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Objective:To investigate the correlation of monocyte/lymphocyte ratio (MLR) with the prognosis and adverse event in critically ill patients.Methods:Basic information of patients were extracted from Medical Information Mart for Intensive Care-Ⅲ (MIMIC-Ⅲ), including demographics, blood routine, biochemical indexes, systemic inflammatory response syndrome score (SIRS), sequential organ failure assessment (SOFA) score, and outcome, etc. MLR on the first day of intensive care unit (ICU) admission was calculated. The receiver operating characteristic curve (ROC curve) was applied to evaluate the prognostic value of MLR on the 30-day mortality and its cut-off value. According to the cut-off value, the patients were divided into two groups, and the differences between the groups were compared. Logistic regression model was used to analyze the relationship of MLR with 30-day mortality, continuous renal replacement therapy (CRRT), mechanical ventilation, the length of ICU stay, and total hospitalization time.Results:① A total of 43 174 critically ill patients were included. ROC curve showed that area under ROC curve (AUC) of MLR in predicting 30-day mortality was 0.655 [95% confidence interval (95% CI) was 0.632-0.687]. The cut-off value of MLR calculated according to the maximum Yoden index was 0.5. There were 16 948 patients with MLR ≥ 0.5 (high MLR group) and 26 226 patients with MLR < 0.5 (low MLR group). ② Compared with the low MLR group, the high MLR group had higher age, proportion of male, body mass index (BMI) [age (years old): 66.0 (51.7, 78.4) vs. 57.6 (27.1, 74.6), proportion of male: 57.2% vs. 52.5%, BMI (kg/m 2): 26.5 (22.5, 31.1) vs. 24.7 (14.3, 29.7)]. The high MLR group also had higher incidence of complications (hypertension: 49.2% vs. 44.6%, chronic heart failure: 32.6% vs. 21.7%, diabetes mellitus: 27.0% vs. 23.4%, chronic obstructive pulmonary disease: 21.5% vs. 16.1%, renal insufficiency: 19.3% vs. 13.1%), and higher white blood cell count (WBC), blood glucose, lactate (Lac), serum creatinine (SCr), SIRS score and SOFA score [WBC (×10 9/L): 13.8 (9.6, 19.2) vs. 11.5 (8.4, 15.6), blood glucose (mmol/L): 8.66 (6.88, 11.49) vs. 8.27 (6.55, 10.88), Lac (mmol/L): 2.2 (1.5, 3.7) vs. 2.1 (1.4, 3.3), SCr (μmol/L): 106.1 (70.7, 176.8) vs. 88.4 (70.7, 132.6), SIRS score: 3 (2, 4) vs. 2 (2, 3), SOFA score: 4 (2, 7) vs. 3 (1, 5)]. The 30-day mortality, and the proportion of patients with length of ICU stay > 5 days, total hospitalization time > 14 days, CRRT and mechanical ventilation > 5 days were significantly higher in high MLR group (30-day mortality: 20.0% vs. 8.3%, length of ICU stay > 5 days: 33.2% vs. 20.4%, total hospitalization time > 14 days: 33.7% vs. 16.2%, CRRT: 3.6% vs. 0.7%, mechanical ventilation > 5 days: 18.4% vs. 5.7%), with statistically significant differences (all P < 0.05). ③ After adjusted with the related factors, multivariate Logistic regression analysis showed that elevated MLR was an independent risk factor for increased 30-day mortality [odd ratio ( OR) = 1.54, 95% CI was 1.37-1.72, P < 0.001]. Moreover, the increased MLR was independently associated with the increased risk of usage of CRRT ( OR = 2.77, 95% CI was 2.18-3.51), mechanical ventilation > 5 days ( OR = 2.45, 95% CI was 2.21-2.72), the length of ICU stay > 5 days ( OR = 2.29, 95% CI was 2.10-2.49), and total hospitalization time > 14 days ( OR = 2.28, 95% CI was 2.08-2.49), all P < 0.001. Conclusions:Retrospective analysis of large sample shows that MLR elevation is an independent risk factor for 30-day mortality, usage of CRRT, prolonged mechanical ventilation time, prolonged hospitalization, prolonged length of ICU stay. MLR can be used for risk stratification of severe patients.
