ArchiveTo investigate the effect and mechanism of dexmedetomidine (Dex) pretreated pericytes (Dex-PCs) on acute lung injury (ALI) in septic mice.
Mouse model of sepsis-ALI was established with intraperitoneal injection of lipopolysaccharide (LPS) at a dose of 10 mg/kg. A total of 96 C57BL/6J mice were randomly divided into sham operation (Sham) group,ALI group,PC treatment group and Dex-PCs treatment group. The mice of the PCs and Dex-PCs groups received a tail venous injection of 5×105 PC cells,respectively,whereas those of the Sham and ALI groups received equal volume of normal saline. Flow cytometry,immunofluorescence assay,whole-body volume tracing system and ELISA were used to observe the changes in the colonization of PCs,pulmonary vascular permeability,lung function,serum TNF-α and IL-6 levels,as well as the survival rate and survival time of mice at 72 h after LPS stimulation. After PCs and Dex-PCs were exposed to 10 μg/mL LPS,the level of intracellular reactive oxygen species (ROS) was measured.
Compared with the Sham group,the ALI group had increased permeability of pulmonary vascular endothelial cells,extensive extravasation of Evans blue,severely destructed of lung tissue structure and massive inflammatory cell infiltration,higher lung wet/dry weight ratio,elevated serum TNF-α and IL-6 levels,and declined lung function,and no mice survived for 72 h after modeling (P<0.05). Both PC cell treatment effectively alleviated the pulmonary vascular endothelial leakage,reduced Evans blue content per unit tissue,improved lung pathological structure,lung function and inflammatory responses,and significantly improved the survival rates in the PC group and the Dex-PC group (P<0.05). What’s more,the therapeutic effect of Dex-PC cells was significantly better than that of the PC cells (P<0.05). LPS stimulation induced ROS accumulation greatly in PCs,but no such effect was observed in the PCs after Dex pretreatment (P<0.05).
Dex pretreatment significantly enhances PCs’ protective effect on pulmonary vascular endothelial barrier functions in septic mice,which may be due to its enhancing anti-oxidative capacity of PCs.
To investigate the protective effect of β-glucan (BG) against intestinal ischemia reperfusion (II/R) injury by regulating the secretion of glucagon-like peptide-1 (GLP-1).
Male C57BL/6 mice (6~8 weeks old) were subjected, and finally, the experiments had sham group, II/R group, II/R+BG group (0.1 mg/mL BG in drinking water for 2 weeks before modeling), II/R+liraglutide (LLT, GLP-1 analogue) group (0.2 μg/g LLT injected every 12 hours for 3 consecutive days before modeling), and II/R+BG+Ex9-39 (GLP-1R antagonist) group (intraperitoneal injection of 2 μg/g Ex9-39 1 h before modeling). After modeling, HE staining was used to observe intestinal morphological changes, and RT-qPCR and Western blotting were employed to evaluate the molecules (Occludin, ZO-1 and Claudin-1) related to intestinal barrier damage. The effect of 0.1 mg/mL BG treatment on the GLP-1 level in the serum and intestinal tissues of normal mice was determined with ELISA and immunofluorescence assay, respectively, and RT-PCR for the molecules related to GLP-1 expression (Gcg, Pcsk1/2, GIP and Foxa2). The effects of LLT and Ex9-39 pretreatment on intestinal morphology and intestinal barrier damage were also determined by morphological observation and expression levels of related molecules.
II/R induced significant decreases in the mRNA levels of Occludin, ZO-1 and Claudin-1 and increase in Chiu's score when compared with sham control mice (P<0.05). While, the mRNA levels of the 3 molecules were obviously higher and the Chiu's score was lower in the II/R+BG group than the II/R group (P<0.05). BG pretreatment induced notably enhanced secretion of GLP-1 in the serum and intestinal tract of normal mice, and improved the mRNA expression of GLP-1-related molecules (P<0.05). The intervention of GLP-1 analogue LLT could attenuate the II/R damage and decreased Chiu's score, with statistical difference in comparison with the II/R group (P<0.05). GLP-1 receptor antagonist Ex9-39 reversed the protective effects of BG pretreatment against II/R damage, with notably differences in the expression of Occludin, ZO-1 and Claudin-1 and Chiu's score (P<0.05).
