Preparation, characterization, and anticancer effects of an inclusion complex of coixol with ß-cyclodextrin polymers.

CONTEXT: Coix [Coix lacryma-jobi L. var. mayuen (Roman.) Stapf (Poaceae)], a crop of medicinal and edible significance, contains coixol, which has demonstrated anticancer properties. However, the limited solubility of coixol restricts its potential therapeutic applications. OBJECTIVE: This study prepared a water-soluble coixol-ß-cyclodextrin polymer (CDP) inclusion compound and evaluated its anticancer effect. MATERIALS AND METHODS: The coixol-CDP compound was synthesized through a solvent-stirring and freeze-drying technique. Its coixol content was quantified using HPLC, and its stability was tested under various conditions. The anticancer effects of the coixol-CDP compound (4.129, 8.259, 16.518, and 33.035 mg/L for 24, 48, and 72 h) on the proliferation of non-small cell lung cancer (NSCLC) A549 cells were evaluated using an MTT assay; cell morphology was examined by Hoechst nuclear staining; apoptosis and cell cycle was detected by flow cytometry; and the expression of apoptosis-related proteins was assessed by Western blots. RESULTS: The water-soluble coixol-CDP inclusion compound was successfully prepared with an inclusion ratio of 86.6% and an inclusion yield rate of 84.1%. The coixol content of the compound was 5.63% and the compound remained stable under various conditions. Compared to coixol alone, all 24, 48, and 72 h administrations with the coixol-CDP compound exhibited lower IC50 values (33.93 ± 2.28, 16.80 ± 1.46, and 6.93 ± 0.83 mg/L) in A549 cells; the compound also showed stronger regulatory effects on apoptosis-related proteins. DISCUSSION AND CONCLUSIONS: These findings offer a new perspective for the potential clinical application of Coix in NSCLC therapy and its future research.

The association between serum anion gap and acute kidney injury after coronary artery bypass grafting in patients with acute coronary syndrome.

BACKGROUND: The purpose of this study was to explore the association between serum anion gap (SAG) and acute kidney injury (AKI) after coronary artery bypass grafting (CABG) in patients with acute coronary syndrome (ACS) in the Intensive Care Unit (ICU). METHODS: We retrospectively analyzed the clinical data of 2,428 ACS patients who underwent CABG in the Medical Information Mart for Intensive Care IV (Mimic-IV) database. The endpoint of this study was AKI after CABG. The baseline data of the two groups (non-AKI group vs. AKI group) was compared, and the restricted cubic spline (RCS) plot, multivariable logistic regression model, and subgroup analysis were used to explore the relationship between SAG and the risk of AKI after CABG. RESULTS: In the adjusted multivariate logistic regression model, SAG was an independent predictor of AKI after CABG (OR = 1.12, 95% CI: 1.02-1.23, P = 0.015). The RCS revealed that the relationship between SAG levels and risk of AKI was J-shaped. When the SAG was ≥ 11.58 mmol/L, the risk of AKI increased by 26% for each unit increase in SAG. Additionally, we further divided the SAG into quartiles. In the fully adjusted model, compared with the first quartile of SAG, the odds ratios (ORs) and 95% confidence intervals (CIs) for AKI risk across the SAG quartiles were 0.729 (0.311, 1.600), 1.308 (0.688-2.478), and 2.221 (1.072, 4.576). CONCLUSIONS: The SAG level was associated with the risk of AKI after CABG in a J-shaped curve in the ICU. However, the underlying causes of the problem need to be investigated.

Integrated Metabolomic and Transcriptomic Analysis Reveals the Flavonoid Regulatory Network by Eutrema EsMYB90.

