Objective To investigate the correlation between serum adiponectin level and severity of coronary artery lesion. Methods The serum concentrations of adiponectin in 112 patients whom had received coronary arteriongraphy (CAG) were measured. Among them,58 cases had acute coronary artery syndromes(ACS)(ACS group), 25 cases had stable angina cordis(stable angina cordis group) and 29 cases had non-coronary disease (control group ). The severity of coronary artery lesion was evaluated by the number of stenosis vessel and Gensini score. All the patients were divided into single vessel lesion group (24 cases),double-vessel lesion group (26 cases ), triple-vessel lesion group (33 cases) by extent of disease; and 0- 1 score group (29 cases),2-20 scores group (28 cases),21-40 scores group (30 cases), ＞40 scores group (25 cases) by Gensini score. Results The serum concentrations of adiponectin in ACS group were lower than those in control group and stable angina cordis group[(6.43 ± 4.22 ) mg/L vs. ( 12.68 ± 6.47 ), (9.94 ± 8.48 ) mg/L]( P ＜ 0.01 or ＜ 0.05 ). The serum concentrations of adiponectin in control group were higher than those in single vessel lesion group, double-vessel lesion group and triple-vessel lesion group[( 12.68 ± 6.47 ) mg/L vs. (8.80 ±6.23), (8.04 ±5.93), (6.43 ±5.12) mg/L](P ＜0.01). The serum concentrations of adiponectin in single vessel lesion group were higher than those in triple-vessel lesion group (P＜ 0.01 ). The serum concentrations of adiponectin in 0-1 score group[.( 12.68 ±6.47) mg/L]and 2-20 scores group [(8.74 ± 6.68) mg/L]were respectively higher than those in 21-40 scores group[(7.64 ± 5.32) mg/L]and ＞ 40 scores group[(6.32 ± 5.46 ) mg/L](P ＜ 0.01 ). The serum concentrations of adiponectin in 21-40 scores group were higher than those in ＞ 40 scores group(P＜ 0.05 ). The serum concentrations of adiponectin were negatively correlated with the log of Gensini score (r = -0.584,P ＜ 0.01 ). Conclusion The decrease in serum adiponectin might reflect the increase in severity of coronary artery lesion.

ObjectiveTo investigate the correlation between serum uric acid level and severity of coronary artery disease.MethodsThe concentrations of serum uric acid in 112 patients whom had received coronary arteriongraphy(CAG) was measured,among of them,acute coronary artery syndrome (ACS) with 58 cases( ACS group ),stable angina cordis with 25 cases( stable angina cordis group),non-coronary disease with 29 cases(control group).The severity of coronary artery lesion was evaluated by the number of stenosis vessel and Gensini score.They were divided into control group (29 cases),single vessel lesion group (24 cases),double vessel lesion group(26 cases),triple vessel lesion group(33 cases ) according to the number of stenosis vessel and 0-1 score group(29 cases),2-20 scores group(28 cases),21-40 scores group(30 cases),＞40 scores group (25 cases) according to the Gensini score.ResultsThe concentrations of serum uric acid in ACS group were higher than those in control group and stable angina cordis group[ (369.61 ± 91.97 ) μ mol/Lvs. (298.33 ±92.46),(330.43 ±87.42)μmol/L] (P ＜0.05).The concentrations of serum uric acid in control group were lower than those in single vessel lesion group,double vessel lesion group and triple vessel lesion group [(298.33 ±92.46)μmol/L vs. (331.77 ±86.33),(368.24 ±95.21),(396.82 ±94.45) μ mol/L] (P ＜ 0.05).The concentrations of serum uric acid in single vessel lesion group were significantly lower than those in double vessel lesion group and triple vessel lesion group (P ＜ 0.05 ).The concentrations of serum uric acid in 0-1 score group [ (298.33 ± 92.46) μ mol/L] and 2-20 scores group [ (320.77 ± 86.33 ) μ mol/L ] were respectively lower than those in 21-40 scores group [ (366.61 ± 91.97 ) μ mol/L ] and ＞ 40 scores group [ (402.82 ± 91.97 ) μ mol/L](P ＜ 0.05 ).The concentrations of serum uric acid in ＞ 40 scores group was higher than that in 21-40 scores group (P ＜ 0.05 ).Serum uric acid concentrations was positively correlated with the log of Gensini score (r =0.348,P ＜ 0.05 ).ConclusionThe increase in serum uric acid might reflect increase in severity of coronary artery stenosis.

OBJECTIVETo detect the role of surviving (SVV) in the protective effect of resveratrol against hypoxia/reperfusion injury (H/RI) of cardiac microvascular endothelial cells (CMECs).

