Objective To explore the feasibility and effectiveness of interventional transcatheter destruction of the aortic valve to establish an animal model with acute aortic valve regurgitation. Methods Eight healthy goats were used for this study. A limited sternotomy approach was used to access the apex of the heart. Puncturing of the apex of the heart was performed to establish a wire track, then, under fluoroscopic guidance a 10 F sheath was inserted along this track of hard wire until to the ascending aorta above the aortic valve. The internal sheath was removed. Via the 10 F sheath a 10 mm occluder of ventricular septal defect (VSD) was introduced into the ascending aorta above the aortic valve. The sheath was pulled back to the left ventricle, while the occluder remained in the ascending aorta above the aortic valve. Then the occluder was quickly pulled back into the left ventricle in order to make some certain damage to the aortic valve. And an acute aortic valve regurgitation model was thus established. Angiography of ascending aorta above the aortic Among the 8 animals, two died of acute left ventricular failure on the spot due to excessive regurgitation blood flow after the operation. Macroscopically, damage of the aortic valve was seen. In the six survivors, angiography of ascending aorta above the aortic valve and Doppler echocardiography showed that moderate degree of regurgitation was detected in 5 and small amount of regurgitation in one. Two experimental goats with moderate degree of regurgitation died of heart failure separately at seven days and fifteen days after the operation. The remaining four experimental goats survived for more than three months. Follow- up checkups with echocardiography suggested the presence of mild- moderate degree of regurgitation. Conclusion Acute aortic valve regurgitation model in experimental goats can be established through transapical transcatheter damage of aortic valve by quickly pulling back a VSD occluder which has been placed in the ascending aorta above the aortic valve. This method is clinically feasible, technically simple and repeatable, the result is reliable, and the degree of regurgitation is controllable.

OBJECTIVE:To establish a risk scoring system for identifying invasive fungal infection(IFI)patients with hematologic diseases. METHODS:Risk factors were investigated among 200 patients diagnosed with IFI and 200 control patients at the same time from Jan. 2008 to Dec. 2015. The single factor analysis and Logistic multivariate regression analysis were conducted for potential risk factors to screen and assign risk factors of IFI. The risk scoring system of IFI was established,the performance of scoring system was evaluated by receiver operating characteristic(ROC)curve. Using the scoring system,103 patients of validation group were scored during Jan. to Jun. in 2016.The incidence of IFI in each group was compared. 18 high-risk patients were intervened by the scoring system. RESULTS:Community acquired infection,the reduction of neutrophils,fungal infection history,corticosteroids and broad-spectrum antibiotics(Enzyme inhibitors,glycopeptides,quinolones,aminoglycosides and carbapenems)were risk factors of IFI(P<0.001),and the score of them were 17,10,39,14,14 according to the regression coefficients. IFI risk scoring system was divided into low,medium and high risk(scoring 0-30,31-40,≥41),AUC of ROC curve was 0.916. The incidence of IFI in low-risk,medium-risk and high risk groups were 3.0%,10.7% and 62.5%,high-risk group was significantly higher than low and medium-risk groups(P<0.05).The incidence of IFI was 16.7% in intervention group, there was statistical significance compared to high-risk group of validation group(P<0.05). CONCLUSIONS:This scoring system shows good ability to distinguish risk stratification. It can help clinicians identifying IFI high-risk groups and timely guiding timely intervention for patients.

Ferroptosis is a newly discovered regulatory cell death induced by the accumulation of iron-dependent lipid peroxides, with the morphological manifestations of decreased mitochondrial volume, increased mitochondrial membrane density, and reduction or disappearance of mitochondria. The mechanism of ferroptosis is mainly associated with disturbance of iron metabolism, imbalance of amino acid antioxidant system, and accumulation of lipid peroxides. Studies have shown that ferroptosis plays different roles in different liver diseases, and ferroptosis can participate in the progression of various liver inflammatory diseases and inhibit the formation of liver fibrosis, the development of hepatocellular carcinoma, and sorafenib resistance. This article summarizes the advances in the mechanism of ferroptosis and its role in liver diseases, so as to provide a reference for further research and treatment of liver diseases.

T cell immunoglobulin and mucin domain-containing protein 3(Tim-3)is a member of the Tim family,which is widely expressed on the surface of various cells and can be involved in the occurrence and development of diseases such as autoimmune,infection and cancer.Clinical trials have found that a combination of blocking Tim-3 and programmed cell death 1(PD-1)can improve the anti-cancer immune response and regression of tumors in patients with advanced cancer.This arti-cle reviewed the basic biological structure of Tim-3,corresponding ligand and its role in tumor micro-environment,and summarized the ongoing clinical trials of TIM-3.These data suggested that Tim-3 could be used as a potentially significant checkpoint receptor for future anti-tumor therapy,and sum-marized the ongoing clinical trials of drugs,indicating that Tim-3 can be used as a potential check-point receptor for future anti-tumor therapy.

T cell immunoglobulin and mucin domain-containing protein 3(Tim-3)is a member of the Tim family,which is widely expressed on the surface of various cells and can be involved in the occurrence and development of diseases such as autoimmune,infection and cancer.Clinical trials have found that a combination of blocking Tim-3 and programmed cell death 1(PD-1)can improve the anti-cancer immune response and regression of tumors in patients with advanced cancer.This arti-cle reviewed the basic biological structure of Tim-3,corresponding ligand and its role in tumor micro-environment,and summarized the ongoing clinical trials of TIM-3.These data suggested that Tim-3 could be used as a potentially significant checkpoint receptor for future anti-tumor therapy,and sum-marized the ongoing clinical trials of drugs,indicating that Tim-3 can be used as a potential check-point receptor for future anti-tumor therapy.

