Evidence indicates that lung cancer development is a complex process that involves interactions between tumor cells, stromal fibroblasts, and immune cells. Tumor-infiltrating immune cells play a ...significant role in the promotion or inhibition of tumor growth. As an integral component of the tumor microenvironment, tumor-infiltrating B lymphocytes (TIBs) exist in all stages of cancer and play important roles in shaping tumor development. Here, we review recent clinical and preclinical studies that outline the role of TIBs in lung cancer development, assess their prognostic significance, and explore the potential benefit of B cell-based immunotherapy for lung cancer treatment.
Exosomes extracted from mesenchymal stem cells (MSCs) was reported to reduce myocardial ischemia/reperfusion damage. Besides, stromal‐derived factor 1 (SDF1a) functions as cardiac repair after ...myocardial infarction (MI). Therefore, the present study aims to identify whether exosomes (Exo) released from SDF1‐overexpressing MSCs display a beneficial effect on ischemic myocardial infarction. Initially, a gain‐of‐function study was performed to investigate the function of SDF1 in ischemic myocardial cells and cardiac endothelial cells. Coculture experiments were performed to measure potential exosomic transfer of SDF1 from MSCs to ischemic myocardial cells and cardiac endothelial cells. During the coculture experiments, exosome secretion was disrupted by neutral sphingomyelinase inhibitor GW4869 and upregulated exosomal SDF1 using SDF1 plasmid. Effects of Exo‐SDF1 on cardiac function in MI mice were investigated in vivo. MSCs suppressed myocardial cell apoptosis and promoted microvascular regeneration of endothelial cells through secretion of exosomes. The addition of GW4869 led to increased apoptotic capacity of myocardial cells, decreased microvascular formation ability of endothelial cells, enhanced autophagy ability, and elevated Beclin‐1 level as well as ratio of LC3II/LC3I. Overexpression of SDF1 and Exo‐SDF1 inhibited apoptosis and autophagy of myocardial cells, but promoted tube formation of endothelial cells. The interference of PI3K signaling pathway promoted apoptosis and autophagy of myocardial cells, but inhibited tube formation of endothelial cells. SDF1 activated the PI3K signaling pathway. Exo‐SDF1 protected cardiac function of MI mice and inhibited myocardial tissue damage. This study provided evidence that SDF1 overexpression in MSCs‐derived exosomes inhibited autophagy of ischemic myocardial cells and promoted microvascular production of endothelial cells.
Stromal‐derived factor 1 (SDF1) overexpression in mesenchymal stem cells (MSCs)‐derived exosomes inhibited autophagy of ischemic myocardial cells and promoted microvascular production of endothelial cells.
Circular RNAs (circRNAs) are stable and abundantly expressed in vivo but are abnormally expressed in several diseases. This study aimed to identify circRNAs acting as potential biomarkers for ...cardiovascular disease (CVD). Research were retrieved from the articles published by September 2018 in eight databases to compare circRNA expression profiles between CVD and non‐CVD in human and animal models. Meta‐analysis under a random effects model was conducted. Subgroup analysis of tissue, species, and disease‐specific circRNAs was examined. Sensitivity analysis was performed to explain the uncertainty among all studies. Diagnostic accuracy of circRNAs in CVD was analyzed to testify the discriminative ability. Bioinformatics analysis including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was conducted. Among 6,284 differentially expressed circRNAs from 32 original studies, only 322 circRNAs were reported in three or more studies. The meta‐analysis identified 63 significantly dysregulated circRNAs, 44 upregulated and 19 downregulated. Among the tissue‐specific or disease‐specific circRNAs identified in the subgroup analysis, two circRNAs (circCDKN2BAS and circMACF1) showed the potential to be circulating biomarkers for CVD. Sensitivity analysis demonstrated 69% of circRNAs were in conformity with the overall analysis. The pooled diagnostic odds ratio was 2.94 (95% confidence interval CI, 2.35–3.58), and the overall area under the curve value was 0.86 (95% CI, 0.83–0.89). GO and KEGG enrichment analyses indicated that the target genes of circRNAs participate in cardiogenesis‐related processes and pathways. This study demonstrates circRNAs have a high diagnostic value as potential biomarkers for CVD, and two candidate circRNAs, circCDKN2BAS and circMACF1, are potential circulating biomarkers for CVD diagnosis and treatment.
This study aimed to identify circRNAs acting as potential biomarkers for cardiovascular disease (CVD).Research were retrieved from the articles published by September 2018 in eight databases to compare circRNA expression profiles between CVD and non‐CVD in human and animal models. Meta‐analysis under a random effects model was conducted.
•Gallic acid (GA) showed protective effects against ethanol-induced gastric ulcer in rats.•The gastroprotective effect of GA could be partly related to the stimulations of gastric nitric oxide and ...prostaglandin.•Nrf2/HO-1 signaling activation is involved in the protection of GA against ethanol-induced gastric mucosa injury.•Pretreatment with GA could inhibit the apoptosis of gastric mucosal cells.
