BACKGROUND: Anxiety disorders are highly prevalent and associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation. (AS) and (SC) individually exhibit anxiolytic properties, but the efficacy and mechanism o...BACKGROUND: Anxiety disorders are highly prevalent and associated with hypothalamic-pituitary-adrenal (HPA) axis dysregulation. (AS) and (SC) individually exhibit anxiolytic properties, but the efficacy and mechanism of their combination remain unclear. METHODS: The putative bioactive profile of the AS-SC combination was characterized. Its anxiolytic effects were evaluated in a rat model of conditioned fear-induced anxiety using behavioral tests, ELISA, and immunohistochemistry. RESULTS: The AS-SC combination markedly alleviated anxiety-like behaviors, decreased circulating corticosterone and adrenocorticotropic hormone concentrations, suppressed the release of IL-1β, IL-6, and TNF-α, modulated hippocampal dopamine and serotonin levels, and reduced neuronal injury. Mechanistically, the combination decreased hypothalamic CRH expression and restored hippocampal glucocorticoid receptor (GR) balance. CONCLUSION: The AS-SC combination exerts anxiolytic effects primarily by restoring hippocampus-HPA axis negative feedback and suppressing neuroinflammation, highlighting its potential as a therapeutic strategy.
Cerebral ischemic stroke (CIS) is a devastating cerebrovascular disease with high global morbidity, mortality, and disability rates, posing a severe burden on public health and socioeconomic development. Conventional Wes...Cerebral ischemic stroke (CIS) is a devastating cerebrovascular disease with high global morbidity, mortality, and disability rates, posing a severe burden on public health and socioeconomic development. Conventional Western medical interventions, while effective in the acute phase, are limited in mitigating long-term neurological sequelae and improving functional outcomes. Traditional Chinese medicine (TCM) has accumulated rich experience in CIS treatment over millennia, with Banxia-Baizhu-Tianma Decoction (BBTD) and acupuncture as pivotal evidence-based therapies. This review synthesizes the latest advances in CIS pathophysiological mechanisms and elaborates the therapeutic effects and molecular mechanisms of BBTD, acupuncture, and their combination. BBTD, a classical TCM formula for resolving phlegm, calming wind, invigorating the spleen and eliminating dampness, exerts neuroprotective, anti-inflammatory, antioxidant, and vascular-protective effects via multi-targeted regulation, with its constituent herbs acting synergistically. Acupuncture, a WHO-endorsed TCM component, alleviates CIS by inhibiting glutamate excitotoxicity, calcium overload and inflammatory cascades, promoting angiogenesis, neurogenesis and synaptic plasticity, mediated by regulating neurotransmitters, cytokines, growth factors and key signaling pathways. Preliminary clinical studies suggest that combined BBTD and acupuncture may be superior to monotherapy, showing potential in improving cerebral perfusion, reducing inflammatory markers and blood lipids, enhancing motor function and daily activities, and lowering disability rates. Despite limitations, preclinical and clinical evidence supports this integrative TCM strategy. This review concludes that BBTD and acupuncture may exert synergistic effects by targeting overlapping CIS pathophysiological pathways, and highlights the need for large-scale, high-quality RCTs and in-depth mechanistic studies to validate efficacy and promote clinical translation.
BACKGROUND: Cancer remains a leading cause of global morbidity and mortality. Although conventional therapies such as chemotherapy, radiotherapy, and immunotherapy improve survival, their effectiveness is often limited b...BACKGROUND: Cancer remains a leading cause of global morbidity and mortality. Although conventional therapies such as chemotherapy, radiotherapy, and immunotherapy improve survival, their effectiveness is often limited by resistance and toxicity. Fasting and fasting-mimicking diets (FMDs) have emerged as potential adjunctive interventions due to their effects on cellular metabolism, stress responses, and tumor-host interactions. AIM: To critically evaluate the biological rationale, molecular mechanisms, and clinical evidence supporting fasting and FMDs as adjuncts in cancer therapy. METHODS: A comprehensive literature review was conducted using PubMed, PubMed Central, and Google Scholar to identify relevant preclinical and clinical studies on fasting, caloric restriction, and FMDs in cancer. RESULTS: Preclinical studies demonstrate that fasting induces metabolic and oxidative stress, selectively sensitizing cancer cells while protecting normal cells. Early-phase clinical trials suggest that fasting and FMDs are safe, feasible, and capable of influencing metabolism and immune responses, with potential improvements in treatment tolerance and efficacy. However, these studies are limited by small sample sizes and heterogeneous designs. CONCLUSION: Fasting and FMDs represent promising adjunctive strategies in cancer therapy. While mechanistic data and preliminary clinical findings are encouraging, larger, well-designed trials are required to confirm their efficacy, safety, and long-term benefits.