[ ABSTRACT] AIM: To explore the effects of Mcl-1 signal pathway blockers on Mcl-1 expression, macrophage apoptosis and Mycobacterium tuberculosis in the model of mice infected with Mycobacterium tuberculosis H37Rv.METH-ODS:A mouse infection model was established by intraperitoneal injection of H37Rv suspension.The signaling pathway blockers AG490, PD98059 and LY294002 for JAK/STAT, MAPK and PI3K, respectively, were intraperitoneally injected into the mice infected with H37Rv.Cell acid-fast staining was used to observe whether the mouse peritoneal macrophages infected with H37Rv were successfully established.Immunocytochemical method was employed to detect Mcl-1 expression in the mouse peritoneal macrophages infected with H37Rv.The apoptotic rate in each group was measured by flow cytomer-ty.The scavenging capacity of apoptotic macrophages against H37Rv was determined by Mycobacterium tuberculosis colony counting.RESULTS:The result of cell acid-fast staining revealed the existence of dispersive arrangement of red short anti-acid Mycobacterium tuberculosis within infected macrophages.The result of cell immunocytochemistry showed strongly posi-tive expression of Mcl-1 protein in H37Rv infection group, AG490 treatment group and LY294002 treatment group, weakly positive expression of Mcl-1 protein in PD98059 treatment group, and negative expression of Mcl-1 protein in control group. The result of flow cytometry found that the macrophage apoptotic rate in H37Rv infection group was higher than that in con-trol group, while that in PD98059 treatment group was high than that in other groups with statistically significant differences (P<0.05).The result of Mycobacterium tuberculosis colony counting showed that PD98059 treatment had the most signifi-cant inhibitory effect on H37Rv strain.CONCLUSION: Mcl-1 signaling pathway blockers increase the apoptotic rate of macrophages infected with Mycobacterium tuberculosis H37Rv and inhibit the growth of Mycobacterium tuberculosis by inhibi-ting the signaling pathways of JAK/STAT, MAPK and PI3K, among which the MAPK has the most obvious interfering effect on Mcl-1, and leads to the highest apoptotic rate of infected macrophages and the strongest bacteriostasis.

Alcoholic liver disease is often complicated with sepsis at the end stage of the disease, inducing acute-on-chronic liver failure and multiple organ and system injuries, with high short-term mortality. At present, there is still a lack of effective methods for early diagnosis and prognosis, and measures for prevention and treatment in alcoholic liver disease complicated with sepsis. This article reviews the research progress of alcoholic liver disease complicated with sepsis to provide reference for clinical practice.

OBJECTIVE: To explore the clinical features and genetic basis for a Chinese pedigree diagnosed with congenital glycosylation disease (CGD). METHODS: Clinical manifestations of two brothers were analyzed. Whole exome sequencing was carried out for the sib pair. Suspected variants were verified by Sanger sequencing. RESULTS: Both the proband and her younger brother were found to carry compound heterozygous variants of the PMM2 gene, which included a known pathogenic mutation of c.395T>C (p.I132T) and a previously unreported c.448-1(delAG) in the 5' end of exon 6 of the gene. CONCLUSION The compound heterozygous variants of the PMM2 gene probably underlay the CGD in the sib pair.
Asians/genetics* ; China ; Female ; Glycosylation ; Humans ; Male ; Mutation ; Pedigree ; Whole Exome Sequencing

Objective To study the changes in morphology , phenotypes and gene expression pro-files of dendritic cells (DCs) following treatment with Seabuckthorn flavones (SF).Methods DCs were treated with 200μg/ml of SF and then cultured for 7 days.Changes in the morphology of DCs were observed under light microscope .Flow cytometry was used to detect DC surface molecules .Total RNA was extracted to construct the library for digital gene expression profiling ( DGE ) .Differentially expressed genes were screened out and further analyzed by gene ontology ( GO) enrichment analysis and Kyoto encyclopedia of genes and genomes ( KEGG ) pathway enrichment analysis .Results Compared with control group , SF treatment significantly enhanced the expression of HLA-DR, CD80, CD83 and CD86 on DCs.A total of 355 differentially expressed genes were screened out by DGE , including 176 up-regulated genes and 179 down-regulated genes .GO enrichment was mainly involved in the regulation and development of the immune sys -tem and other biological processes .KEGG pathway analysis showed that the significantly enriched pathways were closely related to inflammation , the immune system, cancer and other diseases .Conclusion SF can promote the expression of DC co-stimulatory molecules and pro-mature molecules, and regulate the expres-sion of immunity-related genes such as CD11a, SLAMF6, LMCD1, TSC22D3 and IKZF3.

Pancreatic cancer is the malignant tumor of the digestive tract with the lowest 5-year survival rate, and current first-line treatment regimens cannot significantly improve the overall prognosis of patients, so it is necessary to explore new treatment methods. A large number of studies have shown that the tumor microenvironment of pancreatic cancer, such as stromal barrier, immune microenvironment, and exosomes, plays an important role in promoting the proliferation, invasion, metastasis, and chemoradiotherapy resistance of pancreatic cancer cells. This article summarizes the potential targets associated with the tumor microenvironment of pancreatic cancer and related clinical research advances, in order to provide new ideas for the treatment of pancreatic cancer.