BG can attenuate intestinal mucosal and functional injury after II/R by promoting intestinal GLP-1 secretion.
To explore the roles of transfer RNA-derived small RNAs (tsRNAs) in the oncogenesis and progression of lung adenocarcinoma by analyzing the differential expression of tsRNAs in lung adenocarcinoma and the relationship between the expression levels of tsRNAs in lung adenocarcinoma and the prognosis of patients in order to further screen and validate the tsRNAs associated with lung adenocarcinoma.
The differential expression of tsRNAs between lung adenocarcinoma tissues and normal tissues was analyzed based on the database of the Computational Medicine Center. The effects of tsRNAs expression levels on the prognosis of lung adenocarcinoma patients were analyzed based on the Cancer Genome Atlas (TCGA) database (TCGA-LUAD). The target genes were predicted based on TRFtarget2.0 and tRFTar databases. Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed based on DAVID and KOBA KEGG online websites. The expression levels of target genes in lung adenocarcinoma tissues and normal tissues were analyzed based on the University of ALabama at Birmingham CANcer data analysis Portal (UALCAN) database. In vitro cell proliferation,migration,and invasion assays were performed to investigate the biological functions of tRF-19-69M8LOJX in lung adenocarcinoma cells.
Compared with the normal tissues,tRF-19-69M8LOJX was up-regulated in lung adenocarcinoma tissues (log2FC=4.28,FDR<0.05). High expression level of tRF-19-69M8LOJX was associated with shorter progression-free survival (HR=1.565,95%CI=1.142-2.145,P=0.005). And its overexpression promoted cell proliferation and migration (P<0.001),and invasion (P=0.009) of A549 cells,and up-regulated COL1A1 (P=0.002) and VCAN (P=0.022) significantly in the tRF-19-69M8LOJX overexpression cell model.
tRF-19-69M8LOJX is up-regulated in lung adenocarcinoma tissues. And its high expression is closely associated with poor prognosis. The tsRNA may play an important role in the pathogenesis and development of lung adenocarcinoma.
To investigate the role and mechanism of paeoniflorin (PF) in sepsis-associated acute kidney injury (SA-AKI) in mice.
Mouse SA-AKI model was constructed by intraperitoneal injection of 15 mg/kg LPS. Twenty-four male C57BL/6J mice (6~8 weeks old,weighing 20~25 g) were randomly divided into Control group,model group,PF group (intraperitoneally injected with 50 mg/kg PF 30 min before LPS administration),and β-catenin specific agonist BML284 group (10 mg/kg BML284 by intraperitoneal injection after 50 mg/kg PF administration). The renal histopathological changes were observed by HE staining and Paller scoring. ELISA was used to determine the contents of serum creatinine (Scr),neutrophil gelatinase-associated lipocalin (NGAL) and lactate,and renal contents of hexokinase 2 (HK2),lactate dehydrogenase A (LDHA),IL-1β and IL-18. Western blotting was performed to detect the expression of total β-catenin,p-β-cateninY654,nucleus β-catenin and c-Myc.
Compared with the Control group,the LPS group showed obviously damaged renal tissue,higher Paller score (P<0.05),increased serum Scr and NGAL levels (P<0.05),elevated renal contents of aerobic glycolytic indexes such as HK2,LDHA and serum lactate,as well as contents of IL-1β and IL-18 (P<0.05),and enhanced expression of total β-catenin,p-β-cateninY654,nucleus β-catenin and c-Myc in the renal tissue (P<0.05). PF treatment attenuated the renal tissue damage,decreased Paller score (P<0.05),reduced serum Scr and NGAL levels (P<0.05),HK2,LDHA and serum lactate levels,and contents of IL-1β and IL-18 in renal tissues (P<0.05),and down-regulated the renal expression of total β-catenin,p-β-cateninY654,nucleus β-catenin and c-Myc when compared with the levels in the model group (P<0.05). While,addition of BML284 reversed above effects of PF treatment with significant differences (P<0.05).
