Humans ; Transcatheter Aortic Valve Replacement ; Aortic Valve/surgery* ; Heart Valve Prosthesis Implantation ; Aortic Valve Stenosis/surgery* ; Treatment Outcome ; Heart Valve Prosthesis

Objective: To investigate the expression of CD24 gene in human malignant pleural mesothelioma (MPM) cells and tissues, and evaluate its relationship with clinicopathological characteristics and clinical prognosis of MPM patients. Methods: In February 2021, UALCAN database was used to analyze the correlation between CD24 gene expression and clinicopathological characteristics in 87 cases of MPM patients. The TIMER 2.0 platform was used to explore the relationship between the expression of CD24 in MPM and tumor immune infiltrating cells. cBioportal online tool was used to analyze the correlation between CD24 and MPM tumor marker gene expression. RT-qPCR was used to analyze the expressions of CD24 gene in human normal pleural mesothelial cell lines LP9 and MPM cell lines NCI-H28 (epithelial type), NCI-H2052 (sarcoma type), and NCI-H2452 (biphasic mixed type). RT-qPCR was performed to detect the expressions of CD24 gene in 18 cases of MPM tissues and matched normal pleural tissues. The expression difference of CD24 protein in normal mesothelial tissue and MPM tissue was analyzed by immunohistochemistry. A Kaplan-Meier model was constructed to explore the influence of CD24 gene expression on the prognosis of MPM patients, and Cox regression analysis of prognostic factors in MPM patients was performed. Results: The CD24 gene expression without TP53 mutation MPM patients was significantly higher than that of patients in TP53 mutation (P<0.05). The expression of CD24 gene in MPM was positively correlated with B cells (r(s)=0.37, P<0.001). The expression of CD24 gene had a positive correlation with the expressions of thrombospondin 2 (THBS2) (r(s)=0.26, P<0.05), and had a negative correlation with the expression of epidermal growth factor containing fibulin like extracellular matrix protein 1 (EFEMP1), mesothelin (MSLN) and calbindin 2 (CALB2) (r(s)=-0.31, -0.52, -0.43, P<0.05). RT-qPCR showed that the expression level of CD24 gene in MPM cells (NCI-H28, NCI-H2052 and NCI-H2452) was significantly higher than that in normal pleural mesothelial LP9 cells. The expression level of CD24 gene in MPM tissues was significantly higher than that in matched normal pleural tissues (P<0.05). Immunohistochemistry showed that the expressions of CD24 protein in epithelial and sarcoma MPM tissues were higher than those of matched normal pleural tissues. Compared with low expression of CD24 gene, MPM patients with high expression of CD24 gene had lower overall survival (HR=2.100, 95%CI: 1.336-3.424, P<0.05) and disease-free survival (HR=1.800, 95%CI: 1.026-2.625, P<0.05). Cox multivariate analysis showed that compared with the biphasic mixed type, the epithelial type was a protective factor for the prognosis of MPM patients (HR=0.321, 95%CI: 0.172-0.623, P<0.001). Compared with low expression of CD24 gene, high expression of CD24 gene was an independent risk factor for the prognosis of MPM patients (HR=2.412, 95%CI: 1.291-4.492, P=0.006) . Conclusion: CD24 gene and protein are highly expressed in MPM tissues, and the high expression of CD24 gene suggests poor prognosis in MPM patients.
