Clinical evaluation of deep learning-based risk profiling in breast cancer histopathology and comparison to an established multigene assay.

PURPOSE: To evaluate the Stratipath Breast tool for image-based risk profiling and compare it with an established prognostic multigene assay for risk profiling in a real-world case series of estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative early breast cancer patients categorized as intermediate risk based on classic clinicopathological variables and eligible for chemotherapy. METHODS: In a case series comprising 234 invasive ER-positive/HER2-negative tumors, clinicopathological data including Prosigna results and corresponding HE-stained tissue slides were retrieved. The digitized HE slides were analysed by Stratipath Breast. RESULTS: Our findings showed that the Stratipath Breast analysis identified 49.6% of the clinically intermediate tumors as low risk and 50.4% as high risk. The Prosigna assay classified 32.5%, 47.0% and 20.5% tumors as low, intermediate and high risk, respectively. Among Prosigna intermediate-risk tumors, 47.3% were stratified as Stratipath low risk and 52.7% as high risk. In addition, 89.7% of Stratipath low-risk cases were classified as Prosigna low/intermediate risk. The overall agreement between the two tests for low-risk and high-risk groups (N = 124) was 71.0%, with a Cohen's kappa of 0.42. For both risk profiling tests, grade and Ki67 differed significantly between risk groups. CONCLUSION: The results from this clinical evaluation of image-based risk stratification shows a considerable agreement to an established gene expression assay in routine breast pathology.

Neonicotinoid insecticides and metabolites levels in neonatal first urine from southern China: Exploring links to preterm birth.

Neonicotinoids (NEOs) have indeed become the most widely used insecticides worldwide. Concerns have been raised about their potential impact on newborns due to maternal exposure and their unique neurotoxic mode of action. However, it is still poorly understood whether in utero exposure of pregnant women to environmental NEOs and their metabolites can cause carryover effects on vulnerable newborns and subsequent health consequences. In this study, we determined the concentrations of 13 NEOs and their metabolites in the first urine collected from 92 newborns, both preterm and full-term, in southern China during 2020 and 2021. NEOs and their metabolites were identified in 91 urine samples, with over 93% of samples containing a cocktail of these compounds, confirming their maternal-fetal transfer. N-desmethyl-acetamiprid, imidaclothiz, clothianidin and flonicamid were the most commonly detected analytes, with detection frequencies of 59-87% and medians of 0.024-0.291 ng/mL in the urine. The relative abundance of imidaclothiz was significantly higher in preterm newborns, those with head circumferences below 33 cm, birth lengths less than 47 cm, and weights below 2500 g (p < 0.05). When comparing newborns in the 2nd quartile of imidaclothiz concentrations with those in the 1st quartile, we observed a significant increase in the odds of preterm outcomes in the unadjusted model (odds ratio = 3.24, 95% confidence interval = 1.02-10.3). These results suggest that exposure to elevated concentrations of imidaclothiz may be associated with preterm birth.

Association between serum TSH levels and all-cause mortality in critically ill patients.

Thyroid dysfunction is common in critical illness and may influence prognosis. However, the value of TSH in patients with severe diseases remains unclear. The aim of this study was to investigate the association between TSH and the clinical prognosis of critically ill patients. Methods: This retrospective study identified patients who were admitted to the ICU in the Medical Information Mart for Intensive Care (MIMIC-IV) database (version 2.2). A total of 6432 patients were divided into four groups based on TSH quartiles (Q1, <0.92 mIU/L; Q2, 0.92-1.07 mIU/L; Q3, 1.07-3.10 mIU/L; Q4, >3.10 mIU/L). The clinical outcomes were defined as all-cause 7-, 30-, and 90-year mortality after ICU admission. Restricted cubic splines (RCSs) for nonlinear associations were generated to visualize the relationship between TSH levels and clinical outcomes. The survival differences among the four groups were also analyzed using Kaplan‒Meier curves and log rank tests. Univariable and multivariable Cox proportional hazards regression were further used to assess the association between TSH levels and clinical outcomes. Results: After multivariate adjustment, a U-shaped relationship was observed between TSH levels and all-cause 7-, 30-, and 90- mortality among patients with severe disease (all P < 0.05 for nonlinearity). The plot showed a risk reduction in the low range of TSH, which reached the lowest risk at approximately 2.9 µIU/mL and then increased thereafter. Compared with patients with Q3 TSH levels, those with Q1, Q2, and Q4 TSH levels had a significantly higher risk of all-cause 30-day mortality (Q1: hazard ratio, 1.28; 95% CI, 1.06-1.54; Q2: hazard ratio, 1.22; 95% CI, 1.01-1.48; Q4: hazard ratio, 1.25; 95% CI, 1.04-1.50). For all-cause 90-day mortality, only the Q4 group had a significantly higher mortality risk than the Q3 group (hazard ratio, 1.24; 95% CI, 1.07-1.44). In subgroup analyses, we found that Q1 TSH levels were associated with higher mortality risk in men and older (≥65 years) patients, while Q4 TSH had a greater risk in men and younger (<65 years) patients. Conclusions: TSH was significantly associated with all-cause 7-, 30-, and 90-day mortality in critically ill patients after admission to the ICU. TSH may serve as a valuable biomarker for risk stratification in critically ill patients.

