CCAAT enhancer binding protein A (CEBPA) and its product transcription factor CCAAT enhancer binding protein α (C/EBPα) play pivotal roles in early granulocyte development. C/EBPα induces the transition and keeps the balance of differentiation and proliferation of myeloid progenitors. The mutation and dysregulation of CEBPA at transcription, translation or post-translation level lead to differentiation block and over proliferation of immature hematopoietic cells, which are important mechanisms of acute myeloid leukemia (AML). The mutation and dysregulation of CEBPA also provide clues for evaluating the outcome of AML patients and potential targets for differentiation-inducing therapies. This review focus on CEBPA mutation and AML, dysregulation of C/EBPα protein expression and AML, as well as C/EBPα protein and targeting therapy.
CCAAT-Enhancer-Binding Proteins ; genetics ; metabolism ; Humans ; Leukemia, Myeloid, Acute ; genetics ; metabolism ; Mutation

Heart rate variability (HRV) is a reliable, innocuous and sensitive new index to measure cardiac autonomic nervous function. Anxiety disorder is often accompanied by autonomic nerve dysfunction and its main sign is abnormal HRV. Acupuncture can affect HRV indices, correct abnormal HRV and improve cardiac autonomic nerve dysfunction to relieve anxiety. This article sorts out and analyzes recent years’ studies on abnormal HRV in anxiety disorder, the effect of acupuncture on HRV and acupuncture regulation of abnormal HRV in anxiety disorder to provide a therapeutic basis for clinical acupuncture intervention in abnormal HRV in anxiety disorder.

Objective To evaluate the effects of Chuanglingye decoction on angiogenesis and wound healing. Methods With a series of dosages of Chuanglingye decoction, their optimal effects of angiogenesis were searched for through the chicken embryo allantois membrane model(CAM). The vascular endothelial cell proliferation experiment (MTT) and the migration assay were used for the detection of effects. The gauze loading with Chuanglingye decoction of 0.2 ml as the experimental group and with saline of 0.2ml as the control group were applied on the total skin mechanical round wound of 1.5cm diameter and changed every other day. The sizes of area were detected on the day of 0,3,7,14 and 28 as well as the scores of inflammatory response, contains of TNF-αand Il-6 were detected on the day of 3 and 7. Results The CAM experiments showed that the angiogenic effects of 0.2 ml and 0.3 ml dosage of the Chuanglingye group were significantly lower than those of the control group(P<0.05). The 0.2 ml dosage of Chuanglingye decoction was chosen for the further experiment. The HUVEC proliferation rate of the experimental group decreased 21%, as compared with the results of control group. The cell migration movement of 12 hours, 24 hours in the experimental group were significantly lower than those in the control group. For theanimal experiments, the area sizes of the wound were similar in the experimental and control group without any significant differences. The scores of inflammatory response and contains of TNF-α(768±107)ng/L,(380±47)ng/L and Il-6(664±133)ng/L,(363±43)ng/L in the experimental group were significant decreased than those of the control group on the day of 3(958± 140)ng/L,(2215±314)ng/Land 7(512±62)ng/L,(1562±174)ng/L. Conclusion It showed that Chuanglingye decoction had negative effects on vascular endothelial cell migration and proliferation and thus inhibiting angiogenesis. These effects did not infer the process of the wound healing due to its ameliorating the inflammatory response which may be a help to wound healing.