Humans ; Mesothelioma, Malignant ; Mesothelioma/diagnosis* ; Lung Neoplasms/genetics* ; Pleural Neoplasms/diagnosis* ; Prognosis ; Biomarkers, Tumor/analysis* ; Extracellular Matrix Proteins ; CD24 Antigen/genetics*

Objective : To establish a laboratory model of heroin addiction in C57BL /6 mice based on associative learning mechanisms． Methods: The black box and white box were selected as the memory training environment， and three behavioral training paradigms were studied : ① Pavlovian conditional position preference ( CPP) training paradigm，mice were placed in the white box for memory reinforcement training for 30 min after intraperitoneal injection of 0. 1 ml of corresponding concentrations (5. 0，10. 0，20. 0 mg / kg) of heroin at 9 :00 a．m．，and 24 h later 0. 1 ml of 0. 9% NaCl solution was injected intraperitoneally into the black box for training，and after the training，the mice were tested for their memory preference for the black and white boxes (movement time of different boxes) . ② A naloxone conditional position aversion ( CPA) training paradigm was conductedbased on the results of the CPP training paradigm. ③ Behavioral sensitization training paradigm，heroin addiction rating scale was established based on the statistical results of 3 behavioral experiments and the lethality of experimental animal disease mice after drug administration．Three different doses of heroin (5. 0，10. 0，20. 0 mg / kg) were selected to induce heroin addiction，and the most appropriate heroin concentration was selected by the results on the rating scale. Results: In the CPP training paradigm，CPP was observed in all heroin groups (P＜0. 05，P＜0. 001，P＜0. 05) ．In the CPA training paradigm，the CPA induction rate was highest in the 10. 0 mg / kg heroin group compared to the control group (P ＜0. 01 ) ．In the behavioral sensitization training paradigm ，all heroin groups caused behavioral sensitization changes (P＜0. 001) ; but the 5. 0 and 10. 0 mg / kg heroin groups did not cause animal mortality．Overall，the 10. 0 mg / kg heroin group had the highest dose score on the rating scale．It could be used as a concentration to establish a stable experimental animal model of heroin addiction． Conclusion The study was effective in establishing a heroin addiction model in mice，and it was suitable for modeling drug concentration screening，with high animal survival rate and simple and practical．The combined learning mechanism can effectively shorten the model establishment period.

Objective: To establish a rat model of preeclampsia (PE) in early pregnancy and to observe the changes in phenotype，pregnancy outcome and cognitive ability of offspring． Methods : The pregnant rats were randomly divided into model group and control group．Ultra-low dose lipopolysaccharide (LPS) (0. 5 μg / kg) and an equal volume of normal saline were injected into the tail vein of pregnant rats on the fifth day of pregnancy．The levels of blood pressure ，12-hour urinary protein ，peripheral blood coagulation factors and placental cytokines in the two groups were measured．Furthermore，placental pathology，pregnancy outcomes，and cognitive abilities of offspring were observed. Results: Blood pressure and urinary protein levels of model group were significantly higher than those of control group levels．Compared with the control group，the levels of platelet and antithrombin Ⅲ (AT Ⅲ) in the peripheral blood of pregnant rats in the model group were lower than those in the control group，while D-dimer was higher than that in the control group，the weight of the fetus and placenta in the model group decreased (P ＜0. 001) ，the expression levels of interleukin ( IL) -6，tumor necrosis factor α ( TNF-α) and interferon gamma (INF-γ) in peripheral blood increased，while the expression level of transforming growth factor β1 (TGF-β1) decreased(P＜0. 001) ．The water maze test showed that the latency of the offspring of the model group to the plat- form was longer than that of the control group (P＜0. 05) ，while the frequency of crossing the platform quadrant and the time of staying in the platform quadrant of the model group were lower than those of the control group (P < 0. 05 ) ．HE and PAS staining showed that there were infiltration of inflammatory cells in the basal layer of placenta， obvious decrease of blood vessels in labyrinthine area，slight edema of renal interstitium and degeneration of local renal tubular epithelial cells in the model group，while there were no above pathological changes in placenta and kidney in the control group． Conclusion A single injection of LPS in early pregnancy can successfully induce PE- related symptoms and adverse pregnancy outcomes such as fetal growth restriction and lead to the decline of cogni- tive ability of offspring.

