Changshu No. 2 People's Hospital

Poorly cohesive gastric carcinoma, particularly signet-ring cell (SRC) carcinoma, is an aggressive gastric cancer (GC) subtype with high metastatic potential and poor prognosis. Sialylation plays a critical role in tumor progression, but its functional significance in SRC malignancy and microenvironmental regulation remains unclear. This study investigated ST6Gal-Ⅰ's mechanistic contributions to SRC aggressiveness, focusing on epithelial-mesenchymal transition (EMT), stromal interactions, and metastatic signaling.

Multiple SRC and non-SRC GC cell lines, patient-derived organoids, and stromal cells (MSCs, HUVECs) were utilized. Techniques included co-culture models (transwell and direct contact), immunohistochemistry, western blotting, functional assays (transwell migration, wound healing, sphere/colony formation, EdU proliferation), and lectin staining. ST6Gal-Ⅰ expression was modulated via shRNA knockdown or overexpression. Mechanistic analyses focused on integrin-β1 (ITGβ1)/FAK/Paxillin signaling and stromal reprogramming. Statistical significance was determined using ANOVA with post hoc tests.

ST6Gal-Ⅰ exhibited microenvironment-dependent regulation: low in vitro expression in SRC cells was rescued by stromal co-culture or extracellular matrix (ECM) contact, mirroring high in vivo expression. ST6Gal-Ⅰ overexpression promoted EMT, stemness, angiogenesis, and proliferation. It facilitated MSCs differentiation into cancer-associated fibroblasts (CAFs) via α-SMA/FAP upregulation. Mechanistically, ST6Gal-Ⅰ activated the ITGβ1/FAK/Paxillin axis to enhance cell-ECM adhesion. Silencing ST6Gal-Ⅰ reversed these phenotypes, suppressing malignancy and stromal crosstalk.

ST6Gal-Ⅰ is a microenvironment-sensitive driver of SRC progression, orchestrating EMT, stemness, angiogenesis, and stromal reprogramming through ITGβ1/FAK/Paxillin signaling. Its dual role in tumor-autonomous behaviors and stromal co-option highlights its potential as a therapeutic target. Targeting ST6Gal-Ⅰ or downstream effectors (e.g., FAK, CAF-derived signals) may disrupt SRC metastasis and improve clinical outcomes.

This study aimed to investigate the prognostic impact of completing 30 mL/kg fluid resuscitation within 1 h in elderly septic shock patients.

This was a multicenter prospective observational cohort study. We applied logistic regression to assess the impact of completing 30 mL/kg fluid resuscitation within 1 h on respiratory support escalation including new-onset mechanical ventilation, bilevel positive airway pressure (BiPAP), and high-flow nasal cannula (HFNC) as well as heart failure (HF). We plotted Kaplan-Meier (K-M) curves to evaluate survival in patients completing 30 mL/kg fluid resuscitation within 1 h. We performed mediation analyses to determine the influence of HF on mortality associated with completing 30 mL/kg fluid resuscitation within 1 h.

Completing 30 mL/kg fluid resuscitation within 1 h increased the odds ratios of new-onset BiPAP (adjusted OR = 3.411; 95% confidence interval (CI) = [1.526, 7.620]) and HFNC (adjusted OR = 2.576; 95% CI = [1.252, 5.297]) within 24 h as well as the odds ratio of HF (adjusted OR = 2.291; 95% CI = [1.266, 4.149]). The adjusted K-M curve showed that patients completing 30 mL/kg fluid resuscitation within 1 h had higher 30-d mortality than those completing it over longer periods. The mediation effect suggested that completing 30 mL/kg fluid resuscitation within 1 h could be fatal primarily because it increased the risk of HF.

For elderly patients with septic shock, completing 30 ml/kg of fluid resuscitation within 1 h ought to be more cautious, particularly considering the patient's cardiac function and overall clinical status.

Subclinical thyroid dysfunction (STD) is associated with an elevated risk of non-vertebral fractures. However, whether STD is associated with the risk of vertebral fracture remains controversial. This study aimed to determine the relationship between STD and the risk of vertebral fracture using a meta-analysis approach.

PubMed, Embase, and the Cochrane Library databases were searched for eligible studies published until March 01, 2025. Only prospective cohort studies that reported effect estimates with 95% confidence intervals (CIs) of vertebral fractures in participants with subclinical hyperthyroidism (SCH) and subclinical hypothyroidism (SH) compared to those with euthyroidism were included. A random-effects model was used to pool risk ratios (RRs), and analyses accounted for key covariates, including demographic factors, lifestyle variables, and disease history where reported.

Ten prospective cohort studies involving 61,219 individuals were included in this meta-analysis. SCH was associated with an increased risk of vertebral fracture (RR: 2.20; 95% CI: 1.60-3.02; p < 0.001). Moreover, the risk of vertebral fracture in individuals with SH was higher than that in those with euthyroidism (RR, 1.22; 95% CI: 1.01-1.49; p = 0.044). The pooled conclusions for the association between SCH and vertebral fracture risk were robust, whereas the significant association between SH and vertebral fracture was variable. The relationship between SH and vertebral fracture risk was affected by the median age of individuals (p = 0.047).

Our study found that SCH was an independent risk factor for vertebral fracture, and that SH may increase the risk of vertebral fracture. Clinically, these findings support the need for regular monitoring of thyroid function, particularly in older adults, to identify individuals with STD who may benefit from targeted interventions to reduce vertebral fracture risk.