This retrospective study aimed to explore the value of DAT-FAT serological profiles confirmed by AET in classifying neonatal jaundice, evaluating its severity, and guiding clinical management. A total of 915 jaundiced newborns (584 pathological, 331 physiological) admitted from July 2018 to August 2021 were included. Univariate and multivariate logistic regression analyses were conducted to identify risk factors. To assess predictive ability for jaundice type and early risk stratification of jaundice severity, the 426 patients with ABO incompatibility were stratified into subgroups based on the results of the DAT-FAT-AET serological panel. Maternal pregnancy count, gestational weeks, direct bilirubin at admission, and ABO incompatibility were identified as independent predictors of jaundice type (p < 0.05). Those who tested triple-positive in the DAT-FAT-AET serological panel (Group 2) had the highest predictive value for pathological jaundice (area under the curve, 0.920 [0.788-0.994]), indicating the maximum severity of pathological jaundice (p < 0.01). AET serves as the definitive criterion for confirming ABO-incompatible jaundice, while DAT-FAT profiles enable early risk stratification of severity. Subgrouping by AET-confirmed DAT-FAT serology helps assess etiology and severity in ABO-incompatible neonatal jaundice, supporting clinical early risk stratification.
This retrospective cohort study utilized the Medical Information Mart for Intensive Care database to investigate the association between the triglyceride-glucose (TyG) index and in-hospital intensive care unit (ICU) readmission in patients with ischemic stroke (IS). Among 2929 patients, 24.0% experienced ICU readmission. Logistic regression analysis demonstrated that the continuous TyG index was associated with a 17% higher risk of ICU readmission (odds ratio [OR], 1.17; 95% confidence interval [CI], 1.01-1.36; p = 0.04). Compared with the lowest quartile (Q1), the higher TyG index quartiles showed a progressively increased risk of ICU readmission (Q2: OR, 1.49; 95% CI, 1.13-1.96; Q3: OR, 1.46; 95% CI, 1.10-1.95; Q4: OR, 1.53; 95% CI, 1.14-2.05; P for trend = 0.02). Restricted cubic spline analysis revealed a significant nonlinear relationship (P for nonlinearity = 0.027), with an inflection point at a TyG index value of 9.82 (P for log-likelihood ratio = 0.007). Incorporating the TyG index into conventional models significantly improved the predictive performance for ICU readmission, as evidenced by increases in the area under the curve, net reclassification improvement and integrated discrimination improvement. In conclusion, an elevated TyG index was associated with an increased risk of in-hospital ICU readmission in patients with IS and exhibited a nonlinear dose-response relationship. The TyG index enhanced the predictive accuracy of existing scoring tools, suggesting its potential clinical value for risk stratification and early intervention.
This study aimed to evaluate the predictive value of the estimated dose of radiation to immune cells (EDRIC) in patients with esophageal cancer receiving radical radiotherapy. We retrospectively reviewed the data of patients with esophageal cancer who underwent definitive radiotherapy at our institution. The Kaplan-Meier method and log-rank test were used to assess the survival curves. Univariate and multivariate Cox regression analyses were performed to identify the prognostic factors associated with overall survival (OS) and progression-free survival (PFS). Additionally, binary logistic regression analyses were used to identify factors associated with severe lymphopenia. A total of 166 patients, with a median follow-up duration of 59 months, were evaluated. The median EDRIC was 7.23 Gy. The 1-, 3-, and 5-year OS rates were 81.9%, 49.4%, and 33.7% in the EDRIC < 7.23 Gy group, compared with 62.7%, 21.7%, and 19.3% in the EDRIC ≥ 7.23 Gy group (p < 0.001). Prognostic analysis identified Eastern Cooperative Oncology Group performance status, TNM stage, treatment, EDRIC, and lymphopenia as significant independent prognostic factors of OS (p < 0.05). Higher EDRIC, N stage, and lymphopenia were identified as independent risk factors for PFS. Logistic regression analysis indicated that treatment and EDRIC were significantly associated with severe lymphopenia (p < 0.05). EDRIC serves not only as a prognostic marker for radical radiotherapy in esophageal cancer, but also as a potential biomarker for radiation-induced lymphopenia.