BACKGROUND: The apolipoprotein B to apolipoprotein A1 (ApoB/A1) ratio has emerged as a superior lipid marker for cardiovascular risk assessment. This study aimed to develop and validate a nomogram incorporating the ApoB/...BACKGROUND: The apolipoprotein B to apolipoprotein A1 (ApoB/A1) ratio has emerged as a superior lipid marker for cardiovascular risk assessment. This study aimed to develop and validate a nomogram incorporating the ApoB/A1 ratio for predicting major adverse cardiovascular events (MACE) in patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). METHODS: This retrospective cohort study included 2459 patients undergoing PCI, randomly allocated to training (n=1721) and validation (n=738) cohorts. LASSO regression and multivariable Cox regression were used for variable selection and model development. Model performance was evaluated using C-index, calibration curves, and decision curve analysis. RESULTS: During a median follow-up of 33.8 months, MACE occurred in 187 patients (7.6%). The ApoB/A1 ratio was independently associated with MACE (HR 1.12 per 0.1 increase, 95% CI 1.06-1.19, <0.001). The nomogram incorporating 10 predictors demonstrated good discrimination (C-index: 0.67 in training, 0.72 in validation) and calibration. Decision curve analysis confirmed superior clinical utility across threshold probabilities of 5%-35%. Risk stratification showed distinct separation among low-, intermediate-, and high-risk groups, with 5-year MACE-free survival rates of 93.0%, 89.9%, and 83.1%, respectively (log-rank <0.001). CONCLUSION: The ApoB/A1 ratio may be an independent predictor of MACE in CAD patients after PCI. The developed nomogram showed promising performance for risk prediction and stratification in this retrospective cohort. External validation in prospective studies is warranted before clinical implementation.
BACKGROUND: Although the presence of cerebral small vessel disease (CSVD) on neuroimaging closely parallels overall stroke risk, it is still uncertain whether combining these structural markers with blood-based profiles...BACKGROUND: Although the presence of cerebral small vessel disease (CSVD) on neuroimaging closely parallels overall stroke risk, it is still uncertain whether combining these structural markers with blood-based profiles can reliably predict functional outcomes in patients suffering from acute basal ganglia hemorrhage (BGH). METHODS: We enrolled 242 BGH patients admitted between January and December 2024. The least absolute shrinkage and selection operator (LASSO) with ten‑fold cross‑validation selected candidate predictors. Backward elimination in multiple logistic regression identified independent risk variables and built the final model. Discrimination was assessed by the area under the receiver operating characteristic curve (AUC), calibration by the Hosmer‑Lemeshow test and calibration plots. The DeLong test and decision curve analysis evaluated model comparison and clinical utility. A risk stratification chart enabled individualized risk assessment. RESULTS: Multivariable analysis identified four independent predictors of poor prognosis: total load (adjusted OR = 9.25, 95% CI: 3.52-24.28, P < 0.001), triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio (adjusted OR = 8.39, 95% CI: 3.21-21.92, P < 0.001), non-high-density lipoprotein cholesterol ratio (NHHR) (adjusted OR = 4.95, 95% CI: 2.50-9.82, P < 0.001), and systemic inflammation response index (SIRI) (adjusted OR = 3.35, 95% CI: 1.89-5.93, P < 0.001). The prediction model showed excellent discrimination, with an AUC of 0.929 (95% CI: 0.89-0.97). At a cutoff value of 0.29, sensitivity was 86% and specificity was 91%. Evaluation of the model's calibration demonstrated a good concordance between the estimated probabilities and the actual clinical endpoints. CONCLUSION: Evaluating BGH patients through an integrated lens of blood-based biomarkers and neuroimaging substantially enhances prognostic clarity. Rather than being considered in isolation, systemic indices such as the TG/HDL‑C ratio, NHHR, and SIRI combine with cumulative CSVD severity to independently flag high‑risk clinical trajectories.
BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is a prevalent malignancy of the head and neck, characterized by a complex tumor microenvironment (TME) that hinders the effectiveness of immunotherapy. OBJECTIVE: Thi...BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is a prevalent malignancy of the head and neck, characterized by a complex tumor microenvironment (TME) that hinders the effectiveness of immunotherapy. OBJECTIVE: This study aimed to comprehensively characterize the features, interactions, and clinical significance of POSTN cancer-associated fibroblasts (CAFs) and APOE tumor-associated macrophages (TAMs) within the LSCC TME through integrative multi-omics analysis. METHODS: We integrated single-cell RNA sequencing, spatial transcriptomics, and bulk RNA-seq data from the GEO and TCGA databases. Differential expression, functional enrichment, cell-cell communication, multiplex immunofluorescence, spatial colocalization, molecular docking, and survival analyses were performed, with independent validation in the IMvigor210 immunotherapy cohort. RESULTS: A total of 206,399 cells were obtained from 29 LSCC single-cell samples (Tumor=16, Normal=13) and POSTN CAF/APOE TAM gene sets were identified. POSTN CAFs and APOE TAMs were enriched in LSCC tissues, and associated with epithelial-mesenchymal transition (EMT) and M2 macrophage polarization, respectively. Cell-cell communication and spatial analyses revealed close bidirectional signaling and spatial colocalization between the two cell types. Multiplex immunofluorescence staining further confirmed their close spatial proximity. Molecular docking suggested a potential structural compatibility between POSTN and APOE. Bulk RNA-seq analysis showed that their co-enrichment correlated with poor prognosis and resistance to immunotherapy, which were further confirmed in pan-cancer datasets. CONCLUSION: The POSTNCAF/APOETAM axis is cooperatively associated with aggressive tumor behavior in LSCC and shapes an immunosuppressive microenvironment. This cellular axis may serve as a potential biomarker and therapeutic target for predicting prognosis and responsiveness to immunotherapy in LSCC.
OBJECTIVE: To identify perioperative clinical and surgical variables associated with intracranial infection (ICI) after craniotomy, and establish an accurate machine learning prediction model for clinical risk stratifica...OBJECTIVE: To identify perioperative clinical and surgical variables associated with intracranial infection (ICI) after craniotomy, and establish an accurate machine learning prediction model for clinical risk stratification and early intervention. METHODS: A retrospective study included 419 patients who underwent craniotomy surgery at Xiangyang Central Hospital from May 2017 to April 2024. Perioperative variables were collected. Univariate and multivariate logistic regression were used to screen for risk factors. Four models (LR, RF, XGBoost, LightGBM) were constructed and validated through AUC, sensitivity, specificity, PPV, NPV, calibration curve, and DCA were used to evaluate the performance. RESULTS: 53 patients (12.6%) developed ICI. Independent risk factors included prolonged surgical time, significant intraoperative bleeding, postoperative cerebrospinal fluid leakage, multiple surgeries (≥ 2), and frequent cerebrospinal fluid sampling/drug injection through drainage tubes. LightGBM achieved the best performance: training set AUC 0.873 (95% CI 0.819-0.927), test set AUC 0.811 (95% CI 0.758-0.924), sensitivity 81.0%, specificity 79.3%, PPV 38.6%, NPV 95.7%. Good calibration and high clinical practicality were confirmed. CONCLUSION: Machine learning models, especially LightGBM, can effectively predict postoperative ICI. The identified risk factors and best models support personalized risk assessment and clinical prevention.
PURPOSE: This study aims to investigate the role of coenzyme Q10B (COQ10B) in esophageal squamous cell carcinoma (ESCC) and elucidate its potential mechanisms in regulating the tumor immune microenvironment. PATIENTS AND...PURPOSE: This study aims to investigate the role of coenzyme Q10B (COQ10B) in esophageal squamous cell carcinoma (ESCC) and elucidate its potential mechanisms in regulating the tumor immune microenvironment. PATIENTS AND METHODS: This study integrates bioinformatics, in vitro cell experiments, and in vivo animal models. First, the TCGA and GEO databases were used to analyze correlations between COQ10B expression and ESCC prognosis, signaling pathways, and immune cell infiltration, and single-cell sequencing data were combined to establish its cellular expression profile. Second, TE-1 cells were lentivirally transfected to overexpress COQ10B, and colony formation, EdU, scratch, and Transwell assays were conducted to assess the effects on proliferation, migration, and invasion. Finally, a subcutaneous xenograft model in C57BL/6 mice evaluated COQ10B overexpression and PI3K inhibitor (LY294002) effects on tumor growth, PD-L1 expression, PI3K/AKT/HIF-1A pathway, and immune cell (CD4+ T cells, M2 macrophages) infiltration via Western blotting and flow cytometry. RESULTS: Bioinformatics showed that COQ10B was highly expressed in ESCC and was significantly associated with poor prognosis. Its expression positively correlated with the PI3K-AKT and HIF1 pathways, cancer stem cell genes, and macrophage infiltration. In vitro, COQ10B overexpression enhanced ESCC cell proliferation, migration, and invasion. In vivo, it promoted tumor growth, upregulated PD-L1, p-PI3K, p-AKT, and HIF-1A, reduced CD4+ T cells, and increased M2 macrophages. The PI3K inhibitor LY294002 reversed these pro-tumor and immunosuppressive effects. CONCLUSION: High COQ10B expression is closely associated with ESCC progression and poor prognosis. These malignant biological behaviors and the associated immunosuppressive tumor microenvironment are potentially mediated via the activation of the PI3K/AKT/HIF-1A signaling pathway.
