Background: and Purpose This study aimed to construct an optimal dynamic nomogram for predicting malignant brain edema (MBE) in acute ischemic stroke (AIS) patients after endovascular thrombectomy (ET). Methods: We enrolled AIS patients after ET from May 2017 to April 2021. MBE was defined as a midline shift of >5 mm at the septum pellucidum or pineal gland based on follow-up computed tomography within 5 days after ET. Multivariate logistic regression and LASSO (least absolute shrinkage and selection operator) regression were used to construct the nomogram. The area under the receiver operating characteristic curve (AUC) and decisioncurve analysis were used to compare our nomogram with two previous risk models for predicting brain edema after ET. Results: MBE developed in 72 (21.9%) of the 329 eligible patients. Our dynamic web-based nomogram (https://successful.shinyapps.io/DynNomapp/) consisted of five parameters: basal cistern effacement, postoperative National Institutes of Health Stroke Scale (NIHSS) score, brain atrophy, hypoattenuation area, and stroke etiology. The nomogram showed good discrimination ability, with a C-index (Harrell’s concordance index) of 0.925 (95% confidence interval=0.890–0.961), and good calibration (Hosmer-Lemeshow test, p=0.386). All variables had variance inflation factors of <1.5 and tolerances of >0.7, suggesting no significant collinearity among them. The AUC of our nomogram (0.925) was superior to those of Xiang-liang Chen and colleagues (0.843) and Ming-yang Du and colleagues (0.728). Conclusions Our web-based dynamic nomogram reliably predicted the risk of MBE in AIS patients after ET, and hence is worthy of further evaluation.

The aim of this study was to investigate the effects of polarization program on the ability of macrophages to regulate iron metabolism. M1 and M2 macrophages were propagated in vitro from porcine alveolar macrophages 3D4/2 and polarized by cytokines. The 3D4/2 macrophages were treated with 20 ng/mL interferon gamma (IFN-γ) and 10 ng/mL interleukin-4 (IL-4) combined with 10 ng/mL macrophage colony-stimulating factor (M-CSF) to induce polarization to M1 and M2, respectively. After incubation for 24 h, the expression levels of inflammatory factors and iron-metabolism genes were determined using real-time qPCR, Western bot and immunofluorescence. The M1/M2 macrophages culture media supernatant was collected and used to treat porcine intestinal epithelial cells IPEC-J2. The proliferation ability of IPEC-J2 was detected using CCK-8 assay kit. Following exogenous addition of ammonium ferric citrate (FAC) to M1/M2 macrophages, the phagocytic function of macrophages was detected using fluorescein isothiocyanate-dextran (FITC-dextran) and flow cytometry. The results showed that, compared with control, M1 macrophages had higher mRNA levels of iron storage proteins (ferritin heavy and light polypeptide, i.e. FtH and FtL), hepcidin and lipocalin-2, as well as iron content. Moreover, iron enhanced the ability of M1 macrophages to phagocytize FITC-dextran. There was no significant change in these mRNA expression levels in M2 macrophages, but the mRNA expression levels of ferroportin and transferrin receptor were up-regulated. In addition, the conditioned media supernatant from M2 macrophages promoted cell proliferation of IPEC-J2. These findings indicate that M1 macrophages tend to lock iron in the cell and reduce extracellular iron content, thereby inhibiting the proliferation of extracellular bacteria. While M2 macrophages tend to excrete iron, which contributes to the proliferation of surrounding cells and thus promotes tissue repair.
Animals ; Cytokines ; Ferritins ; Iron/metabolism* ; Macrophages/metabolism* ; Macrophages, Alveolar/metabolism* ; Swine

Background:Clinical outcomes of undifferentiated arthritis (UA) are diverse,and only 40 ％ of patients with UA develop rheumatoid arthritis (RA) after 3 years.Discovering predictive markers at disease onset for further intervention is critical.Therefore,our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.Methods:We performed a prospective,multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals.Clinical and serological parameters were obtained at recruitment.Follow-up was undertaken in all patients every 12 weeks for 2 years.Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.Results:A total of 234 patients were recruited in this study,and 17 (7.3％) patients failed to follow up during the study.Among the 217 patients who completed the study,83 (38.2％) patients went into remission.UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9％ vs.16.8％,x2=8.228,P=0.008),anti-cyclic citrullinated peptide (CCP) antibodypositivity (66.7％ vs.10.7％,x2 =43.897,P ＜ 0.001),and double-positivity rate of RF and anti-CCP antibody (38.1％ vs.4.1％,x2 =32.131,P ＜ 0.001) than those who did not.Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017,95％ confidence interval:5.803-55.938;P ＜ 0.001).Conclusion:As an independent predictor of RA,anti-CCP antibody should be tested at disease onset in all patients with UA.

OBJECTIVETo investigate the effects of cycle-dependent kinase (CDK) inhibitor SNS-032 on apoptosis in human acute myeloid leukemia (AML) HL-60 cells and its molecular mechanisms.

METHODSCultured AML HL-60 cells were treated with various concentrations of SNS-032. Cell apoptosis was determined with flow cytometry;cell viability was measured by MTT assay; the profiles of microRNA expression of HL-60 cells were analyzed by microRNA microarray;the protein expressions of JAK2/STAT3 pathway were detected by Western blotting.