Flavonoids are representative secondary metabolites with different metabolic functions in plants. Previous study found that ectopic expression of EsMYB90 from Eutremasalsugineum could strongly increase anthocyanin content in transgenic tobacco via regulating the expression of anthocyanin biosynthesis genes. In the present research, metabolome analysis showed that there existed 130 significantly differential metabolites, of which 23 metabolites enhanced more than 1000 times in EsMYB90 transgenic tobacco leaves relative to the control, and the top 10 of the increased metabolites included caffeic acid, cyanidin O-syringic acid, myricetin and naringin. A total of 50 markedly differential flavonoids including flavones (14), flavonols (13), flavone C-glycosides (9), flavanones (7), catechin derivatives (5), anthocyanins (1) and isoflavone (1) were identified, of which 46 metabolites were at a significantly enhanced level. Integrated analysis of metabolome and transcriptome revealed that ectopic expression of EsMYB90 in transgenic tobacco leaves is highly associated with the prominent up-regulation of 16 flavonoid metabolites and the corresponding 42 flavonoid biosynthesis structure genes in phenylpropanoid/flavonoid pathways. Dual luciferase assay documented that EsMYB90 strongly activated the transcription of NtANS and NtDFR genes via improving their promoter activity in transiently expressed tobacco leaves, suggesting that EsMYB90 functions as a key regulator on anthocyanin and flavonoid biosynthesis. Taken together, the crucial regulatory role of EsMYB90 on enhancing many flavonoid metabolite levels is clearly demonstrated via modulating flavonoid biosynthesis gene expression in the leaves of transgenic tobacco, which extends our understanding of the regulating mechanism of MYB transcription factor in the phenylpropanoid/flavonoid pathways and provides a new clue and tool for further investigation and genetic engineering of flavonoid metabolism in plants.

Identification of the Eutrema salsugineum EsMYB90 gene important for anthocyanin biosynthesis.

BACKGROUND: Anthocyanins contribute to coloration and antioxidation effects in different plant tissues. MYB transcription factors have been demonstrated to be a key regulator for anthocyanin synthesis in many plants. However, little information was available about the MYB genes in the halophyte species Eutrema salsugineum. RESULT: Here we report the identification of an important anthocyanin biosynthesis regulator EsMYB90 from Eutrema salsugineum, which is a halophyte tolerant to multiple abiotic stresses. Our phylogenetic and localization analyses supported that EsMYB90 is an R2R3 type of MYB transcription factor. Ectopic expression of EsMYB90 in tobacco and Arabidopsis enhanced pigmentation and anthocyanin accumulation in various organs. The transcriptome analysis revealed that 42 genes upregulated by EsMYB90 in 35S:EsMYB90 tobacco transgenic plants are required for anthocyanin biosynthesis. Moreover, our qRT-PCR results showed that EsMYB90 promoted expression of early (PAL, CHS, and CHI) and late (DFR, ANS, and UFGT) anthocyanin biosynthesis genes in stems, leaves, and flowers of 35S:EsMYB90 tobacco transgenic plants. CONCLUSIONS: Our results indicated that EsMYB90 is a MYB transcription factor, which regulates anthocyanin biosynthesis genes to control anthocyanin biosynthesis. Our work provides a new tool to enhance anthocyanin production in various plants.

Intracerebroventricular infusion of secretoneurin inhibits neuronal NLRP3-Apoptosis pathway and preserves learning and memory after cerebral ischemia.

