Thoracic aortic aneurysm (TAA) significantly endangers the lives of individuals with Marfan syndrome (MFS), yet the intricacies of their biomechanical origins remain elusive. Our investigation delves into the pivotal role of hemodynamic disturbance in the pathogenesis of TAA, with a particular emphasis on the mechanistic contributions of the mammalian target of rapamycin (mTOR) signaling cascade. We uncovered that activation of the mTOR complex 1 (mTORC1) within smooth muscle cells, instigated by the oscillatory wall shear stress (OSS) that stems from disturbed flow (DF), is a catalyst for TAA progression. This revelation was corroborated through both an MFS mouse model (Fbn1 ^+/C1039G) and clinical MFS specimens. Crucially, our research demonstrates a direct linkage between the activation of the mTORC1 pathway and the intensity in OSS. Therapeutic administration of rapamycin suppresses mTORC1 activity, leading to the attenuation of aberrant SMC behavior, reduced inflammatory infiltration, and restoration of extracellular matrix integrity-collectively decelerating TAA advancement in our mouse model. These insights posit the mTORC1 axis as a strategic target for intervention, offering a novel approach to manage TAAs in MFS and potentially pave insights for current treatment paradigms.

ObjectiveTo discuss the effects of Cistanches Herba phenylethanoid glycosides （CHPhGs） on the intestinal mucosal barrier and gut microbiota in alcoholic liver disease （ALD） mice were discussed. MethodThe 36 C57BL/6N female mice were randomly divided normal group， normal group of CHPhGs， model group， and low， medium， and high-dose groups （175， 350， 700 mg·kg^-1） of CHPhGs， with six mice in each group. The ALD mouse model was built using Lieber-Decarli alcohol liquid feed. The normal group and low， medium， and high-dose groups of CHPhGs were given CHPhGs by gavage daily. Serum aspartate aminotransferase aminotransferase （ALT）， alanine aminotransferase （AST）， triglycerides （TG）， and total cholesterol （TC） levels were detected by an automatic biochemical analyzer. Serum tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， lipopolysaccharide （LPS）， lipopolysaccharide-binding protein （LBP）， D-lactic acid （D-LA）， diamine oxidase （DAO）， and LBP of liver were detected by enzyme-linked immunosorbent assay （ELISA）. The levels of TG and TC in the liver were detected by colorimetry. Liver tissue was treated by oil red O and hematoxylin-eosin （HE） staining. The microstructure of jejunum epithelial cells was observed by electron microscope. Jejunum and colon were treated by HE staining and alcian blue-periodate-scheff (AB-PAS) staining staining， and mucin 2 （Muc2） was treated by immunohistochemistry. The intestinal contents of the normal group， normal group of CHPhGs， model group， and high-dose group of CHPhGs were collected and sequenced. ResultThe ALD model was established successfully. Compared with the normal group， the levels of serum ALT， AST， and TG， as well as the levels of liver TG and TC in the model group were significantly increased （P<0.05）. Histopathology showed that compared with the normal group， the liver cells in the model group showed obvious steatosis. Compared with the model group， the levels of serum TG and liver TG and TC in the low， medium， and high-dose groups of CHPhGs decreased significantly （P<0.05）. The serum ALT， AST， TNF-α， IL-1β， LPS， and LBP in the high-dose group of CHPhGs were also significantly decreased （P<0.05）. The number of liver cells with steatosis in the high-dose group of CHPhGs was significantly reduced， and the microvilli structure of jejunum epithelial cells was basically intact. The expression of Muc2 was reduced in the colon， and the gut microbiota of the high-dose group of CHPhGs changed significantly （P<0.05）. Compared with the normal group， the Allobaculum was significantly up-regulated in the model group （P<0.05）. Compared with the model group， the abundance of Akkermansia in the high-dose group of CHPhGs was significantly increased （P<0.01）. The abundance of Akkermansia was negatively correlated with that of Allobaculum （r=-0.701， P<0.01）. ConclusionCHPhGs can reduce the intestinal barrier injury caused by ALD， which may play a protective role by regulating the abundance and structure of Akkermansia and Allobaculum and affecting the homeostasis of intestinal mucus.

Objective To investigate the role and mechanism of miRNAs in alcoholic liver injury in rats.Methods Thirty male SD rats were randomly divided into model and control groups.The model group was gavaged with 56%liquor and the control group was gavaged with distilled water for 8 weeks.Liver tissue was collected,miRNAs were analyzed,and target genes of differentially expressed miRNAs were predicted by a rat miRNA chip.Gene ontology(GO)and KEGG pathway enrichment analysis were used to understand the function of differentially expressed miRNA target genes.A differentially expressed miRNA-mRNA-pathway regulatory network was constructed using Cytoscape to further screen important regulatory miRNAs versus important pathways.RT-qPCR was performed for selected miRNAs to validate the expression analysis.Results Twelve differentially expressed miRNAs(P<0.05,Fold change≥2)were screened out,including two upregulated and 10 downregulated miRNAs by comparative analysis of microarray data between model and control groups.GO classification annotation of differential miRNA target genes showed close associations between differentially expressed miRNAs and biological functions such as signal transduction,metabolic processes,antioxidant activity,cell killing,enzyme regulatory activity and biological regulation.Differentially expressed miRNA target genes in KEGG pathway analysis revealed that the AMPK signaling pathway,PI3K-Akt signaling pathway,Hippo signaling pathway,Wnt signaling pathway,cancer,autophagy,insulin resistance,Ras signaling pathway,and other signaling pathways might play major regulatory roles in alcoholic liver injury lesions.Hub miRNAs and pathways screened by constructing the differentially expressed miRNA-mRNA-pathway regulatory network were miR-145-5p,miR-107-3p,miR-297,Hippo signaling pathway,cancer,PI3K-Akt signaling pathway,and AMPK signaling pathway.qRT-PCR validated the gene expression trends,and gene chip result were consistent.Conclusions We established an miRNA profile of alcoholic liver injury in rats,which suggests that miR-145-5p,miR-107-3p,and miR-297 play major roles in the process of alcoholic liver pathology.

