Objective:To assess the predictive value for the risk of cardiogenic stroke (CS) in patients with paroxysmal atrial fibrillation (PAF) using quantification of left atrial appendage early blood stasis (LAA-BS) signs derived from left atrium-pulmonary vein CT examination.Methods:A retrospective analysis of 187 patients with PAF, who were confirmed to have LAA-BS by left atrium-pulmonary vein CT examinations, was conducted at Second Affiliated Hospital of Nantong University from January 2019 to December 2021. The ratio of LAA-BS CT values to ascending aorta (AA) CT values (HU BS/HU AA) and the ratio of LAA-BS volume to LAA volume (V BS/V LAA) were measured at the peak time of AA enhancement, which were used as characteristic quantitative indicators of LAA-BS. Using the median values of HU BS/HU AA and V BS/V LAA as cut-off points for grouping, the differences between the high-ratio and low-ratio groups were compared in terms of general information, clinical characteristics, and imaging characteristics. All enrolled patients were followed up with the primary outcome event of CS occurrence. The differences in the proportion of CS occurrence between the high-ratio and low-ratio groups were compared. The risk stratification analysis of the occurrence of CS in PAF patients was performed using Kaplan-Meier curves. Additionally, the predictive value of HU BS/HU AA, V BS/V LAA and other imaging indices for the risk of CS occurrence was assessed using Cox proportional risk regression models. Results:The incidence of hypertension and the proportion of patients with atrial fibrillation-stroke risk score (CHA 2DS 2-VASc)≥3 in the high V BS/V LAA group were higher than that in the low V BS/V LAA group, and the difference was statistically significant ( P=0.041, P=0.011). The left atrial volume (LAV) in patients in the low HU BS/HU AA group was greater than in the high HU BS/HU AA group, and the difference was statistically significant ( P=0.040). Kaplan-Meier analysis showed a higher incidence of CS in the low HU BS/HU AA group than in the high HU BS/HU AA group ( P=0.012). Similarly, the high V BS/V LAA group had a higher incidence of CS compared with the low V BS/V LAA group ( P=0.019). Subgroup analysis revealed a significantly higher incidence of CS in the subgroup with low HU BS/HU AA and high V BS/V LAA compared to other subgroups (all P<0.05). The Cox proportional hazards regression model, adjusting for confounding factors, identified low HU BS/HU AA and high V BS/V LAA as independent risk factors for CS occurrence in PAF patients ( P=0.005 and P=0.029). Conclusion:The HU BS/HU AA and V BS/V LAA quantified using left atrium-pulmonary vein CT imaging are predictive factors for CS occurrence in patients with PAF. These ratios synergistically contribute to the risk assessment of CS.

