Hypercholesterolemia is a significant risk factor for the development of atherosclerosis. 2',3',5'-Tri-O-acetyl-N ⁶-(3-hydroxyphenyl) adenosine (IMM-H007), a novel AMPK agonist, has shown protective effects in metabolic diseases. However, its impact on cholesterol and triglyceride metabolism in hypercholesterolemia remains unclear. In this study, we aimed to elucidate the effects and specific mechanisms by which IMM-H007 regulates cholesterol and triglyceride metabolism. To achieve this goal, we used Apoe ^-/- and Ldlr ^-/- mice to establish a hypercholesterolemia/atherosclerosis model. Additionally, hepatocyte-specific Ampka1/2 knockout mice were subjected to a 5-week high-cholesterol diet to establish hypercholesterolemia, while atherosclerosis was induced via AAV-PCSK9 injection combined with a 16-week high-cholesterol diet. Our results demonstrated that IMM-H007 improved cholesterol and triglyceride metabolism in mice with hypercholesterolemia. Mechanistically, IMM-H007 modulated the AMPKα1/2-LDLR signaling pathway, increasing cholesterol uptake in the liver. Furthermore, IMM-H007 activated the AMPKα1-FXR pathway, promoting the conversion of hepatic cholesterol to bile acids. Additionally, IMM-H007 prevented hepatic steatosis by activating the AMPKα1/2-ATGL pathway. In conclusion, our study suggests that IMM-H007 is a promising therapeutic agent for improving hypercholesterolemia and atherosclerosis through the activation of AMPKα.

Objective:Bioinformatics was used to analyze the gene expression profile of renal chromophobe cell carcinoma (RCCC) to find out the key genes of RCCC.Methods:Chromophobe renal cell carcinoma gene chip data GSE15641 and GSE11151 were downloaded from the GEO database. Using R software packages such as " Affy" and " limma" in R software to screen differentially expressed genes, combining with David and STRING online bioinformatics tools to analyze the regulatory network of differentially expressed genes and construct protein-protein interaction (PPI) network, the Hub gene was screened through the Cytohubba plug-in of Cytoscape software.Results:A total of 261 differentially expressed genes were screened, including 194 down-regulated genes and 67 up-regulated genes. Gene enrichment (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to explore their biological functions. In GO enrichment analysis, biological processes were mainly enriched in cell secretion, gluconeogenesis and cell proliferation regulation; in cell composition, they were mainly enriched in exosomes, plasma membranes and their components; in molecular function, they were mainly enriched in heparin binding; in KEGG pathway analysis, they were mainly enriched in metabolic pathway, antibody biosynthesis pathway and renin angiotensin system pathway. PPI network was constructed by using online bioinformatics tools. The top 10 Hub genes were screened by using cytohubba plug-in in Cytoscape software, which were pipecolic acid and sarcosine oxidase (PIPOX), hydroxyacid oxidase 2 (HAO2), kynurenine 3-monooxygenase (KMO), solute carrier family 2 member 2 (SLC2A2), formimidoyltransferase cyclodeaminase (FTCD), angiogenin (ANG), APOBEC1 complementation factor (A1CF), aldehyde dehydrogenase 8 family member A1 (ALDH8A1), vitamin D binding protein (GC), histidine rich glycoprotein (HRG).Conclusions:Bioinformatics analysis of differentially expressed genes in renal chromophobe cell carcinoma can effectively explore the interaction information of these differentially expressed genes, and provide new ideas for the treatment of renal chromophobe cell carcinoma.

TORCH, which is considered as a series of pathogens, including the Toxoplasma gondii, Rubella virus, Cytomegalovirus or Herpes simplex virus, often infects the pregnant women to induce the the fetus or newborn infection by transplacental infection or exposure to contaminated genital tract secretions at delivery. Increasing evidence have been confirmed that the infection of TORCH may cause the miscarriage, premature birth, malformed fetus, stillbirth, intrauterine growth retardation, neonatal multiple organ dysfunction and other adverse pregnancy outcomes. For most TORCH-infections cases may lacking the effective treatments during pregnancy, and it is important to achieve the effacing monitoring of TORCH infections before and during pregnancy. The laboratory testing of TORCH has the great significance. However, the consensus opinions still need to improve the the standardization of TORCH testing process and the correct interpretation. Based on the characteristics of the TORCH detection method, this article gives a consensus opinion on the standardized detection and clinical application of TORCH from the laboratory perspective according to the characteristics and types of infection of different pathogens.

Flash radiotherapy is a kind of radiotherapy method using ultra-high dose rate radiation. Compared with the traditional dose rate radiotherapy, it has unique radiobiological advantages. In this paper, the principle of flash radiotherapy, the process and results of biological experiments are summarized. At the same time, the advantages and challenges of flash radiotherapy are analyzed, and the future clinical application is prospected.
Radiotherapy/methods* ; Radiotherapy Dosage ; Technology

OBJECTIVETo detect potential mutation of MLC1 gene in a child affected with megalencephalic leukoencephalopathy with subcortical cysts (MLC).