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Objective To study the expressions of regulatory T cell (Treg) and T helper cell 17 (Thl7) in post liver transplantation (LT) acute rejection in pediatric recipients diagnosed with biliary atresia.Methods 12 pediatric recipients with post-LT acute rejection in Tianjin First Center Hospital from July 2016 to April 2017 were included in the rejection group,and 22 patients with normal graft functions for more than 1 year post-LT were included in the stable group.The pre-LT primary disease in all the recipients was biliary atresia with cholestatic cirrhosis.Ten healthy children were included in the control group.Peripheral blood samples were taken before and at 1 week after anti-rejection treatment in the rejection group.Blood samples were taken during follow-up in the stable group and in the normal control.The proportions of Treg cell and Th17 cell were detected by flow cytometry.Results The proportions of Treg cells in the rejection group and the stable group were both significantly lower than the control group (P＜0.05).There was no significant difference between the rejection group and the stable group (P＞0.05).The proportion of Th17 cells in the rejection group was significantly higher than the stable group (P＜0.05) and the control group (P＜ 0.05),respectively;and the proportion in the stable group was significantly higher than the control group (P＜0.05).Meanwhile,there was also significant increase in the proportion of CD3+CD8+CD28+T in the rejection group (P＜0.05).After anti-rejection therapy,the proportions of Treg cell and Th17 cell became significantly lower than before therapy (P＜0.05).Conclusions The balance in Treg/Th17 cells occurred in the acute phase of rejection post-LT in pediatric recipients with biliary atresia,which persisted into the early period after anti-rejection therapy.
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Objective To explore the effects of bone marrow mesenchymal stem cells (BMSCs) in different concentrations on the balance of regulatory T cell / T-helper cell 17 (Treg / Th17). Methods BMSCs were isolated from SPF grade male Wistar rats with age of 3 weeks old and weight of 50 g. BMSCs were cultured and identified when they were expanded to the 4th generation. CD4+ T lymphocytes were isolated from SPF grade male Wistar rat with age of 6 weeks old and weight of 200 g and assayed for cell purity by flow cytometry. BMSCs were divided into 0.5-fold concentration group, basal concentration group, 2-fold concentration group and 4-fold concentration group by their concentrations of 1×105/well, 2×105/well, 4×105/well and 8×105/well, which were cultured with CD4+ T lymphocytes for 72 hours, respectively. Then the proportion of Treg cells and Th17 cells in each group was detected by flow cytometry, and cytokines were detected by cytometric bead array. Results The purities of BMSCs and CD4+ T lymphocytes were both higher than 95%. In the co-culture of BMSCs and CD4+ T lymphocytes, the proportions of Treg cells were statistically different among different concentration groups of BMSCs (F = 10.071, P = 0.001), in which BMSCs in 2-fold concentration group had the strongest ability to promote the Treg cells proliferation. The proportion of Treg cells in 2-fold concentration group was significantly higher than that in 0.5-fold concentration group, basal concentration group and 4-fold concentration group [(9.24±2.68)% vs. (3.87±0.38)%, (5.16±1.69)%, (3.86±0.36)%, all P < 0.01]. The level of interleukin-10 (IL-10) was lowest in 0.5-fold concentration group, and it was significantly lower than that in basal concentration group, 2-fold concentration group and 4-fold concentration group (ng/L: 39.80±14.48 vs. 148.43±64.49, 156.40±59.27, 126.92±42.95, all P < 0.05). Transforming growth factor-β (TGF-β) was the highest in basal concentration group, and it was significantly higher than that in 0.5-fold concentration group, 2-fold concentration group and 4-fold concentration group [ng/L: 3.17 (1.88, 5.74) vs. 0.71 (0.32, 1.38), 1.22 (0.47, 2.97), 0.52 (0.37, 1.23), all P < 0.05]. The proportions of Th17 cells were statistically different among the different concentration groups (F = 21.069, P = 0.000), with the highest proportion in basal concentration group which was significantly higher than that in 0.5-fold concentration group or 4-fold concentration group [(0.89±0.08)% vs. (0.64±0.15)%, (0.37±0.10)%, both P < 0.01], but no significant difference was found as compared with 2-fold concentration group [(0.83±0.06)%, P > 0.05]. However, the expressions of IL-17 and IL-6 were not different among the different concentration groups respectively (IL-17: χ2 = 0.550, P = 0.760;IL-6: χ2 = 0.010, P = 0.995). Conclusions BMSCs in moderate concentrations [(2-4)×105/well] could promote proliferation both in Treg cells and Th17 cells, but no change could be found in higher concentrations of BMSCs (8×105/well). However, the changes in related cytokines were not synchronized with Treg / Th17 cells.