Objective:To assess the predictive value for the risk of cardiogenic stroke (CS) in patients with paroxysmal atrial fibrillation (PAF) using quantification of left atrial appendage early blood stasis (LAA-BS) signs derived from left atrium-pulmonary vein CT examination.Methods:A retrospective analysis of 187 patients with PAF, who were confirmed to have LAA-BS by left atrium-pulmonary vein CT examinations, was conducted at Second Affiliated Hospital of Nantong University from January 2019 to December 2021. The ratio of LAA-BS CT values to ascending aorta (AA) CT values (HU BS/HU AA) and the ratio of LAA-BS volume to LAA volume (V BS/V LAA) were measured at the peak time of AA enhancement, which were used as characteristic quantitative indicators of LAA-BS. Using the median values of HU BS/HU AA and V BS/V LAA as cut-off points for grouping, the differences between the high-ratio and low-ratio groups were compared in terms of general information, clinical characteristics, and imaging characteristics. All enrolled patients were followed up with the primary outcome event of CS occurrence. The differences in the proportion of CS occurrence between the high-ratio and low-ratio groups were compared. The risk stratification analysis of the occurrence of CS in PAF patients was performed using Kaplan-Meier curves. Additionally, the predictive value of HU BS/HU AA, V BS/V LAA and other imaging indices for the risk of CS occurrence was assessed using Cox proportional risk regression models. Results:The incidence of hypertension and the proportion of patients with atrial fibrillation-stroke risk score (CHA 2DS 2-VASc)≥3 in the high V BS/V LAA group were higher than that in the low V BS/V LAA group, and the difference was statistically significant ( P=0.041, P=0.011). The left atrial volume (LAV) in patients in the low HU BS/HU AA group was greater than in the high HU BS/HU AA group, and the difference was statistically significant ( P=0.040). Kaplan-Meier analysis showed a higher incidence of CS in the low HU BS/HU AA group than in the high HU BS/HU AA group ( P=0.012). Similarly, the high V BS/V LAA group had a higher incidence of CS compared with the low V BS/V LAA group ( P=0.019). Subgroup analysis revealed a significantly higher incidence of CS in the subgroup with low HU BS/HU AA and high V BS/V LAA compared to other subgroups (all P<0.05). The Cox proportional hazards regression model, adjusting for confounding factors, identified low HU BS/HU AA and high V BS/V LAA as independent risk factors for CS occurrence in PAF patients ( P=0.005 and P=0.029). Conclusion:The HU BS/HU AA and V BS/V LAA quantified using left atrium-pulmonary vein CT imaging are predictive factors for CS occurrence in patients with PAF. These ratios synergistically contribute to the risk assessment of CS.

The myocardial infarction is an important clinical feature of ischemic heart disease,and its various stages of histopathological changes are closely related to the prognosis of patients.In recent years,with the continuous development and improvement of MRI software and hardware techniques,the cardiac MR (CMR) can assess the pathological changes of the myocardial infarction by its multi-parameter and multi-sequence imaging techniques qualitatively and quantitatively.And the CMR can provide the clinical reference information for the patients in short-term diagnosis and long-term prognostic risk assessment accurately and comprehensively.The progresses of CMR in assessing the pathology of myocardial infarction were reviewed in this article.

[ ABSTRACT] AIM:To investigate the protective effect of 1, 3-dicyclopentyl-1, 2, 3, 6-tetrahydropyrimidine-4, 5-dicarboxylic acid diethyl ester (ZL-5015) on lethal endotoxin-challenged mice and to explore the underlying mechanism. METHODS:Mouse model of lethal endotoxin challenge and endotoxemia were established by intraperitoneal administration of lipopolysaccharide (LPS) at a dose of 70 mg/kg to the C57BL/6J mice.Mouse peritoneal macrophages stimulated with LPS (10 mg/L) were used as an in vitro inflammatory model.The levels of interleukin-1β( IL-1β) , interleukin-10 ( IL-10) and tumor necrosis factor-α(TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA).Real-time PCR was used to evaluate the mRNA expression of the cytokines.RESULTS:Prophylactic treatment of the mice with ZL-5015 (100 and 200 mg/kg, ig) slightly increased the survival rate, extended the survival time, decreased the serum levels of IL-1βand TNF-α, and increased the serum level of IL-10 in the early stage of endotoxemia as compared with model group.The results of in vitro study demonstrated that treatment of the endotoxin-stimulated mouse peritoneal macrophages with ZL-5015 (10, 20 and 40μmol/L) inhibited the expression of IL-1βand TNF-αat both mRNA and protein levels but promoted the expression of IL-10 at both mRNA and protein levels.CONCLUSION: The tetrahydropyrimidine derivative ZL-5015 shows a moderate anti-endotoxin effect by increasing the survival rate and extending the survival time of the mice challenged by endotoxin, which may result from inhibition of the expression of pro-inflammatory cytokines such as IL-1βand TNF-α, and promotion of the expression of anti-inflammatory cytokine IL-10.

OBJECTIVETo optimize the experimental model of nitric oxide (NO) production in mouse peritoneal macrophages in response to lipopolysaccharides (LPS) stimulation.