PF can alleviate SA-AKI,and its mechanism may be through its inhibiting the β-catenin/c-Myc pathway,thus reducing the aerobic glycolysis level and inflammatory response in renal tissue.
To investigate the killing effect of the recombinant oncolytic influenza virus OvFlu-GM-CSF,constructed using reverse genetics (RG) technology,in combination with chemotherapy drug,gemcitabine (GEM),against pancreatic cancer cells.
The recombinant oncolytic virus OvFlu-GM-CSF was successfully rescued using RG technology in our previous study. The virus was then comprehensively characterized through chicken red blood cell hemagglutination assay,transmission electron microscopy,and viral replication assay. CCK-8 assay was utilized to determine the impact of OvFlu-GM-CSF viruses [multiplicities of infection (MOI):0,0.1,1.0,3.0] on the survival rate of pancreatic cancer cell lines (Panc02,PANC-1,SW1990,BxPC-3) and normal pancreatic ductal epithelial cells (HPDE6-C7) after treatment for 24,48 or 72 h. Using a subcutaneous tumor-bearing mouse model of pancreatic cancer,36 female C57BL/6 mice (6 weeks old) were randomly divided into PBS group,recombinant oncolytic virus group,GEM group,and the combined treatment group,with 9 mice in each group. PBS (100 μL/animal) or OvFlu-GM-CSF virus (1×107 PFU/100 μL) was given to the mice of the corresponding groups through intratumoral injection,while GEM (100 mg/kg) was injected intraperitoneally,once per 3 days,for totally 9 times. Changes in tumor volume and survival rate were monitored. Multi-immunofluorescence staining was employed to analyze T cell infiltration and proliferation in the tumor tissues. HE staining was performed to observe the pathological changes in major organs (heart,liver,lungs,kidneys and brain),and the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured to evaluate the safety of the recombinant oncolytic virus.
The recombinant oncolytic influenza virus OvFlu-GM-CSF has a hemagglutination titer of 28,typical morphological features of influenza virus,and can selectively replicate within pancreatic cancer cells. At the cellular level,the viruses demonstrated a significant selective cytotoxic effect on Panc02,PANC-1,SW1990,and BxPC-3 cells under the conditions of 48 h post-infection and MOI=3.0,when compared to 48 h post-infection and MOI=0 (P<0.01). The cell survival rate was gradually decreased with the increase in MOI value and the extension of infection time (P<0.01),but the viruses showed no significant effect on normal pancreatic ductal epithelial cells (HPDE6-C7). In the pancreatic cancer tumor-bearing mouse model,the combined treatment of the viruses+GEM significantly reduced the tumor volume than simple virus treatment and simple GEM treatment (P<0.01),and enhanced the infiltration of T cells in the tumor tissues. No obvious pathological changes were observed in the above-mentioned major organs. Additionally,there were no significant differences in the serum levels of ALT and AST in the OvFlu-GM-CSF group,GEM group,and OvFlu-GM-CSF+GEM group compared to the PBS group.
RS technology-constructed recombinant oncolytic influenza virus OvFlu-GM-CSF,when combined with the chemotherapeutic agent GEM,enhances the cytotoxic efficacy against pancreatic cancer cells and effectively activates the host’s anti-tumor immune response.
To explore the association between the relative expression level of SNORD55 in peripheral blood and the outcomes of all-cause mortality and stroke in patients with atrial fibrillation (AF),and to evaluate the predictive value of SNORD55 for prognosis.
A total of 133 patients with non-valvular AF admitted in Department of Cardiology of the First Affiliated Hospital of Army Medical University from January 2014 to December 2017 were enrolled in this study. Their baseline information was collected,and the relative expression level of plasma SNORD55 was detected. Cox proportional hazards model was used to explore the association between the relative expression level of SNORD55 in peripheral blood and all-cause mortality as well as stroke in the patients. The predictive performance of CHA2DS2-VASc score for all-cause mortality and stroke was compared with the score combined with the relative expression level of SNORD55 in the AF patients. The area under the receiver operating characteristic curve (AUC) was utilized to evaluate the discrimination,and the net reclassification index (NRI) and comprehensive discriminant improvement index (IDI) were calculated to evaluate the improvement of reclassification ability. Decision curve analysis (DCA) was applied to analyze the change in clinical net benefit.