Lysyl oxidase like 4 (LOXL4) is one member of the LOX protein family and is a secreted copper-dependent amine oxidase involved in the assembly and maintenance of extracellular matrix (ECM). LOXL4 is up-regulated in human liver cancer, gastric cancer, breast cancer, cervical cancer, head and neck squamous cell carcinoma, esophageal carcinoma and colorectal cancer, but down-regulated in human bladder and lung cancer. It also inhibits tumor growth in bladder and lung cancer, suggesting that L0XL4 has a dual role of promoting or inhibiting tumors in different types of human malignant tumors. L0XL4 in tumor cell exosomes promotes cell matrix adhesion and cell migration by activating the FAK/Src pathway, which is dependent on its amine oxidase activity through a hydrogen peroxide-mediated mechanism. Exosome-mediated L0XL4 can also promote tumor cell proliferation and immune escape by activating the PI3K/Akt signaling pathway. L0XL4 can be transported to macrophages via exosomes in tumor cells, where it further activates the immunosuppression function of cells and the expression of programmed death ligand 1 (PD-L1) via STAT1- and STAT3-mediated signaling pathways. It then will trigger the immunosuppressive function of macrophages and promote the immune escape of tumor cells. In addition, LOXL4 can also exert the tumor suppressive function by activating p53 and inhibiting the Ras/ERK pathway. This paper mainly reviews the structure and the function of LOXL4, and the relationship between LOXL4 and the pathogenesis and development of human malignant tumors. We then further explore the application of LOXL4 in the study of malignant tumors, laying a theoretical foundation for its future utilization in the clinical diagnosis and treatment, and screening of prognostic markers of human malignant tumors.

Objective:To explore the predictive value of peripheral perfusion index (PI) combined with central venous-arterial carbon dioxide tension to arterial-venous oxygen content ratio(Pv-aCO 2/Ca-vO 2)for prognosis after initial resuscitation of septic shock. Methods:A total of 76 cases of patients with septic shock from January 2019 to January 2021 in emergency intensive care unit (EICU) of Harrson international peace hospital affiliated to Hebei Medical University were enrolled. All recovered according to 2016 Severe Sepsis and Septic Shock Treatment International Guidelines 2016 (SSC 2016) , and PI was monitored, central vein and arterial blood gas analysis was performed, and the ratio of Pv-aCO 2/Ca-vO 2 was calculated.The PI and Pv-aCO 2/Ca-vO 2 at 3 h,hemodynamic variables,oxygen metabolism indexes,APACHEⅡ and SOFA score were recorded.Patients were divided into survival group and death group according to 28 d survival condition, the dfferences in demographics and clinical data were compared between two groups.The Kaplan-Meier urviving curve was created and the survival of the patients was analyzed by the Log-rank test. Risk factors associated with the prognosis were analyzed using the Cox regression analysis. The role of PI and Pv-aCO 2/Ca-vO 2 in prediting death was evaluated by receiver operating characteristic curves(ROC). Results:There were 37 cases in survival group and 39 cases in death group.Compared with death group, PI in survival group [(1.77±0.63) vs. (0.89±0.69)]was significantly higher,and Pv-aCO 2/Ca-vO 2[(1.52±0.52) vs. (2.57±0.86)] was significantly lower ( P<0.05). Kaplan-Meier survival curve showed that the median survival time in the high PI group [20.09 d (95% CI:16.95-23.24) vs.11.00d (95% CI:7.14-14.86)] was longer than that in the low PI group(χ 2=12.424, P=0.000),and that in low Pv-aCO 2/Ca-vO 2 group [23.74 d (95% CI:20.35-27.13) vs.12.85d (95% CI:9.75-15.95)] was longer than that in the high Pv-aCO 2/Ca-vO 2 group (χ 2=12.200, P=0.000) .Cox regression analysis showed that both PI ( RR=0.397, 95% CI: 0.230-0.687, P =0.001) and Pv-aCO 2/Ca-vO 2 ( RR=1.878, 95% CI: 1.169-3.019, P =0.009) were predictors of 28 d mortality.The area under the ROC curve of PI and Pv-aCO 2/Ca-vO 2 for predicting 28 d death in patients with septic shock were 0.828 (95% CI: 0.732-0.923) and 0.785 (95% CI: 0.6777-0.893)respectively. The optimal cutoff values were 0.52 (sensitivity 58.3% and specificity 94.4%) and 0.35 (sensitivity 88.9% and specificity 63.9%)respectively, and the AUC of the combined prediction of the two indicators was 0.903 (95% CI: 0.835-0.971). Conclusions:Combination of PI and Pv-aCO 2/Ca-vO 2 is better to predict the risk of adverse outcomes of septie shock patients,and may provide useful information for the resuscitation at early stage.