METHODSMouse resident peritoneal macrophages were collected by lavaging the peritoneal cavity of mice with Hank's solution and stimulated with Pseudomonas aeruginosa LPS for NO production. NO concentration in the culture supernatants was measured with Griess Reagent. The influences of cell density, LPS concentration, LPS stimulation duration and culture medium volume on NO production were investigated. Finally, the feasibility of the model was confirmed with specific anti-inflammatory drugs.

RESULTSThe density of macrophages produced the most significant effect on NO production (P<0.001), and optimal results were obtained at the macrophage density of 6×10(6) cells/ml with a volume of 100 µl in each well in 96-well plate. At a LPS concentration below 1 µg/ml, NO production increased proportionally with the increment of LPS concentration (P<0.001), but the increment of NO production declined obviously at LPS concentrations beyond 1 µg/ml, and the peak NO production occurred at a LPS concentration of 10 µg/ml. NO production also increased significantly with the prolongation of LPS stimulation (P<0.05), and the increments were greater within 24-48 h than those in 48-72 h. NO content in the culture supernatant was associated with the medium volume, and the highest level occurred in a system volume of 100 µl. Aspirin (1 mmol/L), dexamethasone (10 µmol/L), and cyclosporin A (10 µmol/L) all significantly inhibited LPS-stimulated production of NO in mouse resident peritoneal macrophages (P<0.001).

CONCLUSIONSMacrophage density, LPS concentration, and the duration of LPS stimulation are the main factors affecting LPS-stimulated NO production in mouse resident peritoneal macrophages. The optimal results can be obtained with a macrophage density of 5×10(6) cells/ml (100 µl per well), LPS concentration of 10 µg/ml, LPS stimulation duration of 24 h or 48 h, and a culture medium volume of 100 to 200 µl.

Animals ; Cells, Cultured ; Female ; Lipopolysaccharides ; pharmacology ; Macrophages, Peritoneal ; drug effects ; secretion ; Male ; Mice ; Mice, Inbred Strains ; Nitric Oxide ; biosynthesis

OBJECTIVETo study the anti-inflammatory and analgesic activities of diethyl 1,3-dicyclohexyl-1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylate (ZL-5010) in vivo and in vitro.

METHODSThe analgesic effect of ZL-5010 was evaluated by acetic acid-induced writhing response in mice, and the anti-inflammatory effects was assessed in mice with xylene-induced ear edema and in rats with carrageenan-induced paw edema. Mouse peritoneal exudate cells activated by bacterial lipopolysaccharides (LPS) were used to evaluate the anti-inflammatory effect of ZL-5010 in vitro. The levels of interleukin-1β (IL -1β) and tumor necrosis factor-α (TNF-α) in the cell culture supernatant were measured using enzyme-linked immunosorbent assay (ELISA).

RESULTSAt the doses of 0.25 and 0.5 mmol/kg, ZL-5010 administered by gavage once daily for 3 days significantly reduced acetic acid-induced writhing frequency and suppressed xylene-induced ear edema in mice, and alleviated paw edema induced by carrageenan in rats (P<0.05). The agent also inhibited the production of the pro-inflammatory cytokines IL-1β and TNF-α by LPS-induced mouse peritoneal exudate cells in vitro, with the statistically significant minimum effective concentrations of 10 and 20 µmol/L, respectively (P<0.05).

CONCLUSIONZL-5010 administered by gavage has anti-inflammatory and analgesic effects in mice and rats, and in mouse peritoneal exudate cell cultures, the agent also inhibits the production of the pro-inflammatory cytokines IL-1β and TNF-α.