Papillary thyroid carcinoma (PTC) is the most prevalent subtype of thyroid cancer; however, the regulatory mechanisms by which mitophagy influences its progression remain inadequately elucidated. This study sought to examine the role of myoferlin (MYOF) in mitophagy and its molecular basis during PTC development. Utilizing three paired PTC and adjacent normal tissues, we observed elevated MYOF expression at both protein and mRNA levels through western blot and qRT-PCR analyses. Stable MYOF knockdown cell lines were established in PTC (TPC-1, KTC-1) and normal thyroid (Nthy-ori 3-1) cells using lentiviral shRNA. Functional assays, including CCK-8, wound healing, transwell, flow cytometry, immunofluorescence, and mitophagic flux analysis, along with a xenograft mouse model, were employed. Subsequent evaluations involved hematoxylin and eosin staining, immunohistochemistry, western blot, and qRT-PCR. As a result, MYOF was significantly upregulated in PTC tissues and TPC-1 cells. Knockdown of MYOF inhibited PTC cell proliferation, invasion, migration, and colony formation, while promoting apoptosis. Mechanistically, MYOF was found to regulate PTC progression through the PINK1/Parkin-mediated mitophagy pathway. In vivo xenograft experiments demonstrated that MYOF silencing suppressed tumor growth and increased the expression of mitophagy-related proteins BNIP3 and NIX. In conclusion, MYOF drives PTC progression by repressing mitophagy. Targeted inhibition of MYOF activates tumor-suppressive mitophagy via the PINK1-Parkin axis, indicating MYOF as a potential therapeutic target in PTC.
The study aimed to investigate the effect of thoracic paravertebral block (TPVB) with liposomal bupivacaine (LB) before anesthesia induction on postoperative pain, quality of recovery (QoR), and opioid consumption in older patients after video-assisted thoracoscopic surgery (VATS). A total of 116 older patients who were scheduled to undergo VATS were allocated into a SB group (TPVB with standard bupivacaine [SB] before anesthesia induction) and a LB group (TPVB with LB before anesthesia induction). The primary outcome was the Numerical Rating Scale (NRS) scores of patients measured at 6, 12, 24, 36, 48, and 72 h postoperatively. The secondary outcomes were score of the QoR-15 questionnaire at 24 h postoperatively, effective times of patient-controlled intravenous analgesia (PCIA), cumulative sufentanil consumption, first time to request for analgesia, incidence of adverse events, and incidence of postoperative delirium. The LB group had significantly lower NRS scores at 24 and 36 h postoperatively than those in the SB group. The LB group exhibited significantly higher QoR-15 scores at 24 h postoperatively, fewer effective times of PCIA, less cumulative sufentanil consumption from 24 to 72 h postoperatively, and longer time to first request for analgesia than the SB group. The two groups did not differ in incidences of adverse events and postoperative delirium. The study provides evidence that TPVB with LB is effective in alleviating postoperative pain at 24 and 36 h postoperatively, improving QoR, and providing opioid savings for older patients after VATS.
This study utilized a cross-sectional survey via a structured questionnaire to evaluate disease-related knowledge, treatment preferences, and unmet needs among 200 adults with confirmed inflammatory bowel disease (IBD) at a tertiary referral center. The questionnaire specifically assessed disease knowledge using the 24-item IBD-KNOW score, priorities for treatment attributes, preferred administration modalities, and self-reported unmet needs. Results indicated a mean IBD-KNOW score of 14.8/24, reflecting moderate overall knowledge, with female sex identified as an independent predictor of higher knowledge levels (OR: 1.87, p = 0.044). In terms of treatment, patients prioritized efficacy (8.9/10) over safety (8.5) and convenience (8.1); notably, 49% ranked efficacy as the most important factor, whereas 88% ranked convenience as the least important. The most preferred administration modalities were once-daily oral therapy (31%) and bimonthly subcutaneous injection (29.5%). While 43.5% of respondents reported no unmet needs, significant concerns persisted regarding the fear of disease progression (24.5%), medication cost (22.5%), and long waiting times for care (20.5%). These findings suggest that although IBD patients possess moderate disease-specific knowledge and place a strong emphasis on treatment efficacy and long-interval regimens, clinical focus is still needed to address ongoing anxieties regarding long-term outcomes, financial burdens, and healthcare access.