OBJECTIVE: To analyze the difference in clinical efficacy of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) under Quadrant channel system combined with microscope and percutaneous pedicle screw in the treatment of degenerative lumbar spondylolisthesis. METHODS: A total of 114 patients with single-segment degenerative lumbar spondylolisthesis from June 2015 to February 2019, were divided into three groups according to the surgical methods, such as the MIS-TLIF under the microscope surgery group ( microscope group), MIS-TLIF combined with percutaneous pedicle screw technique surgery group(percutaneous group) and posterior lumbar interbody fusion surgery group (open group). In the microscope group, there were 12 males and 26 females, aged from 42 to 83 years with an average of (63.29±9.09) years. In the percutaneous group, there were 16 males and 22 females, aged from 45 to 82 years with an average of (63.37±7.50) years. In the open group, there were 12 males and 26 females, aged from 51 to 82 years with an average of (63.76±8.21) years. The general conditions of operation, such as operation time, intraoperative blood loss, postoperative drainage, length of surgical incision, frequency of intraoperative fluoroscopy and postoperative time of lying in bed were recorded to analyze the differences in surgical related indicators. Visual analogue scale (VAS) of waist and leg pain in preoperative and postoperative period (3 days, 3 months, 6 months and 12 months) were recorded to evaluate pain remission;Oswestry Disability Index(ODI), Japanese Orthopaedic Association (JOA) score were recorded to evaluate the recovery of waist and leg function on preoperative and postoperative 12 months. The lumbar spondylolisthesis rate and intervertebral height at 12 months after operation were recorded to evaluate the reduction of spondylolisthesis. The Siepe intervertebral fusion standard was used to analyze the intervertebral fusion rate at 12 months after operation. RESULTS: ①All 114 patients were followed up more than 1 year, and no complications related to incision infection occurred. In the microscope group, there was 1 case of subcutaneous effusion 8 days after operation. After percutaneous puncture and drainage, waist compression, and then the healing was delayed. In the percutaneous group, 2 cases of paravertebral muscle necrosis occurred on the side of decompression, and the healing was delayed after debridement. In open group, there was 1 case of intraoperative dural tear, which was packed with free adipose tissue during the operation. There was no postoperative cerebrospinal fluid leakage and other related complications.① Compared with microscope group, percutaneous group increased in operation time, intraoperative blood loss, postoperative wound drainage, surgical incision length, intraoperative fluoroscopy times, and postoperative bed rest time. In open group, intraoperative blood loss, postoperative wound drainage, surgical incision length, and postoperative bed rest time increased, but the intraoperative fluoroscopy time decreased. Compared with percutaneous group, the intraoperative blood loss, wound drainage, surgical incision length, and postoperative bed rest time in open group increased, but operative time and the intraoperative fluoroscopy time decreased(P<0.05). ②ODI and JOA scores of the three groups at 12 months after operation were improved compared with those before operation (P<0.05), but there was no significant difference between the three group(P>0.05). ③Compared with microscope group, the VAS of low back pain in percutaneous group increased at 3 days after operation, and VAS of low back pain in open group increased at 3 days, and 12 month after operation. Compared with percutaneous group, the VAS low back pain score of the open group increased at 3 months after operation (P<0.05). ④ The lumbar spondylolisthesis rate of the three groups of patients at 12 months afrer operation was decreased compared with that before operation(P<0.05), and the intervertebral heigh was increased compared with that before operation(P<0.05), however, there was no significant difference among three groups at 12 months afrer operation(P>0.05). ⑤ There was no significant difference between three groups in the lumbar fusion rate at 12 months afrer operation(P>0.05). CONCLUSION The MIS-TLIF assisted by microscope and the MIS-TLIF combined with percutaneous pedicle screw are safe and effective to treat the degenerative lumbar spondylolisthesis with single-segment, and the MIS-TLIF assisted by microscope may be more invasive, cause less blood loss and achieve better clinical efficacy.
