FLASH radiotherapy: A new milestone in the field of cancer radiotherapy.

Radiotherapy plays a pivotal role in the control and eradication of tumors, but it can also induce radiation injury to surrounding normal tissues while targeting tumor cells. In recent years, FLASH-Radiotherapy (FLASH-RT) has emerged as a cutting-edge research focus in the field of radiation therapy. By delivering high radiation doses to the treatment target in an ultra-short time, FLASH-RT produces the FLASH effect, which reduces the toxicity to normal tissues while achieving comparable tumor control efficacy to conventional radiotherapy. This review provides a brief overview of the development history of FLASH-RT and its impact on tumor control. Additionally, it focuses on introducing the protective effects and molecular mechanisms of this technology on various normal tissues, as well as exploring its synergistic effects when combined with other tumor therapies. Importantly, this review discusses the challenges faced in translating FLASH-RT into clinical practice and outlines its promising future applications.

Two-sided roles of adipose tissue: Rethinking the obesity paradox in various human diseases from a new perspective.

Overweight and obesity, as a result of excess fat accumulation, have become a worldwide public health issue. Recent studies have shown that obesity is closely related to many human diseases, such as cancer, cardiovascular diseases, and type 2 diabetes mellitus, in which adipose tissue plays a dual role. In addition to thermal and mechanical insulation and a critical role in energy storage and heat production, adipose tissue is also a highly plastic endocrine and signaling organ that secretes multiple bioactive molecules for inter-organ crosstalk. The phenotypic and biological changes of adipose tissue under pathological conditions, especially in obesity, increase the challenge of deciphering the positive or negative effects of adipose tissue in disease. Despite numerous studies on obesity and adipose tissue, the ambiguous role of adipose tissue on specific organs or tissues in different diseases is not fully understood, and the definite mechanisms remain obscure. In this review, we first summarize the basic biological characteristics of adipose tissue in the physiological state and the abnormal remodeling of adipose tissue during obesity. We then discuss the complex and disparate effects of obesity on various human diseases, with a particular focus on the dual roles and underlying mechanisms of adipose tissue, a quintessential player in obesity, in this process. More importantly, rethinking the causes of the "obesity paradox" phenomenon in diseases from the perspective of adipose homeostasis and dysfunction provides a novel strategy for disease treatment by intervening in fat function.

Checkpoint Inhibitor Pneumonitis Induced by Anti-PD-1/PD-L1 Therapy in Non-Small-Cell Lung Cancer: Occurrence and Mechanism.

Immune checkpointty inhibitors (ICIs), particularly those targeting programmed death 1 (PD-1) and anti-programmed death ligand 1 (PD-L1), enhance the antitumor effect by restoring the function of the inhibited effector T cells and produce durable responses in a large variety of metastatic and late patients with non-small-cell lung cancer. Although often well tolerated, the activation of the immune system results in side effects known as immune-related adverse events (irAEs), which can affect multiple organ systems, including the lungs. The occurrence of severe pulmonary irAEs, especially checkpoint inhibitor pneumonitis (CIP), is rare but has extremely high mortality and often overlaps with the respiratory symptoms and imaging of primary tumors. The development of CIP may be accompanied by radiation pneumonia and infectious pneumonia, leading to the simultaneous occurrence of a mixture of several types of inflammation in the lungs. However, there is a lack of authoritative diagnosis, grading criteria and clarified mechanisms of CIP. In this article, we review the incidence and median time to onset of CIP in patients with non-small-cell lung cancer treated with PD-1/PD-L1 blockade in clinical studies. We also summarize the clinical features, potential mechanisms, management and predictive biomarkers of CIP caused by PD-1/PD-L1 blockade in non-small-cell lung cancer treatment.

Use of Tregs as a cell-based therapy via CD39 for benign prostate hyperplasia with inflammation.

Benign prostatic hyperplasia (BPH) occurs most commonly among older men, often accompanied by chronic tissue inflammation. Although its aetiology remains unclear, autoimmune dysregulation may contribute to BPH. Regulatory T cells (Tregs) prevent autoimmune responses and maintain immune homeostasis. In this study, we aimed to investigate Tregs frequency, phenotype, and function in BPH patients and to evaluate adoptive transfer Tregs for immunotherapy in mice with BPH via CD39. Prostate specimens and peripheral blood from BPH patients were used to investigate Treg subsets, phenotype and Treg-associated cytokine production. Sorted CD39+/- Tregs from healthy mice were adoptively transferred into mice before or after testosterone propionate administration. The Tregs percentage in peripheral blood from BPH patients was attenuated, exhibiting low Foxp3 and CD39 expression with low levels of serum IL-10, IL-35 and TGF-ß. Immunohistochemistry revealed Foxp3+ cells were significantly diminished in BPH prostate with severe inflammatory. Although the Tregs subset was comprised of more effector/memory Tregs, CD39 was still down-regulated on effector/memory Tregs in BPH patients. Before or after testosterone propionate administration, no alterations of BPH symptoms were observed due to CD39- Tregs in mice, however, CD39+ Tregs existed more potency than Tregs to regulate prostatic hyperplasia and inhibit inflammation by decreasing IL-1ß and PSA secretion, and increasing IL-10 and TGF-ß secretion. Furthermore, adoptive transfer with functional Tregs not only improved prostate hyperplasia but also regulated muscle cell proliferation in bladder. Adoptive transfer with Tregs may provide a novel method for the prevention and treatment of BPH clinically.

GMM logistic regression models for longitudinal data with time-dependent covariates and extended classifications.

When analyzing longitudinal data, it is essential to account both for the correlation inherent from the repeated measures of the responses as well as the correlation realized on account of the feedback created between the responses at a particular time and the predictors at other times. As such one can analyze these data using generalized estimating equation with the independent working correlation. However, because it is essential to include all the appropriate moment conditions as you solve for the regression coefficients, we explore an alternative approach using a generalized method of moments for estimating the coefficients in such data. We develop an approach that makes use of all the valid moment conditions necessary with each time-dependent and time-independent covariate. This approach does not assume that feedback is always present over time, or if present occur at the same degree. Further, we make use of continuously updating generalized method of moments in obtaining estimates. We fit the generalized method of moments logistic regression model with time-dependent covariates using SAS PROC IML and also in R. We used p-values adjusted for multiple correlated tests to determine the appropriate moment conditions for determining the regression coefficients. We examined two datasets for illustrative purposes. We looked at re-hospitalization taken from a Medicare database. We also revisited data regarding the relationship between the body mass index and future morbidity among children in the Philippines. We conducted a simulated study to compare the performances of extended classifications.