Cerebral ischemia-reperfusion injury (CI/RI) is a major cause of secondary neuronal damage following ischemic stroke. This study investigated whether terazosin (TZ) exerts neuroprotective effects by regulating mitophagy and the reactive oxygen species (ROS)/NOD-like receptor protein 3 (NLRP3) inflammasome axis. A mouse model of CI/RI was established and treated with TZ alone or in combination with the mitophagy inhibitor Mdivi-1 or the NLRP3 activator nigericin. Neurological function, infarct volume, histopathological changes in the hippocampal CA1 region, mitophagy (Mito-Tracker+LC3B+), and neuronal pyroptosis (NeuN+GSDMD-N+) were evaluated. In parallel, an oxygen-glucose deprivation/reperfusion (OGD/R) model was established in HT-22 cells to assess cell viability, cytotoxicity, mitochondrial membrane potential, ROS production, inflammatory cytokine release, and expression of autophagy- and pyroptosis-related proteins. The CI/RI exhibited was characterized by worsened neurological deficits, increased infarct volume, enhanced neuronal pyroptosis, and elevated interleukin-1β (IL-1β), IL-18, ROS, p62, and pyroptosis proteins, as well as prominent vacuolation and edema in the hippocampal CA1 region. These changes were accompanied by reduced mitophagy and decreased expression of LC3B II/I and Beclin-1. TZ treatment markedly ameliorated these abnormalities. Mechanistic analyses showed that TZ inhibited OGD/R-induced neuronal pyroptosis by promoting mitophagy, which reduced ROS accumulation and subsequently suppressed NLRP3 inflammasome activation. Importantly, blockade of mitophagy or activation of NLRP3 weakened the protective effects of TZ. Collectively, these findings indicate that TZ mitigates CI/RI-induced neuronal injury by enhancing mitophagy and inhibiting ROS/NLRP3-dependent pyroptosis.
Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy with a high rate of recurrence and metastasis, necessitating the identification of novel therapeutic targets. WD repeat-containing protein 72 (WDR72) has been linked to various cancers, but its specific biological function and underlying mechanism in ESCC remain largely unexplored. Herein, we investigated whether WDR72 promotes ESCC progression by suppressing autophagy via the PI3K/Akt/mTOR pathway. We first analyzed WDR72 expression using GEO (GSE213565) and validated using the GEPIA public databases. WDR72 mRNA/protein levels were then examined in patient-derived ESCC tissues and cell lines (EC109, KYSE150). Loss- and gain-of-function models (shRNA knockdown and pcDNA3.1-WDR72 overexpression) were used to evaluate proliferation, clonogenicity, apoptosis, migration/invasion, and autophagy. PI3K/Akt/mTOR activity was examined by measuring PI3K, p-Akt, and p-mTOR, with pathway dependence tested using the dual PI3K/mTOR inhibitor BEZ235. In vivo tumor growth and metastasis were analyzed in xenograft and lung metastasis models. We found that WDR72 was significantly overexpressed in ESCC tissues and cell lines. WDR72 depletion suppressed malignant phenotypes in vitro and substantially inhibited tumor growth and metastasis in vivo. Mechanistically, WDR72 overexpression activated the PI3K/Akt/mTOR pathway (indicated by elevated p-Akt and p-mTOR levels) and concurrently suppressed autophagy (evidenced by decreased Beclin-1 and LC3-II/LC3-I ratio, and increased P62). Notably, the PI3K/mTOR inhibitor BEZ235 abolished the pro-malignant effects and reversed the autophagy suppression induced by WDR72 overexpression. Collectively, our findings establish that WDR72 acts as an oncogene in ESCC by promoting proliferation, survival, and metastasis via activating the PI3K/Akt/mTOR signaling to suppress autophagy.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly prevalent among lean Asian populations, yet effective strategies for identifying high-risk individuals remain limited. We investigated the associations of body fat percentage (BF%) and the triglyceride-glucose (TyG) index with lean MASLD and evaluated their incremental diagnostic value in two independent studies (the NAGALA cohort and a Chinese health check-up study). Lean MASLD was defined as imaging-confirmed hepatic steatosis in individuals with BMI < 23 kg/m2. In both studies, participants with MASLD were older, more often male, and exhibited less favorable metabolic profiles. Multivariable analyses showed that the TyG index was consistently associated with increased odds of lean MASLD (adjusted OR per unit increase: 3.41 in NAGALA and 6.37 in the Chinese study), whereas associations of BF% varied by cohort and sex, with significant associations observed in NAGALA men and Chinese women (adjusted OR per unit increase: 1.20 and 1.24, respectively). In ROC analyses, the TyG index showed good discrimination (C-statistics 0.778-0.875), and the addition of BF% further improved performance (0.805-0.901), corresponding to an absolute increase of approximately 0.02-0.05, with consistent improvements in net reclassification and discrimination (all p < 0.05). Mendelian randomization analyses supported a potential causal association between the TyG index and NAFLD, while no significant causal association was observed for BF%. Overall, BF% and the TyG index provide complementary information, and their combined use improves the identification of lean MASLD.