Mechanically Durable Superhydrophobic Strain Sensors with High Biocompatibility and Sensing Performance for Underwater Motion Monitoring.

Much progress has been made toward the development of wearable flexible strain sensors with high sensing performance to monitor human motion, but continuous function in harsh aqueous environments remains a significant challenge. A promising strategy has been the design of sensors with highly durable superhydrophobicity and maintenance of unique sensing properties. Herein, an extremely durable superhydrophobic strain sensor with an ultrawide sensing range was simply fabricated by directly brushing conductive carbon black nanoparticles (CBNPs) onto an elastic silicone rubber sheet (SS) with poly(dimethylsiloxane) (PDMS) coatings (i.e., SS/PDMS-CBNPs sensors). First, this method avoided the use of toxic solvents and a conventional prestretching treatment. Second, considering the easily destroyed rough structures and surface chemistry for conventional superhydrophobic sensors during practical applications, the prepared SS/PDMS-CBNP sensors showed excellent mechanical durability of both superhydrophobicity and sensing as examined by harsh abrasion (300 cycles), stretching (up to 200%), and ultrasonication (40 min) treatments. Third, the prepared superhydrophobic strain sensor exhibited high sensitivity (gauge factor of 101.75), high stretchability (0.015-460%), low hysteresis (83 ms), and long-term stability (10000 cycles). Fourth, the high biocompatibility of the SS/PDMS-CBNP sensor was demonstrated by rabbit skin irritation tests. Finally, the remarkable water-repellent and sensing properties of the SS/PDMS-CBNP sensor allowed its application to monitor a swimmer's real-time situation and send distress signals when needed.

Anti-parietal cell antibodies as a potential biomarker for interstitial lung disease associated with primary Sjögren's syndrome / Anticuerpos contra las células parietales como biomarcadores potenciales de enfermedad pulmonar intersticial relacionada con el síndrome de Sjögren primario

Background ILD is a common manifestation in pSS and is associated with an increased risk of death. APCA are strongly expressed by hyperplastic alveolar epithelial cells in the fibrotic lung and are associated with an accelerated decline in lung function in IPF. In the present study, we aimed to evaluate the clinical utility of APCA in ILD patients with pSS. Methods Clinical, laboratory, PFTs and imaging data from pSS patients were reviewed, and the ESSDAI was utilized to evaluate disease activity. HRCT semiquantitative scoring was conducted. We compared the clinical characteristics of pSS patients with and without ILD and carried out logistic regression analysis of risk factors for ILD in pSS. Results A total of 74 patients with pSS and 40 HCs were included in the study. ILD was more commonly observed in the APCA-positive group than in the APCA-negative group. The quantitative levels of APCA were positively correlated with the imaging score. Multivariate analysis found that the long disease duration, elevated APCA and elevated KL-6 level were independent risk factors for ILD in pSS patients. The area under ROC curve for APCA was 0.6618, and the threshold concentration was 153.82ng/ml (sensitivity 45.24%, specificity 87.50%). Conclusion APCA level is an independent risk factor and might be a potential biomarker for ILD in patients with pSS (AU)