OBJECTIVE: To evaluate the incremental predictive value of the Global Registry of Acute Coronary Events (GRACE) score combined with the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria for bleeding...OBJECTIVE: To evaluate the incremental predictive value of the Global Registry of Acute Coronary Events (GRACE) score combined with the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria for bleeding risk after percutaneous coronary intervention (PCI) in patients with ST‑segment elevation myocardial infarction (STEMI). METHODS: This prospective observational study enrolled 338 STEMI patients who underwent their first PCI at Fuyang People's Hospital from January 2023 to March 2024. Bleeding events were defined according to the Bleeding Academic Research Consortium (BARC) types 1-5. Patients were stratified by GRACE score (low/middle/high) and ARC‑HBR status (high/low). The predictive performance of the model was assessed using receiver operating characteristic (ROC) curves, net reclassification improvement (NRI), integrated discrimination improvement (IDI), decision curve analysis (DCA), and calibration plots. Internal validation was performed via bootstrap resampling (1,000 iterations). RESULTS: Bleeding occurred in 83 patients (24.56%), with 63 in‑hospital events (18.64%) and 34 out‑of‑hospital events (10.06%). The majority were mild (BARC type 1, 82.54% in‑hospital; 73.53% out‑of‑hospital). The combined GRACE + ARC‑HBR model achieved an area under the ROC curve (AUC) of 0.774 (95% CI 0.726-0.818), compared with 0.712 (95% CI 0.660-0.759) for GRACE alone and 0.667 (95% CI 0.614-0.717) for ARC‑HBR alone. Versus GRACE, the combined model showed a non‑significant NRI (-0.0509; P = 0.0945) but a significant IDI (0.0560; P = 0.0006). Versus ARC‑HBR, both NRI (0.3277; P = 0.0007) and IDI (0.0768; P < 0.0001) were significantly positive. DCA demonstrated the highest net benefit for the combined model across most threshold probabilities. The calibration curve yielded a Brier score of 0.147, and the Hosmer-Lemeshow test confirmed good calibration (χ=3.568, P=0.8938). Bootstrap internal validation produced a bias‑corrected AUC of 0.775. CONCLUSION: Compared with either score alone, the combination of the GRACE score and the ARC-HBR criteria provides incremental predictive value for post-PCI bleeding in STEMI patients.
BACKGROUND: The COVID-19 pandemic and its associated nonpharmaceutical interventions have profoundly changed the epidemiology of respiratory pathogens. Following the lifting of COVID-19 restrictions in December 2022 and...BACKGROUND: The COVID-19 pandemic and its associated nonpharmaceutical interventions have profoundly changed the epidemiology of respiratory pathogens. Following the lifting of COVID-19 restrictions in December 2022 and its adjustment to Class B management, respiratory infections have resurged in China. This study aimed to understand the infection spectrum, mixed infection pattern and temporal dynamic changes of respiratory pathogens in the first autumn-winter after the outbreak of COVID-19 in Beijing. METHODS: A total of 864 unique throat swab specimens from patients with respiratory infections at Beijing Tongren Hospital were analyzed, with no repeated testing. Respiratory pathogens were detected by multiplex PCR against 31 viral, bacterial, and atypical pathogens. Detection rates, co-infection patterns, and temporal trends were analyzed across age groups and clinical settings. RESULTS: The total detection rate of respiratory bacteria was 79.63% (688/864), the highest was in children (86.67%), and the lowest was in elderly patients (70.49%). The detection rate of outpatients and emergency patients was significantly higher than that of inpatients (p < 0.001). Co-infections were found in 59.16% of the positive cases, mainly viral-bacterial and bacterial-bacterial combinations. The highest detection rates of viruses were influenza A virus (27.31%), influenza B virus (10.42%) and human adenovirus (5.09%). Among bacterial pathogens, (26.62%), (18.75%) and (14.47%) were most frequently detected. Weekly analyses showed alternating circulation of influenza A and B viruses, with an increase in bacterial load late in the influenza season. CONCLUSION: The first autumn-winter after COVID-19 outbreak in Beijing was characterized by extensive co-circulation of multiple respiratory pathogens, with high viral infection burden and frequent bacterial co-infection. These findings highlight the importance of continued molecular surveillance and integrated pathogen testing strategies for clinical management and public health response in a post-COVID-19 era.