Transient global cerebral ischemia (GCI) results in delayed neuronal death, primarily apoptosis, in the hippocampal CA1 subregion, which leads to severe cognitive deficits. While therapeutic hypothermia is an approved treatment for patients following cardiac arrest, it is associated with various adverse effects. Secretoneurin (SN) is an evolutionarily conserved neuropeptide generated in the brain, adrenal medulla and other endocrine tissues. In this study, SN was infused into the rat brain by intracerebroventricular injection 1 day after GCI, and we demonstrated that SN could significantly preserve spatial learning and memory in the Barnes maze tasks examined on days 14-17 after GCI. To further investigate underlying pathways involved, we demonstrated that, on day 5 after GCI, SN could significantly inhibit GCI-induced expression levels of Apoptosis Inducing Factor (AIF) and cleaved-PARP1, as well as neuronal apoptosis and synaptic loss in the hippocampal CA1 region. Additionally, SN could attenuate GCI-induced activation of both caspase-1 and caspase-3, and the levels of pro-inflammatory cytokines IL-1ß and IL-18 in the CA1 region. Mechanically, we observed that treatment with SN effectively inhibited NLRP3 protein elevation and the bindings of NLRP3-ASC and ASC-caspase-1 in hippocampal neurons after GCI. In summary, our data indicate that SN could effectively attenuate NLRP3 inflammasome formation, as well as the activation of caspase-1 and -3, the production of pro-inflammatory cytokines, and ultimately the neuronal apoptotic loss induced by GCI. Potential neuronal pyroptosis, or caspase-1-dependent cell death, could also be involved in ischemic neuronal death, which needs further investigation.

Association of pulsatility index with total burden of cerebral small vessel disease and cognitive impairment.

OBJECTIVE: This study investigated the correlation between the pulsatility index (PI) of the middle cerebral artery with the total burden of cerebral small vessel disease and cognitive impairment. METHOD: Information on patients hospitalized in the Department of Neurology was collected retrospectively. These patients had complete clinical and laboratory data. The middle cerebral artery PI was measured using transcranial Doppler, a Mini-Mental State Examination (MMSE) was used to assess cognitive function, and the total cerebral small vessel disease burden was assessed using magnetic resonance imaging. Patients were grouped according to their scores for total imaging burden of cerebral small vessel disease and cognitive function. Logistic regression analysis assessed the association between the PI, total imaging burden, and cognitive impairment. Spearman analysis was used to evaluate the correlation between the PI and total imaging burden and cognitive impairment, and receiver operating characteristic (ROC) curves were used to determine the predictive value of the PI for cognitive function. RESULTS: The PI was higher in the cognitive impairment (CI) group than in the no-CI group. Binary logistic regression analysis showed that increased PI was an independent risk factor for CI (OR = 1.582; 95% CI: 1.043-2.401; p = .031) and total imaging burden (OR = 1.842; 95% CI: 1.274-2.663; p = .001). Spearman analysis found that the PI correlated negatively with the MMSE score (r = -.627, p < .001). ROC curve analysis showed the PI predicted CI with an area under the curve of 0.784. The PI combined with the total imaging burden predicted CI in cerebral small vessel disease with an area under the curve of 0.832. CONCLUSION: An increased PI was associated with CI and a high imaging burden in cerebral small vessel disease patients. The PI combined with the total burden score shows a high predictive value for CI.

[Predictive value of lung ultrasound score on weaning outcome in patients with intro-abdominal infection undergoing mechanical ventilation].

