Objective:To investigate the therapeutic effects of the copper chelator ammonium tetrathiomolybdate (TTM) on rheumatoid arthritis (RA) in a mouse model.Methods:Twenty-four male dilution brown non-Agoutia/1 mice were randomly divided into 4 groups: a blank control group (Ctrl group, n=6), a collagen-induced arthritis (CIA) + phosphate buffer saline (PBS) treatment group (PBS group, n=6), a CIA+TTM treatment group (TTM group, n=6), and a CIA+Elesclomol treatment group (Eles group, n=6). Eles, a copper ion carrier, served as a control for administration of TTM, a copper ion chelator. One week after treatment, the swelling of mouse paw was observed, and the clinical scoring of the arthritis in mice was evaluated once a week. Paw mechanical pain detection was performed and photographs were taken to observe the severity of paw swelling before the mice were sacrificed. Catwalk gait analysis system was used to evaluate the gait changes in mice. HE and saffron O solid green staining were used to evaluate pathomorphologic changes in the mice knee joints and paws. Immunostaining techniques were used to detect the protein expression of MMP3, CD31, and VEGF in the mice paws. Luminex technology was used to detect alterations in the serum inflammatory factors. Results:Compared with the Ctrl group, in the PBS and Eles groups, the joints were red, swollen and deformed; the arthritis clinical scores were significantly higher; the bone destruction, synovial hyperplasia and inflammatory cell infiltration and pathological changes in the joint tissues were obvious; the expression levels of inflammatory factors, such as serum MCP-1, IL-1 β, IL-9, and IFN- γ, were significantly higher while the expression level of IL-10 was significantly lower. Simultaneously, the expression of CD31 and VEGF factors was significantly enhanced. Compared with the PBS group, in the TTM group, the joint swelling and deformation were significantly improved, the arthritis clinical score was reduced, and the joint bone destruction, inflammatory cell infiltration and synovial hyperplasia were alleviated, and the levels of serum MCP-1, IL-1 β, IL-9 and IFN- γ were significantly decreased while the level of anti-inflammatory factor IL-10 was increased. There was no significant difference in the expression of MMP-3, CD31 or VEGF factors between the CTRL group and the TTM group. Conclusion:TTM can block synovial inflammation, angiogenesis, and bone destruction multiple times by simultaneously targeting multiple inflammatory factors, VEGF factors, and bone destruction mediators, thereby alleviating the pathological damage to the joint tissues induced by CIA in RA mice.

Objective:To investigate the therapeutic effects of the copper chelator ammonium tetrathiomolybdate (TTM) on rheumatoid arthritis (RA) in a mouse model.Methods:Twenty-four male dilution brown non-Agoutia/1 mice were randomly divided into 4 groups: a blank control group (Ctrl group, n=6), a collagen-induced arthritis (CIA) + phosphate buffer saline (PBS) treatment group (PBS group, n=6), a CIA+TTM treatment group (TTM group, n=6), and a CIA+Elesclomol treatment group (Eles group, n=6). Eles, a copper ion carrier, served as a control for administration of TTM, a copper ion chelator. One week after treatment, the swelling of mouse paw was observed, and the clinical scoring of the arthritis in mice was evaluated once a week. Paw mechanical pain detection was performed and photographs were taken to observe the severity of paw swelling before the mice were sacrificed. Catwalk gait analysis system was used to evaluate the gait changes in mice. HE and saffron O solid green staining were used to evaluate pathomorphologic changes in the mice knee joints and paws. Immunostaining techniques were used to detect the protein expression of MMP3, CD31, and VEGF in the mice paws. Luminex technology was used to detect alterations in the serum inflammatory factors. Results:Compared with the Ctrl group, in the PBS and Eles groups, the joints were red, swollen and deformed; the arthritis clinical scores were significantly higher; the bone destruction, synovial hyperplasia and inflammatory cell infiltration and pathological changes in the joint tissues were obvious; the expression levels of inflammatory factors, such as serum MCP-1, IL-1 β, IL-9, and IFN- γ, were significantly higher while the expression level of IL-10 was significantly lower. Simultaneously, the expression of CD31 and VEGF factors was significantly enhanced. Compared with the PBS group, in the TTM group, the joint swelling and deformation were significantly improved, the arthritis clinical score was reduced, and the joint bone destruction, inflammatory cell infiltration and synovial hyperplasia were alleviated, and the levels of serum MCP-1, IL-1 β, IL-9 and IFN- γ were significantly decreased while the level of anti-inflammatory factor IL-10 was increased. There was no significant difference in the expression of MMP-3, CD31 or VEGF factors between the CTRL group and the TTM group. Conclusion:TTM can block synovial inflammation, angiogenesis, and bone destruction multiple times by simultaneously targeting multiple inflammatory factors, VEGF factors, and bone destruction mediators, thereby alleviating the pathological damage to the joint tissues induced by CIA in RA mice.