Antecedentes La enfermedad pulmonar intersticial (EPI) es una manifestación común del síndrome de Sjögren primario (SSp) y está relacionada con un mayor riesgo de muerte. Los anticuerpos anticélulas parietales (AACP) están fuertemente expresados por células epiteliales alveolares proliferantes en los pulmones fibróticos y están relacionados con la disminución acelerada de la función pulmonar en la gibrosis pulmonar idiopática. En este estudio, pretendemos evaluar la aplicación clínica de la AACP en pacientes con EPI con SSp. Método Se revisaron los datos clínicos, de laboratorio, de función pulmonar e imágenes de los pacientes con SSp y se utilizó la ESSDAI para evaluar la actividad de la enfermedad en general. Se registraron 5 características principales de imagen pulmonar de la EPI y 2 radiólogos ciegos experimentados realizaron una puntuación semicuantitativa de HRCT de forma independiente. Comparamos las características clínicas de los pacientes con y sin EPI con SSp y realizamos un análisis de regresión logística de los factores de riesgo de EPI en SSp. Resultados Un total de 74 pacientes con SSp y 40 controles sanos fueron incluidos en el estudio. La EPI es más común en el grupo positivo de AACP que en el grupo negativo de APCA. El nivel cuantitativo de AACP, está positivamente relacionado con la puntuación de imagen. El análisis multifactorial encontró que la larga duración, el aumento de los niveles de AACP y el aumento de los niveles de KL-6 fueron factores de riesgo independientes para la EPI en pacientes con SSp. El área bajo la curva ROC de AACP es de 0,6618 y la concentración umbral fue de 153,82 ng/ml (sensibilidad 45,24% y especificidad 87,50%). Conclusiones Los niveles de AACP son un factor de riesgo independiente y pueden ser biomarcadores potenciales de EPI en pacientes con SSp (AU)

Drug recommendation for optimization on treatment outcome for MDR/RR-TB based on a multi-center, large scale, retrospective cohort study in China.

OBJECTIVE: With the change in drug-resistant pattern, MDR/RR-TB was faced with underlying changes in regimens. A multi-center, large-scale, retrospective study performed aims to provide a recommendation of drug selection on optimization of outcome for the patients. METHOD: The study was conducted in six TB-specialized hospitals in China. Patients were included from 2018-2021 and followed up throughout the treatment. Using a multivarariable and propensity score-matched logistic regression analysis, we evaluated associations between outcomes and drug use, as well as clinical characteritics. RESULTS: Of 3112 patients, 74.29% had treatment sucess, 14.52% lost to follow-up, 9.67% failure, and 1.51% died. Treatment success was positively associated with Bedaquiline(Bdq), Linezolid(Lzd), and Cycloserin(Cs). Capreomycin(Cm) increased the risk of unfavorable outcomes. other drugs such as Amikacin(Amk) and clofazimine had no significant effect on outcomes. If isolates were susceptible to fluoroquinolones(FQs), FQs could decrease the risk of unfavorable outcomes. CONCLUSIONS: The recommendation order for the treatment of MDR/RR-TB is Bdq, Lzd, and Cs. FQs were decreased in use intensity. Injection drugs, whether Amk or Cm, are not recommended.

Sn Whiskers from Ti2 SnC Max Phase: Bridging Dual-Functionality in Electromagnetic Attenuation.

In the ever-evolving landscape of complex electromagnetic (EM) environments, the demand for EM-attenuating materials with multiple functionalities has grown. 1D metals, known for their high conductivity and ability to form networks that facilitate electron migration, stand out as promising candidates for EM attenuation. Presently, they find primary use in electromagnetic interference (EMI) shielding, but achieving a dual-purpose application for EMI shielding and microwave absorption (MA) remains a challenge. In this context, Sn whiskers derived from the Ti2 SnC MAX phase exhibit exceptional EMI shielding and MA properties. A minimum reflection loss of -44.82 dB is achievable at lower loading ratios, while higher loading ratios yield efficient EMI shielding effectiveness of 42.78 dB. These qualities result from a delicate balance between impedance matching and EM energy attenuation via adjustable conductive networks; and the enhanced interfacial polarization effect at the cylindrical heterogeneous interface between Sn and SnO2 , visually characterized through off-axis electron holography, also contributes to the impressive performance. Considering the compositional diversity of MAX phases and the scalable fabrication approach with environmental friendliness, this study provides a valuable pathway to multifunctional EM attenuating materials based on 1D metals.

Generating detailed intercellular communication patterns in psoriasis at the single-cell level using social networking, pattern recognition, and manifold learning methods to optimize treatment strategies.

