Serum Lipid Profiles and All-Cause Mortality: A Retrospective Single Center Study on Chinese Inpatient Centenarians.

Objectives: To analyze the serum lipid profiles and investigate the relationship between the lipoprotein cholesterol levels and all-cause mortality in Chinese inpatient centenarians. Design: Retrospective study. Methods: Centenarians aged 100 years and older were admitted from January 2010 to January 2021 in our hospital. All centenarians completed a follow up visit till April 2021 of all-cause mortality and serum lipid profiles, including total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) levels. Cox proportional hazard models were used to assess the association between lipid profiles and all-cause mortality. Results: (1) These 121 centenarians on average were 100.85 ± 1.37 years old (100~107 years), including 114 males and 7 females. (2) The rate of treatment with lipid-lowering drugs was 69.4%, and the lipid-lowering drugs were mainly statins (63.6%). (3) The results of serum lipid profiles were as follows: TC 3.90 ± 0.69 mmol/L, TG 1.36 ± 0.55 mmol/L, HDL-C 1.14 ± 0.24 mmol/L, and LDL-C 2.05 ± 0.46 mmol/L. (4) The median follow-up time was 589 days (95% CI: 475, 703), and the all-cause mortality rate was 66.1%. (5) Multivariable analysis showed that higher TC level (HR = 1.968, 95% CI = 1.191-3.253, P = 0.008), lower LDL-C level (HR = 0.379, 95% CI = 0.212-0.677, P = 0.001) was independent factors contributed to all-cause mortality. Sensitivity analysis showed that the above results were stable. The therapy and complication morbidity did not present significant publication bias. Conclusions: The serum lipid profiles of Chinese inpatient centenarians were lower than those of the previous studies. Low LDL-C level was associated with an increased risk of all-cause mortality, which may indicate that more intensive lowering of LDL-C had a potential adverse effect on all-cause mortality for centenarians.

[Effect of Down-Regulation of LncRNA-HOTAIRM1 to Proliferation, Apoptosis and KIT/AKT Pathway of Jurkat Cells].

OBJECTIVE: To observe the effects of down-regulation of long non-coding RNA HOX antisense intergenic RNA myeloid 1 (LncRNA-HOTAIRM1) to the proliferation and apoptosis of Jurkat in human leukemia T lymphocytes, and explore its mechanism. METHODS: Jurkat cells were cultured in vitro and randomly divided into control group, HOTAIRM1 siRNA-NC group and HOTAIRM1 siRNA group; the expressions of LncRNA-HOTAIRM1 mRNA, KIT receptor tyrosine kinase (KIT) mRNA and serine threonine kinase (AKT) mRNA in Jurkat cells were detected by real-time fluorescence quantification (RT-qPCR); the proliferation of Jurkat cells in each groups was detected by CCK-8 method; the apoptosis of Jurkat cells in each groups was detected by Annexin V-FITC/PI double staining; the expressions of KIT, AKT, p-KIT, p-AKT, B-lymphoma-2 gene (BCL-2) and Caspase-3 were detected by Western blot. RESULTS: Compared with the cells in the control group and HOTAIRM1 siRNA-NC group, the expression level of LncRNA-HOTAIRM1 mRNA, cell survival rate, expression levels of KIT mRNA, AKT mRNA, p-KIT, p-AKT and BCL-2 proteins in Jurkat cells in HOTAIRM1 siRNA group were significantly lower (P<0.05), while the expression level of Cleared Caspase-3 protein and Jurkat cell apoptosis rate were significantly higher (P<0.05). CONCLUSION: LncRNA-HOTAIRM1 may inhibit Jurkat cell proliferation and induce apoptosis through KIT/AKT signaling pathway.

Genetic polymorphisms of high platelet reactivity in Chinese patients with coronary heart disease under clopidogrel therapy.