Response to neoadjuvant chemoradiotherapy (NACRT) in locally advanced colorectal cancer (CRC) varies widely, and accurately identifying poor responders is crucial for guiding timely treatment modification. This study aimed to develop an integrated predictive model combining radiomics derived from routine radiotherapy non-contrast planning computed tomography (CT) images with serum biomarkers to achieve better predictive accuracy than modality alone in identifying the therapeutic response of CRC patients receiving NACRT. Ninety-two patients with stages II-III CRC who received NACRT and surgery were retrospectively analyzed. CT-based radiomic features were extracted from pre-treatment non-contrast planning CT images using LIFEx software. Patients were randomly divided into derivation (n = 65) and validation (n = 27) cohorts while least absolute shrinkage and selection operator logistic regression was used to construct a radiomics score (Rad-score). Univariate and multivariate analyses evaluated the independent predictive value of Rad-score and patients' clinicopathological features. A nomogram was established and calibrated using bootstrap resampling, and of 111 usable radiomic features, seven were selected to construct the Rad-score. The CT-based radiomics signature showed strong discriminative performance in predicting pathological complete response (pCR) (AUC: derivation 0.854; validation 0.818). In multivariate analysis, Rad-score (adjusted OR = 10.20, p = 0.002) and low pretreatment serum carcinoembryonic antigen (CEA) level (adjusted OR = 15.20, p = 0.024) were independent predictors of pCR. The integrated nomogram demonstrated excellent calibration in both cohorts [mean absolute error (MAE) = 0.042 and 0.045]. A combined model incorporating CT-based radiomics and pretreatment serum CEA provides a robust and resource-efficient tool for predicting therapeutic response following NACRT in CRC.
Myocardial ischemia/reperfusion (I/R) injury is characterized by cardiomyocyte death, excessive oxidative stress, inflammation, and ferroptosis, which collectively limit the efficacy of reperfusion therapy. In this study, we investigated whether kaempferol (KAE), a natural flavonol with antioxidative and antiinflammatory properties, could protect against myocardial I/R injury by modulating the KEAP1-Nrf2-GPX4 signaling pathway. Using hypoxia/reoxygenation (H/R)-injured AC16 cardiomyocytes and a mouse myocardial I/R model, we observed that KAE significantly enhanced cardiomyocyte viability, promoted Nrf2 nuclear translocation, and upregulated downstream antioxidant and antiferroptotic proteins, including HO-1, NQO1, GPX4, and SLC7A11, while reducing KEAP1 and ACSL4 expression. KAE also markedly attenuated lipid peroxidation, iron accumulation, reactive oxygen species generation, apoptosis, and inflammatory responses in vitro and in vivo. These protective effects were partially abolished by Nrf2 knockdown and were replicated by the ferroptosis inhibitor ferrostatin-1 (Fer-1), indicating a ferroptosis-dependent mechanism. Consistently, KAE pretreatment attenuated myocardial injury, preserved cardiac histology, restored GPX4 and SLC7A11 expression, and lowered serum cTnI, CK-MB, TNF-α, and IL-6 levels in I/R mice. Taken together, these results demonstrate that KAE alleviates myocardial I/R injury by activating the KEAP1-Nrf2-GPX4 axis and suppressing ferroptosis and oxidative stress, highlighting its potential as a therapeutic agent in ischemic heart disease.
Venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, is a major complication in women with epithelial ovarian cancer (EOC). We aimed to develop and externally validate an early postoperative risk score to identify EOC patients at increased risk of VTE after debulking surgery. We retrospectively analyzed a development cohort (N = 358) to derive and internally validate a prediction model and an independent external cohort (N = 158) for external validation. Candidate clinical and laboratory variables were evaluated using least absolute shrinkage and selection operator (LASSO) and multivariable logistic regression. The final model was presented as a nomogram and converted into an integer-based scoring system. Postoperative VTE within 30 days of surgery occurred in 12.01% of patients in the development cohort. Age, body mass index (BMI), preoperative international normalized ratio (INR), preoperative aspartate aminotransferase (AST), postoperative C-reactive protein (CRP), and postoperative platelet count (PLT) were retained as predictors. The score incorporated age, BMI, INR, AST, CRP, and postoperative platelet count. Using a cutoff of 5 points, discrimination was high in the training and internal validation cohorts and acceptable in external validation (AUC 0.990 [95% CI 0.981-1.000], 0.934 [0.874-0.995], and 0.791 [0.653-0.929], respectively). In external validation, discrimination was comparable to the G-Caprini score (AUC 0.759 [0.627-0.892]) with overlapping confidence intervals. Because the proposed score incorporates postoperative biomarkers, it is intended for early postoperative risk reassessment to support targeted surveillance and individualized post-surgical prevention strategies, rather than preoperative prophylaxis decision-making.
Non-small cell lung cancer (NSCLC) is characterized by high incidence, mortality, and poor patient prognosis, with chemotherapy resistance being a common challenge. This research intends to identify key molecules involved in NSCLC and elucidate the regulatory role of the LINC01605/miR-7111-5p/ELK1 axis in chemotherapy resistance. LINC01605 and its downstream targets were predicted using the lncRNASNP2-human and miRDB databases. RT-qPCR was employed to measure the expression of LINC01605 across different NSCLC patients, and its prognostic value was assessed through ROC curve, Kaplan-Meier curve, and Cox regression. Dual-luciferase reporter assay was conducted to verify interactions between miR-7111-5p and LINC01605 or ELK1. Transwell assay evaluated cell invasion capabilities, while CCK8 assay confirmed changes in chemotherapy drug sensitivity in chemotherapy-resistant cells across different treatment groups. Elevated expression of LINC01605 was observed in NSCLC patients, correlating with reduced survival rates, and its expression was further elevated in patients with chemotherapy resistance. The upregulation of miR-7111-5p inhibited the proliferation and invasion of NSCLC cells induced by LINC01605. Mechanistically, LINC01605 negatively regulated miR-7111-5p expression while positively influencing ELK1 expression. Silencing ELK1 and upregulating miR-7111-5p levels reversed the chemotherapy resistance of A549 cells induced by LINC01605. By targeting the miR-7111-5p/ELK1 regulatory axis, LINC01605 induced chemotherapy resistance in NSCLC, highlighting its potential as a significant biomarker for NSCLC.
The stress hyperglycemia ratio (SHR), a novel marker reflecting relative hyperglycemia, has been increasingly recognized for its prognostic value in cardiovascular and metabolic diseases. However, its association with early renal damage in hypertensive patients remains underexplored. This study aims to investigate the independent relationship between SHR and albuminuria in a nationally representative cohort of adults with hypertension. This cross-sectional analysis included 8732 adults with hypertension from the National Health and Nutrition Examination Survey 2005-2018. Multivariable logistic regression models were used to evaluate the independent association between SHR and albuminuria, with adjustment for demographic, lifestyle, and clinical covariates. Restricted cubic splines (RCS) were employed to model nonlinear relationships. Stratified analyses were conducted across various subgroups. The prevalence of albuminuria was 15%. After full adjustment for confounders, compared to the reference quartile (Q2), the highest SHR quartile was significantly associated with an increased odds of albuminuria (OR: 2.34; 95% CI: 1.62-3.36; p < 0.001). RCS analysis revealed a nonlinear, J-shaped association between continuous SHR and albuminuria (p for nonlinearity < 0.001), with risk markedly increasing beyond an SHR of approximately 0.91. Subgroup analyses confirmed the robustness of this association across most strata, including age, gender, BMI, eGFR, diabetes status, and cancer history, with no significant interactions observed (all p-interaction > 0.05). In this large, population-based study, an elevated SHR is significantly and independently associated with a higher prevalence of albuminuria among US adults with hypertension.