Psoriasis, a complex and recurrent chronic inflammatory skin disease involving various inflammatory cell types, requires effective cell communication to maintain the homeostatic balance of inflammation. However, patterns of communication at the single-cell level have not been systematically investigated. In this study, we employed social network analysis tools, pattern recognition, and manifold learning to compare molecular communication features between psoriasis cells and normal skin cells. Utilizing a process that facilitates the discovery of cell type-specific regulons, we analyzed internal regulatory networks among different cells in psoriasis. Advanced techniques for the quantitative detection of non-targeted proteins in pathological tissue sections were employed to demonstrate protein expression. Our findings revealed a synergistic interplay among the communication signals of immune cells in psoriasis. B-cells were activated, while Langerhans cells shifted into the primary signaling output mode to fulfill antigen presentation, mediating T-cell immunity. In contrast to normal skin cells, psoriasis cells shut down numerous signaling pathways, influencing the balance of skin cell renewal and differentiation. Additionally, we identified a significant number of active cell type-specific regulons of resident immune cells around the hair follicle. This study unveiled the molecular communication features of the hair follicle cell-psoriasis axis, showcasing its potential for therapeutic targeting at the single-cell level. By elucidating the pattern of immune cell communication in psoriasis and identifying new molecular features of the hair follicle cell-psoriasis axis, our findings present innovative strategies for drug targeting to enhance psoriasis treatment.

Anti-parietal cell antibodies as a potential biomarker for interstitial lung disease associated with primary Sjögren's syndrome.

BACKGROUND: ILD is a common manifestation in pSS and is associated with an increased risk of death. APCA are strongly expressed by hyperplastic alveolar epithelial cells in the fibrotic lung and are associated with an accelerated decline in lung function in IPF. In the present study, we aimed to evaluate the clinical utility of APCA in ILD patients with pSS. METHODS: Clinical, laboratory, PFTs and imaging data from pSS patients were reviewed, and the ESSDAI was utilized to evaluate disease activity. HRCT semiquantitative scoring was conducted. We compared the clinical characteristics of pSS patients with and without ILD and carried out logistic regression analysis of risk factors for ILD in pSS. RESULTS: A total of 74 patients with pSS and 40 HCs were included in the study. ILD was more commonly observed in the APCA-positive group than in the APCA-negative group. The quantitative levels of APCA were positively correlated with the imaging score. Multivariate analysis found that the long disease duration, elevated APCA and elevated KL-6 level were independent risk factors for ILD in pSS patients. The area under ROC curve for APCA was 0.6618, and the threshold concentration was 153.82ng/ml (sensitivity 45.24%, specificity 87.50%). CONCLUSION: APCA level is an independent risk factor and might be a potential biomarker for ILD in patients with pSS.

Relationship between elevated circulating thrombospondin-1 levels and vascular complications in diabetes mellitus.

AIMS/INTRODUCTION: Thrombospondin-1 (TSP-1) participates in a series of physiological and pathological processes by binding to various receptors regulating cell proliferation, adhesion and apoptosis. Elevated circulating TSP-1 is linked with diabetic vascular complications (DVC). This study aimed to determine the relationship between circulating TSP-1 levels and DVC. MATERIALS AND METHODS: A comprehensive search of PubMed, Embase, Web of Science and CNKI databases was carried out. A meta-analysis was carried out to compare circulating TSP-1 levels between diabetes patients without vascular complications (DNVC), diabetes patients with DVC and non-diabetes patients. The correlation between TSP-1 and metabolic parameters was also analyzed. Subgroup analysis was carried out according to complication type, defined as diabetic retinopathy, diabetic nephropathy and diabetic cardiovascular disease (DCVD). RESULTS: A total of eight studies were included. Compared with non-diabetes patients, diabetic patients, including DNVC and DVC, had significantly higher circulating TSP-1 levels (standardized mean difference [SMD] 2.660, 95% CI 1.17-4.145, P = 0.000). DNVC had significantly higher circulating TSP-1 levels than non-diabetes patients (SMD 3.613, 95% CI 1.607-5.619, P = 0.000). DVC had significantly higher TSP-1 levels than DNVC (SMD 0.568, 95% CI 0.100-1.036, P = 0.017). TSP-1 was significantly positively correlated with fasting plasma glucose (overall Fisher's z = 0.696, 95% CI 0.559-0.833) and HbA1c (overall Fisher's z = 0.849, 95% CI 0.776-0.923). CONCLUSIONS: Elevated circulating TSP-1 levels are closely related to DVC, especially in diabetic nephropathy and diabetic cardiovascular disease. Circulating TSP-1 detection might be helpful in the timely diagnosis and treatment of DVC.