Objective To study the changes of intracellular calcium ion concentration in pulmonary artery smooth muscle cells (PASMCs) of hypoxic-induced persistent pulmonary hypertension (PPH) induced by calcium-sensitive receptor (CaSR) in a newborn mouse model.Method Ninety-six newbom C57BL/6 mice were randomly divided into control group,PPH group,PPH + agonist group and PPH + inhibitor group,with 24 mice in each group.The PPH model was induced by 12％ oxygen for 14 days.In the beginning,intraperitoneal injection of CaSR agonist (GdCl3) and CaSR inhibitor (NPS2390) were performed to mice in PPH + agonist group and PPH + inhibitor group respectively daily.After 14 days of modeling,pulmonary artery smooth muscle cells (PASMCs) of all four groups were cultured in vitro.Changes of Ca2+ fluorescence intensity in PASMCs of the four groups were detected by laser confocal microscope continuously.Result The ratio of pulmonary small vascular wall thickness to the vascular diameter and right ventricle/left ventricular thickness in PPH group were greater than those in the control group [(21.1％ ±1.8％) vs.(27.0％ ±0.9％),(0.62 ±0.22) vs.(0.83±0.45)],the differences were statistically significant (P ＜ 0.05),which imply that PPH mouse model was constructed successfully.The average Ca2+ fluorescence intensity in PASMCs of control group,PPH group,PPH + agonist group and PPH+ antagonist group were 122.5 ± 3.0,2 058.8 ±46.3,2 286.6 ±51.4 and 1 134.8 ± 8.5,respectively.The average Ca2+ fluorescence intensity in PASMCs of the PPH group,PPH + agonist group and PPH + antagonist group was higher than that of the control group respectively,the average Ca2+ fluorescence intensity in PASMCs of PPH group was higher than that of PPH + antagonist group,the differences were statistically significant (P ＜ 0.05).Whereas the difference of average Ca2 + fluorescence intensity in PASMCs of PPH group and PPH + agonist group was of no statistical significance (P ＞ 0.05).Conclusion CaSR may be involved in the occurrence and development of hypoxic-induced PPH in neonatal mice by affecting the intracellular Ca2+ concentration in pulmonary artery smooth muscle cells.

OBJECTIVE: To explore the effect of Euonymus alatus on the blood glucose and hemorheology in rat model of Type 2 diabetes mellitus with blood stagnation (DMBS). METHODS: High fat diet with streptozocin was used to establish the rat model of Type 2 diabetes mellitus, followed by the prednisolone and adrenaline muscle injection to obtain DMBS. DMBS rats were divided into a DMBS group (treated with saline gavage), an Euonymus alatus group (treated with Euonymus alatus gavage), and a glybenzoylamide group (treated with glybenzoylamide gavage).A blank group was treated with saline gavage. The experiment lasted 4 weeks, followed by the evaluation of rats' behavior, and detection of fasting blood glucose and hemorheology. RESULTS: Compared with DMBS rats, the symptoms of polydipsia and diuresis in Euonymus alatus rats were improved, with increased body weight (P<0.05), better fur and mental state, increased resistance for being caught, and reduced tongue stagnation. Compared with DMBS group, though body weight increased, resistance for being caught decreased in the glybenzoylamide group with bad fur and mental state,and tongue stagnation. As to the fasting blood glucose, there was significant difference between the Euonymus alatus group and the DMBS group (P<0.05). As to the hemorheology, including whole blood viscosity (shear rates 1,5,50, and 100 s(-1)), plasma viscosity, and hematocrit, the Euonymus alatus rats had a better efficacy than DMBS rats and glybenzoylamide rats (P<0.05 or P<0.01). CONCLUSION Euonymus alatus can reduce the fasting blood glucose of DMBS and improve blood stagnation.
Animals ; Blood Glucose ; analysis ; Blood Viscosity ; drug effects ; Diabetes Mellitus, Experimental ; blood ; drug therapy ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Diagnosis, Differential ; Drugs, Chinese Herbal ; pharmacology ; Euonymus ; chemistry ; Hemorheology ; drug effects ; Male ; Medicine, Chinese Traditional ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Objective:To explore the predictive value of neutrophil to lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) of inflammatory markers of peripheral blood cells on the prognosis in the advanced non-small cell lung cancer (NSCLC) patients with immune therapy.Methods:The hematologic and clinical data of 58 patients with advanced non-small cell lung cancer who received the treatment of immune therapy in the First People's Hospital of Chuzhou of Anhui Province from January 2018 to June 2022 were retrospectively analyzed. X-tile software was used to calculate the optimal cut-off values of NLR and SII. All patients were divided into high and low groups according to the optimal cut-off values. The relationship between different NLR, SII and clinicopathological features, clinical efficacy, prognosis of the advanced non-small cell lung cancer patients with immune therapy were analyzed. Cox regression models were used to perform univariate and multivariate analyses of factors affecting patient prognosis.Results:The optimal cut-off values for NLR and SII were 3.2 and 546.5, respectively. There were statistically significant differences in regional lymph node metastasis ( χ2=5.03, P=0.025) and the number of metastatic sites ( χ2=11.60, P=0.001) between patients in the low-NLR group (NLR<3.2, n=26) and the high-NLR group (NLR≥3.2, n=32). There were statistically significant differences in location of the primary site ( χ2=8.34, P=0.004) between patients in the low-SII group (SII<546.5, n=28) and the high-SII group (SII≥546.5, n=30). The objective response rate (ORR) of the low-NLR group [50.00% (13/26) ] was higher than that of the high-NLR group [21.88% (7/32) ], and there was a statistically significant difference ( χ2=5.02, P=0.025) ; the disease control rate (DCR) of the low-NLR group [69.23% (18/26) ] was higher than that of the high-NLR group [50.00% (16/32) ], but there was no statistically significant difference ( χ2=2.19, P=0.139). The ORR of the low-SII group [53.57% (15/28) ] was higher than that of the high-SII group [26.67% (8/30) ]; The DCR of the low-SII group [67.86% (19/28) ] was higher than that of the high-SII group [33.33% (10/30) ], and there were statistically significant differences ( χ2=4.38 , P=0.036; χ2=6.91 , P=0.009). The median overall survival (OS) of patients in the low-NLR group (17.6 months) was longer than that of the high-NLR group (11.7 months), and there was a statistically significant difference ( χ2=11.07, P=0.001). The median OS of patients in the low-SII group (16.5 months) was longer than that of the high-SII group (12.3 months), and there was a statistically significant difference ( χ2=5.53, P=0.019). Univariate analysis showed that Eastern Cooperative Oncology Group (ECOG) score ( HR=2.20, 95% CI: 1.10-4.39, P=0.025), brain metastases ( HR=3.24, 95% CI: 1.61-6.50, P=0.001), the number of transferred sites ( HR=2.83, 95% CI: 1.44-5.57, P=0.003), NLR ( HR=3.22, 95% CI: 1.56-6.66, P=0.002) and SII ( HR=2.18, 95% CI: 1.12-4.24, P=0.021) were all independent influence factors affecting the prognosis of the advanced non-small cell lung cancer patients with immune therapy; multivariate analysis showed that brain metastases ( HR=2.91, 95% CI: 1.22-6.94, P=0.016), NLR ( HR=2.88, 95% CI: 1.17-7.13, P=0.022) and SII ( HR=3.63, 95% CI: 1.40-9.39, P=0.008) were all independent risk factors affecting the prognosis of the advanced non-small cell lung cancer patients with immune therapy. Conclusion:NLR and SII can be used as important indicators for predicting the efficacy of immunotherapy in the advanced NSCLC and elevated NLR and SII can indicate poor prognosis of patients.