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OBJECTIVE@#To explore the effects of bone marrow mesenchymal stem cells (BMSCs) in different concentrations on the balance of regulatory T cell/T-helper cell 17 (Treg/Th17).@*METHODS@#BMSCs were isolated from SPF grade male Wistar rats with age of 3 weeks old and weight of 50 g. BMSCs were cultured and identified when they were expanded to the 4th generation. CD4+ T lymphocytes were isolated from SPF grade male Wistar rat with age of 6 weeks old and weight of 200 g and assayed for cell purity by flow cytometry. BMSCs were divided into 0.5-fold concentration group, basal concentration group, 2-fold concentration group and 4-fold concentration group by their concentrations of 1×105/well, 2×105/well, 4×105/well and 8×105/well, which were cultured with CD4+ T lymphocytes for 72 hours, respectively. Then the proportion of Treg cells and Th17 cells in each group was detected by flow cytometry, and cytokines were detected by cytometric bead array.@*RESULTS@#The purities of BMSCs and CD4+ T lymphocytes were both higher than 95%. In the co-culture of BMSCs and CD4+ T lymphocytes, the proportions of Treg cells were statistically different among different concentration groups of BMSCs (F = 10.071, P = 0.001), in which BMSCs in 2-fold concentration group had the strongest ability to promote the Treg cells proliferation. The proportion of Treg cells in 2-fold concentration group was significantly higher than that in 0.5-fold concentration group, basal concentration group and 4-fold concentration group [(9.24±2.68)% vs. (3.87±0.38)%, (5.16±1.69)%, (3.86±0.36)%, all P < 0.01]. The level of interleukin-10 (IL-10) was lowest in 0.5-fold concentration group, and it was significantly lower than that in basal concentration group, 2-fold concentration group and 4-fold concentration group (ng/L: 39.80±14.48 vs. 148.43±64.49, 156.40±59.27, 126.92±42.95, all P < 0.05). Transforming growth factor-β (TGF-β) was the highest in basal concentration group, and it was significantly higher than that in 0.5-fold concentration group, 2-fold concentration group and 4-fold concentration group [ng/L: 3.17 (1.88, 5.74) vs. 0.71 (0.32, 1.38), 1.22 (0.47, 2.97), 0.52 (0.37, 1.23), all P < 0.05]. The proportions of Th17 cells were statistically different among the different concentration groups (F = 21.069, P = 0.000), with the highest proportion in basal concentration group which was significantly higher than that in 0.5-fold concentration group or 4-fold concentration group [(0.89±0.08)% vs. (0.64±0.15)%, (0.37±0.10)%, both P < 0.01], but no significant difference was found as compared with 2-fold concentration group [(0.83±0.06)%, P > 0.05]. However, the expressions of IL-17 and IL-6 were not different among the different concentration groups respectively (IL-17: χ2 = 0.550, P = 0.760; IL-6: χ2 = 0.010, P = 0.995).@*CONCLUSIONS@#BMSCs in moderate concentrations [(2-4)×105/well] could promote proliferation both in Treg cells and Th17 cells, but no change could be found in higher concentrations of BMSCs (8×105/well). However, the changes in related cytokines were not synchronized with Treg/Th17 cells.
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Animales , Masculino , Ratas , Citocinas/metabolismo , Células Madre Mesenquimatosas/metabolismo , Ratas Wistar , Linfocitos T Reguladores/metabolismo , Células Th17/metabolismoRESUMEN
Objective To observe the changes of serum complements and proinflammatory cytokines in rats with sepsis, and to explore the possible mechanism.Methods 120 healthy male Wistar rats were randomly divided into three groups: normal control group (n = 15), sham operation group (n = 15) and sepsis group [cecum ligation and puncture (CLP) operation,n = 90]. The sepsis rats were sacrificed on 24, 48 and 72 hours after modeling. The level of serum complements (C5, C5a) and cytokines tumor necrosis factor-α (TNF-α), interleukin (IL-1, IL-6), high mobility group box 1 (HMGB1), macrophage migration inhibitory factor (MIF) were detected by enzyme linked immunosorbent assay (ELISA).Results Compared with normal control group and sham operation group, the levels of serum complements C5, C5a and IL-1β were significantly increased at 24 hours after CLP in sepsis group [C5 (ng/L): 1.60±0.19 vs. 1.04±0.20, 1.09±0.09; C5a (ng/L): 0.20±0.02 vs. 0.18±0.01, 0.18±0.02; IL-1β (ng/L): 700.20±111.41 vs. 475.87±108.96, 592.29±121.57; allP < 0.05]; then the levels of C5, C5a and IL-1β declined, the level of serum C5 were also higher than normal control group at 48 hours and 72 hours after CLP (ng/L: 1.17±0.24, 1.27±0.24 vs. 1.04±0.20, bothP < 0.05). In sepsis group the level of serum TNF-α (ng/L: 51.33±1.96, 51.06±1.64) was lower than that in normal control group (59.53±3.06) and sham operation group (57.91±2.72) at 48 hours and 72 hours (allP < 0.05). There was a time dependent rise of serum HMGB1 in sepsis group, which level was much higher than that in normal control group and sham operation group at 72 hours after CLP (ng/L: 472.21±20.94 vs. 406.00±43.16, 404.41±35.39, bothP < 0.05). There were no significant differences of MIF, and IL-6 level between groups at each time points.Conclusions Complement system led to uncontrolled inflammatory response and immune dysfunction through the release of proinflammatory cytokines and inflammatory mediators, which maybe one of the important mechanism of the pathology of sepsis.