OBJECTIVE: To evaluate the value of lung ultrasound score (LUS) on predicting weaning outcome in patients with intro-abdominal infection (IAI) undergoing mechanical ventilation. METHODS: Patients with IAI undergoing mechanical ventilation admitted to Research Institute of General Surgery of East War Zone Hospital and intensive care unit (ICU) of the First People's Hospital of Lianyungang from January to December in 2018 were included. The patients who satisfied weaning criteria were enrolled in the weaning process, which included spontaneous breathing trial (SBT) and extubation. They were divided into SBT success group and SBT failure group according to whether passed 120-minute SBT or not. LUS scores before and after SBT were compared between the two groups. The patients in the SBT success group were extubated, and they were divided into successful extubation group and failed extubation group for sub-group analysis according to whether re-intubation was needed in 48 hours after extubation. LUS score before extubation (at the end of SBT) and 48 hours after extubation (48 hours after extubation in the successful extubation group or before re-intubation in the failed extubation group) were compared. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of LUS score before SBT for SBT failure and LUS score before extubation for the failure. RESULTS: A total of 76 patients with IAI undergoing mechanical ventilation were included. Twenty-three patients had duration of mechanical ventilation less than 48 hours, severe chronic obstructive pulmonary disease (COPD), tracheotomy or automatic discharge were excluded, and 53 patients were enrolled. SBT was failed in 9 patients, and successfully performed in 44 patients, of whom 23 patients with successful extubation, and 21 with failed extubation. The LUS scores before and after SBT in the SBT failure group were significantly higher than those in the SBT success group (before SBT: 13.22±1.99 vs. 10.79±1.64, t = -3.911, P = 0.000; after SBT: 19.00±1.12 vs. 13.41±1.86, t = -8.665, P = 0.000). ROC curve analysis showed that the area under ROC curve (AUC) of LUS score before SBT for predicting SBT failure was 0.82 [95% confidence interval (95%CI) was 0.67-0.98, P = 0.002]. When the optimum cut-off value was 12.5, the sensitivity was 66.7%, and the specificity was 84.1%. Sub-group analysis showed that the LUS scores before and after extubation in the failed extubation group were significantly higher than those in the successful extubation group (before extubation: 14.19±1.60 vs. 12.69±1.81, t = -2.881, P = 0.006; after extubation: 16.42±1.59 vs. 12.78±1.54, t = -7.710, P = 0.000). ROC curve analysis showed that the AUC of LUS score before extubation for predicting the failure was 0.81 (95%CI was 0.69-0.92, P = 0.000). When the optimum cut-off value was 13.5, the sensitivity was 80.0%, and the specificity was 65.2%. CONCLUSIONS: LUS score can effectively predict SBT outcome, risk of re-intubation after extubation in patients with IAI undergoing mechanical ventilation.

[Effects of interposed abdominal pulling-pressing cardiopulmonary resuscitation on hemodynamics and oxygen metabolism in patients with cardiac arrest].