METHODSCMECs isolated from the hearts of adult rats were exposed to hypoxia (94% N₂, 5% CO₂, 1% O₂) for 2 h followed by 4 h reoxygenation (95% O₂, 5% CO₂). The cell proliferation of CMECs was measured by MTT assay and Transwell method was used to detect migration ability of CMEC, PI-AnnexinV double staining and flow cytometry technique were employed to observe the apoptotic rate of CMECs. The SVV protein expression was detected with Western blot method.

RESULTSCompared to control group, the proliferation (0.19 ± 0.03 vs. 0.42 ± 0.07, P < 0.01) and migration ((28 ± 2)/5HPF vs. (50 ± 3)/5 HPF, P < 0.01) abilities were impaired and the apoptosis index ((19.7 ± 0.8)% vs. (5.4 ± 0.3)%, (P < 0.05) of CMEC was increased after H/RI. The proliferation (0.36 ± 0.07 vs. 0.19 ± 0.03, P < 0.05) and migration ((55 ± 3)/5HPF vs. (28 ± 2)/5HPF, P < 0.05) abilities of CMEC were significantly improved while the apoptosis index ((9.6 ± 0.7)% vs. (19.7 ± 0.8)%, P < 0.05) was significantly decreased in H/RI+resveratrol group compared to H/RI group.SVV protein expression was also upregulated in H/RI+resveratrol group compared to H/RI group (P < 0.05). To further ascertain the role of SVV in the protective effects of resveratrol, PI3K specific inhibitor LY294002 was added to H/RI+resveratrol group, the proliferation (0.25 ± 0.05 vs. 0.36 ± 0.07, P < 0.05) and migration ((34 ± 3)/5HPF vs. (55 ± 3)/5HPF, P < 0.05) abilities were significantly decreased, the apoptosis index ((16.2 ± 0.6)% vs. (9.6 ± 0.7)%, P < 0.05) was increased and the protein expression of SVV was downregulated (P < 0.05) in LY294002+H/RI+resveratrol group compared to H/RI+resveratrol group.

CONCLUSIONResveratrol could significantly reduce H/RI induced apoptosis and attenuate H/RI induced cardiac microvascular endothelial cells dysfunction through up-regulating PI3K/Akt/SVV pathways.

Animals ; Apoptosis ; Cell Proliferation ; Chromones ; Endothelial Cells ; Enzyme Inhibitors ; pharmacology ; Heart ; Hypoxia ; Morpholines ; Myocardium ; Myocytes, Cardiac ; Phosphatidylinositol 3-Kinases ; drug effects ; metabolism ; Proto-Oncogene Proteins c-akt ; drug effects ; metabolism ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; drug therapy ; Stilbenes ; pharmacology ; Up-Regulation

Objective:To investigate the relationship between the levels of serum cytokines and chemokines and the prognosis of patients with acute B-ALL after receiving chimeric antigen receptor (CAR)-T cell immunotherapy and acute graft-versus-host disease (aGVHD) in patients after bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:According to the case-control principle, Forty-two patients with B-ALL who received CD19-CAR-T cell immunotherapy bridged to allo-HSCT at Heibei Yanda Ludaopei Hospital from September 18, 2019 to May 9, 2022 were enrolled. Mann-Whitney U test was used to compare the changes of aGVHD-related cytokines and chemokine levels between CAR-T cell immunotherapy and bridging transplantation in different patients at the same time. Their plasma levels of cytokines and chemokines related to aGVHD were monitored at the day before CAR-T therapy and after CAR-T treatment at day 4, 7,14,21,28. The receiver operating characteristic curve was drawn to evaluate the predictive value of cytokines and chemokines in predicting the occurrence and the death of aGVHD patients. Kaplan-Meier method and Log-rank tests were used for Overall survival (OS) analysis. Results:Twenty-four of total 42 patients had aGVHD, of which 11 patients died and 31 patients survived. There was no significant difference in cytokines and chemokines between the aGVHD group and the non-aGVHD group on the day before CAR-T cell treatment. According to statistical analysis, the serum Elafin levels of aGVHD group was higher than that of non-aGVHD group at the 21st day [4 482 (2 811, 6 061) ng/L vs 2 466 (1 948, 3 375) ng/L, Z=3.145, P=0.001] and the 28st day [4 391 (2 808, 5594) ng/L vs 2 463 (1 658, 2 830) ng/L, Z=2.038, P=0.048] separately. At the 14th day, serum cytokines and chemokines levels between the two group were as follows,MIP-1 α [21.02 (12.36, 30.35) ng/L vs 5.56 (3.64, 10.79) ng/L], sCD25 [422.47 (257.99, 1 233.78) IU/ml vs 216.11 (133.75,457.39) IU/ml], Elafin [4 101 (2 393, 5 006) ng/L vs 2 155 (1 781, 3 033) ng/L], IL-6 [119.08 (23.97, 183.43) ng/L vs 8.39 (2.91, 17.42) ng/L] and IL-8 [13.56 (12.50, 24.52) ng/L vs 2.83 (1.73,6.87) ng/L] were at higher levels ( Z=2.653, P=0.007; Z=2.176, P=0. 030; Z=2.058, P=0.041; Z=3.329, P<0.001; Z=3.162, P=0.001). The KM survival curve showed that the cumulative survival rates of patients with higher serum levels of MIP-1α, sCD25, Elafin, IL-6 and IL-8 were lower than those with low levels at day 14, and the difference was statistically significant (χ 2=12.353, 4.890, 6.551, 10.563, 20.755, P<0.05). Conclusion:The outcomes of patients treated with CAR-T cell therapy bridged to allo-HSCT was correlated with serum MIP-1α, sCD25, Elafin, IL-6 and IL-8 levels after receiving CAR-T therapy. High concentrations of MIP-1α, sCD25, Elafin, IL-6 and IL-8 suggest poor prognosis and can be used as biomarkers to suggest appropriate clinical selection of therapy.

