Objective To investigate the effects of S-allylcysteine ( SAC ) , on nitric oxide ( NO ) production and antioxidant enzyme activities in hyperlipidemic rats. Methods Male Wistar rats were randomly divided into seven groups. Five groups including normal control group ( normal diet) , model control group ( high-fat diet, HFD) and SAC low,medium,high treated group (high-fat diet +25,50,100 mg·kg-1 SAC) were sacrificed after 4 weeks dosing,while the other two groups including L-arginine group (normal diet+ 20 mg·kg-1 L-arginine) and SAC+L-arginine group (50 mg·kg-1 SAC+20 mg·kg-1 L-arginine) were sacrificed at 4 h after dosing. The serum, livers and kidneys were collected. The levels of NO, the activities of nitric oxide synthase ( NOS ) , antioxidant enzymes in vivo and L-arginine contents in serum were determined. Results Comparing with model control group, the activities of total NOS in serum and liver were significantly reduced in SAC-treated groups (P<0. 05). The level of L-arginine in SAC-treated groups was (8. 25 ± 1. 15), (7. 76 ± 1. 24) and (7. 22 ± 1. 64)μg·mL-1 , respectively. Compared with model control group, the level of L-arginine were significantly reduced in SAC-treated groups (P<0. 05). Comparing with L-arginine group, the activities of total NOS (T-NOS) and iNOS were reduced in SAC+L-arginine group. SAC treatment (100 mg·kg-1) significantly increased the activities of superoxide dismutase (SOD) (P<0. 01) and the level of glutathione (GSH) (P<0.01), and decreased the level of malondialdehyde (MDA) in serum and liver of hyperlipidemic rats. Conclusion These data suggest that SAC inhibits the NO production by reducing iNOS activity, arginine concentration and exhibited antioxidant activity, which may play a pharmacologically important role in protection from oxidative injury and pathogenesis of atherosclerosis.

Objective To construct c-Met CAR-T cells secreting PD-1 antibodies to reduce immune inhibitory effect of tumor cells and enhance the efficacy of CAR-T cell therapy against pancreatic cancer.Methods Kaplan-Meier Plotter,GEPIA,and Timer 2.0 bioinformatics databases were used to analyze c-Met expression in pancreatic cancer and its correlation with survival and immune infiltration status.In clinical samples of pancreatic cancer and pancreatic cancer Aspc-1 cells,c-Met and PD-L1 expressions were detected using immunohistochemistry or flow cytometry.Using gene editing technology,PD-1 secretory antibodies and HIS tags were linked to second-generation c-Met CAR molecules to construct PD-1/c-Met CAR plasmids,which were then packaged into lentiviruses for infection of activated T cells.The positive rate and cell subset distribution of CAR-T cells were analyzed with flow cytometry,and secretory PD-1 antibodies in cell supernatants were detected using Western blotting.The target cell killing efficiency and proliferative activity of the modified CAR-T cells were evaluated after activation,and cytokine secretion was analyzed using ELISA.Results The expression of c-Met was significantly higher in pancreatic cancer than in normal tissues,and its expression level was negatively correlated with the patients'survival and positively correlated with immune cell infiltration.The clinical samples of pancreatic cancer tissues expressed significantly higher levels of c-Met and PD-L1 than the adjacent tissues,and 90.7%and 57.7%of Aspc-1 cells were positive for c-Met and PD-L1,respectively.The constructed PD-1/c-Met CAR-T cells were capable of secreting PD-1 antibodies and showed a significantly higher killing efficiency against tumor cells than c-Met CAR-T cells at an effector-to-target ratio of 20:1,with also a higher proliferative activity after target cell stimulation and higher levels of IL-2 and TNF-α secretin.Conclusion PD-1/c-Met CAR-T cells have higher killing efficiency against pancreatic cancer cells with also higher proliferative activity than c-Met CAR-T cells.