BACKGROUND: The variability in the clinical response to clopidogrel treatment has been attributed to genetic factors, but the specific genes and other risk factors remain unclear. OBJECTIVE: To investigate the incidence of high on-treatment platelet reactivity in coronary heart disease patients following clopidogrel therapy by analyzing the correlation between genetic polymorphisms and high on-treatment platelet reactivity. SETTING: This study was conducted in the Chinese People's Liberation Army (PLA) general hospital. METHOD: 578 patients with coronary heart disease undergoing percutaneous transluminal coronary intervention treatment were enrolled. They received dual antiplatelet therapy with aspirin (300 mg) plus clopidogrel (300 mg) over 24 h, or aspirin (100 mg/day) and clopidogrel (75 mg/day) over 3 days. Patients were divided into two groups according to the adenosine diphosphate inhibition rate. The follow-up lasted at least 12 months and adverse endpoint events were recorded. MAIN OUTCOME MEASURE: The single nucleotide polymorphisms were detected by MassArray genotyping system. RESULTS: The incidence of HTPR was 15.74% in total, being higher in females than in males (24.29% vs. 13.01%, P < 0.01). Diabetes mellitus, homocysteine and high sensitivity C-reactive protein (hs-CRP) levels were significantly higher in the HTPR group than those in the non-HTPR group (P < 0.05). Polymorphisms of rs1057910 (OR 2.90, P = 0.003), rs2246709 (OR 0.69, P = 0.039), and rs776746 (OR 0.66, P = 0.034) were associated with the incidence of high on-treatment platelet reactivity. Female patients were prone to polymorphisms of rs1057910 (OR 3.24, P = 0.004) and rs776746 (OR 0.57, P = 0.025). Compared to non-high on-treatment platelet reactivity group, no differences in high reactivity group were observed with coexisting single nucleotide polymorphisms (14.6% vs. 14.8%, P > 0.05). The adverse endpoint events were significantly higher in the high on-treatment platelet reactivity group than in the non-treatment reactivity group. The survival analysis showed that high on-treatment platelet reactivity was significantly associated with the risk of the endpoint events (P = 0.0219). CONCLUSION: Gender (female), diabetes mellitus, high levels of homocysteine and hs-CRP were risk factors for high on-treatment platelet reactivity, and high reactivity was a strong predictor for adverse endpoint events in the coronary heart disease patients. The polymorphism of rs1057910 was a risk factor of high on-treatment platelet reactivity while rs2246709 and rs776746 polymorphisms were protective factors, and coexisting single nucleotide polymorphisms didn't increase the incidence of high on-treatment platelet reactivity.

[Evaluation of PFA P2Y assay in monitoring platelet function in elderly patients with cardiovascular disease receiving clopidogrel treatment].

OBJECTIVE: To evaluate the value of a new platelet function test PFA P2Y (PFA-200) in monitoring clopidogrel treatment for cardiovascular disease in elderly patients. METHODS: Fifty-six elderly patients receiving clopidogrel therapy in the Department of Cardiology of General Hospital of PLA from March to August in 2016 and 85 healthy volunteers were recruited for analysis. All the subjects underwent PFA P2Y, LTA (light transmittance aggregometry) and TEG (Thromboelastograph) tests, and Spearman correlation coefficients were used to test the associations between test results. The agreement among the 3 platelet function test methods was assessed using Cohen's kappa coefficient. RESULTS: Correlation coefficient (r) was -0.701 (P<0.001) between PFA P2Y and LTA, and 0.475 (P<0.001) between PFA P2Y and TEG. The agreement was 75% between PFA P2Y and LTA and 67.9% between PFA P2Y and TEG. The κ value was 0.434 (P=0.001) between PFA P2Y and LTA and 0.242 (P=0.046) between PFA P2Y and TEG. With ADP-induced maximum platelet aggregation rate of LTA >50% as the laboratory clopidogrel resistance, the cut-off value of PFA P2Y was 119 s (AUC=0.733) with a sensitivity of 75.6% and a specificity of 73.3%. CONCLUSION: PFA P2Y has a moderate correlation and agreement with LTA, but has a poor correlation and agreement with TEG. PFA P2Y can be useful for assessing the effects of clopidogrel therapy and the association of the cut-off value (119 s) with the long-term clinical ischemic events needs be confirmed in further study.

[Effects of extracellular calcium concentration on platelets aggregation, coagulation indices and thromboelastography].