Objectives:To analyze the impact of target lesion calcification evaluated by coronary angiography on immediate procedure success rate and long-term clinical outcome in patients underwent percutaneous coronary intervention(PCI). Methods:Consecutive patients received angiographic calcification evaluation and underwent PCI in Fuwai Hospital,Chinese Academy of Medical Sciences from January 2017 to December 2018 were prospectively enrolled in this study.Patients are divided into 4 groups,including non-calcification group(n=14 387),mild calcification group(n=8 231),moderate calcification group(n=3 208)and severe calcification group(n=886).The primary endpoint was immediate post-PCI procedure success rate,which was defined as residual stenosis<50%without major operational complications(including coronary artery perforation,coronary artery dissection,intraoperative stent thrombosis)and failure to cross the lesion.The long-term clinical endpoint was the 3-year major adverse cardiovascular events(MACE),which included composite endpoint events such as all cause death,myocardial infarction(MI),and revascularization. Results:The severe calcification group had a lower success rate of interventional therapy(80.59%vs.94.23%vs.94.29%vs.91.49%),a higher incidence of residual stenosis≥50%(17.72%vs.5.03%vs.4.84%vs.7.29%),a higher incidence of coronary artery dissection(1.81%vs.0.66%vs.0.78%vs.1.25%),and a higher incidence of coronary artery perforation(2.14%vs.0.51%vs.0.38%vs.0.69%),and a higher incidence of failure to cross the lesion(0.23%vs.0.12%vs.0.04%vs.0.16%)compared to the non-calcification group,mild calcification group,and moderate calcification group(all P<0.05).Multivariate Cox regression analysis showed that patients with severe calcification had a higher risk of MACE(12.98%vs.9.35%,HR=1.21,95%CI:1.00-1.47,P=0.046),all-cause mortality(4.29%vs.1.80%,HR=1.55,95%CI:1.10-2.18,P=0.013),and MI(2.14%vs.0.97%,HR=1.97,95%CI:1.21-3.20,P=0.006)compared to patients without calcification. Conclusions:Patients with angiographic-detected severe calcification after PCI treatment face higher risk of PCI procedure failure,MACE,all-cause death,and MI compared to patients without,with mild,and moderate calcification.

Thirteen patients with colorectal lesions underwent laparoscopic surgery from January to December 2019. Before surgery, 5.0 ml autogenous blood was injected under colonoscopy into the inferior margin and opposite sides of the lesion for localization. The operation time，success rate，complications，location efficiency and postoperative pathology were evaluated. The autologous blood tattooing was easily applied for all patients without complication. At laparoscopic surgery，the lesions of all patients were clearly visualized except one obese patients with rectal tumors, because the tumor was located below the retroperitoneal fold. No blood diffusion and leakage，and local inflammatory responses were observed. The surgical margins of all samples were tumor negative. Preoperative tattooing with autologous blood is recommended as an easy，safe and economical procedure for colonoscopic surgery in patients with colorectal lesions.