Objective:To screen the main active components of Danggui Buxue Decoction in improving chemotherapy-induced myelosuppression; To predict the key targets and signaling pathways; To establish a multi-level network structure and comprehensively reveal the synergistic mechanism of Danggui Buxue Decoction in improving chemotherapy-induced myelosuppression.Methods:Main components of Danggui Buxue Decoction were searched in TCMSP detabase, combined with literature reports to supplement and improve information. The protein targets of compounds were standardized in the UniProt protein database. Myelosuppression targets were obtained by querying TTD database, GeneCards database, DrugBank detabase and OMIM database. The effective components and common targets of Danggui Buxue Decoction were screened, and the protein-protein interaction (PPI) network of intersection targets was analyzed by String platform to construct the PPI network of effective components and disease targets. Gene ontology (GO) analysis and enrichment pathway analysis of Kyoto gene and genome encyclopedia (KEGG) of key target proteins were conducted through Metascape data platform. Both the results of GO and KEGG analysis were presented. AutoDock software was used for molecular docking to explore the interaction between core targets and active components, and the results were imported into PyMOL software for visual analysis.Results:Danggui Buxue Decoction has a total of 22 active components of Chinese materia medica for improving chemotherapy-induced myelosuppression, 294 potential targets, 3 301 disease targets, and 210 common targets of Chinese materia medica and diseases. Core targets were obtained through network topology analysis and molecular docking. The first five were ESR1, MAPK1, RELA, AKT1, PIK3R1; GO enrichment results obtained 2 430 biological processes, 125 cellular components and 217 molecular functions, including responses to inorganic substances, membrane rafts, micro-organisms membrane region, transcription factor binding, etc.; KEGG enriched 385 pathways, of which cancer pathway, PI3K-Akt signaling pathway, AGE-RAGE signaling pathway, etc. were the main signaling pathways; molecular docking results showed that β-sitosterol has the best binding performance with HSP90AA1, formononetin and RELA in astragalus when it was in Angelicae Sinensis Radix.Conclusion:Danggui Buxue Decoction regulates ESR1, MAPK1, RELA, AKT1 and other core targets through various active components such as quercetin, formononetin, and β-sitosterol. PI3K-AKT and other related signaling pathways can improve chemotherapy-induced myelosuppression and provide a basis for its clinical application.

