Qiliqiangxin (QLQX) capsule- a traditional Chinese medicine used for treating heart failure (HF), can modulate inflammatory cytokines in rats with myocardial infarction. However, its immune-regulating effect on dilated cardiomyopathy (DCM) remains unknown. The aim of this study was to investigate whether QLQX has a unique regulatory role in the imbalance of pro- and anti-inflammatory cytokines in patients with DCM.
The QLQX-DCM is a randomized- double-blind trial conducted at 24 tertiary hospitals in China. A total of 345 patients with newly diagnosed virus-induced DCM were randomly assigned to receive QLQX capsules or placebo while receiving optimal medical therapy for HF. The primary endpoints were changes in plasma inflammatory cytokines and improvements in left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDd) over the 12-month treatment.
At the 12-month follow-up, the levels of IFN-γ, IL-17, TNF-α, and IL-4 decreased significantly, while the level of IL-10 increased in both groups compared with baselines (all P<0.0001). Furthermore-these changes, coupled with improvements in LVEF, NT-proBNP and New York Heart Association (NYHA) functional classification, excluding the LVEDd in the QLQX group, were greater than those in the placebo group (all P<0.001). Additionally, compared with placebo, QLQX treatment also reduced all-cause mortality and rehospitalization rates by 2.17% and 2.28%, respectively, but the difference was not statistically significant.
QLQX has the potential to alleviate the imbalance of inflammatory cytokines in patients with DCM, potentially leading to further improvements in cardiac function when combined with anti-HF standard medications.
To investigate the distribution characteristics of common bacteria and changes in antimicrobial resistance in intensive care unit (ICU) patients in 58 hospitals in Hubei Province from 2020–2023.
The antimicrobial agents for antimicrobial susceptibility tests was selected based on the 2022 China Antimicrobial Resistance surveillance system (CARSS) technical scheme, and the specific experimental operation was based on the requirements of the CLSI M02 and M07 documents. The commercial instruments were used following the manufacturer’s instructions. The interpretation of antimicrobial susceptibility test results was based on the 2023 CLSI M100 standard.
There were 15 585, 19 258, 23 423 and 22 395 clinical isolates in the ICU from 2020 to 2023, respectively. Among them, gram-positive bacteria accounted for 20.5% (3190/15 585), 21.2% (4089/19 258), 21.6% (5067/23 423) and 21.6% (4 831/22 395), respectively. Gram-negative bacteria accounted for 79.5% (12 395/15 585), 78.8% (15 169/19 258), 78.4% (18 356/23 423) and 78.4% (17 564/22 395) of the bacteria, respectively. The top 5 isolates of gram-positive bacteria were Staphylococcus aureus, Enterococcus faecium, Streptococcus pneumoniae, Enterococcus faecalis, Staphylococcus epidermidis and gram-negative bacteria were Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, Pseudomonas aeruginosa and Stenotrophomonas maltophil, respectively, but the proportions and rankings of the isolates in different years slightly differed. The detection rate of methicillin-resistant S. aureus (MRSA) decreased from 44.4% in 2020 to 36% in 2023, and that of methicillin-resistant coagulase-negative Staphylococcus (MRCNS) decreased from 79.8% in 2020 to 73.8% in 2022 and increased to 78.4% in 2023. The detection rates of both vancomycin-resistant E. faecium and E. faecalis were lower than 1%. The detection rate of carbapenem-resistant P. aeruginosa (CRPA) decreased from 25% in 2020 to 19.7% in 2022 and increased slightly to 20.6% in 2023. The detection rate of carbapenem-resistant A. baumannii (CRAB) decreased from 81.9% in 2020 to 79.7% in 2022 and increased to 82.9% in 2023. The detection rate of third-generation cephalosporin-resistant E. coli decreased from 59.8% in 2020 to 53.1% in 2022 and increased to 52.5% in 2023. The detection rate of fluoroquinolone-resistant E. coli decreased from 62.7% in 2020 to 50.2% in 2022 and increased slightly to 51.0% in 2023. The detection rate of carbapenem-resistant E. coli (CRECO) decreased from 3.3% in 2020 to 1.8% in 2022 and slightly increased to 2.1% in 2023. The detection rate of third-generation cephalosporin-resistant K. pneumoniae decreased from 34.3% in 2020 to 26.3% in 2022 and then increased to 32.4% in 2023. The detection rate of carbapenem-resistant K. pneumoniae (CRKPN) increased from 17.9% to 19.4% in 2020, decreased to 13.2% in 2022, and rose sharply to 20.4% in 2023.