OBJECTIVE: To analyze the effect of interposed abdominal pulling-pressing cardiopulmonary resuscitation (IAPP-CPR) and standard cardiopulmonary resuscitation (S-CPR) on hemodynamics and oxygen metabolism in patients with cardiac arrest, and to evaluate the treatment effect of IAPP-CPR. METHODS: The patients with cardiac arrest, cardiac arrest time less than 30 minutes, and with S-CPR indications admitted to intensive care unit (ICU) of the First People's Hospital of Lianyungang from January 2017 to January 2019 were enrolled. The patients were divided into IAPP-CPR group and S-CPR group according to whether the patients had IAPP-CPR indication or not. The patients in the S-CPR group were operated according to the 2015 American Heart Association (AHA) CPR guidelines; and the patients in the IAPP-CPR group received the IAPP-CPR on the basis of the S-CRP. During the relaxation period, the patients were subjected to abdominal lifting and compressing with amplitude of 4-5 cm, frequency of 100-120 times/min, and the time ratio of lifting to compressing was 1:1. Hemodynamic changes during resuscitation were recorded in the two groups. Hemodynamics, oxygen metabolism, arterial blood gas analysis and prognostic indicators were recorded at 30 minutes after successful resuscitation. RESULTS: During the study period, 77 patients were selected, 24 patients were excluded from giving up treatment and quitting, 53 patients were enrolled in the analysis finally, with 28 patients in the S-CPR group and 25 in the IAPP-CPR group. (1) The heart rate (HR), mean arterial pressure (MAP) and coronary perfusion pressure (CPP) showed an upward trend during resuscitation, and a more significant increase was shown in the IAPP-CPR group. (2) Hemodynamics after successful resuscitation: there were 16 patients with successful resuscitation in the IAPP-CPR group and 13 in the S-CPR group. The MAP, CPP, global ejection fraction (GEF) and stroke volume (SV) of patients with successful resuscitation at 30 minutes after resuscitation in the IAPP-CPR group were significantly higher than those in the S-CPR group [MAP mmHg (1 mmHg = 0.133 kPa): 52.88±3.11 vs. 39.39±4.62, CPP (mmHg): 36.56±6.89 vs. 29.61±6.92, GEF: 0.217±0.036 vs. 0.178±0.027, SV (mL): 38.43±5.25 vs. 32.92±8.28, all P < 0.05], but there was no significant difference in central venous pressure (CVP) or HR between the two groups. (3) Oxygen metabolism after successful resuscitation: the cardiac output (CO), arterial oxygen content (CaO2), oxygen transport (DO2) and oxygen consumption (VO2) of patients with successful resuscitation at 30 minutes after resuscitation in the IAPP-CPR group were significantly higher than those in the S-CPR group [CO (L/min): 2.23±0.38 vs. 1.99±0.29, CaO2 (mL/L): 158.0±11.8 vs. 141.4±8.2, DO2 (mL/L): 245.8±29.9 vs. 209.1±28.0, VO2 (mL/L): 138.2±24.9 vs. 112.8±18.1, all P < 0.05]. (4) Arterial blood gas after successful resuscitation: the values of the pH, arterial oxygen partial pressure (PaO2), arterial partial pressure of carbon dioxide (PaCO2), oxygenation index (PaO2/FiO2) and central venous oxygen saturation (ScvO2) of patients with successful resuscitation at 30 minutes after resuscitation in the IAPP-CPR were significantly higher than those in the S-CPR group [pH value: 7.13±0.22 vs. 7.00±0.23, PaO2 (mmHg): 73.68±13.80 vs. 65.32±15.32, PaCO2 (mmHg): 36.24±11.77 vs. 29.12±7.82, PaO2/FiO2 (mmHg): 73.68±13.80 vs. 65.32±15.32, ScvO2: 0.628±0.074 vs. 0.589±0.066, all P < 0.05], and the blood lactic acid (Lac) level was significantly lower than that in the S-CPR group (mmoL/L: 9.80±4.28 vs. 12.18±3.63, P < 0.05). (5) The patients in the IAPP-CPR group had a shorter time for cardiac arrest to restoration of spontaneous circulation (ROSC) than that in the S-CPR group (minutes: 10.63±2.94 vs. 14.54±3.84, P < 0.01), and the rate of ROSC, CPR successful rate and 28-day survival rate were significantly higher than those in the S-CPR group [64.0% (16/25) vs. 46.4% (13/28), 60.0% (15/25) vs. 28.6% (8/28), 52.0% (13/25) vs. 21.4% (6/28), all P < 0.05]. There was no significant difference in incidence of rib fracture between the IAPP-CPR and S-CPR groups [92.0% (23/25) vs. 89.3% (25/28), P > 0.05], and no abdominal bleeding was found in both group. CONCLUSIONS: IAPP-CPR can produce better hemodynamic effect during and after resuscitation than S-CPR, and oxygen metabolism and arterial blood gas analysis parameters at 30 minutes after resuscitation were better than S-CPR, with higher ROSC rate, CPR successful rate and 28-day survival rate, and no significant difference in complications between the two resuscitation methods.

[An experimental study on cardiopulmonary resuscitation by cardiac massage under diaphragmatic muscle for rabbit with cardiac arrest].