Objective To investigate the possible presence of radiation brain injury (RBI) in vascular injury and blood-brain barrier (BBB) damage.Methods Seventy 8 weeks old male BALB/C mice were randomly divided into irradiation group and control group;mice in the two groups received whole-brain exposure with a single dose of 10 Gy irradiation or sham irradiation.Tissue samples were taken 1,7,30,90 and 180 days after irradiation (7 mice in each time point per group);HE staining was used to observe the microvascular morphology and density changes;immune-fluorescence staining was used to visualize the differential expressions of factor Ⅷ related antigen (vWF) and zonulaoccludens-1 (ZO-1).Results Micro-vascular disorders began to appear from the first day of irradiation,deteriorating with time extension gradually.After the X-ray irradiation exposure,the protein expressions of vWF and ZO-1 in the irradiation group were significantly decreased as compared with those in the control group 1,7,30,90 and 180 days after irradiation (vWF:23.17±2.93 vs 15.80±2.39,21.25±2.33 vs 11.60±2.3,19.78±2.16 vs 8.20±1.64,17.21±3.31 vs 6.00±2.12 and 16.98±1.92 vs 3.80±2.59;ZO1:26.17±3.31 vs 15.40±1.82,23.20±2.93 vs 12.00±1.58,20.88±2.20 vs 9.10±2.55,18.32±1.87 vs 6.20±1.92 and 17.50±1.91 vs 2.40±1.52,P＜0.05);besides,the decreased expression ofvWF and ZO-1 in the irradiation group showed a time-depended manner,with significant differences between each two time points (P＜0.05).Conclusion X-rays may induce persistent micro-vascular injury and destroyed BBB tight junctions,which may be closely related to the occurrence and development of RBI.

Post traumatic depression (PTD) is a serious complication after traumatic brain injury, with high incidence rate; PTD seriously affects the rehabilitation, outcome and quality of life of patients. Due to unclear pathogenesis of PTD, effective treatments have not yet been found in clinical practice. Repetitive transcranial magnetic stimulation (rTMS), as a new non-invasive neuroregulatory technique, has been used in major depression disorder (MDD). Few clinical evidence on PTD treated by rTMS is noted and optimal rTMS treatment regimen has not yet been defined.This article reviews the clinical studies of rTMS in PTD in recent years, with a view to provide references for clinical application.

Objective: To observe the predictive value of serial platelet function testing (PFT) on outcome in patients undergoing complex percutaneous coronary intervention (PCI). Methods: Six hundred and two consecutive patients undergoing complex PCI in Anzhen hospital were enrolled during October 2011 to June 2012.Adenosine diphosphate(ADP)-induced platelet aggregation was measured by light transmission aggregometry on the first, sixth and twelfth month after PCI and the mean value was calculated.The cut-off value of high on-treatment platelet reactivity (HTPR) was defined as 40%.The primary endpoint was major adverse cardiovascular and cerebral event (MACCE). Clinical outcomes were analyzed by the Kaplan-Meier method and differences were compared using the log-rank test.Multivariate analyses by Cox proportion hazards regression were applied to identify variables independently associated with the adverse outcomes. Results: Five hundred and eighty-five patients (HTPR, n=285; non-HTPR, n=280) finished the follow-up ((28.47±7.45) months). A total of 33 cases of MACCE were observed during the follow-up, among which 29 cases(8.42%) were in HTPR group and 9 cases (3.21%) in the non-HTPR group.Kaplan-Meier analysis suggested that HTPR was associated with an increased incidence of MACCE (log-rank test, P=0.01). The Cox multivariate analysis indicated that HTPR was an independent risk factor of MACCE (HR=2.69, 95%CI 1.23-5.85, P=0.01) in patients undergoing complex PCI.Incidence of MACCE was similar between HTRP patients receiving standard dual antiplatelet therapy (DAPT) or prolonged DAPT (>12 months). Conclusion Serial PFT could predict the long-term prognosis of patients underwent complex PCI.