MRSA showed a continuous downwards trend from 2020 to 2023, while the detection rates of MRCNS and most multidrug-resistant gram-negative bacteria continuously decreased from 2020 to 2022 but tended to increase in 2023. Therefore, it is still necessary to strengthen the monitoring of bacterial resistance and rational application of antibiotics and actively and effectively control nosocomial infections.
Jianpi huoxue decoction (JHD), a Chinese herbal formula, is commonly used for treating alcohol-associated liver disease (ALD). This study aimed to investigate the mechanism by which JHD affects intestinal barrier function in ALD rats.
The Sprague-Dawley rats were randomly divided into three groups: control group, model group and JHD group. They were pair-fed a modified Lieber-DeCarli liquid diet containing alcohol (model group, n=10; JHD group, n=10) or isocaloric maltose dextrin (control group, n=10) for 6 weeks. After 3 weeks of feeding, the mice in the JHD group were given JHD (10 mL/kg/day) by gavage for 3 weeks, and those in the control and model groups received equal amounts of double-distilled water for the same period of time. Afterwards, all the rats were given lipopolysaccharide (LPS) by gavage and sacrificed 3.5 h later. LPS levels were measured in the portal blood to evaluate gut leakage. Transmission electron microscopy (TEM) was used to observe ultrastructural changes in the intestinal tract. Adherens junction (AJ) and tight junction (TJ) proteins were detected by Western blotting, immunofluorescence or immunohistochemistry.
JHD ameliorated Lieber-DeCarli liquid diet-induced hepatic steatosis, inflammation and LPS expression. It improved pathological changes in the liver and alleviated intestinal ultrastructure injury. Moreover, it significantly enhanced the integrity of tight junctions by increasing the expression of zonula occludens-1 (ZO-1) and occludin. It suppressed the activation of myosin light chain (MLC) phosphorylation.
JHD improves intestinal barrier function and reduces gut leakiness in ALD rats.
Imbalances in liver lipid metabolism and inflammatory reactions driven by oxidized lipid deposition in blood vessels constitute the core of atherosclerosis. Insufficient degradation of cholesterol in the liver promotes oxidative modification of lipid particles and their deposition on the blood vessel wall in the peripheral circulation. The blood vessel wall engulfs and processes oxidized low-density lipoprotein (Ox-LDL) as foreign matter through pattern recognition receptors, ultimately forming lipid-encapsulated plaques. Among them, endothelial cell oxidized low density lipoprotein receptor 1 (LOX1) phagocytosis is an important link in initiating and promoting this mechanism, and hepatocytes, which are the core of lipid metabolism, are unable to process oxidized lipid particles because of the lack of receptors for the uptake of Ox-LDL. The objective of this study was to investigate whether continuous clearance of Ox-LDL through the liver metabolic pathway could provide better protection against statins therapy.
This study used statins combined with an adeno-associated virus (AAV8-TBG-LOX-1) liver-specific transfection system developed by our research group, in which statins reduced the level of LDL and promoted the ectopic expression of LOX-1 in hepatocytes to clear the continuous production of Ox-LDL. An ApoE knockout mouse model was used to study the effects of virus transfection and liver uptake and degradation of Ox-LDL. Laser confocal detection, Oil red staining and immunofluorescence staining were used to observe the effects of combined therapy on anti-atherosclerotic lesions.
Laser confocal microscopy revealed that the recombinant viral vector AAV8-TBG-LOX-1 could specifically transfect hepatocytes and express LOX-1, which mediate hepatocyte phagocytosis and clearance of Ox-LDL. Oil red O staining of the aorta and valvular ring suggested that statins combined with AAV8-TBG-LOX-1 significantly inhibited atherosclerotic lesions. Tissue immunofluorescence staining suggested that statins could reduce the aggregation of macrophages in plaques and that combined therapy could further reduce the aggregation of macrophages in plaques.