OBJECTIVE: To compare the hemodynamic effect of standard-cardiopulmonary resuscitation (S-CPR) and of CPR by cardiac massage under the diaphragmatic muscle (D-CPR), and to evaluate the feasibility of D-CPR. METHODS: Twenty healthy New Zealand rabbits were randomly divided into two groups: one group receiving S-CPR (n=10) and the other group receiving D-CPR (n=10). Cardiac arrest was induced by asphyxiation at the end expiration for 8 minutes. After the hemodynamic situation was stable for 5 minutes before asphyxiation, the readings of ascending aorta systolic pressure (AOS) and diastolic pressure (AOD), transcutaneous oxygen saturation (SpO(2)), right atrial systolic pressure (RASP), right atrial diastolic pressure (RADP), and electrocardiogram were recorded consecutively to the end of the experiment . The mean arterial pressure (MAP) of ascending aorta and coronary perfusion pressure (CPP) were calculated. The rate of restoration of spontaneous circulation (ROSC) and the survival rate in a short duration of 6 hours were observed. RESULTS: Five rabbits in S-CPR group and 8 in D-CPR group were successfully resuscitated and obtained ROSC (50%, 80%, P=20.05). Six hours survival rate was 40% in S-CRP group and 50% in D-CPR group. The comparisons between the two groups on AOS, AOD, MAP and CPP respectively showed that at 1 minute and 5 minutes during resuscitation the respective variables were higher in the D-CPR group than that in the S-CPR group (all P<0.05). Compared to the hemodynamics before asphyxiation, the MAP and CPP in the D-CPR group increased 54.1% and 33.4% of basic value at 1 minute, and they were 60.0% and 41.8% at 5 minutes, while the AOS and AOD in the S-CPR group only increased by an average of 37.3% and 16.5% at 1 minute, and they were 38.5% and 17.1% at 5 minutes, respectively. After ROSC, the hemodynamic variations of the D-CPR rabbits were more stable than those of S-CPR rabbits. CONCLUSION: D-CPR can provide higher arterial pressure, cardiac output, rate of ROSC and survival rate in a short period than S-CPR can induce, so that D-CPR is superior to S-CPR.

[Correlation of Serum Concentration of Nilotinib with Clinical Efficacy in Patients with Chronic Myeloid Leukemia].

OBJECTIVE: To investigate the correlation of the serum minimal concentrations (Cmins) of nilotinib(NIL) with the clinical efficacy and adverse events (AEs) in CML patients. METHODS: A total of 54 patients were divided into two groups according to the dosage of nilotinib. 44 cases received dose of 600-800 mg/d were classified as group A; while 10 cases received dose of 400 mg/d as group B. The Cmins of nilotinib were determmined by liquid chromatography-tandem mass spectrometry. RESULTS: Median Cmins of nilotinib in 54 patients was 1.71 (0.52-5.93) µg/ml. Cmins of nilotinib in group A and group B were 2.09± 1.21 µg/ml and 0.94± 0.27 µg/ml respectively, Cmins of group A was significantly higher than that of group B (P=0.001). In group A, 24 out of 44 cases obtained major molecular response (MMR) in 12 months, while 20 cases did not reach MMR in 12 months; the serum drug concentrations were 1.70± 0.75 µg/ml and 2.03± 0.82 µg/ml respectively, without statistically significant differences between these 2 subgroups(P=0.154). However, Cmins of nilotinib in patients with III-IV grade of adverse events were significantly higher than those in patients with 0-II grade of adverse events (3.09± 1.76 µg/ml vs 1.76± 0.68 µg/ml)(P=0.018). There was no statistic diffence in Cmins of nilotinib with MMR in 12 months of group A MMR 1.15± 0.27 µg/ml vs no MMR 0.83± 0.24 µg/ml(P=0.051). The MMR rate at 12 months in group A was 54.5%(24/44) and that in group B was 40%(4/10) (P=0.494). But the incidence of grade III-IV adverse events in group A was 29.5%(13/44), which was significantly higher than that of group B[0/10(0%)]. CONCLUSION: Cmins of nilotinib shows significant individual differences. The Cmins of nilotinib relate with the dosage and grade III-IV of adverse events. The lower dose of nilotinib may maintain a good therapeutic effect and significantly reduce the adverse events.

[Significance of peripheral perfusion index in early diagnosis and goal-directed therapy of septic shock patients: a prospective single-blind randomized controlled trial].