The results of multivariate Cox regression showed that high expression of SNORD55 in peripheral blood was an independent risk factor for all-cause mortality and stroke in the AF patients. In predicting the outcomes of all-cause mortality and stroke,the addition of relative expression SNORD55 level with the CHA2DS2-VASc score obtained higher AUC value [0.80 (95%CI:0.67~0.93) vs 0.67 (95%CI:0.53~0.81),P<0.05]. In predicting the outcome of all-cause death and stroke,combination of the relative expression level of SNORD55 with CHA2DS2-VASc score increased both NRI [54.3 (95%CI:10.6~61.9) vs 31.9 (95%CI:2.8~47.5),P<0.05] and IDI [16.1 (95%CI:2.4~27.0) vs 7.9 (95%CI:0.5~14.8),P<0.05]. The results of DCA showed that our combination of CHA2DS2-VASc score relative expression level of SNORD55 had higher clinical net benefits than the foreign ABC score in the prediction of the outcomes.
Peripheral blood SNORD55 level is an independent risk factor for all-cause mortality and stroke in AF patients,and has good predictive performance for all-cause mortality and stroke in the patients.
To summarize the clinical efficacy of robotic-assisted left thoracic small-incision minimally invasive direct coronary artery bypass grafting (MIDCAB).
A retrospective analysis was conducted on the procedures and treatment outcomes of robotic-assisted MIDCAB in the Army Medical Center of PLA from October 2016 to June 2023. Baseline clinical information,MIDCAB-related data,perioperative conditions and data during follow-up were collected and analyzed.
There were 23 patients subjected,including 21 males and 2 females,with a mean age of 58.17±7.49 years,and a body mass index (BMI) of 23.99±3.25 kg/m2. All of them experienced angina pectoris,and 1 had a history of myocardial infarction,1 had dilated cardiomyopathy,2 patients had chronic obstructive pulmonary disease (COPD),and 10 had a history of percutaneous coronary intervention (PCI). Robotic-assisted MIDCAB procedure was successfully completed. No internal mammary artery injury or transformation of the procedure occurred in these cases,and excellent bridging vessel flow was achieved after anastomosis of the internal mammary artery to left anterior descending branch. The incision length in the left chest was 8 (8,8) cm,the operation time was 380 (300,465) min,the intraoperative bleeding volume was 300 (100,400) mL,the length of ICU stay was 3 (2,3) d,the amount of thoracic drainage was 780 (525,1 040) mL,and the postoperative length from surgery to discharge was 11.17±2.38 d. No mortality was observed during or within 30 d of hospitalization,and 1 patient was readmitted due to pericardial effusion within 30 d,and was discharged after symptomatic treatment including pericardiocentesis and drainage. No deaths,major adverse cardiovascular and cerebrovascular events (MACCE),or re-revascularization occurred in all patients during outpatient and telephone follow-up.
Robotic-assisted internal mammary artery dissection is a delicate and safe technique,and coronary artery bypass grafting in minimally invasive small-incision off-pump is effective,safe and feasible,with satisfactory short- and mid-term outcomes. The technique is suitable for minimally invasive coronary artery disease surgery and is worthy of popularization and application.
To analyze the diversity and composition changes of gut fungal communities between patients with chronic kidney disease (CKD) and healthy controls.
A total of 8 CKD patients admitted in Department of Nephrology of our hospital,and another 5 age- and gender-matched healthy individuals were recruited in this study. Fresh fecal samples were collected from the CKD patients and healthy controls. ITS DNA sequencing was employed to determine the composition of intestinal fungi,and then bioinformatics analysis was applied to compare the differences in fungal community diversity,structure,and function between the 2 groups.
There were no statistical differences between the 2 groups in terms of age,gender composition,BMI,and so forth. The results of Alpha diversity assessment showed statistical differences were observed in Simpson index and Shannon index in the intestinal fungi between the 2 groups (P<0.01). So was in the Beta diversity between them (P<0.01). The relative abundance of Candida was increased significantly (P<0.01),while those of Cladosporium and Penicillium were decreased in the CKD group (P<0.05). LEfSe analysis revealed that Candida was significantly enriched in CKD patients,whereas Cladosporium and Penicillium were significantly lower in abundance when compared to the healthy control group.
