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.

To study the influences of LncRNA H19 (H19) on malignant liver tumor cells and elucidate the underlying molecular mechanisms.

H19 expression in liver tumor tissues, matched normal liver tissues, human liver malignant tumor cell lines and the human hepatocyte line LO2 was assessed via quantitative RT-PCR. Cell viability analysis and Matrigel invasion analysis were performed to evaluate the effects of H19 on cell proliferation and invasion. Luciferase reporter analysis was carried out to assess the interaction between miR-140-5p and SOS Ras/Rac guanine nucleotide exchange factor 1 (SOS1). The influence of H19 on the Ras-MAPK signalling pathway was evaluated by detecting key protein levels via active Ras pull-down analysis and Western blot analysis.

H19 expression was lower in liver cancer samples than in matched normal liver tissue samples. H19 overexpression enhanced the proliferation and invasion of HepG2 and SMMC-7721 cells. H19 overexpression increased the level of activated Ras. The expression levels of phosphorylated Raf, phosphorylated ERK and phosphorylated MEK were increased by H19 overexpression. H19 knockdown had the opposite effect. Treatment with a MAPK inhibitor significantly reversed the influence of H19 overexpression on liver malignant tumor cell growth and invasion. The MAPK activator reversed the opposing effects of H19 silencing. H19 overexpression increased the protein level of SOS1, and miR-140-5p directly targeted SOS1.

H19 can activate the Ras-MAPK signalling pathway via the miR-140-5p/SOS1 axis in malignant liver tumour cells.

Alternative splicing affects gene expression during placental development. The present study aimed to identify poly (ADP-ribose) polymerase 1 (PARP1)-regulated alternative splicing events in HTR-8/Svneo cells.

Decidual tissues were collected from women with induced abortion and spontaneous abortion. PARP1 transcription was quantified by RT-qPCR. Small interfering RNA (siRNA) was used to knock down the PARP1 expression in HTR-8/Svneo cells. The transfection efficiency was verified by RT-qPCR and Western blotting. Total RNA was extracted, and the RNA-sequencing approach was used to identify alternative splicing events and transcriptomes. The PARP1 knockdown-induced differentially expressed genes with changes in alternative splicing events were quantified by RT-qPCR. Functional analysis, which included the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways, was performed.

The PARP1 mRNA expression increased in decidual tissues in the spontaneous abortion group, when compared to the induced abortion group. However, the PARP1 knockdown significantly downregulated 1491 genes and upregulated 881 genes in HTR-8/Svneo cells. Furthermore, 227 genes that underwent alternative splicing were identified, and these were differentially expressed in siPARP1 cells, when compared to siNC cells.

The functional analysis revealed that these alternative splicing genes affected the functional phenotypes of extravillous cytotrophoblasts. Furthermore, the PARP1 knockdown led to alterations in gene expression and specific alternative splicing patterns in extravillous trophoblasts.

This prospective randomized controlled study was conducted to evaluate the safety and efficacy of the Pringle hepatic hilar occlusion with a bulldog clamp in laparoscopic liver resection.

From March 1, 2020 to July 31, 2021, 80 patients were enrolled, including 40 undergoing intraperitoneal Pringle maneuver (IPM) and 40 extraperitoneal Pringle maneuver (EPM). The observation indices included basic preoperative clinical characteristics and intraoperative and postoperative liver function indices.

There were no significant differences in the basic characteristics or types of hepatectomy, intraoperative blood loss, intraoperative blood transfusion, or hepatectomy time between the IPM and EPM groups. However, the blocking and operation time in the IPM group was shorter than that in the EPM group. There were no significant differences in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels on the first day after surgery or in total bilirubin (TBIL) or albumin (ALB) levels on the first, third, or fifth days after surgery. However, C-reactive protein (CRP) levels on the first and third days, ALT and AST levels on the third and fifth days were lower, and hospital stay after surgery was shorter in the IPM group than in the EPM group.

IPM using bulldog clamps is simple, safe, and effective. The inflammatory reaction is less severe, the degree of liver function injury is lower, and recovery is faster.

Human adipose-derived stem cells (ASCs) have shown considerable potential for tissue regeneration. FK506 binding protein (FKBP) 5 is a cochaperone of several proteins. The purpose of this work was to explore the function of FKBP5 in ASC osteogenesis.

Lentivirus infection was used to overexpress or knock down FKBP5 in ASCs. To inhibit FKBP5, SAFit2, a specific inhibitor of FKBP5, was used. Next, the osteogenic capacity of ASCs was evaluated via alkaline phosphatase (ALP) staining, and extracellular calcium precipitation was detected via Alizarin red S staining. The binding proteins of FKBP5 were assessed via proteomics and validated via coimmunoprecipitation experiments.

Following osteogenic induction, FKBP5 expression increased at both the mRNA and protein levels. Interestingly, FKBP5 upregulation by lentivirus infection increased the ability of ASCs to differentiate into osteoblasts, as revealed by ALP staining, while ALP activity also increased. Moreover, increased extracellular calcium precipitation confirmed that FKBP5 overexpression promoted ASC osteogenesis into osteocytes. On the other hand, FKBP5 knockdown or functional suppression with SAFit2 decreased this process. Furthermore, the proteomics and coimmunoprecipitation data demonstrated that FKBP5 bound to a variety of proteins in ASCs. These proteins serve as the molecular chaperone base upon which the osteogenesis-regulating activity of FKBP5 rests.

Our study revealed that FKBP5 enhances the osteogenesis of ASCs, providing a feasible method for clinical bone tissue engineering applications.

Menstrual blood-derived stem cells from endometriosis patients (E-MenSCs) have different gene expression patterns than those from healthy nonendometriotic females (NE-MenSCs). Exosomes extracted from mesenchymal stem cells and plants are considered for the treatment of various diseases. This study aimed to compare the effects of exosomes derived from NE-MenSCs (C-exos) and those from the roots of ginger (P-exos) on E-MenSCs.

E-MenSCs at the third passage were used, and after evaluating the effective dosage with MTT, C-exos (200 µg/mL) or P-exos (100 µg/mL) were added to treat them. Following a 72-h incubation, the cells were analyzed with annexin V/PI test to evaluate the apoptosis rate. Also, genes related to inflammation (IL-6, IL-8, IL-1β, NF-κB, COX2), cell cycle (Cyclin D1), the steroid pathway (ESR1), migration and invasion (MMP-2, MMP-9, VEGF), and the apoptosis pathway (BAX, BCL2) were detected by real-time PCR.

Apoptosis was increased in both the P- and C-exos groups. The expression levels of IL-6 and IL-1β were significantly lower in the P-exos group than in the E-MenSCs group. The expression levels of IL-8, NF-κB, COX-2, and MMP-9 were significantly decreased in both the P-exos group and the C-exos group. The expression level of VEGF was significantly lower in the P-exos group than in the E-MenSCs group. The BAX/BCL2 ratio was much lower in the P-exos group than in the E-MenSCs group.

In this study, we established the feasibility of using a novel natural nontoxic material to target endometriotic mesenchymal stem cells to modify their gene expression and function toward healthy cells. Both C-exos and P-exos showed positive effects on the gene expression and function of endometriotic cells. Considering that plant exosomes are easier to access and less expensive, they can be considered for clinical use in improving the symptoms of endometriosis patients.