METHODSClinical symptoms of the patient were retrieved. Peripheral blood DNA samples from the patient, her parents and healthy controls were collected. Potential mutation of the MLC1 gene was detected by polymerase chain reaction and Sanger sequencing.

RESULTSThe patient presented with severe motor developmental delay and a giant skull. Magnetic resonance scan showed diffuse white matter swelling in bilateral hemispheres. DNA sequencing identified a novel homozygous c.177-c.180delC mutation of the MLC1 gene. The parents of the patient both carried a heterozygous mutation c.177-c.180delC but had a normal phenotype.

CONCLUSIONA novel MLC1 mutation c.177-c.180delC has been identified in a patient with MLC. The mutation is presumably disease-causing and has derived from parents who are both carriers.

Child, Preschool ; Cysts ; genetics ; Female ; Hereditary Central Nervous System Demyelinating Diseases ; genetics ; Humans ; Membrane Proteins ; genetics ; Mutation

The clinical data of 192 patients undergoing endoscopic thyroidectomy via thoracic and mammary approach from June 2010 to July 2015 were retrospectively analyzed.Tunnel bleeding occurred in 11 cases (hemorrhage group),which was associated with the incorrect level of puncture(P ＜ 0.01).The tunnel bleeding was stopped by percutaneous packet-suturing in all 11 cases.There were no significant differences in postoperative drainage [(65.4 ± 7.5) and (63.8 ± 7.1) ml],subcutaneous petechiae [1/11 and 1.1％ (2/181)],nursing costs[(135 ±20) and(132 ± 16) yuan],postoperative hospital stay[(4.5 ± 1.6) and (4.4 ± 1.3) d] and rehemorrhage [0/11 and 0.6％ (1/181)] between hemorrhage and nonhemorrhage groups.The results show that percutaneous packet-suturing is reliable and effective method for tunnel bleeding without additional postoperative complications.

Adolescent ; Female ; Humans ; Pituitary Apoplexy ; complications ; physiopathology ; Pituitary Diseases ; etiology ; physiopathology

Objective To explore the effect of airway humidification on lung injury as a result of mechanical ventilation with different tidal volume(VT). Methods Twenty-four male Japanese white rabbits were randomly divided into four groups:low VT with airway humidification group,high VT with airway humidification group,low VT and high VT group without humidification,with 6 rabbits in each group. Mechanical ventilation was started after intubation and lasted for 6 hours. Low VT denoted 8 mL/kg,while high VT was 16 mL/kg,fraction of inspired oxygen (FiO2)denoted 0.40,positive end-expiratory pressure(PEEP)was 0. Temperature at Y piece of circuit in airway humidification groups was monitored and controlled at 40℃. Arterial blood gas analysis,including pH value,arterial partial pressure of oxygen(PaO2),arterial partial pressure of carbon dioxide(PaCO2),lung mechanics indexes, including peak airway pressure(Ppeak)and airway resistance(Raw),and lung compliance was measured at 0,2,4, 6 hours of mechanical ventilation. The levels of tumor necrosis factor-α(TNF-α)and interleukin-8(IL-8)in plasma and bronchoalveolar lavage fluid(BALF)were determined by enzyme linked immunosorbent assay(ELISA). The animals were sacrificed at the end of mechanical ventilation. The wet to dry(W/D)ratio of lung tissues was calculated. Histopathologic changes in the lung tissueies were observed with microscope,and lung injury score was calculated. Scanning and transmission electron microscopies were used to examine the integrity of the airway cilia and the tracheal epithelium. Results Compared with low VT group,pH value in high VT group was significantly increased,PaCO2 was significantly lowered,and no difference in PaO2 was found. Ppeak,Raw,and lung compliance were significantly increased during mechanical ventilation. There were no significant differences in blood gas analysis and lung mechanics indexes between low VT with airway humidification group and low VT group. Compared with high VT group,PaCO2 in high VT with airway humidification group was significantly decreased,Ppeak raised obviously,and no difference in pH value,PaO2,Raw and pulmonary compliance was found. Compared with low VT with airway humidification group,no difference in blood gas analysis(PaCO2,mmHg,1 mmHg=0.133 kPa)was found,but Ppeak(cmH2O,1 cmH2O=0.098 kPa),Raw(cmH2O),and lung compliance(mL/cmH2O)were increased significantly in high VT with airway humidification group(PaCO2 at 2 hours:27.96±4.64 vs. 36.08±2.11,4 hours:28.62±2.93 vs. 34.55±5.50, 6 hours:29.33±2.14 vs. 35.01±5.53;Ppeak at 0 hour:14.34±1.97 vs. 8.84±1.32,2 hours:17.33±0.52 vs. 11.17±2.14,4 hours:17.83±0.98 vs. 12.67±2.06,6 hours:18.67±1.22 vs. 13.50±2.16;Raw at 0 hour:37.36±5.14 vs. 27.05±2.93,2 hours:43.94±6.58 vs. 31.95±3.56,4 hours:48.04±6.07 vs. 35.24±3.50, 6 hours:50.33±6.34 vs. 36.66±3.64;pulmonary compliance at 6 hours:2.28±0.18 vs. 1.86±0.37,all P<0.05). The lung W/D ratio in high VT group was significantly higher than that of the low VT group(6.17±2.14 vs. 3.50±1.52, P<0.05). W/D in high VT with airway humidification group was higher than that of low VT with airway humidification group but without statistically significant difference(5.17±2.14 vs. 3.00±1.10,P>0.05). Microscopic observation showed that cilia were partially detached,adhered and sparse in low VT group,while cilia in high VT group showed serious detachment and lodging. Remaining cilia were sparse,with lodging,and cellular structure was damaged. Lung tissue pathological injury score in the high VT group was significantly higher than that of low VT group(6.17±2.14 vs. 3.50±1.52,P<0.05). Cilia density and cellularity were normal in low VT with airway humidification group,and no difference in lung tissue pathological injury score was found compared with low VT group(3.00±1.10 vs. 3.50±1.52, P>0.05). Cilia were severely detached,adhered and lodging,and cellularity were not obvious in high VT with airway humidification group,and lung tissue pathological injury score was elevated significantly than that of the low VT with airway humidification group but without statistically significant difference(5.17±2.14 vs. 3.00±1.10,P>0.05). TNF-α and IL-8 concentrations showed no change in plasma and BALF in all groups during ventilation,and no significant difference was found among the groups. Conclusions Airway humidification can alleviate pathological lung injury,damage of cilia and cellular structure in trachea caused by mechanical ventilation with low and high VT. High VT with humidification can result in serious pulmonary edema.