BACKGROUND: Accurate assessment of illness severity is crucial in critically ill patients. The APACHE II score is widely used but complex and fails to reflect underlying immune-inflammatory dysregulation. C-type lectin d...BACKGROUND: Accurate assessment of illness severity is crucial in critically ill patients. The APACHE II score is widely used but complex and fails to reflect underlying immune-inflammatory dysregulation. C-type lectin domain family 4 member D (CLEC4D), a pattern recognition receptor on myeloid cells, is pivotal in immune responses. We investigated whether circulating CLEC4D levels could serve as a novel biomarker for severity of illness. METHODS: 368 adult ICU patients were enrolled. Serum CLEC4D levels, APACHE II scores, and immune-inflammatory parameters were measured within 24 hours of admission. Associations were analyzed using generalized additive models and multiple linear regression. RESULTS: Patients with high APACHE II scores (≥16) exhibited significantly elevated CLEC4D levels compared with those with lower scores (344.20 ± 65.75 pg/mL vs. 321.28 ± 73.31 pg/mL, = 0.002). Multiple linear regression demonstrated a robust positive association between CLEC4D and APACHE II scores, with each 1 pg/mL increase in CLEC4D corresponding to a 0.016-point rise in APACHE II ( < 0.05). CLEC4D was inversely correlated with lymphocyte (β = -0.028, < 0.001) and IL-6 (β = -1.404, = 0.021) but positively correlated with PCT (β = 0.022, = 0.031). Subgroup analyses confirmed the stability of this correlation across tumor and non-tumor cohorts and revealed a markedly stronger association among patients with sepsis (β = 0.030, < 0.001). CONCLUSION: Circulating CLEC4D levels positively correlate with APACHE II scores in critically ill patients, potentially associated with dynamic shifts in immune-inflammatory markers. CLEC4D represents a promising biomarker for assessing illness severity, especially in sepsis.
BACKGROUND: Left atrial thrombus (LAT) is the main cause of ischemic stroke in patients with atrial fibrillation. Left atrial thrombus or spontaneous echo contrast (SEC) can be best displayed by transesophageal echocardi...BACKGROUND: Left atrial thrombus (LAT) is the main cause of ischemic stroke in patients with atrial fibrillation. Left atrial thrombus or spontaneous echo contrast (SEC) can be best displayed by transesophageal echocardiography (TEE). This study aimed to evaluate non-valvular atrial fibrillation (NVAF) patients with LAT/SEC confirmed by transesophageal echocardiography compared with those without LAT/SEC, using residual cholesterol inflammatory index (RCII) as a sensitive biomarker. METHODS: This study was a retrospective study of 967 NVAF patients who underwent transesophageal echocardiography at a single center. Patients were divided into two groups based on the presence or absence of LAT/SEC on TEE. The levels of RCII and left atrium diameter (LAD) were compared. RESULTS: RCII was identified as an independent variable in patients with LAT/SEC detected by transesophageal echocardiography. (OR: 1.232, CI:1.159-1.309, < 0.001) The combination of RCII, LAD, and CHA2DS2-VASc scores had the highest area under the curve (AUC) value (AUC:0.787 CI:0.748-0.826 <0.001). CONCLUSION: Our study demonstrates that RCII and LAD are risk factors for LAT/SEC. CHA2DS2-VASc score combined with RCII and LAD can significantly improve the predictive ability of LAT/SEC.