OBJECTIVE: To investigate the application of peripheral perfusion index (PPI) in early diagnosis and goal-directed therapy of septic shock, and to provide reference for the early clinical diagnosis and treatment of septic shock. METHODS: A prospective single-blind randomized controlled trial (RCT) was conducted. Adult patients with sepsis admitted to emergency medical department and intensive care unit (ICU) of the First People's Hospital of Lianyungang City in Jiangsu Province from January 2013 to December 2016 were enrolled. The patients were randomly divided into two groups (n = 46). The PPI group was defined using PPI < 1.4 as diagnosis of septic shock standard, and PPI > 2 as treatment guide target. Control group was defined according to the traditional diagnostic criteria of shock which systolic blood pressure was less than 90 mmHg (1 mmHg = 0.133 kPa) or systolic blood pressure value decrease > 40 mmHg baseline and bundle treatment was performed. The volume of fluid resuscitation, organ dysfunction, the sequential organ failure score (SOFA), acute physiology and chronic health evaluation II (APACHE II) score, continuous renal replacement therapy (CRRT) time, mechanical ventilation (MV) time, the length of ICU stay and 28-day mortality were observed. RESULTS: There were 39 and 27 septic shock patients in PPI group and control group respectively. The diagnostic criteria of traditional septic shock with blood pressure as "gold standard", the sensitivity of PPI < 1.4 for septic shock was 94.3%, the specificity was 28.2%, the authenticity was 66.3%, the positive predictive value was 64.1%, the negative predictive value was 78.6%, the positive likelihood ratio was 1.31, the negative likelihood ratio was 0.18. The per capita fluid replacement within 24 hours in the PPI group was significantly higher than that in the control group (mL: 4 601±1 250 vs. 3 458±1 006, P < 0.01), but there was no significant difference in the per capita volume of the patients diagnosed as septic shock (mL: 4 596±1 320 vs. 4 205±1 058, P > 0.05). Compared with the control group, the PPI group treated patients within 48 hours with less vascular active drugs (cases: 6 vs. 15), APACHE II and SOFA score were lower (48 hours: APACHE II was 10.2±2.1 vs. 12.0±3.2; 72 hours: SOFA was 5.1±1.8 vs. 6.0±2.1, APACHE II was 8.9±1.8 vs. 9.8±2.2), the period of CRRT and the length of ICU stay were shorter [the period of CRRT (days): 3.0±0.9 vs. 3.6±1.4, the length of ICU stay (days): 5.2±2.1 vs. 6.3±2.9), the difference was statistically significant (all P < 0.05). There was no significant difference in the liver and kidney function index, arterial blood lactic acid (Lac), MV time (days: 3.3±1.4 vs. 3.5±1.2) and 28-day mortality (15.22% vs. 19.57%) between two groups (all P > 0.05). CONCLUSIONS: The inadequacy of microcirculatory perfusion by oximetry-derived PPI is more sensitive to the diagnosis of septic shock than hypotension of systemic circulation. With PPI guiding the fluid resuscitation of septic shock patients, vasopressors can be withdrawn earlier and the duration of the CRRT and ICU can be decreased.

Allicin induces the upregulation of ABCA1 expression via PPARγ/LXRα signaling in THP-1 macrophage-derived foam cells.