Objective To compare the image quality and adverse effects among different concentrations of nonionic iodinated con-trast media in hysterosalpingography (HSG).Methods 99 female infertile patients were recruited in this study for HSG and were averagely divided into Group A,B and C.The application of contrast media were as follows:iomeprol injection(400 mg I/mL)for Group A,iopamidol injection (370mg I/mL)for Group B,iohexol injection(300 mg I/mL)for Group C.The image quality was in-dependently evaluated by two doctors using a 3-point scale (1 -3 score)and adverse effects were recorded.Results (1 )Scores of image quality:all images met diagnostic desire with (2.55±0.5 1)score in Group A,(2.42±0.50)score in Group B,(2.21±0.42) score in Group C.There were statistically significant differences among goups(H =7.790,P =0.022).Kappa values were 0.693 in Group A,0.687 in Group B,0.672 in Group C.(2)Adverse effects:4 cases in Group A(12.12%),3 cases in Group B(9.09%), 2 cases in Group C(6.06%),which showed no statistically significant differences(χ2 = 0.733,P =0.693).Conclusion The three kinds of concentrations of nonionic iodinated contrast media can all be applied in HSG.The higher of iodinated concentration,the better of image contrast.

This study was aimed to analyze the correlation between CT perfusion parameters, e. g. perfusion (PF), blood volume (BV), peak enhancement image (PEI), time to peak (TTP), and the microvessel density (MVD) of cervical cancer. CT perfusion scans were carried out in 31 patients with cervical cancer. After their surgical resections, we obtained 31 cases of cervical cancer specimens, and 15 cases of adjacent normal cervical specimens as control group, then these 46 specimens were used in MVD detection through immunohistochemical CD34 staining. The MVDs of the tumor group were significantly higher than those in the control group, and the former seems to increase with the clinical stages with a positive correlation. The PF and PEI values have positive correlations with corresponding MVD values. The PF value of squamous carcinoma group has correlation with corresponding MVD value. The PF and PEI values of poorly differentiated group have correlations with corresponding MVD values. The PF, PEI and BV values of II-III stage group are positively correlated with corresponding MVD values. The PF value of lymph metastasis or non-lymph metastasis group both have correlations with corresponding MVD values. We found that CT perfusion parameters were positively correlated with corresponding MVD values in cervical cancer. Our results suggest that CT perfusion is a new method which could reflect tumor angiogenesis, histological malignant grade, invasion, and clinical stage. It will help us determine the tumor staging and prognosis.
Adenocarcinoma ; blood supply ; diagnostic imaging ; Adult ; Aged ; Carcinoma, Squamous Cell ; blood supply ; diagnostic imaging ; Contrast Media ; Female ; Humans ; Microvessels ; pathology ; Middle Aged ; Neovascularization, Pathologic ; diagnostic imaging ; Perfusion Imaging ; Radiographic Image Interpretation, Computer-Assisted ; Tomography, Spiral Computed ; methods ; Uterine Cervical Neoplasms ; blood supply ; diagnostic imaging ; Young Adult