TGFß1 Stimulates Lymphatic Endothelial Cells to Produce IL7 and IL15, Which Act as Chemotactic Factors for Breast Cancer Cells with Mesenchymal Properties.

The lymphatic system is a major gateway for tumor cell dissemination but the mechanisms of how tumor cells gain access to lymphatic vessels are not completely understood. Breast cancer cells undergoing epithelial-mesenchymal transition (EMT) gain invasive and migratory properties. Overexpression of the cytokine transforming growth factor ß1 (TGFß1), a potent inducer of EMT, is frequently detected in the tumor microenvironment and correlates with invasion and lymph metastasis. Recently, we reported that TGFß1 stimulated breast cancer cells with mesenchymal properties to migrate in a targeted fashion towards the lymphatic system via CCR7/CCL21-mediated chemotaxis, similar to dendritic cells during inflammation. Here, we aimed to identify additional chemotactic factors and corresponding receptors that could be involved in guiding breast cancer cells through the lymphatic system. Through a combination of RNA sequencing analysis, database screening and invasion assays we identified IL7/IL7R and IL15/IL15R as pairs of chemokines and receptors with potential roles in promoting chemotactic migration of breast cancer cells with mesenchymal properties towards the lymphatics. The results demonstrate the capacity of TGFß1 to orchestrate crosstalk between tumor cells and lymphatic endothelial cells and warrant further studies to explore the roles of IL7 and IL15 in promoting lymph metastasis of breast cancer.

Efficacy and safety of the all-oral bedaquiline-containing regimen as treatment for pediatric multidrug/rifampicin-resistant tuberculosis: a multicenter, retrospective, cohort study.

OBJECTIVE: The study aimed to observe the efficacy and safety of an all-oral bedaquiline (BDQ)-containing regimen for pediatric multidrug/rifampicin-resistant tuberculosis (MDR/RR-TB) through a multicenter, retrospective study in China. METHODS: In the study, pediatric patients receiving all-oral BDQ-containing regimen (BDQ group) with clinical matched control group were included, the control group received an injection-containing regimen. The treatment outcomes and the incidence of adverse events (AEs) were compared and analyzed. RESULTS: 79 pediatric patients were enrolled, including 37 cases in BDQ group and 42 cases in the control group, the median age was 12 {8-16} and 11 {9-15} in both groups respectively. Favorable treatment outcome and cure rate in BDQ group were significantly higher than those in control group (100%vs 83.3%, p 0.03; 94.6%vs 63.3%, p 0.00). Median time of sputum culture conversion in BDQ group was significantly shorter than that in the control group (4 weeks vs 8 weeks, p 0.00). The incidence of AEs in the BDQ group was significantly less than that in the control group (48.6% vs 71.4%, p 0.03). No AEs leading to treatment discontinuation of BDQ occurred. CONCLUSIONS: The all-oral BDQ-containing regimens may be effective and safe in the Chinese pediatric population.

Real-world efficacy of belimumab in systemic lupus erythematosus: a prospective cohort from a single center in China.

OBJECTIVES: To explore the efficacy and safety of belimumab among Chinese patients with systemic lupus erythematosus (SLE) in a real-world setting. METHODS: A prospective cohort study was performed, and SLE patients taking belimumab on a background of standard-of-care (SoC) treatment were consecutively enrolled from June 2021 to December 2022. Based on baseline characteristics, patients were divided into three groups: the newly diagnosed group, the relapsed group and the refractory group. Patients in the newly diagnosed group were newly diagnosed with SLE within 4 weeks of starting belimumab. Patients in the relapse group experienced a severe flare. Refractory patients were patients with unsatisfactory glucocorticoid taper and/or disease activity control. Clinical data were collected, and disease assessments were conducted regularly. Newly diagnosed patients with SoC alone and healthy controls (HCs) were also enrolled. RESULTS: A total of 123 SLE patients were included in the analysis, with a median follow-up period of 12 months (range 3-18 months). Thirty-three out of 123 patients were newly diagnosed, 32 had relapsed disease, and 58 had refractory disease. The SRI-4 response was achieved with good tolerance by 55.77% of patients at 3 months, 56.63% at 6 months, 63.24% at 9 months, 63.64% at 12 months, and 57.14% at 18 months. Serological parameters (anti-dsDNA and C3/C4), SLEDAI-2K and daily prednisone intake were improved overall and in each group. Among the 3 groups, the newly diagnosed group had the highest SRI-4 rate as well as the greatest improvement in serological parameters and SLEDAI-2K. Compared with newly diagnosed patients with SoC alone, the cumulative prednisone intake of newly diagnosed patients taking belimumab was significantly decreased. CONCLUSION: Our data supported the efficacy of belimumab in Chinese SLE patients in a real-life setting. Our study also provided new evidence showing remarkable achievement of the SRI-4 response during belimumab treatment in newly diagnosed SLE patients.

