients with bladder cancer, the mutation frequency of TP53, PIK3CA, and ATM ranked in the top 20 mutated genes. The TP53/PIK3CA/ATM mutation classifier was constructed based on the Memorial Sloan Kettering Cancer Center (MSKCC) ICI cohort and only showed predictive value for patients with bladder cancer who received ICI therapy (median overall survival: low-risk group, not reached; moderate-risk group, 13.0 months; high-risk group, 8.0 months; P<0.0001). Similar results were found in subgroups of MSKCC ICI cohort defined by tumor mutation burden. Multivariate Cox analysis revealed that the risk group defined by the classifier served as an independent prognostic factor for overall survival in patients with bladder cancer. Efficacy of the classifier was verified in a validation set consisting of IMvigor210 cohort and Broad/Dana-Farber cohort. Lower expression of PD-1/PD-L1 and less tumor immune infiltration were observed in the high-risk group than the other two groups of the TCGA cohort and the IMvigor210 cohort. Conclusion: Our study constructed a TP53/PIK3CA/ATM mutation classifier to predict the benefit of immune checkpoint inhibitor therapy for patients with bladder cancer. This classifier can potentially complement the tumor mutation burden and guide clinical ICI treatment decisions according to distinct risk levels.

The Association Between Sarcopenic Obesity and Hypertension, Diabetes, and Abnormal Lipid Metabolism in Chinese Adults.

OBJECTIVE: Sarcopenic obesity is associated with several negative health outcomes. However, there are only a few studies on the relationship between SO and metabolic diseases such as diabetes, hypertension, and abnormal lipid metabolism in Chinese adults. The aim of this work was to evaluate the association between SO and hypertension, diabetes, and abnormal lipid metabolism in Chinese adults, and explore the prediction of SO using relevant anthropometric indicators. MATERIALS AND METHODS: All participants underwent a questionnaire interview for the collection of demographic data. Thereafter, they underwent physical examination for the measurement of anthropometric variables, which was performed using bioelectrical impedance analysis. Biochemical measurements were determined according to standard laboratory procedures used for the evaluation of blood parameters. RESULTS: We included 14,926 patients aged 35-74 years old. The mean age of the participants was 56.75 ± 9.76 years old, and 39.80% of them were male. The mean body mass index (BMI) was 24.94 ± 3.40 kg/m2, and the overall prevalence of SO was 65.1%. The results showed that shorter people; people with faster heart rate; heavier weight; lower waist circumference (WC), BMI, triglyceride level, total cholesterol, and low-density lipoprotein cholesterol levels; and higher high-density lipoprotein cholesterol level are at risk for SO. CONCLUSION: The prevalence of SO is high (65.1%) in Chinese adults aged 35-74 years old. The occurrence of SO is related to hypertension, diabetes, and abnormal lipid metabolism. BMI, WC, and waist-hip ratio may be predictive indicators of SO. The incidence of SO may be reduced by timely intervention and health education for persons at risk of the condition.