The composition of intestinal fungi in CKD patients is different from that in healthy individuals,exhibiting characteristic changes. Dysfunction of gut fungal flora may promote the progression of CKD. Regulating gut fungi and restoring gut microbiota homeostasis may become a new strategy for CKD treatment.
To investigate the diagnostic value of our regression model based on quantitative parameters of dual-energy CT and clinical features for stages T2 and T3 colorectal cancer.
A cross-section study was performed on 91 patients with colorectal cancer confirmed by postoperative pathology in our hospital from January 2022 to November 2023. All of them underwent dual-energy CT examination. According to the pathological T staging criteria of Chinese Colorectal Cancer Diagnosis and Treatment Standard (2020 Edition),they were divided into T2 group (n=43) and T3 group (n=48). Univariate analysis was used to compare the differences in quantitative CT parameters and clinical features between the 2 groups,and the obtained significant variables were employed to construct diagnosis models by univariate or multivariate logistic regression analysis. The area under receiver operating characteristic curve (AUC) of the CT parametric model and the model combined with clinical features was compared to evaluate the efficacy of diagnosing T2 and T3 stages.
Univariate analysis showed that carcinoembryonic antigen (CEA),N stage,tumor location,tumor longest diameter (LD),CT value of virtual noncontrast (CT-VNC),fat fraction,electron density (Rho) and dual energy index (DEI) were significantly different between the T2 and T3 groups (P<0.05). Multivariate logistic regression analysis found that N stage,tumor location,LD,fat fraction and DEI were independent risk factors for the diagnosis of stage T3. The AUC value of the model of above CT parameters in diagnosing stage T3 colorectal cancer was 0.671 (95%CI:0.558~0.783),and the AUC value of the combined model of above CT parameters and clinical features was 0.886 (95%CI:0.815~0.957),and statistical difference was observed in the AUC value between the combined model and the CT parametric model (P<0.01).
The regression model constructed with dual-energy CT quantitative parameters combined with clinical features has high value in the preoperative diagnosis of stages T2 and T3 colorectal cancer before surgery.
To investigate the influencing factors of pain during ultrasound-guided puncture sclerotherapy in the treatment of ovarian chocolate cyst (OEC).
A retrospective cohort study was conducted on 209 OEC patients undergoing ultrasound-guided puncture sclerotherapy in our department from September 2021 to September 2023. Demographic data, medical history and surgical information were collected. According to surgical approach, they were divided into transabdominal surgery group (n=57) and transvaginal surgery group (n=152). Pain scores were assessed at 5 surgical time points: needle insertion, irrigation, displacement, sclerosis, and needle withdrawal. Pain scores were compared between the 2 groups at each surgical moment. According to the pain scores at the moments of needle insertion and replacement, the patients were divided into the no/mild pain group (pain score ≤3) and the moderate/severe pain group (pain score ≥4), and the related factors of the incidence of moderate/severe pain were analyzed.
There was no statistical difference in intraoperative pain between different surgical approaches (transabdominal/transvaginal) in treating OEC under the guidance of ultrasound. At the moment of needle insertion, significantly higher incidence of moderate/severe pain was observed in the patients with a body mass index (BMI) >23.9 kg/m² than those with BMI ≤23.9 kg/m², and those with a history of dysmenorrhea than those without (P<0.05). At the time point of displacement, BMI and history of dysmenorrhea had no correlation with the incidence of moderate/severe pain. Age, obstetric history, mode of delivery, time of menarche, menstrual volume, history of pelvic surgery, history of combined adenomyosis, size of cysts, duration of surgery, and surgical approach had no notable impacts on intraoperative pain.
Different surgical approaches for ultrasound-guided puncture sclerotherapy of OEC have no effect on pain levels at various surgical moments. From the aspect of humanistic care, transabdominal puncture should be preferred. During needle insertion and displacement, particular attention should be given to the overweight patients and those with a history of dysmenorrhea, and appropriate pain intervention measures should be formulated.