Chronic Diseases and Translational Medicine最新文献

High blood pressure is a significant contributor to premature mortality, resulting in nearly 10 million deaths and over 200 million disabilities worldwide.¹ In recent years, hypertension treatment has shifted focus not only to average blood pressure but also to blood pressure variability (BPV), categorized into very short-term, short-term, and long-term BPV based on the time period of occurrence.^{2, 3} Long-term BPV has emerged as clinically significant, with studies demonstrating its superiority in predicting long-term cardiovascular events, stroke, and mortality compared to short-term variability. Given its association with pre-renal function decline, reducing blood pressure fluctuations is imperative.

Chronic kidney disease (CKD) poses a global public health challenge, with its incidence rising alongside aging populations and increasing rates of conditions like diabetes and hypertension. Hypertension and kidney disease are closely intertwined, with hypertension exacerbating renal damage. At present, the management of hypertension mainly focuses on average blood pressure, but the average blood level does not accurately reflect the long-term control status of blood pressure. Notably, some patients with ostensibly controlled average blood pressure still experience renal function deterioration within 5–10 years, potentially due to blood pressure fluctuations. Emerging evidence suggests a link between cardiovascular events, renal injury, and BPV, independent of average blood pressure.^{4, 5} However, the precise relationship between BPV and renal function remains elusive. This study aimed to explore the association between fluctuating blood pressure and rapid renal function decline in a prospective community health checkup-based cohort.

A total of 7153 patients aged ≥18 years who received at least twice regular physical examinations at the Community Health Service Centre in Beijing, between 2015 and 2021, were recruited consecutively in this study. Exclusion criteria included CKD stage 4–5, acute stroke, myocardial infarction, and heart failure (<3 months). Finally, 7130 patients were enrolled in the analysis (Figure S1).

Sociodemographic information, comorbidities, and lifestyle habits were obtained through questionnaires. Blood pressure was measured twice during each visit, and BPV indices were calculated based on measurements across all visits. Additionally, blood samples were collected after an 8-h fast for biochemical analyses. We calculated several indicators as measures of BPV based on data from all visits, including standard deviation (SD), coefficient of variation (CV), variation independent of the mean (VIM), and average successive variability (ASV). The measures have been used in previous studies.^{6, 7}

Baseline data for this study were derived from the results of the initial annual health checkup, while endpoint data we

Calcium-sensing receptor (CaSR), a family C G-protein-coupled receptor, plays a crucial role in regulating calcium homeostasis by sensing small concentration changes of extracellular Ca²⁺, Mg²⁺, amino acids (e.g., L-Trp and L-Phe), small peptides, anions (e.g., HCO₃⁻ and PO₄³⁻), and pH. CaSR-mediated intracellular Ca²⁺ signaling regulates a diverse set of cellular processes including gene transcription, cell proliferation, differentiation, apoptosis, muscle contraction, and neuronal transmission. Dysfunction of CaSR with mutations results in diseases such as autosomal dominant hypocalcemia, familial hypocalciuric hypercalcemia, and neonatal severe hyperparathyroidism. CaSR also influences calciotropic disorders, such as osteoporosis, and noncalciotropic disorders, such as cancer, Alzheimer's disease, and pulmonary arterial hypertension. This study first reviews recent advances in biochemical and structural determination of the framework of CaSR and its interaction sites with natural ligands, as well as exogenous positive allosteric modulators and negative allosteric modulators. The establishment of the first CaSR protein–protein interactome network revealed 94 novel players involved in protein processing in endoplasmic reticulum, trafficking, cell surface expression, endocytosis, degradation, and signaling pathways. The roles of these proteins in Ca²⁺-dependent cellular physiological processes and in CaSR-dependent cellular signaling provide new insights into the molecular basis of diseases caused by CaSR mutations and dysregulated CaSR activity caused by its protein interactors and facilitate the design of therapeutic agents that target CaSR and other family C G-protein-coupled receptors.

Lung cancer (LC) is the leading cause of cancer-related death worldwide, with non-small cell lung cancer (NSCLC) comprising 85% of all cases. COX-2, an enzyme induced significantly under stress conditions, catalyzes the conversion of free arachidonic acid into prostaglandins. It exhibits high expression in various tumors and is closely linked to LC progression. COX-2 functions as a pivotal driver in cancer pathogenesis by promoting prostaglandin E2 synthesis and facilitating tumor cell occurrence and development. Furthermore, COX-2 holds potential as a predictive marker for early-stage NSCLC, guiding targeted therapy in patients with early COX-2 overexpression. Additionally, combining COX-2 inhibitors with diverse treatment modalities enhances tumor therapeutic efficacy, minimizes adverse effects on healthy tissues, and improves overall patient survival rates posttreatment. In conclusion, combined therapy targeting COX-2 presents a promising novel strategy for NSCLC treatment, offering avenues for improving prognosis and effective tumor treatment. This review provides novel insights and ideas for developing new treatment strategies to improve the prognosis of NSCLC.