Abdallah HM, Osheba IS, Salman AA
… +12 more, Gaballa NK, Helmi MO, Ibrahim AR, Atta ASS, Saad MG, Aboagiza SM, Abdel Hafez HS, El Helbawy MGED, GabAllah GMK, Elewa A, Salman MA, Abdelmegeed NA
BACKGROUND: Esophageal varices (EVs) are a serious consequence of portal hypertension in chronic liver disease, particularly in hepatitis C virus (HCV) infection. While endoscopy remains the gold standard for diagnosis,...BACKGROUND: Esophageal varices (EVs) are a serious consequence of portal hypertension in chronic liver disease, particularly in hepatitis C virus (HCV) infection. While endoscopy remains the gold standard for diagnosis, there is growing interest in human platelet antigen (HPA) polymorphisms as potential non-invasive markers associated with EV development. AIM: To assess the association between HPA-1, HPA-2, and HPA-3 gene polymorphisms and the presence and severity of EVs in cirrhotic patients. METHODS: In this case-control study, 150 patients with HCV-related cirrhosis were enrolled and divided into two groups based on endoscopic findings: 75 with EVs and 75 without. HPA genotyping was performed using polymerase chain reaction with sequence-specific primers (PCR-SSP). Statistical analysis included univariate and multivariate logistic regression, with odds ratios (ORs) and 95% confidence intervals (CIs) calculated. RESULTS: The HPA-3 (ab + aa) genotypes were significantly associated with the presence of EVs in univariate analysis (OR: 2.244, 95% CI: 1.039-4.847, p = 0.040), but this association was not maintained in multivariate analysis (OR: 0.679, 95% CI: 0.209-2.211, p = 0.521). Higher grades of varices were significantly associated with HPA-1 (a), HPA-2 (b), and HPA-3 (a) alleles (p < 0.05). Platelet count and platelet count-to-spleen diameter (PC/SD) ratio were also significantly associated with EVs in univariate analysis (p < 0.001). In multivariate analysis, serum creatinine (OR: 0.234, 95% CI: 0.116-0.473, p < 0.001) and portal vein diameter (OR: 1.542, 95% CI: 1.231-1.930, p < 0.001) were identified as independent predictors of EVs. CONCLUSION: HPA polymorphisms were associated with the presence and severity of esophageal varices but were not independent predictors. Further multicenter prospective studies are needed to clarify their clinical utility.
INTRODUCTION: Trastuzumab deruxtecan (T-DXd) has become an important treatment option for patients with HER2-positive and HER2-low solid tumors, yet real-world evidence on its safety remains limited, particularly in Midd...INTRODUCTION: Trastuzumab deruxtecan (T-DXd) has become an important treatment option for patients with HER2-positive and HER2-low solid tumors, yet real-world evidence on its safety remains limited, particularly in Middle Eastern populations. This study evaluates the safety profile of T-DXd in routine clinical practice at a major tertiary center in Makkah, Saudi Arabia. METHODS: A retrospective cohort study was conducted at King Abdullah Medical City and included adults with HER2-positive or HER2-low metastatic breast cancer who received at least one dose of T-DXd between 2022 and 2024. Electronic medical records were reviewed for demographic data, prior treatments, and adverse events. Toxicities were graded according to CTCAE v5.0. The primary outcome was the incidence and severity of T-DXd-related adverse events. Secondary outcomes included treatment discontinuation rates and adherence to recommended interstitial lung disease (ILD) monitoring protocols. RESULTS: Thirty-one patients were included (93.5% female; median age 50-59 years). Hematologic toxicities were most common, occurring in 87.1% of patients. Respiratory events including ILD and pneumonitis were documented in 28% of patients. Among patients who underwent imaging according to recommended intervals, respiratory events were identified more frequently (36%) than in those with less consistent monitoring (11%), likely reflecting increased detection of subclinical events rather than a true difference in incidence. Treatment discontinuation occurred in 25.8% of patients, primarily due to adverse events or progression. CONCLUSION: T-DXd was generally tolerable in this small Saudi cohort, with hematologic and respiratory toxicities being the most frequent. The relatively higher frequency of respiratory events and the observed differences by monitoring adherence should be interpreted cautiously given the descriptive design. Larger multicenter studies are needed to better define safety patterns and optimal monitoring strategies.