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Objective To explore the trend of changes of Th1 and Th2 cytokines within 6 months after adult liver transplantation (LT). Methods Twenty-three patients from Tianjin First Center Hospital were chosen as the patient group with an average age of (52.7 ± 7.6), range from 37 to 63 years old, including 21 males and 2 females. Twenty healthy staffs from Tianjin First Center Hospital formed the control group (C) with 15 males and 2 females whose average age was (31.0 ± 6.1) ranged from 22 to 24 years old. The patient group was treated with tacrolimus after LT as main immunosuppressive drug. The peripheral blood at time points before (T0) and 1 month (T1), 3 months (T3), 6 months (T6) after LT at 9:00 AM were collected. The blood sample was also collected form control group but only one time. Levels of IL-2, IFN-γ, IL-10 and TGF-βwere detected by ELISA. Results (1) The concentration of IL-2 showed a continuous up-going trend, which was not such obvious between T1 and T0, and until T3 reached a higher concentration than T0. The concentration at T6 was higher than T0 and T1. There were no significant differences in concentrations of T0 to T3 between patient group and control group, while T6 reached a higher concentration in patient group than that of the control group. (2) The concentration of IFN-γexperienced a shortly down-going trend from T0 to T3, and started rising, reached the peak at 3 months after the operation, then started its down-going trend. There were no significant differences in the concentrations of IFN-γfrom T1 to T6, and T3 reached a higher concentration than T1 while T6 was lower than T3. Only at T3, the concentration of IFN-γwas higher in patient group than that of control group. (3) There were no significant differences in the concentrations of IL-10 at various time points in patient group, and there were no significant differences in the concentrations of IL-10 at different time points between two groups (P>0.05). (4) The concentration of TGF-βshowed a gradual decline after the operation, and reached its bottom at T6, and which was lower than T0 to T3. Compared with the control group, the down-going trend was not such obviously at T0 and T1, and the concentration was down at T3 and T6(P<0.05). Conclusion Our results suggest that there is a tendency of an increasing Th1 cytokine expression at early stage in post-transplantation, while the TGF-βof Th2 cytokine is a decreasing trend. This tendency may associate with the autoimmunity response caused by LT and the immunosuppressive drugs.
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Objective Leucine-rich repeat transmembrane neuronal protein 2 (LRRTM2) localizes to excitatory glutamatergic synapses,and triggers the formation of excitatory synapses.This study aims to investigate the expression of LRRTM2 protein in the temporal lobe tissue of SD rats induced by lithiumpilocarpine,and explore its roles in epilepsy.Methods Fifty-six Sprague-Dawley (SD) rats were induced by lithium-pilocarpine and randomly divided into 6h,24h,72h,7d,14d,30d and 60d subgroups.Eight SD rats were treated with normal saline instead of pilocarpine as controls. Expression of LRRTM2 protein was accessed by immunohistochemistry,immunofluorcscence and Western blot analysis. Results LRRTM2 protein mainly expressed in neurons of temporal lobe,gradually decreased in acute phase,and then up-regulated in latent and chronic periods.The immunohistochemistry A values in model rats from 6 h,24h,72h,7d,14d,30d and 60d subgroups were 0.286 ±0.012,0.227 ± 0.008,0.425 ± 0.015,0.509 ±0.019,0.579 ± 0.018,0.488 ± 0.018 and 0.566 ± 0.014,respectively,compared to 0.330 ±0.016 in control group ( t =3.965,11.987,9.131,14.121,20.452,12.929 and 22.786,all P＜0.05). Gray value ratios of LRRTM2/β-actin in different groups of model rats were 0.0354 ± 0.0043,0.0174 ± 0.0026,0.0685 ± 0.0064,0.0957 ± 0.0125,0.1044 ± 0.0103,0.0910 ± 0.0108,and 0.1012 ±0.0063,respectively,which were significant differences from control group (0.0471 ± 0.0033,t=4.354,14.191,5.989,7.541,10.565,7.730and15.316,allP＜0.05).Conclusions LRRTM2 protein gradually increases in the neurons of temporal lobe of SD rats treated by lithium-pilocarpine in silence and chronic phases,which indicates that it may play an important role in cpileptogenesis.
