Objective:To compare the effectiveness and safety profile of centrifugal and membrane plasma separation model in artificial liver therapy with a dual plasma molecular adsorption system (DPMAS).Method:A retrospective study was conducted. Data of inpatients with liver failure who were treated with DPMAS therapy in the Liver Disease Center of Nanfang Hospital, Southern Medical University, from October 2022 to June 2024 were included. Clinical data such as demographic characteristics, etiology, DPMAS treatment-related indicators (including plasma separation method, vascular access, frequency of treatment, treatment duration, type of anticoagulant drugs, and membrane rupture condition), and laboratory test indicators before and after DPMAS treatment were collected. Categorical variables were compared by the χ2 test. Continuous variables were compared using a t-test or a non-parametric test between groups. Result:Data of 232 cases with liver failure who received artificial liver therapy with DPMAS were included. A total of 473 times DPMAS treatment was given. The average age was 50 years old, and males accounted for 82.3%. Centrifugal plasma separation was the initial DPMAS treatment in 176 (75.9%) cases, while membrane plasma separation was used in 56 cases (24.1%). The most common vascular access for DPMAS treatment was the internal jugular vein. The most commonly used anticoagulant was unfractionated heparin. The treatment duration of DPMAS was significantly higher with centrifugal separation than that with membrane separation ( P<0.001). Hemoglobin levels (mean before and after treatment in the centrifugal: 112.8 g/L vs. 106.3 g/L, P<0.001; mean before and after treatment in the membrane group: 108.4 g/L vs. 103.3 g/L, P<0.001), red blood cell count (mean before and after treatment in the centrifugal group: 3.7×10 9/L vs. 3.5×10 9/L, P<0.001; mean before and after treatment in the membrane group: 3.5×10 9/L vs. 3.3×10 9/L, P<0.001) and platelet count (mean before and after treatment in the centrifugal group: 134.5×10 9/L vs. 119.6×10 9/L, P<0.001; mean before and after treatment in the membrane group: 120.7 ×10 9/L vs. 97.3 ×10 9/L, P<0.001) were slightly decreased following initial DPMAS treatment in both groups. The decrease in platelets was significantly lower in centrifugal separation than that in membrane separation (median: 10.4% vs. 17.0%; P=0.003). There was no statistically significant difference observed in the proportion of puncture site bleeding in terms of plasma separation-related adverse events between the two groups, but plasma separator membrane rupture occurred two times in the DPMAS treatment. Conclusion:Centrifugal and membrane separation, both with DPMAS therapy, can cause a slight decrease in hemoglobin, red blood cell count, and platelets in patients with liver failure. Membrane separation causes a larger drop in platelets than centrifugal plasma separation. The operational convenience of medical personnel, the risk of membrane rupture, the coagulation markers, the patient's vascular condition, and other factors should be comprehensively considered when choosing the plasma separation model.

Objective:To compare the effectiveness and safety profile of centrifugal and membrane plasma separation model in artificial liver therapy with a dual plasma molecular adsorption system (DPMAS).Method:A retrospective study was conducted. Data of inpatients with liver failure who were treated with DPMAS therapy in the Liver Disease Center of Nanfang Hospital, Southern Medical University, from October 2022 to June 2024 were included. Clinical data such as demographic characteristics, etiology, DPMAS treatment-related indicators (including plasma separation method, vascular access, frequency of treatment, treatment duration, type of anticoagulant drugs, and membrane rupture condition), and laboratory test indicators before and after DPMAS treatment were collected. Categorical variables were compared by the χ2 test. Continuous variables were compared using a t-test or a non-parametric test between groups. Result:Data of 232 cases with liver failure who received artificial liver therapy with DPMAS were included. A total of 473 times DPMAS treatment was given. The average age was 50 years old, and males accounted for 82.3%. Centrifugal plasma separation was the initial DPMAS treatment in 176 (75.9%) cases, while membrane plasma separation was used in 56 cases (24.1%). The most common vascular access for DPMAS treatment was the internal jugular vein. The most commonly used anticoagulant was unfractionated heparin. The treatment duration of DPMAS was significantly higher with centrifugal separation than that with membrane separation ( P<0.001). Hemoglobin levels (mean before and after treatment in the centrifugal: 112.8 g/L vs. 106.3 g/L, P<0.001; mean before and after treatment in the membrane group: 108.4 g/L vs. 103.3 g/L, P<0.001), red blood cell count (mean before and after treatment in the centrifugal group: 3.7×10 9/L vs. 3.5×10 9/L, P<0.001; mean before and after treatment in the membrane group: 3.5×10 9/L vs. 3.3×10 9/L, P<0.001) and platelet count (mean before and after treatment in the centrifugal group: 134.5×10 9/L vs. 119.6×10 9/L, P<0.001; mean before and after treatment in the membrane group: 120.7 ×10 9/L vs. 97.3 ×10 9/L, P<0.001) were slightly decreased following initial DPMAS treatment in both groups. The decrease in platelets was significantly lower in centrifugal separation than that in membrane separation (median: 10.4% vs. 17.0%; P=0.003). There was no statistically significant difference observed in the proportion of puncture site bleeding in terms of plasma separation-related adverse events between the two groups, but plasma separator membrane rupture occurred two times in the DPMAS treatment. Conclusion:Centrifugal and membrane separation, both with DPMAS therapy, can cause a slight decrease in hemoglobin, red blood cell count, and platelets in patients with liver failure. Membrane separation causes a larger drop in platelets than centrifugal plasma separation. The operational convenience of medical personnel, the risk of membrane rupture, the coagulation markers, the patient's vascular condition, and other factors should be comprehensively considered when choosing the plasma separation model.