BACKGROUND: Acute myeloid leukemia (AML) remains a therapeutic challenge, necessitating the identification of novel targets and repurposable drugs. This study integrates multi‑omics and Mendelian randomization (MR) to in...BACKGROUND: Acute myeloid leukemia (AML) remains a therapeutic challenge, necessitating the identification of novel targets and repurposable drugs. This study integrates multi‑omics and Mendelian randomization (MR) to investigate the role of lysosomal acid lipase (LIPA) in AML and to explore the potential of lovastatin as a LIPA‑targeting agent. METHODS: We combined transcriptomic data from TCGA and GTEx with MR analysis using eQTLs to assess the causal relationship between LIPA expression and AML risk. A prognostic signature was constructed via LASSO and validated in external GEO cohorts. Network pharmacology, molecular docking, and molecular dynamics simulations were employed to identify drugs targeting LIPA. In vitro, AML cell lines (THP‑1, K562) were treated with lovastatin and/or the ER stress inhibitor 4‑PBA; apoptosis, ER stress markers, and ultrastructure were assessed by flow cytometry, qPCR, Western blot, and transmission electron microscopy. RESULTS: MR established a causal link between elevated LIPA expression and increased AML risk (OR=1.32, p=0.003). A 16‑gene prognostic signature including LIPA effectively stratified patients (p<0.0001). Lovastatin was identified as a potential high‑affinity LIPA inhibitor. In vitro, lovastatin induced marked apoptosis in AML cells, which was accompanied by downregulation of ER stress markers (ATF6, CHOP, IRE1) and constricted ER morphology. Notably, the ER stress inhibitor 4‑PBA phenocopied these effects, consistent with lovastatin exerting its anti‑AML activity through suppression of ER stress. CONCLUSION: This multi-omics study establishes LIPA as a causal prognostic biomarker in AML and reveals that lovastatin triggers apoptosis by inhibiting ER stress, providing a mechanistic rationale for repurposing lovastatin in AML therapy.
BACKGROUND AND PURPOSE: Evidence regarding the associations of serum albumin and apolipoprotein-related markers with acute cognitive impairment (CI) after stroke remains limited. This study investigated the associations...BACKGROUND AND PURPOSE: Evidence regarding the associations of serum albumin and apolipoprotein-related markers with acute cognitive impairment (CI) after stroke remains limited. This study investigated the associations of serum albumin and the apolipoprotein B/apolipoprotein A1 ratio (ApoB/ApoA1) with acute CI assessed within 7 days after first-ever ischemic stroke (IS). METHODS: This retrospective single-center case-control study included patients with first-ever IS who completed the Chinese version of the Mini-Mental State Examination (MMSE) within 7 days after stroke onset. Patients with an MMSE score of ≤25 were classified into the CI group, and those with an MMSE score of >25 into the non-CI group. Propensity score matching was performed in a 1:1 ratio (caliper = 0.07; without replacement) based on age, sex, and education level. Associations were evaluated using logistic regression analyses. RESULTS: Among 371 eligible patients, 175 were in the CI group and 196 were in the non-CI group. After matching, 144 pairs were included. In the matched cohort, albumin, ApoB, and ApoB/ApoA1 were lower in the CI group. In multivariable analysis, higher albumin (adjusted odds ratio 0.934, 95% confidence interval 0.887-0.983; P=0.009) and higher ApoB/ApoA1 (adjusted odds ratio 0.429, 95% confidence interval 0.200-0.919; P=0.030) were independently associated with lower odds of acute CI after stroke. The lowest odds of acute CI were observed at albumin levels of 39.300-41.400 g/L and an ApoB/ApoA1 ratio of ≥0.883. CONCLUSION: In patients with first-ever IS, higher serum albumin levels and a higher ApoB/ApoA1 ratio were associated with lower odds of acute CI within 7 days after stroke. Multicenter prospective studies are needed to validate these findings and clarify the underlying mechanisms.