Statins combined with AAV8-TBG-LOX-1 can alleviate the inflammatory response driven by lipids in the vascular wall, reduce the deposition of macrophages in plaques and inhibit atherosclerosis.
There are several types of brain tumors but glioblastoma (GBM) is one of the highly malignant tumors. A primary concern with GBM is that the treatment is inadequate. Even after giving many multi-stacked combinations of therapies to patients, inclusive of chemotherapy, radiation, and surgery, the median survival rate remains poor. Due to its heterogeneous nature, the use of selective therapy for specific targeting of tumor cells is of particular importance. Although many treatment alternatives which include surgery with adjuvant chemotherapy and radiotherapy are available, the prognosis of the disease is very poor. Combination therapy is becoming the foundation of modern antitumor therapy and it is continuously evolving and developing innovative drug regimens as evidenced by ongoing preclinical and clinical trials. In this review, we discuss the current treatment options and emerging therapeutic approaches for the treatment of GBM. The prospects for alternative glioblastoma therapy are also discussed.
Cystic fibrosis (CF) is a hereditary disorder characterized by mutations in the CFTR gene, leading to impaired chloride ion transport and subsequent thickening of mucus in various organs, particularly the lungs. Despite significant progress in CF management, current treatments focus mainly on symptom relief and do not address the underlying genetic defects. Stem cell and gene therapies present promising avenues for tackling CF at its root cause. Stem cells, including embryonic, induced pluripotent, mesenchymal, hematopoietic, and lung progenitor cells, offer regenerative potential by differentiating into specialized cells and modulating immune responses. Similarly, gene therapy aims to correct CFTR gene mutations by delivering functional copies of the gene into affected cells. Various approaches, such as viral and nonviral vectors, gene editing with CRISPR-Cas9, small interfering RNA (siRNA) therapy, and mRNA therapy, are being explored to achieve gene correction. Despite their potential, challenges such as safety concerns, ethical considerations, delivery system optimization, and long-term efficacy remain. This review provides a comprehensive overview of the current understanding of CF pathophysiology, the rationale for exploring stem cell and gene therapies, the types of therapies available, their mechanisms of action, and the challenges and future directions in the field. By addressing these challenges, stem cell and gene therapies hold promise for transforming CF management and improving the quality of life of affected individuals.
Hepatocellular carcinoma (HCC) presents substantial genetic and phenotypic diversity, making it challenging to predict patient outcomes. There is a clear need for novel biomarkers to better identify high-risk individuals. Long non-coding RNAs (lncRNAs) are known to play key roles in cell cycle regulation and genomic stability, and their dysregulation has been closely linked to HCC progression. Developing a prognostic model based on cell cycle-related lncRNAs could open up new possibilities for immunotherapy in HCC patients.
Transcriptomic data and clinical samples were obtained from the TCGA-HCC dataset. Cell cycle-related gene sets were sourced from existing studies, and coexpression analysis identified relevant lncRNAs (correlation coefficient >0.4, P<0.001). Univariate analysis identified prognostic lncRNAs, which were then used in a LASSO regression model to create a risk score. This model was validated via cross-validation. HCC samples were classified on the basis of their risk scores. Correlations between the risk score and tumor mutational burden (TMB), tumor immune infiltration, immune checkpoint gene expression, and immunotherapy response were evaluated via R packages and various methods (TIMER, CIBERSORT, CIBERSORT-ABS, QUANTISEQ, MCP-COUNTER, XCELL, and EPIC).
Four cell cycle-related lncRNAs (AC009549.1, AC090018.2, PKD1P6-NPIPP1, and TMCC1-AS1) were significantly upregulated in HCC. These lncRNAs were used to create a risk score (risk score=0.492×AC009549.1+1.390×AC090018.2+1.622×PKD1P6-NPIPP1+0.858×TMCC1-AS1). This risk score had superior predictive value compared to traditional clinical factors (AUC=0.738). A nomogram was developed to illustrate the 1-year, 3-year, and 5-year overall survival (OS) rates for individual HCC patients. Significant differences in TMB, immune response, immune cell infiltration, immune checkpoint gene expression, and drug responsiveness were observed between the high-risk and low-risk groups.