Gallic acid (3,4,5-trihydroxybenzoic acid, GA) is a phenolic compound found in many medicinal plants traditionally used in China or patent medicine such as Feiyangchangweiyan capsule (FY capsule) for the treatment of gastrointestinal diseases for decades. However, the evidence for the gastroprotective effect of GA is deficient and the pharmacological mechanisms remain limited. The present investigation was initiated to demonstrate the gastroprotective effect and to understand potential underlying mechanism of GA on ethanol-induced gastric ulcer in rats. Gastric ulcers were induced by absolute ethanol (5 mL/kg, i.g.) in male Sprague-Dawley rats, GA (10, 30, and 50 mg/kg), FY capsule (0.4 g/kg) and 30 mg/kg Lansoprazole was administered orally. Physiological saline and lansoprazole were used as negative and positive control, respectively. Induction of rats with ethanol resulted in a significant rise in ulcer index, serum levels of inflammatory cytokines markers (IL-1β, IL-6 and TNF-α), TBARS, protein expression of Bax and Caspase-3 and a significant reduction in the activities or levels of endogenous antioxidants (SOD, CAT and GSH), gastric mucosal protective factors (PGE2 and NO) and protein expression of Bcl-2. Pretreatment with GA showed a remarkable decrease in ulcer index, inflammatory cytokines markers, TBARS, protein expression of Bax and Caspase-3 and a significant increase in the activities of endogenous antioxidants, levels of PGE2 and NO, and protein expression of Bcl-2, Nrf2 and HO-1 when compared with ethanol treated groups. This study demonstrated the gastroprotective effect of Gallic acid and FY capsule on ethanol-induced gastric ulcer in rats. The underlying mechanism of GA and FY capsule against gastric ulcer in rats caused by ethanol might be involved in Nrf2/HO-1 anti-oxidative pathway and ultimately played an anti-apoptotic role through regulating Bax, Bcl-2 and Caspase-3.
Objective
To enhance the accuracy in predicting lymph node metastasis (LNM) preoperatively in patients with papillary thyroid microcarcinoma (PTMC), refining the “low‐risk” classification for ...tailored treatment strategies.
Methods
This study involves the development and validation of a predictive model using a cohort of 1004 patients with PTMC undergoing thyroidectomy along with central neck dissection. The data was divided into a training cohort (n = 702) and a validation cohort (n = 302). Multivariate logistic regression identified independent LNM predictors in PTMC, leading to the construction of a predictive nomogram model. The model's performance was assessed through ROC analysis, calibration curve analysis, and decision curve analysis.
Results
Identified LNM predictors in PTMC included age, tumor maximum diameter, nodule‐capsule distance, capsular contact length, bilateral suspicious lesions, absence of the lymphatic hilum, microcalcification, and sex. Especially, tumors larger than 7 mm, nodules closer to the capsule (less than 3 mm), and longer capsular contact lengths (more than 1 mm) showed higher LNM rates. The model exhibited AUCs of 0.733 and 0.771 in the training and validation cohorts respectively, alongside superior calibration and clinical utility.
Conclusion
This study proposes and substantiates a preoperative predictive model for LNM in patients with PTMC, honing the precision of “low‐risk” categorization. This model furnishes clinicians with an invaluable tool for individualized treatment approach, ensuring better management of patients who might be proposed observation or ablative options in the absence of such predictive information.
Traditional Chinese medicinal herbs Cortex Moutan and Radix Salviae Milthiorrhizaeare are prescribed together for their putative cardioprotective effects in clinical practice. However, the rationale ...of the combined use remains unclear. The present study was designed to investigate the cardioprotective effects of paeonol and danshensu (representative active ingredient of Cortex Moutan and Radix Salviae Milthiorrhizae, respectively) on isoproterenol-induced myocardial infarction in rats and its underlying mechanisms.
Paeonol (80 mg kg(-1)) and danshensu (160 mg kg(-1)) were administered orally to Sprague Dawley rats in individual or in combination for 21 days. At the end of this period, rats were administered isoproterenol (85 mg kg(-1)) subcutaneously to induce myocardial injury. After induction, rats were anaesthetized with pentobarbital sodium (35 mg kg(-1)) to record electrocardiogram, then sacrificed and biochemical assays of the heart tissues were performed.
Induction of rats with isoproterenol resulted in a marked (P<0.001) elevation in ST-segment, infarct size, level of serum marker enzymes (CK-MB, LDH, AST and ALT), cTnI, TBARS, protein expression of Bax and Caspase-3 and a significant decrease in the activities of endogenous antioxidants (SOD, CAT, GPx, GR, and GST) and protein expression of Bcl-2. Pretreatment with paeonol and danshensu combination showed a significant (P<0.001) decrease in ST-segment elevation, infarct size, cTnI, TBARS, protein expression of Bax and Caspase-3 and a significant increase in the activities of endogenous antioxidants and protein expression of Bcl-2 and Nrf2 when compared with individual treated groups.
This study demonstrates the cardioprotective effect of paeonol and danshensu combination on isoproterenol-induced myocardial infarction in rats. The mechanism might be associated with the enhancement of antioxidant defense system through activating of Nrf2 signaling and anti-apoptosis through regulating Bax, Bcl-2 and Caspase-3. It could provide experimental evidence to support the rationality of combinatorial use of traditional Chinese medicine in clinical practice.