BACKGROUND: Tuberculosis and lymphoma are the common causes of fever of unknown origin (FUO) and show some similar clinical symptoms. The purpose of this study was to analyze the clinical characteristics of tuberculosis...BACKGROUND: Tuberculosis and lymphoma are the common causes of fever of unknown origin (FUO) and show some similar clinical symptoms. The purpose of this study was to analyze the clinical characteristics of tuberculosis and lymphoma to find effective methods to distinguish them. METHODS: A cohort including 100 tuberculosis and 81 lymphoma patients in FUO was prospectively enrolled. A predictive model of tuberculosis based on clinical parameters was established by using logistic regression equation, and its efficacy was evaluated by Receiving operating curve (ROC). RESULTS: Both lymphoma and tuberculosis were more common in middle-aged and elderly males (P=0.043), and the total fever duration was relatively long (P=0.086). Muscle pain (P=0.017) and chills (P=0.045) were more common in tuberculosis patients, while hepatosplenomegaly (P<0.001) and lymphadenopathy (P<0.001) were more prevalent in lymphoma patients. The positive rate of T-SPOT.TB in the tuberculosis group was significantly higher than that in the lymphoma group (P<0.001). In the lymphoma group, LDH and SF were all significantly increased (P<0.001), while ALB and PLT were significantly decreased (P<0.001). The AUC of the diagnostic prediction model for tuberculosis established by combining parameters was 0.96 (95% CI, 0.935-0.986), with a sensitivity of 90.9% and a specificity of 87.1%. A validation cohort consisted of 42 patients with FUO from other departments during the same period, the AUC of the validation cohort was 0.948 (95% CI, 0.886-0.999), with a sensitivity of 90% and a specificity of 90.9%. CONCLUSION: The integration of clinical parameters facilitates enhanced discriminative capacity between tuberculosis and lymphoma.
OBJECTIVE: Insomnia is a common sleep disorder marked by difficulties in sleep initiation, maintenance, and daytime performance. Pharmacological treatments offer short-term relief but are limited by tolerance, dependence...OBJECTIVE: Insomnia is a common sleep disorder marked by difficulties in sleep initiation, maintenance, and daytime performance. Pharmacological treatments offer short-term relief but are limited by tolerance, dependence, and adverse effects. This review aims to evaluate recent advances in acupuncture for insomnia, with emphasis on clinical efficacy and underlying mechanisms. METHODS: This narrative review was conducted through a structured literature search of PubMed, Web of Science, and CNKI databases covering studies published from January 2020 to December 2025. The search combined keywords including "insomnia", "acupuncture", "mechanism", "autonomic nervous system", "inflammation", and "HPA axis". Both clinical and preclinical studies published in English or Chinese were considered. Studies were screened based on relevance to acupuncture interventions for insomnia and mechanistic outcomes. Although a formal systematic review protocol was not applied, emphasis was placed on representative and high-quality evidence to summarize key mechanistic pathways. RESULTS: Evidence suggests that acupuncture improves subjective sleep quality, alleviates hyperarousal, reduces systemic inflammation, and promotes neuroimmune balance through multidimensional mechanisms. However, limitations remain, including small sample sizes, methodological heterogeneity, inadequate blinding, and insufficient mechanistic exploration. CONCLUSION: Acupuncture is a promising integrative intervention for insomnia with both symptomatic and mechanistic benefits. Future studies should prioritize large-scale, multicenter randomized controlled trials and standardized protocols, while incorporating multi-omics, neuroimaging, and precision medicine approaches. Interdisciplinary collaboration may advance acupuncture from empirical therapy to precision medicine, providing new opportunities for comprehensive insomnia management.
OBJECTIVE: To analyze and construct symptom networks at four postoperative time-points in early-stage lung cancer patients using cross-lagged panel networks (CLPN), so as to examine their dynamic evolution and longitudin...OBJECTIVE: To analyze and construct symptom networks at four postoperative time-points in early-stage lung cancer patients using cross-lagged panel networks (CLPN), so as to examine their dynamic evolution and longitudinal predictive relationships. METHODS: This prospective study captured the incidence and severity of symptoms in patients by employing the Postoperative Symptom Scale for Lung Cancer on postoperative day 1 (T1), day 3 (T2), day 30 (T3) and day 90 (T4). Partial-correlation networks and CLPN were built in R Language, key nodes were identified using longitudinal data to explore the predictive/reciprocal effects among symptoms. RESULTS: Partial-correlation networks showed that fatigue (D4) and dizziness (D5) had the highest strength centrality at T1, pain (D2) and fatigue (D4) were most central at T2, insomnia (D8) and cough (D1) dominated at T3, and insomnia (D8) alone was most central at T4. Furthermore, CLPN revealed that fatigue (D4) exerted the greatest out-expected influence during T1→T2, with the strongest predictive path from T1-fatigue to T2-insomnia. While pain (D2) became the most influential sender during T2→T3, with the strongest predictive path from T2-pain to T3-shortness of breath. There is a time-dynamic postoperative symptom network in early-stage lung cancer patients, with core symptoms shifting across the recovery trajectory. CONCLUSION: Findings in our study highlight the adoption of time-specific symptom management, targeting the dominant symptoms at each phase to achieve precision care and optimize patients' postoperative recovery course.