Objective Benzothiazole derivative BD960 has immunosuppressive activity after cell -based assays for high-throughput screening.The paper aimed to investigate the involved mechanism of BD960 on T cell proliferation. Methods Human peripheral blood T-lymphocytes were isolated and purified by the immunomagnetic microbeads.Then the T cells were activated by anti-CD3/anti-CD28 mAbs or alloantigen.The effect of BD960 on activa-ted T cell proliferation, the cytotoxic effect BD960 on resting T cells and the expression of activated T cells marker CD25 were measured by flow cytometer.Cytokine levels, including IL-2, IL-4, IL-6, IL-10, IL-17A and IFN-γ, were determined by ELISA. Results BD960 significantly inhibited the proliferation of T cells stimulated by anti-CD3/anti-CD28 mAb or alloantigen in a dose-dependent manner.The IC50 value is (2.3 ±0.3)μmol/L or (2.5 ±0.3)μmol/L, respectively.Moreover, BD960 had no obvious cytotoxic effects on rest-ing T cells and peripheral blood mononuclear cells, even at a high concentration ( up to 100μmol/L) .The ratio of CD25 expression on T cell was 69.7%after stimulated by Anti-CD3/CD28 mAbs with 72 h, the concentration (0.625、2.5、10)μmol/L of BD960 also had no potent effects on the ratio, but 0.1μmol/L FK506 could inhibit CD25 expression as low as 9.4%.The G0/G1 phase of activated T cells was 58.5%after stimulated by BD960 with 96 h.BD960 could induce cell cycle arrest at the G0/G1 phase in activated T cells with the increase of concentration and RAPA in the concentration of 0.1 μmol/L was 91.5%.In addition, BD960 (0.625、2.5、10)μmol/L could inhibit the secretion of IFN-γ, IL-6 and IL-17 in activated T cells with the increase of concentration, without any effects on the secretion of IL-2, IL-4 and IL-10. Conclusion BD960 not only exerts the inhibition on the late stage of T cell activation of cell proliferation but also inhibits the secretion of inflammatory cytokines, such as IL-6, IL-17 and IFN-γ, while the mechanism of BD960 on T cell proliferation was not the same as FK506.As a result, BD960 has the potential to be the lead compound to develop a new immunosuppressant.

Obej ctive Abnormal proliferation of T cells plays an important role in the development of autoimmune diseases. The article aimed to study the inhibitory effect of small molecule compound BD691 on T cell proliferation and its mechanism. Methods Human peripheral blood T-lymphocytes were isolated and purified by the immunomagnetic microbeads,then T cells were ac-tivated with anti-CD3/CD28 mAbs or alloantigen.The inhibitory effect of BD691 on activated T cell proliferation, the cytotoxic effect BD891 on resting T cells and the expression of activated T cells marker CD25 were measured by flow cytometry.Furthermore, ELISA was used to detect the secretion of cytokines associated with T cell differentiation. Results BD691 significantly inhibited the prolif-eration of T cells being stimulated by anti-CD3/CD28 mAb or alloantigen in a dose-dependent manner, and IC50 values are (8.5 ± 1.5)μmol/L and (7.2 ±1.3)μmol/L, respectively.However, BD691 had no obvious cytotoxic effects on resting T cells and periph-eral blood mononuclear cells, even at a high concentration ( up to 100μmol/L) .In T cells which were not activated by anti-CD3/CD28 mAb, the percentage of CD25+T cells is only 1.6%of the total cells, while the number increased to 68% after activating treatment.Mean-while, in T cells which were activated by 0, 3.3, 10, 30μmol/L BD691, no obvious change of CD25 expression were observed, while immunosuppressant FK506 (0.1μmol/L) significantly decreased the expression of CD25 +T cells (14.9%).In unactivated T cells, 95.6%cells were at G0/G1 phase, while after activation, the percentage of cells at G0/G1 phase reduced to 57.7%.In addition, BD691 inhibited the secretion of IFN-γ, IL-6 and IL-17 in activated T cells, but had no effects on the secretion of IL-2, IL-4 and IL-10. Co nclusion BD691 exerts no effects on T cell activation, but it inhibits T cell proliferation by inducing T cell cycling arrest at G0/G1 phase.Moreover, BD691 inhibits the secretion of key cytokines (such as IFN-γ, IL-6, IL-17) closely related to the differ-entiation of Th1 and Th17 cells.The results suggest that BD 691 is a potential lead compound to develop a new immunosuppressant for the inhibition of abnormal proliferation and differentiation of T cells.