The risk score model we developed enhances the prognostication of HCC patients by identifying those at high risk for poor outcomes. This model could lead to new immunotherapy strategies for HCC patients.
Cachexia occurs in approximately half of hepatocellular carcinoma (HCC) patients as the disease progresses and is correlated with a poor prognosis. Therefore, early identification of HCC patients at risk of developing cachexia and their prognosis is crucial. This study investigated the functional liver imaging score (FLIS) derived from gadoxetic acid-enhanced magnetic resonance imaging (MRI) to identify cachexia in HCC patients and their prognosis.
Pretreatment clinical and MRI data from 339 HCC patients who underwent gadoxetic acid-enhanced MRI scans were retrospectively collected. Patient weights were recorded for 6 months following the MRI scan to diagnose cachexia. The FLIS was calculated as the sum of the enhancement quality score, the excretion quality score, and the portal vein sign quality score. A Cox proportional hazards model was used to determine the significant factors affecting overall survival (OS). Multivariable logistic regression was then conducted to identify variables predicting cachexia in HCC patients, which were subsequently used to predict OS.
Cox regression analysis revealed a significant association between cachexia and worse OS. Both FLIS (0–4 vs. 5–6 points) (OR, 9.20; 95% CI: 4.68–18.10; P<0.001) and α-fetoprotein >100 ng/mL (OR, 4.08; 95% CI: 2.13–7.83; P<0.001) emerged as significant predictors of cachexia in patients with HCC. Furthermore, FLIS (0–4 vs. 5–6 points) (HR, 1.73; 95% CI: 1.19–2.51; P=0.004) was significantly associated with OS. Patients in the FLIS 0–4 points group had shorter OS than those in the FLIS 5–6 points group [20 months (95% CI, 14.7–25.3) vs. 43 months (95% CI, 27.7–58.3); P=0.001].
Cachexia was associated with worse OS. The functional liver imaging score emerged as a significant predictor of cachexia in HCC patients and their prognosis.
After endoscopic resection of colorectal cancer with submucosal invasion (pT1 CRC), additional surgical treatment is recommended if deep submucosal invasion (DSI) is present. This study aimed to further elucidate the risk factors for lymph node metastasis (LNM) in patients with pT1 CRC, especially the effect of DSI on LNM.
Patients with pT1 CRC who underwent lymph node dissection were selected. The Chi-square test and multivariate logistic regression were used to analyze the relationship between clinicopathological characteristics and LNM. The submucosal invasion depth (SID) was measured via 4 methods and analyzed with 3 cut-off values.
Twenty-eight of the 239 patients presented with LNM (11.7%), and the independent risk factors for LNM included high histological grade (P=0.003), lymphovascular invasion (LVI) (P=0.004), intermediate to high budding (Bd 2/3) (P=0.008), and cancer gland rupture (CGR) (P=0.008). Moreover, the SID, width of submucosal invasion (WSI), and area of submucosal invasion (ASI) were not significantly different. When one, two, three or more risk factors were identified, the LNM rates were 1.1% (1/95), 12.5% (7/56), and 48.8% (20/41), respectively.
Indicators such as the SID, WSI, and ASI are not risk factors for LNM and are subjective in their measurement, which renders them relatively inconvenient to apply in clinical practice. In contrast, histological grade, LVI, tumor budding and CGR are relatively straightforward to identify and have been demonstrated to be statistically significant. It would be prudent to focus on these histological factors rather than subjective measurements.
This study aimed to investigate the reasons behind the lower survival rates in male lung cancer patients than in female lung cancer patients.
Through various techniques, such as Argonaute immunoprecipitation, luciferase assays, and ChIP, this study confirmed the positive effects of androgen receptor (AR) on lung cancer cell invasion across different in vitro cell lines and in vivo mouse models.
The findings suggest that AR enhanced the invasion of lung cancer cells by modifying EPHB2 signals at the protein expression level, which in turn required changes in miRNA-23a-3p. Restoring miRNA-23a-3p could counteract the intensified invasion of lung cancer cells mediated by AR.
This study revealed that AR may facilitate the lung cancer matastasis by modulating miRNA-23a-3p/EPHB2 signaling and that targeting this signaling pathway could provide new approaches to inhibit lung cancer metastasis.