This study explored the association between the composite dietary antioxidant index (CDAI) and cardiovascular-kidney-metabolic (CKM) progression in an older population. Using data from NHANES 2001-2020, we analyzed 4974 adults aged ≥ 60 years with CKM syndrome. The CDAI was calculated from the intake of six dietary antioxidants. Associations between the CDAI and its components and advanced CKM syndrome (Stages 3-4) were assessed using multivariable logistic regression, restricted cubic splines, piecewise logistic regression, and weighted quantile sum (WQS) regression. Participants in the highest CDAI quartile had lower odds of advanced CKM syndrome than those in the lowest quartile (OR = 0.728, 95% CI: 0.594-0.893). Restricted cubic spline analysis showed an L-shaped association between CDAI and odds of advanced CKM syndrome, with an inflection point at 5.857; the inverse association was evident below this threshold and plateaued above it. Furthermore, the WQS regression model identified a protective combined effect of the six dietary antioxidants against advanced CKM syndrome, with vitamin A and vitamin C contributing the largest weights. Higher CDAI levels were associated with a lower risk of advanced CKM syndrome in older adults, with vitamins A and C emerging as the most influential components.
Co-administration of COVID-19 and influenza vaccines has been promoted to improve coverage, but acceptance among healthcare workers (HCWs) remains uncertain. In total, 1238 participants were recruited. Participants were categorized by vaccination pattern including same-day co-administration, non-concurrent vaccination, or single vaccine. Linear regression and multinomial logistic regression were used to assess adverse reactions, association with prior COVID-19 vaccination experiences and future vaccination preferences. HCWs who received same-day co-administration reported higher adverse reaction scores (1.10 ± 0.92) and prevalence (72.5%) compared to non-concurrent vaccination (0.88 ± 0.84, 63.0%) or single vaccine recipients (0.68 ± 0.80, 31%-48%). Prior adverse reactions positively correlated with 2024 reactions (r = 0.30-0.49, p < 0.0001). Non-concurrent vaccination (β = -0.26) and single vaccine receipt (β = -0.45) were associated with lower adverse reaction scores than same-day co-administration. Among non-concurrent vaccination recipients, flu-first vaccination was associated with lower adverse reaction scores than COVID-first (β = 0.30). Past vaccination patterns showed significant association with future choices. In this study, HCWs who received same-day co-administration of COVID-19 and influenza vaccines reported higher adverse reaction scores compared to those who received non-concurrent or single vaccines. These findings suggest that vaccination scheduling preferences warrant consideration in institutional immunization programs. Prospective research is needed to confirm these associations and determine appropriate vaccination strategies.
Sepsis-induced acute lung injury (ALI) remains challenging to treat, with conventional anti-inflammatory therapies offering limited efficacy. The lymphatic system is crucial for removing edema and inflammatory mediators, and its impairment can exacerbate lung injury. Ginsenoside Rg1, a bioactive botanical compound, has diverse pharmacological properties, but its ability to modulate lymphangiogenesis in septic ALI is unclear. This study investigated whether Ginsenoside Rg1 can alleviate lipopolysaccharide (LPS)-induced ALI in mice by promoting lymphangiogenesis via the vascular endothelial growth factor C (VEGFC)/D-VEGF receptor 3 (VEGFR3) signaling pathway. ALI was induced in C57BL/6 mice by intraperitoneal injection of LPS (10 mg/kg). Mice were treated with Rg1 at low (30 mg/kg) or high (60 mg/kg) doses. Lung injury was assessed by wet-to-dry weight ratios, vascular permeability, histopathology, and lymphatic vessel density. Levels of inflammatory cytokines, VEGFC/D, VEGFR3, and downstream signaling molecules were measured by enzyme-linked immunosorbent assay, western blotting, and qPCR. Ginsenoside Rg1 treatment dose-dependently reduced pulmonary edema, vascular leakage, and histological damage. It also reversed LPS-induced decreases in VEGFC/D and increased VEGFR3 expression, resulting in enhanced lymphatic vessel density. Rg1 activated VEGFR3 downstream pathways (ERK/Prox-1, AKT) and upregulated lymphatic function genes (CCL21a, ACKR2). Ginsenoside Rg1 can attenuate septic ALI by stimulating the VEGFC/D-VEGFR3 axis to promote functional lymphangiogenesis, thereby facilitating clearance of edema and inflammatory mediators. This mechanism offers a novel therapeutic strategy focused on enhancing clearance rather than only on suppressing inflammation, potentially reducing tissue damage and the side effects associated with conventional treatments.