The effects of background music tempo on consumer variety-seeking behavior: the mediating role of arousal.

Diversified purchases of consumers can help companies balance sales and inventories, which is of great significance to company profits. While existing research has explored the internal factors and external factors that influence consumers' variety-seeking behavior, little is known about the impact of background music, an important environmental cue in retail establishments, on consumer variety-seeking behavior. The present research investigates the influence of background music tempo on consumer variety-seeking behavior, along with its underlying mechanism and boundary condition. Five experiments revealed that background music tempo affects consumers' variety-seeking behavior (Study 1a, 1b & 4). Specifically, fast-tempo background music increases consumers' variety-seeking behavior (Study 1b). Arousal mediates the main effect (Study 2), as fast-tempo background music increases consumers' variety-seeking behavior by enhancing consumers' arousal. Moreover, participants' familiarity with the background music moderates the impact of background music tempo on consumer variety-seeking behavior (Study 3). Only when consumers have a high degree of familiarity with the background music they listen to, the tempo of the background music will have a significant impact on their variety-seeking behavior. These findings provide important theoretical contributions and management implications.

Establishment and Validation of a Predictive Model for Post-Treatment Anxiety Based on Patient Attributes and Pre-Treatment Anxiety Scores.

Objective: In this study, we aim to establish and evaluate a predictive model for post-treatment anxiety state based on basic patient attributes and pre-treatment SAS scores, with the expectation that this model will guide clinical precision intervention. Methods: Data were collected from 606 patients with breast cancer who underwent surgery at our hospital between January 1, 2015 and December 30, 2018 and 144 newly diagnosed patients with breast cancer who were admitted between June 1, 2019 and December 30, 2019, for a total of 750 patients with breast cancer. The relationship between SAS_A scores and prognosis was verified by analyzing patient baseline characteristics, follow-up data, pre-treatment self-rating anxiety scale (SAS) scores, and SAS_A scores in follow-up period after the end of treatment. A risk prediction model was developed in view of the SAS_A scores, which was then screened, validated, and simplified by scoring, with a nomogram plotted. Results: The SAS_A score can be utilized to differentiate prognosis. In K-M analysis, the high SAS_A score group had a significantly poorer progression-free survival rate than the low score group, p-value < 0.0001. Through model feature selection and clinical analysis, all variables were finally incorporated to establish a predictive model with a ROC AUC of 0.721 (0.637-0.805) for the validation set and external data, and an AUC of 0.810 (0.719-0.902) for external data, demonstrating good predictive performance. Calibration curves and probability distribution maps were constructed. DCA and CIC analyses demonstrated that model intervention could boost clinical benefits more effectively than intervention for all patients. Conclusion: Using a predictive model to guide clinical management for anxiety in breast cancer patients is feasible, but additional research is required.

The Effect of Preventing Oxidative Stress and Its Mechanisms in the Extract from Sonchus brachyotus DC. Based on the Nrf2-Keap1-ARE Signaling Pathway.

As the organ with the largest contact area with the outside world, the intestine is home to a large number of microorganisms and carries out the main functions of food digestion, absorption, and metabolism. Therefore, there is a very active metabolism of substances and energy in the gut, which is easily attacked by oxygen free radicals. What is more, oxidative stress can gradually and slowly cause very serious damage to the gut. Hence, maintaining redox balance is essential for maintaining environmental balance in the gut. Our previous studies have demonstrated that the extract of Sonchus brachyotus DC. (SBE) has been shown to be capable of repairing oxidative damage, while it has not been demonstrated that it can prevent oxidative stress or how it develops. In this work, we investigated the prevention of oxidative stress and its mechanism in SBE based on the H2O2-induced oxidative damage model in Caco-2 cells; the results indicate that SBE can reduce the contents of ROS and MDA and increase the activities of SOD and CAT in preventing oxidative stress. Then, at the mRNA and protein level, SBE can up-regulate and down-regulate the expression of related genes (NFE2L2, KEAP1, HMOX1, NQO1, SOD1, CAT, and GPX1) and proteins involved in the Nrf2-Keap1-ARE signaling pathway. In conclusion, SBE plays a preventive role in oxidative stress through the Nrf2-Keap1-ARE signaling pathway.