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Objective To evaluate the immediate impact of radiofrequencycatheter ablation on left atrial (LA)volumes and function by velocity vector imaging(ⅤⅥ)and compare the LA function with and without atrial fibrillation after the operation.Methods Ten consecutive patients with paroxysmal AF were studied at baseline and within 3 days after ablation.Ten consecutive patients with persistent AF were studied within 3 days after ablation,in sinus rhythm.Ten patients with normal ventricular function were included in the study.ⅤⅥ was performed to assess LA sizes and strain,strain rate,velocity of the septum,lateral wall and the atrial roof from the apical four-chamber view.Results In patients with paroxysmal AF,global and regioal LA function was not significantly impaired after the ablation procedure.Subgroup analysis demonstrated that there were no significant difference in LA function betwwen patients with paroxysmal AF and control subjects,but the indexed LAVmax was significantly larger in all AF patients compared with control subjects.The global function of LA,including LAEF,LAaEF and LA expansion index significantly decreased in persistent AF patients.By contrast,the LA septal strain,velocity and lateral strain were lower than controls.Conclusions Radiofrequency catheter ablation has no influence on LA function assessed by ⅤⅥ within three days after the operation for patients with paroxysmaI AF.The function of persistent AF patients is absolutely lower than control subjects.
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Objective To appraise the clinical value of velocity vector imaging(VVI) by analyzing the peak systolic velocities,strain and strain rate of ventricular segments in patients with DDD pacing. Methods eventeen patients with DDD pacing were enrolled in this study. The peak systolic velocities, strain andstrain rate of ventricular segments were measured with VVI. The difference at baseline and after pacemaker implantation was analyzed. Results Left and right ventricular (LV and RV) longitudinal peak velocities at baseline and after DDD pacing were significantly decreasing from basal, mid to apical segments. But no significant difference was found in longitudinal strain,strain rate and radial motion characteristic of LV. The mean systolic velocities and strain rate at baseline and after pacemaker implantation and strain with pacing of RV posterior septum and free wall were higher than those of posterior septum and lateral segment of LV respectively. The mean strain and strain rate of RV after pacing were higher than that of LV. Compared with the values at baseline, mean strain of LV with pacing was lower significantly. Conclusions VVI can accurately assess ventricular systolic function in patients with DDD pacing, and can become a powerful means in assessing the regional myocardial function.
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Objective To assess the left ventricular(LV)contraction synchrony in patients with DDD pacing by velocity vector imaging(VVI).Methods Acoustic clip capture was performed in 13 patients before and after pacemaker implantation and obtained high-frame rate B-mode echocardiographic images.VVI was done in all three standard LV apical views and parasternal LV short axis(SAX)views.The time to peak systolic longitudinal velocity(Tvl)and systolic longitudinal strain(Ts1)in the LV apical views and the time to peak systolic radial velocity(Tvr)and systolic circumferential strain(Tsc)in the LV SAX views were measured bv VVI.The standard deviation of Tvl,Tsl,Tvr and Tsc(Tvl-SD,Tsl-SD,Tvr-SD and TscSD)and the maximal temporal difference of Tvl,Tsl,Tvr and Tsc(Tvl-d,Tsl-d,Tvr-d and Tsc-d)of 18 segments were calculated.Results Compared with the values at baseline,Tvr-SD,Tsc-SD,Tsl-d,Tvr-d and Tsc-d increased significantly in patients after pacemaker implantation(P＜0.05).Conclusions The longitudinal,radial and circumferential systolic asynchrony of the LV was commonly existed in patients after DDD pacing.VVI can be used to evaluate the systolic synchrony of the LV in patients with DDD pacing.