Cisplatin resistance remains a major obstacle in the treatment of gastric cancer (GC), and autophagy has been increasingly recognized as a key cytoprotective mechanism contributing to chemoresistance. CREB3L4 is an endoplasmic reticulum membrane-bound transcription factor that has been shown to regulate the expression of Bcl-2 associated athanogene 3 (BAG3), a co-chaperone protein involved in autophagy and survival signaling in various cancers. However, whether the CREB3L4/BAG3 axis regulates autophagy and contributes to cisplatin resistance in gastric cancer cells remains unclear. In the present study, we investigated the roles of CREB3L4 and BAG3 in cisplatin-resistant GC cell lines and found that CREB3L4 and BAG3 were overexpressed. Furthermore, BAG3 expression was inhibited following CREB3L4 knockdown in gastric cancer cells. Notably, knockdown of CREB3L4 inhibited autophagy and alleviated cisplatin resistance in gastric cancer cells by down-regulating BAG3. In addition, silencing of CREB3L4 promoted apoptosis and inhibited cell proliferation, which was also associated with decreased BAG3 expression. Taken together, these findings indicate that depletion of CREB3L4 suppressed autophagy and reduced cisplatin resistance in GC cells by downregulating BAG3.
To identify the determinants of the response to neoadjuvant systemic therapy (NST) in triple-positive breast cancer (TPBC), we retrospectively enrolled 520 patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer who were treated at The First Affiliated Hospital of Chongqing Medical University between January 2015 and December 2021. The cohort comprised 299 cases of TPBC and 221 cases of hormone receptor (HR)-negative/HER2-positive breast cancer (HPBC). A comparative analysis revealed that the pathological complete response (pCR) rate was significantly lower in the TPBC group than in the HPBC group (30.1% vs. 50.2%; p < 0.001); however, this differential response did not translate into a significant difference in long-term survival. Within the TPBC cohort, pCR was identified as an independent prognostic factor for prolonged disease-free survival (DFS) (p = 0.014). Multivariate analysis further revealed that the NST regimen (p = 0.001), estrogen receptor (ER) status (p = 0.024), and Ki67 index (p = 0.018) were independent predictors of pCR. A nomogram incorporating these factors was developed using R software to estimate the individual probability of pCR in TPBC. The model was externally validated in an independent cohort of 143 TPBC patients treated between January 2022 and December 2024, and the results demonstrated robust predictive performance and good calibration. This model serves as a tool for early risk stratification in TPBC, thereby facilitating personalized treatment strategies and risk-adapted surveillance to improve patient outcomes.
Mitochondria provide multiple functions for cellular physiology. Transplantation of mitochondria isolated from gastric epithelial cells GES-1 reducing the malignancy of gastric cancer cells AGS was previously reported. To elucidate the underlying mechanisms, TMT-based proteomic analysis coupling ingenuity pathway software prediction revealed that 257 upregulated and 34 downregulated proteins were implicated in 14 signaling pathways, including mitochondrial cell dysfunction (data became available from ProteomeXchange with identifier PXD061705). The upregulation of p53, Bax, p-AktS473, p-mTORS2448 and the downregulation of Sirt 3, p-NRF2S40, and HO-1 were further verified by western blotting. In the metabolomic analysis, 3 upregulated and 8 downregulated metabolites involved in glycolysis, TCA cycle, pentose phosphate pathway (PPP) and ATP production were identified. Aligning the catalytic step of these metabolites in glycolysis and TCA cycle, the lower fructose 1,6-bisphosphate, 2-phosphoglyceric acid and phosphoenolpyruvate was coupled with higher isocitrate while the reduced α-ketoglutarate, malate, ATP and NADH all implied an accumulation of pyruvate in the cytosol. Western blotting, along with pyruvate and lactate assays, showed decreased extracellular lactate due to upregulated MCT1 (lactate importer) and downregulated MCT4 (lactate exporter). The higher pyruvate was caused by increased LDHB (lactate-to-pyruvate conversion) and a decrease in mitochondrial pyruvate carrier (MPC). With the finding that transplanted GES-1 mitochondria led to an accumulation of pyruvate, the inhibitory effect of elevated pyruvate on migrated AGS cells was observed. In conclusion, combining proteomic and metabolomic analysis revealed the underlying mechanisms for understanding how transplanted GES-1 mitochondria attenuate AGS gastric cancer malignancy.