Objective To construct c-Met CAR-T cells secreting PD-1 antibodies to reduce immune inhibitory effect of tumor cells and enhance the efficacy of CAR-T cell therapy against pancreatic cancer.Methods Kaplan-Meier Plotter,GEPIA,and Timer 2.0 bioinformatics databases were used to analyze c-Met expression in pancreatic cancer and its correlation with survival and immune infiltration status.In clinical samples of pancreatic cancer and pancreatic cancer Aspc-1 cells,c-Met and PD-L1 expressions were detected using immunohistochemistry or flow cytometry.Using gene editing technology,PD-1 secretory antibodies and HIS tags were linked to second-generation c-Met CAR molecules to construct PD-1/c-Met CAR plasmids,which were then packaged into lentiviruses for infection of activated T cells.The positive rate and cell subset distribution of CAR-T cells were analyzed with flow cytometry,and secretory PD-1 antibodies in cell supernatants were detected using Western blotting.The target cell killing efficiency and proliferative activity of the modified CAR-T cells were evaluated after activation,and cytokine secretion was analyzed using ELISA.Results The expression of c-Met was significantly higher in pancreatic cancer than in normal tissues,and its expression level was negatively correlated with the patients'survival and positively correlated with immune cell infiltration.The clinical samples of pancreatic cancer tissues expressed significantly higher levels of c-Met and PD-L1 than the adjacent tissues,and 90.7%and 57.7%of Aspc-1 cells were positive for c-Met and PD-L1,respectively.The constructed PD-1/c-Met CAR-T cells were capable of secreting PD-1 antibodies and showed a significantly higher killing efficiency against tumor cells than c-Met CAR-T cells at an effector-to-target ratio of 20:1,with also a higher proliferative activity after target cell stimulation and higher levels of IL-2 and TNF-α secretin.Conclusion PD-1/c-Met CAR-T cells have higher killing efficiency against pancreatic cancer cells with also higher proliferative activity than c-Met CAR-T cells.

Objective:To improve the understanding of newly diagnosed multiple myeloma (NDMM) patients with bone marrow (BM) monoclonal plasma cell ratio of less than 10%.Methods:The clinical characteristics, laboratory examination, response to treatment, and prognosis of 36 NDMM patients with BM plasma cell ratio of less than 10% at Peking Union Medical College Hospital from January 2009 to December 2017 were summarized retrospectively. In the same period, other age- and gender-matched 72 NDMM patients were selected as the control group, whose BM plasma cell ratio was equal to or greater than 10%.Results:First, the patients in the study group accounted for 4.4% of the whole MM population (36/818) , among which only 11 (30.6%) were classified as International Staging System (ISS) Ⅲ, which was significantly lower than that in the control group[45 (62.5%) ] ( P=0.002) . Extramedullary disease (EMD) was more common in the study group (33.3% vs 5.6%, P<0.001) . The median quantity of serum M protein (g/L) in the less than 10% group was 1.04 (0-50.10) , which was significantly lower than that in the control group [4.50 (0-63.10) ] ( P=0.016) , similar to the median quantity of 24-h urinary light chain (510 mg vs 2800 mg, respectively, P=0.023) . Second, the median progression-free survival (PFS) times of front-line regimen in the study and control groups were 26.4 and 19.9 months, respectively ( HR=1.703, 95% CI 0.167-0.233, P=0.002) . In addition, the overall survival (OS) times were 65.8 and 46.2 months, respectively ( HR=2.626, 95% CI 0.439-0.541, P=0.058) . Third, the study group was reclassified based on the quantity of M protein. The median OS times in patients with low/high tumor load were 66.4 and 24.0 months, respectively ( HR=2.349, 95% CI 0.603-0.696, P=0.046) . The median PFS times were 33.1 and 15.5 months, respectively ( HR=1.806, 95% CI 0.121-0.399, P=0.077) . Bortezomib-based regimens did not affect the clinical outcomes. Conclusion:The subpopulation of patients with MM with BM monoclonal plasma cell ratio less than 10% has specific clinical characteristics, including an early disease stage and a lower overall tumor load. Although more patients of this minor group presented with an extramedullary disease, their response rate to the initial treatment and survival outcome are better than those of patients with BM monoclonal plasma cell ratio more than 10%.

Objective     To summarize the progress and trend on clinical drug trials of esophageal squamous cell carcinoma in China. Methods     Based on the clinical drug trial registration and information disclosure platform and the drug data query system of the National Medical Products Administration, the characteristics of clinical trials, investigational drugs and listed drugs of esophageal squamous cell carcinoma in China from 2012 to 2021 were analyzed. Results     From 2012 to 2021, a total of 49 clinical drug trials of esophageal squamous cell carcinoma were registered in China, accounting for 1.6% of all clinical trials of anticancer drugs. Among them, there were 39 (79.6%) trials initiated by domestic pharmaceutical enterprises, 6 (12.2%) for adjuvant and neoadjuvant treatment, and 9 (18.4%) for local treatment. There were differences in the treatment line distribution between global and domestic enterprise-initiated trials (P=0.032). The above trials covered 29 investigational drugs, including 23 (79.3%) targeted drugs, most of which targeted programmed death-1, programmed death-ligand 1 and epidermal growth factor receptor. From 2012 to 2021, there were 2 drugs for esophageal squamous cell carcinoma listed in China, both of which were approved for the first-line and second-line treatment. Conclusion     Great achievements have been made in the clinical development of esophageal squamous cell carcinoma drugs in China. It is suggested that domestic enterprises increase the investment of esophageal squamous cell carcinoma, pay attention to adjuvant and local treatment, explore novel targets and drug categories, and focus on the details of pivotal trials.