Background
The preservation of parathyroid glands is crucial in endoscopic thyroid surgery to prevent hypocalcemia and related complications. However, current methods for identifying and protecting ...these glands have limitations. We propose a novel technique that has the potential to improve the safety and efficacy of endoscopic thyroid surgery.
Purpose
Our study aims to develop a deep learning model called PTAIR 2.0 (Parathyroid gland Artificial Intelligence Recognition) to enhance parathyroid gland recognition during endoscopic thyroidectomy. We compare its performance against traditional surgeon‐based identification methods.
Materials and methods
Parathyroid tissues were annotated in 32 428 images extracted from 838 endoscopic thyroidectomy videos, forming the internal training cohort. An external validation cohort comprised 54 full‐length videos. Six candidate algorithms were evaluated to select the optimal one. We assessed the model's performance in terms of initial recognition time, identification duration, and recognition rate and compared it with the performance of surgeons.
Results
Utilizing the YOLOX algorithm, we developed PTAIR 2.0, which demonstrated superior performance with an AP50 score of 92.1%. The YOLOX algorithm achieved a frame rate of 25.14 Hz, meeting real‐time requirements. In the internal training cohort, PTAIR 2.0 achieved AP50 values of 94.1%, 98.9%, and 92.1% for parathyroid gland early prediction, identification, and ischemia alert, respectively. Additionally, in the external validation cohort, PTAIR outperformed both junior and senior surgeons in identifying and tracking parathyroid glands (p < 0.001).
Conclusion
The AI‐driven PTAIR 2.0 model significantly outperforms both senior and junior surgeons in parathyroid gland identification and ischemia alert during endoscopic thyroid surgery, offering potential for enhanced surgical precision and patient outcomes.
In coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, the relationship between disease severity and the host immune response is not ...fully understood. Here we performed single-cell RNA sequencing in peripheral blood samples of 5 healthy donors and 13 patients with COVID-19, including moderate, severe and convalescent cases. Through determining the transcriptional profiles of immune cells, coupled with assembled T cell receptor and B cell receptor sequences, we analyzed the functional properties of immune cells. Most cell types in patients with COVID-19 showed a strong interferon-α response and an overall acute inflammatory response. Moreover, intensive expansion of highly cytotoxic effector T cell subsets, such as CD4
effector-GNLY (granulysin), CD8
effector-GNLY and NKT CD160, was associated with convalescence in moderate patients. In severe patients, the immune landscape featured a deranged interferon response, profound immune exhaustion with skewed T cell receptor repertoire and broad T cell expansion. These findings illustrate the dynamic nature of immune responses during disease progression.
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Breath analysis is an attractive strategy that holds tremendous potential to achieve non-implantable physical health management enabled by flexible humidity sensors for breathing ...behaviors (e.g., continuity, frequency) related to disease monitoring and chemiresistive gas sensors related early disease diagnosis. Compared to other techniques for breath component detection, non-invasive breathing diagnostics based on chemical sensors can offer several advantages like miniaturization, low power consumption, simple structure and cost-saving, which is helpful to enhance the portability of practical tests. Although extensive research has been carried out over the past two decades to improve sensing performances of breath gas sensors, many problems need to be further addressed when it comes to clinical disease diagnosis. Developing integrated gas sensor arrays have become one of the efficient solutions to improve detection accuracy. To get rid of external power supply, various novel sensors combining with self-powered technology are designed to exhibit a desirable development prospect in breath analysis. Thus, this review aims to summarize the latest research advances on wearable humidity-enabled breathing behaviors monitoring and typical biomarker gases-based disease screening, and also provides the prospects of future development from individual sensors to integrated devices and self-powered health monitoring systems.
Multidimensional fabrication of metal–organic frameworks (MOFs) into multilevel channel integrated devices are in high demanded for Li‐S separators. Such separators have advantages in ...pore‐engineering that might fulfill requirements such as intercepting the diffusing polysulfides and improving the Li+/electrolyte transfer in Li‐S batteries. However, most reported works focus on the roles of MOFs as ionic sieves for polysulfides while offering limited investigation on the tuning of Li+ transfer across the separators. A photoinduced heat‐assisted processing strategy is proposed to fabricate MOFs into multidimensional devices (e.g., hollow/Janus fibers, double‐or triple‐layer membranes). For the first time, a triple‐layer separator with stepped‐channels has been designed and demonstrated as a powerful separator with outstanding specific capacity (1365.0 mAh g−1) and cycling performance (0.03 % fading per cycle from 100th to 700th cycle), which is superior to single/double‐layer and commercial separators. The findings may expedite the development of MOF‐based membranes and extend the scope of MOFs in energy‐storage technologies.
A two‐step photoinduced heat‐assisted processing (PHAP) method is proposed to fabricate a kind of metal–organic framework (MOF)‐based triple‐layer membrane with stepped channels. The membrane can be applied as a high performance separator in a lithium–sulfur battery.