Objective : To investigate the mechanism of miRNAs in glycyrrhizic acid treatment of alcohol⁃induced liver injury in rats . Methods : 45 male SD rats were randomly divided into glycyrrhizin group , model group and control group . The rats in glycyrrhizin group were given 56% liquor and glycyrrhizin , the rats in model group were given 56% liquor , and the rats in control group were given distilled water for 8 weeks . The blood was collected and the serum was separated by centrifugation to detect the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) . RNA were extracted from liver tissues , miRNAs were detected by rat miRNA microarray , and their expression levels were analyzed . The miRNA target genes of differential miRNA were predicted . Gene Ontology (GO) and KEGG Pathway enrichment analysis were used to understand the function of differential miRNA , and the differential miRNA⁃mRNA⁃Pathway regulatory network was constructed using Cytoscape to further screen the regulatory key miRNA and key pathways . qRT⁃PCR was used to verify the expression of selected miRNA . Results : Compared with the model group , the glycyrrhizin group could significantly improve the liver tissue lesions , and reduce the liver serum AST and ALT levels (P < 0. 05) . Compared the microarray data of glycyrrhizin group and model group , a total of 13 differentially expressed miRNA were screened ( P < 0. 05 , fold change ≥ 1 . 5) , of which 10 were up⁃regulated and 3 were down⁃regulated . The GO classification annotation of differential miRNA target genes showed that differential miRNA were related to cell adhesion , antioxidant activity , metabolic process , biological process regulation , cell killing , immune system and other functions . The KEGG Pathway analyling pathway , Hippo signaling pathway , PI3K⁃Akt signaling pathway , wnt signaling pathway , apoptosis and other signaling pathways might play an important regulatory role in the improvement of alcoholic liver injury by glycyrrhic acid . Conclusion This study established the miRNA expression profile of glycyrrhizin in the treatment of alcoholic liver injury in rats , suggested that miR⁃615 , miR⁃107 ⁃3p and miR⁃292⁃5p might play an important role in the treatment of alcoholic liver injury by glycyrrhizin .

Objective To investigate the changes in the expression of cold-inducible RNA-binding protein (CIRBP) in a radiation-induced lung injury model. Methods Thirty male C57BL/6 mice were randomly divided by body weight into control group (no intervention) and model group (single chest X-ray irradiation with a dose of 20 Gy to build a radiation-induced lung injury model). The mice were dissected five weeks after irradiation. Hematoxylin-eosin staining and Masson staining were used to observe the pathological changes of the lung tissue and the deposition of collagen fibers. Immunohistochemistry was used to measure the expression of the inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the lung tissue. qRT-PCR was used to measure the expression of CIRBP mRNA in the lung tissue. The expression of CIRBP protein in the lung tissue was determined by the immunofluorescence assay and Western blot. Results Compared with the control group, the model group showed significant pulmonary vascular congestion, significant inflammatory cell infiltration, significant thickening of some alveolar septa, significantly increased IL-6 expression [(129.41 ± 5.58) vs (187.22 ± 34.77), t = 3.179, P < 0.05], significantly increased TNF-α expression [(137.52 ± 23.53) vs (187.02 ± 19.16), t = 5.069, P < 0.05], significantly increased CIRBP mRNA expression [(1 ± 0.08) vs (1.97 ± 0.39), t = 3.45, P < 0.05], and significantly increased CIRBP protein expression [(9.32 ± 1.26) vs (14.76 ± 1.61), t = 3.751, P < 0.05], by the immunofluorescence assay; [(1.13 ± 0.17) vs (1.49 ± 0.14), t = 2.819, P < 0.05], by Western blot). Conclusion The expression of CIRBP is significantly increased in the radiation-induced lung injury model, which may be an important pro-inflammatory factor in radiation-induced lung injury.

Objective To evaluate the prophylactic effect of abdominal breathing exercises on radiation pneumonitis in patients with chest malignant tumors.Methods 100 patients with chest malignant tumors were given radiotherapy and divided with random digit table into the exercise group and the control group with 50 patients in each group.The incidence rate of radiation pneumonitis in both groups was compared.The prophylactic effect of abdominal breathing exercises on radiation pneumonitis was evaluated.Results The incidence of radiation pneumonitis in abdominal breathing exercise group was significantly reduced [34％ (17/50) vs.56％ (28/50),Z=2.397,P＜0.05],the incidences of grade Ⅰ [22％ (11/50) vs.30％ (15/50)] and grade Ⅱ [12％ (6/50) vs.18％ (9/50)] radiation pneumonitis decreased,and no grade Ⅲ and Ⅳ radiation pneumonitis occurred.Conclusions The incidence of radiation pneumonitis in patients with chest malignant tumors treated with radiation therapy may be decreased by abdominal breathing exercises,which may be widely applied in patients treated with radiation therapy.