The Safety and Efficacy of Prolonged Use of Bedaquiline for the Treatment of Patients with Pulmonary Multi-Drug Resistant/Rifampin-Resistant Tuberculosis: A Prospective, Cohort Study in China.

Objective: To evaluate the safety, tolerability, and efficacy of prolonged bedaquiline (Bdq) treatment in patients with multi-drug/rifampin-resistant tuberculosis (MDR/RR-TB). Methods: This prospective cohort study was performed from August 2018 to August 2021. Patients diagnosed with MDR/RR-TB who met the inclusion criteria were prospectively included. Patients were treated with individual regimens of 18-20 months containing Bdq for six months or a prolonged course of nine or 12 months according to treatment demands, and the efficacy and safety with a different course of Bdq-containing regimens were compared and evaluated. Results: A total of 159 MDR/RR-TB patients were included in the study, including 96 cases with six months of Bdq, 50 cases with nine months of Bdq, and 13 patients with 12 months of Bdq. The treatment success rates were 89.6%, 90%, and 84.6% in Bdq at six months, nine months, and 12 months, respectively, which were not statistically different (P = 0.85). The main adverse events (AEs) were anemia, thrombocytopenia, and liver dysfunction in all patients, with no significant difference among the three groups. Patients who had fewer drugs chosen, disseminated lesions or lesions that were slowly absorbed, and severe cavities were the common reasons for prolonged use of Bdq. Conclusion: Prolonged course use of Bdq from six months to 12 months clinically proved to be safe and efficient, and patients with severe or disseminated lesions had the chance to prolong the use of Bdq for more than six months to achieve optimal treatment outcomes.

Target Exposome for Characterizing Early Gestational Exposure to Contaminants of Emerging Concern and Association with Gestational Diabetes Mellitus.

Characterization of gestational exposure to complex contaminants of emerging concern (CECs) is critical to the identification of environmental risk factors for pregnancy complications. However, determination of various CECs with diverse physicochemical properties in biological fluids is technically challenging. In the present study, we developed a target exposome protocol, consisting of simple liquid-liquid extraction-based sample preparation and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis, to determine 325 CECs covering 11 subclasses, including poly- and perfluoroalkyl substances, organophosphate esters, ultraviolet (UV) stabilizers, synthetic antioxidants, phthalate esters, and several others. The protocol exhibits exceptional advantages over traditional approaches in the coverage of chemicals, sample volume demand, and time and financial cost. The protocol was applied in a prospective nested gestational diabetes mellitus (GDM) study including 120 cases and 240 matched healthy controls. Thirty-three CECs were detected in >70% of the samples, with a combined concentration of 17.0-484.7 ng/mL. Bayesian kernel machine regression analysis showed that exposure to the CEC mixture was significantly associated with a higher GDM risk. For example, when increasing all CECs in the mixture from 50th percentile to 75th percentile, the estimated probit of GDM incidence had an increase of 92% (95% CI: 56%, 127%). Meanwhile, perfluorohexanesulfonic acid, 1,3-diphenylguanidine, and dibutyl fumarate were identified as the key CECs driving the joint effect. This work demonstrates great potential of our target exposome protocol for environmental risk factor identification in large-scale epidemiology or biomonitoring studies.

New progress of tuberculosis scar carcinoma.

It has been demonstrated that scar tissue and fibrosis may increase the likelihood of developing malignancies. Specifically, scar tissue has been linked to the occurrence and progression of lung cancer (LC), though the precise mechanisms necessitate further research for explanation. Lung scarring can stem from various causes, with carcinogenesis on scarring lesions in pulmonary tuberculosis (PTB) being the most frequent (accounting for approximately 75% of cases). Notably, having previously cured, PTB is the second most common risk factor for LC after smoking, with approximately 3% of PTB patients experiencing LC as a secondary condition. This essay will delve into the mechanisms, treatment, and prognosis of tuberculosis scar carcinoma (TSC).