Amino Acids, Diamino ; pharmacology ; therapeutic use ; Analgesics ; pharmacology ; therapeutic use ; Animals ; Anti-Inflammatory Agents ; pharmacology ; therapeutic use ; Cyclohexanes ; pharmacology ; therapeutic use ; Female ; Interleukin-1beta ; metabolism ; Male ; Mice ; Mice, Inbred Strains ; Pyrimidines ; pharmacology ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha ; metabolism

Objective To study the effects of Leptin on the expression of CD86 and HLA-DR in human monocytes.Methods The expression of CD86 and HLA-DR in THP-1 Cells and human primary monocytes were detected by flow cytometry.Results Expression of CD86 and HLA-DR in THP-1 cells was significantly increased after treatment with high-dose Leptin ( CD86Untreated group:8.78 ± 1.66,CD86leptin10:50.76 ± 4.29,CD86leptin100:95.20 ± 4.90; HLAUntreated group:20.75 ± 2.12,HLAleptin10:102.14 ± 5.75,HLAleptin100:104.32 ± 4.75;).The similar results were observed in human primary monocytes ( CD86Untreated group:17.91 ± 1.78,CD86leptin100:48.80 ± 3.60; HLAUntreated group:34.10 ± 2.76,HLAleptin100:88.86 ± 3.53).Conclusions By up-regulating CD86 and HLA-DR expression,Leptin might enhance the ability to present antigen in THP - 1 cells and human monocytes.

Objective To observe the counteraction of Ganoderma lucidum polysaccharide(GLP) on the inhibition of mice splenocyte proliferation and IL-1? and IL-2 mRNA expression induced by prostaglandin E2(PGE2).Methods Mixed lymphocyte culture reaction(MLR) method was used for the experiment.The lymphocyte proliferation was determined by MTT method,and the levels of IL-1? and IL-2 mRNA expression were evaluated by semi-quantitative reverse transcriptase polymerase chain reaction(RT-PCR).Results After co-culture with PGE2 for 48 hours,the splenocyte proliferation was inhibited to some extent,and the difference was significant when the concentration of PGE2 was over 10?mol/L(P

AIM　To extend the approach of the act ion of ganoderma polysacchride on intracellular signal events in T cells. METHODS　Laser scanning confocal microscope imaging of the calcium and p H fluorescent indicator dye Fluo-3/AM and SNARF-1/AM were used to determine th e kinetic changes of ［Ca2+］i and ［pH］i in murine T cells induced b y a ganoderma polysacchride,designated GLB7. RESULTS　It was fou nd that GLB7(20 mg*L-1) could increase ［Ca2+］i and ［pH］i at 1 min were 334.7%±16.4%(n=3)、171.6%±10.4%(n=3) respectively. T he increase in ［Ca2+］i induced by GLB7 was due to the influx of extr acellular Ca2+ and intracellular Ca2+ release through both IP3-se nsitive and IP3-insensitive Ca2+ stores, and increase in ［pH］i indu ced by GLB7 was relative to Na+/H+ exchange systems and ［Ca2+］i. GLB 7 did not influence ［Ca2+］i and ［pH］i in murine T cells induced by Con A(3 mg*L-1). CONCLUSION　Stimulation of the increase in ［Ca2+］i and ［pH］i may be an important channel for gano derma polysacchrides to achieve their pharmacological actions.

AIM：To investigated the effects of Ganoderma polysaccthride(GLB7)on protein kinase A(PKA) and protein kinase C(PKC) activitives in murine T cells.METHODS：A new ion-pair reversed-phase high liquid chromatography method was used to determinate the activities of PKA and PKC in T cells.RESULTS：GLB7 could markedly increase the activities of PKA and PKC in murine T cells in a dose-dependent manner.The peak time was at 5 min and 20 min and the activities of PKA and PKC returned to basic level at 20 min and 1.5h respectively.GLB7 could induce translocation of PKC and antagonize the inhibition effect of staurosporine(10μ mol· L-1) on PKC in T cells.CONCLUSION：The immunopotentiating and antitumour effects of Ganoderma polysacchride may be associated with its activation on PKA and PKC in murine T cells.