OBJECTIVE: To detect the effect of extracellular Ca2+ concentrations on test results of coagulation-related parameters. METHODS: Blood samples of outpatient medical volunteers were collected and then different doses of calcium chloride added. The rate of platelet aggregation (n = 42), prothrombin time (PT), thrombin time (TT) and activated partial thromboplastin time (APTT) (n = 21) and parameters of thromboelastography (n = 30) were detected according to the standard protocols by plasma turbidimetry, coagulation and recalcification respectively. RESULTS: When the plasma Ca2+ concentration was in the range of 0.1 - 33.7 mmol/L, the rate of platelet aggregation gradually increased with a increasing concentration of Ca2+. And the rates induced by adenosine diphosphate (ADP) and arachidonic acid (AA) were (51.8 +/- 9.6)% - (94.7 +/- 4.8)% and (64.4 +/- 12.2)% - (93.2 +/- 5.5)% respectively. When the Ca2+ concentration was 39.0 mmol/L, the rate decreased markedly [ADP (9.1 +/- 5.3)%, AA (11.1 +/- 4.5)%, both P < 0.01]. When the Ca2+ concentration was in the range of 0.1 - 33.7 mmol/L, the values of PT gradually increased with a increasing concentration of Ca2+. The values of TT changed in "V"-type and became minimum when the calcium concentration was 4.4 mmol/L. The values of APTT decreased with higher calcium concentrations and could not be determined when the concentration increased above 0.5 mmol/L. When the Ca2+ concentration was in the range of 0.4 - 27.3 mmol/L, the values of reaction time and coagulation time of thromboelastography changed in "V"-type and became nearly minimal at the Ca2+ concentration of about 2.1 mmol/L. The values of alpha angle and maximum amplitude changed in "V"-type and became maximal at the Ca2+ concentration of 2.1 mmol/L. CONCLUSIONS: The effect of Ca2+ concentration on the testing results of coagulation-related parameters is significant. A high calcium ( > or = 39 mmol/L) can inhibit the platelet aggregation, coagulation factor activity and blood coagulation. The Ca2+ concentration of 2.1 mmol/L seems to be the optimal concentration for thromboelastography by recalcification method.

[Effect of Kidney-Tonifying and Blood-Promoting Recipe on the expression of CD11b/CD18 and Bcl-2/Bax in aged patients with kidney deficiency and blood stasis syndrome].

OBJECTIVE: To study the effect of Kidney-Tonifying plus Blood-Promoting Recipe on the expression of CD11b/CD18 and Bcl-2/Bax in elderly patients with kidney deficiency and blood stasis syndrome. METHODS: Sixty elderly patients with kidney deficiency and blood stasis syndrome were randomized into two groups. Patients in the treatment group received Kidney-Tonifying plus Blood-Promoting Recipe, and those in the control group receive no treatment. The expression of CD11b/CD18, Bcl-2/Bax, D-Dimeride, CD62p, PAC-I and the rate of platelet aggregation in peripheral blood leukocytes before and after the treatment were examined using flow cytometry in both groups. RESULTS: The Recipe significantly decreased the levels of CD11b/CD18, D-Dimeride, CD62p, PAC-I and the rate of platelet aggregation (P<0.01), and increased the levels of Bcl-2/Bax (P<0.01). CONCLUSION: Kidney-Tonifying plus Blood-Promoting Recipe regulates CD11b/CD18 and Bcl-2/Bax expression in blood leukocytes and improves microcirculatory status, which can be one of the mechanisms underlying its therapeutic effect in elderly patients.

[The impact of rhG-CSF mobilization on migration and adhesive function of CD4+ T cells].