Blood Loss, Surgical ; Case-Control Studies ; Female ; Humans ; Low Back Pain ; Lumbar Vertebrae/surgery* ; Male ; Minimally Invasive Surgical Procedures/methods* ; Postoperative Hemorrhage ; Retrospective Studies ; Spinal Fusion/methods* ; Spondylolisthesis/surgery* ; Surgical Wound ; Treatment Outcome

Ischemic stroke is one of the leading causes of death worldwide. In the post-stroke stage, cardiac dysfunction is common and is known as the brain-heart interaction. Diabetes mellitus worsens the post-stroke outcome. Stroke-induced systemic inflammation is the major causative factor for the sequential complications, but the mechanism underlying the brain-heart interaction in diabetes has not been clarified. The NLRP3 (NLR pyrin domain-containing 3) inflammasome, an important component of the inflammation after stroke, is mainly activated in M1-polarized macrophages. In this study, we found that the cardiac dysfunction induced by ischemic stroke is more severe in a mouse model of type 2 diabetes. Meanwhile, M1-polarized macrophage infiltration and NLRP3 inflammasome activation increased in the cardiac ventricle after diabetic stroke. Importantly, the NLRP3 inflammasome inhibitor CY-09 restored cardiac function, indicating that the M1-polarized macrophage-NLRP3 inflammasome activation is a pathway underlying the brain-heart interaction after diabetic stroke.

We prepared moxifloxacin (MXF) loaded nanoparticles by nano-precipitation/self-assembly method, then compared the antibacterial activity of MXF and MXF loaded nanoparticles, and investigated the antibacterial mechanism of MXF loaded nanoparticles against Pseudomonas aeruginosa in vitro. The physicochemical properties such as particle size and zeta potential were investigated by laser particle size analyzer. The in vitro release characteristics were investigated by high performance liquid chromatography (HPLC). The effect of nanoparticles on HBE cells viability was investigated by CCK-8 assay. In addition, the in vitro antibacterial activity was investigated by minimum inhibitory concentration (MIC) assay, biofilm formation assays and transmission electron microscope (TEM) observation, then the antibacterial mechanism was initially explored. The particle size measurement showed that the nanoparticles had a size of 332.5 ± 2.7 nm, a polymer dispersion index (PDI) of 0.125 ± 0.053, a zeta potential of -24.3 ± 1.7 mV, and a uniform particle size distribution, drug loading content was (6.02 ± 1.27) %, encapsulation efficiency was (16.69 ± 1.17) %. The TEM results show that the nanoparticles have a spheroidal structure, and the particle size and distribution are consistent with the particle size measurement results. The nanoparticles can be effectively and rapidly released in phosphate buffer saline (PBS), releasing about 70% in 24 h, and releasing 87% in 72 h, and almost completely releasing the MXF at 120 h. At the same time, compared with moxifloxacin free drug, its MIC value is 8 μg·mL^-1, which is 1/2 of MXF solution, and can significantly inhibit the formation of bacterial biofilms. It has well antibacterial activity in vitro and can be targeted to the surface of bacteria to exert its efficacy and improve the antibacterial effect. The moxifloxacin nanoparticles prepared in this study has a uniform particle size distribution, well drug release performance and antibacterial effect, and provides new ideas and strategies for the treatment of bacterial lung infection and the development of new antibacterial nanoformulations.