ObjectiveTo explore the effects and possible mechanisms of Jianpi Bushen Formula （健脾补肾方） on radiation-induced immune function damage of mice. MethodsFifty mice were randomly divided into four groups： normal group， model group， thymosin group， high- and low-dose groups of Jianpi Bushen Formula， with 10 mice in each group. Except for the normal group， the mice in the other groups were irradiated with a single whole-body dose of 6.0 Gy X-rays to establish a radiation-injured mouse model. After the successful modeling， the low- and high-dose groups of the Jianpi Bushen Formula were given respectively 13 g/（kg·d）、 26 g/（kg·d） of the formula by gavage， while the thymosin group was given 11.7 mg/（kg·d） of thymosin by gavage， and the normal group and model group were given 0.1 ml/（10g·d） of 0.9% sodium chloride solution by gavage. Each group was administered once a day for 7 consecutive days. After the last gavage， the mice were weighed， and their spleens were separated and weighed to calculate the spleen index. The levels of interferon gamma （IFN-γ） and interleukin 2 （IL-2） in the spleen tissue were detected by enzyme linked immunosorbent assay （ELISA）. The autophagosomes in the spleen were observed by transmission electron microscopy. The mRNA expression levels of phosphatidylinositol 3-kinase （PI3K）， protein kinase B （Akt）， and mammalian target of rapamycin （mTOR） in the spleen were detected by real-time fluorescent quantitative PCR. The protein expression of PI3K， Akt， and mTOR in the spleen， as well as the expression of autophagy-related proteins microtubule-associated light chain protein 3 （LC3）， Beclin1， and p62 were detected by Western blot. ResultsCompared with the normal group， the model group showed significant decreases in body weight， spleen index， and levels of IFN-γ and IL-2 in the spleen （P＜0.01）； the mRNA and protein expression levels of PI3K， Akt， and mTOR in the spleen were also significantly reduced （P＜0.01）； the expression of Beclin1 protein， the ratio of LC3-II/LC3-I significantly increased （P＜0.01）， while the level of p62 protein expression significantly decreased （P＜0.01）. And transmission electron microscopy showed a significant increase in the number of autophagosomes in the spleen and severe cell structure damage in the model group. Compared with the model group， all the above indicators in each medication group were significantly improved （P＜0.05 or P＜0.01）. In the high-dose Jianpi Bushen Formula group， partial intact cristae were visible in the fine mitochondria of the spleen， and there were more autophagosomes. In the low-dose Jianpi Bushen Formula group and thymosin group， the structure of the fine mitochondria in the spleen was relatively intact， and there were fewer autophagosomes. The improvement effect of the low-dose Jianpi Bushen Formula group was better than that of the high-dose group （P＜0.05 or P＜0.01）， and there was no significant difference between the low-dose group and the thymosin group in terms of each indicator （P＞0.05）. ConclusionJianpi Bushen Formula may alleviate the structural damage of the spleen， promote the recovery of immune function， and achieve a best effect at a low dose by enhancing the PI3K/Akt/mTOR signaling pathway in the spleen and inhibiting the over-activation of autophagy induced by radiation.