OBJECTIVE: To explore the impact of mobilization with recombinant human granulocyte colony stimulated factor (rhG-CSF) on the migration and adhesive function and their related signal mechanism mediated by the CXCR4 and lymphocyte function antigen-1 (LFA-1) molecules on the surfaces of CD4(+) T cells. METHODS: Before and at day 5 on rhG-CSF mobilization, the expression rates of CXCR4 and LFA-1 (CD11a) on CD4(+) T cells in the peripheral blood were detected by tricolor fluorescence labeling, and the migration and adhesive activities of CD4(+) T cells to stroma cell-derived factor 1 alpha (SDF-1 alpha) and intercellular adhesion molecule-1 (ICAM-1) were also tested. RESULTS: The expression of CXCR4 on CD4(+) T lymphocytes was (84.58 +/- 20.31)% before mobilization and (81.23 +/- 22.46)% at day 5 on mobilization. The expression of LFA-1 on CD4(+) T lymphocytes before and at day 5 on mobilization was 100%. There was no significant difference in the expression CXCR-4 and LFA-1 on CD4(+) T lymphocytes whether mobilization (P > 0.05). SDF-1 alpha induced 4 hours' CD4(+) T cells migration didn't change markedly before and after mobilization \[(28.5 +/- 10.3)% vs (31.2 +/- 8.9)%\] (P > 0.05). The adhesive activity of CD4(+) T cells to ICAM-1 was decreased from (85.59 +/- 14.21)% to (61.45 +/- 15.07)% after mobilization (P < 0.05). CONCLUSIONS: The expression of CXCR4 and LFA-1 on CD4(+) T lymphocytes didn't change markedly during rhG-CSF mobilization, but the adhesive activity of CD4(+) T cells to ICAM-1 was frustrated after that.

[Effects of mobilization with medium dose of rhG-CSF on the immunocyte component of peripheral blood in donors].

To investigate the changes of donor's peripheral blood immunocytes after mobilization with medium-dose recombinant human granulocyte-colony stimulating factor (rhG-CSF), the amounts of immunocytes in peripheral blood cells and the immunocyte components of donor peripheral blood mononuclear cells (PBMNC) in 12 healthy donors were detected by flow cytometry before and after mobilization with rhG-CSF 10 microg/(kg.day). The results showed that the median amounts of peripheral blood leukocytes before mobilization was 6.25 (4.7-7.8) x 10(9)/L, for lymphocytes it was 2.07 (1.63-3.10) x 10(9)/L, and for monocytes it was 0.163 (0.078-0.414) x 10(9)/L. In the fifth day after mobilization, the median amounts of peripheral blood leukocytes was 37.47 (24-72.57) x 10(9)/L, and for lymphocytes it was 3.22 (1.46-5.31) x 10(9)/L, and for monocytes, it was 1.2 (0.706-3.627) x 10(9)/L. The average amount of leukocytes after mobilization was 6.26 +/- 2.14 multiple of that before mobilization (P < 0.01), and the median amounts of lymphocytes after mobilization was 1.45 +/- 0.76 multiple of that before mobilization (P < 0.05), and the amount of monocytes after mobilization was 7.48 +/- 4.41 multiple of that before mobilization (P < 0.01). The median percentage of CD3(+) T lymphocytes before mobilization was 46.96% [(32.36-57.45)%], but 40.94% [(25.31-48.9)%] after mobilization. The ratio of CD4(+)/CD8(+) before mobilization was 1.27 +/- 0.46, while 1.36 +/- 0.51 after mobilization. The median percentage of CD4(+)CD8(+) T lymphocytes was 0.41% [(0.16-1.51)%], and 0.49% [(0.09-2.0)%] after mobilization. The median percentage of CD16(+)CD56(+) NK cells was 13.98% [(4.08-25.08)%] versus 16.65% [(12.06-33.05)%] after mobilization. The median percentage of CD3(+)CD16(+)CD56(+) NK-T cells was 2.75% [(0.37-6.38)%], but 3.13% [(0.46-5.95)%] after mobilization. The median percentage of CD20(+) B cells was 9.28% [(5.97-16.33)%], while 9.94% [(7.36-20.41)%] after mobilization. The median percentage of CD14(+) monocytes was 12.48% [(3.54-19.35)%] versus 29.52% [(16.51-36.76)%] after mobilization. The percentage of CD3(+) T lymphocytes, CD4(+)CD8(+) T lymphocytes, NK cells, NK-T cells and B lymphocytes in PBMNC did not change markedly before and after mobilization with middle-dose rhG-CSF. The ratio of CD4(+)/CD8(+) did not change significantly (P > 0.10). The percentages of CD14(+) monocytes in PBMNC after mobilization increased up to 2.87 +/- 1.51 higher than that before mobilization (P < 0.05). It is concluded that the changes of the CD14(+) monocytes after mobilization with rhG-CSF may be involved in graft rejection and graft versus host disease after allo-PBSCT.