Allicin is considered anti-atherosclerotic due to its antioxidant and anti-inflammatory effects, which makes it an important drug for the prevention and treatment of atherosclerosis. However, the effects of allicin on foam cells are unclear. Thus, in this study, we examined the effects of allicin on lipid accumulation via peroxisome proliferator-activated receptor Î³ (PPARγ)/liver X receptor α (LXRα) in THP­1 macrophage-derived foam cells. THP­1 cells were exposed to 100 nM phorbol myristate acetate (PMA) for 24 h, and then to oxydized low-density lipoprotein (ox-LDL; 50 mg/ml) to induce foam cell formation. The results of Oil Red O staining and high-performance liquid chromatography (HPLC) revealed showed that pre-treatment of the foam cells with allicin decreased total cholesterol, free cholesterol (FC) and cholesterol ester levels in cells, and also decreased lipid accumulation. Moreover, allicin upregulated ATP binding cassette transporter A1 (ABCA1) expression and promoted cholesterol efflux. However, these effects were significantly abolished by transfection with siRNA targeting ABCA1. Furthermore, PPARγ/LXRα signaling was activated by allicin treatment. The allicin-induced upregulation of ABCA1 expression was also abolished by PPARγ inhibitor (GW9662) and siRNA or LXRα siRNA co-treatment. Overall, our data demonstrate that the allicin-induced upregulation of ABCA1 promotes cholesterol efflux and reduces lipid accumulation via PPARγ/LXRα signaling in THP­1 macrophage-derived foam cells.

Tim-3 is highly expressed in T cells in acute myeloid leukemia and associated with clinicopathological prognostic stratification.

T cells immunoglobulin mucin 3 (Tim-3) is an important inhibitory stimulatory molecule, which has been reported to play a vital role in the tumor immune escape and be correlated with clinicopathological prognostic stratification in solid tumor. However, the related research is rare of Tim-3 in non-solid tumor, such as acute myeloid leukemia (AML). In this study, we investigated the expression characteristics of Tim-3 on the peripheral blood T cells of newly diagnosed AML patients and its clinical significance. Peripheral blood was obtained from 36 patients with newly diagnosed AML before intervention, with peripheral blood from 20 cases of healthy volunteers collected as normal control. Expression levels of Tim-3 on the peripheral blood T cells were assayed with flow cytometry. We found that Tim-3 expression on the peripheral blood CD4+ T cells and CD8+ T cells in newly diagnosed AML patients were significantly increased compared with that of normal control. CD4+ T cells/CD8+ T cell ratio (CD4/CD8) of peripheral blood in AML patients was significantly correlated with NCCN high risk group. The higher expression level of Tim-3 on CD4+ T cells in the peripheral blood of AML patients had significant correlation with FLT3-ITD mutation, the higher expression level of Tim-3 on CD8+ T cells in AML patients was significantly correlated with NCCN high risk group. To conclude, our results support the concept that Tim-3 is highly expressed on the peripheral blood T cells of AML patients, and Tim-3 expression significantly correlates with clinicopathological prognostic stratification in AMLTim-3, T cell, acute myeloid leukemia, tumor immune escape, clinicopathological prognostic stratification.

[Second-generation tyrosine kinase inhibitors combined with allogeneic hematopoietic stem cell transplant for Philadelphia chromosome positive leukemia].

OBJECTIVE: To investigate the efficacy and safety of second-generation tyrosine kinase inhibitors (TK-II) combined with allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of high-risk Philadelphia chromosome positive (Ph⁺) leukemia. METHODS: The clinical data of 17 cases of high-risk Ph⁺ leukemia patients underwent allo-HSCT were retrospectively analyzed, including 1 case in accelerated phase and 7 cases in blast crises of chronic myeloid leukemia, and 9 cases of Ph⁺ acute lymphoblastic leukemia. Nilotinib or Dasatinib were administered before and (or) after allo-HSCT in all patients. RESULTS: All patients successfully engrafted. Median times to neutrophil and platelet recovery were 12 days (range 10-14) and 15 days (range 11- 23), respectively. Acute GVHD developed in 7 patients: 6 patients had grade 1 to 2 and 1 patient grade 3. Chronic GVHD developed in 6 patients, all were limited and no lethal GVHD occurred. At a median follow-up of 17(range 3-60) months, 11(64.7%) patients survived disease free, 6 patients relapsed and 5 died. CONCLUSION: TK-II combined with allo-HSCT effectively improved the remission rate of high-risk Ph⁺ leukemia and reduced recurrence after allo-HSCT, which represented an important improvement in the treatment of patients with high-risk Ph+ leukemia.