RESULTSApoptosis of AML HL-60 cells was induced by SNS-032; the rate of apoptosis was (5.9±1.7)%, (12.1±3.1)% and (59.4±3.6)% when HL-60 cells were treated with 0,100 and 200 nmol/L SNS-032. MicroRNA microarray analysis revealed that the levels of miR-30a, miR-183, miR-20b, miR-26b, miR-20a, miR-589, miR-107, miR-181a, miR-106a, miR-17 and miR-378c were down-regulated by SNS-032,whereas the levels of miR-320a and miR-H7* were up-regulated. Western blotting showed that SNS-032 strongly inhibited phosphorylation of STAT3 and protein expression of JAK2,C-MYC and MCL-1.

CONCLUSIONCDK inhibitor SNS-032 can induce apoptosis of AML HL-60 cells, which is associated with the inhibition of MCL-1,C-MYC and JAK2/STAT3, and down-regulation of miR-17-92 family.

Apoptosis ; Cell Survival ; Down-Regulation ; Flow Cytometry ; HL-60 Cells ; Humans ; Janus Kinase 2 ; metabolism ; MicroRNAs ; metabolism ; Oxazoles ; pharmacology ; Phosphorylation ; STAT3 Transcription Factor ; metabolism ; Signal Transduction ; Thiazoles ; pharmacology

OBJECTIVETo investigate whether CYC116 can potentiate matrine-dependent growth inhibition and apoptosis in multiple myeloma (MM) cells.

METHODSThe dose response relationship of matrine to dexamethasone-resistant and dexamethasone-sensitive MM cells was first established. Myeloma RPMI8226 cells were treated with matrine alone or combined with CYC116 for 24 h. Cell proliferation was measured using an MTT assay and apoptosis induction was evaluated by flow cytometry. Activation of the caspase pathway and expression of apoptosis regulator proteins were detected by Western blotting.

RESULTSMatrine significantly induced growth arrest and apoptosis in both drug-resistant and drug-sensitive MM cells. Treatment with the combination of matrine and CYC116 had a stronger cytotoxic effect on MM cells than did single drug treatments. Enhanced apoptosis observed following the combined treatment of matrine and CYC116 was associated with higher levels of activation of caspase-9, caspase-3, and poly adenosine diphosphate ribose polymerase (PARP) and down-regulation of the anti-apoptotic proteins Bcl-2 and Mcl-1 and the signaling proteins p-Akt and nuclear factor κB (NF-κB).

CONCLUSIONCYC116 enhances the growth inhibitory and apoptotic effects of matrine on MM cells.

Alkaloids ; pharmacology ; Apoptosis ; drug effects ; Cell Division ; drug effects ; Cell Line, Tumor ; Humans ; Multiple Myeloma ; pathology ; Pyrimidines ; pharmacology ; Quinolizines ; pharmacology ; Thiazoles ; pharmacology

Objective: To investigate the effects of cycle-dependent kinase ( CDK) inhibitor SNS-032 on apoptosis in human acute myeloid leukemia ( AML) HL-60 cells and its molecular mechanisms .Methods:Cultured AML HL-60 cells were treated with various concentrations of SNS-032 .Cell apoptosis was determined with flow cytometry;cell viability was measured by MTT assay; the profiles of microRNA expression of HL-60 cells were analyzed by microRNA microarray;the protein expressions of JAK 2/STAT3 pathway were detected by Western blotting .Results:Apoptosis of AML HL-60 cells was induced by SNS-032; the rate of apoptosis was (5.9 ±1.7)%, (12.1 ± 3.1)% and (59.4 ±3.6)% when HL-60 cells were treated with 0,100 and 200 nmol/L SNS-032.MicroRNA microarray analysis revealed that the levels of miR-30a, miR-183, miR-20b, miR-26b, miR-20a, miR-589, miR-107, miR-181a, miR-106a, miR-17 and miR-378 c were down-regulated by SNS-032 , whereas the levels of miR-320a and miR-H7* were up-regulated.Western blotting showed that SNS-032 strongly inhibited phosphorylation of STAT 3 and protein expression of JAK 2, C-MYC and MCL-1.Conclusion:CDK inhibitor SNS-032 can induce apoptosis of AML HL-60 cells, which is associated with the inhibition of MCL-1,C-MYC and JAK2/STAT3, and down-regulation of miR-17-92 family .

BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.

METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.

RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).

CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications

OBJECTIVETo explore the effect of ITF2357, a novel histone deacetylase (HDAC) inhibitor, on the growth, differentiation and apoptosis of acute myeloid leukemic (AML) cells and its mechanism.

METHODSAML cell lines kasumi-1 cells as a model for AML1-ETO positive, and THP1 cells for AML1-ETO negative, the leukemic cells proliferation was analyzed by MTT assay, expression of myeloid-specific differentiation antigen and cell cycle by flow cytometry, cell apoptosis by annexin V staining and flow cytometry. AML1-ETO, acetyl-histone, and caspase protein was analyzed by Western blot.

RESULTS0.5 µmol/L ITF2357 treatment significantly inhibited kasumi-1 cells proliferation, with the 48 h half inhibitory concentration (IC(50)) of 0.1 µmol/L. The initial inhibitory concentration of THP1 cell line was 5 µmol/L. ITF 2357 induced apoptosis of kasumi-1 cells in a time- and dose-dependent manner. A dose-dependent increase in early apoptosis occurred at 24 hours treatment and in late apoptosis at 48 hours treatment by ITF2357. Early apoptosis cells increased from (1.44 ± 1.52)% to (24.51 ± 5.79)%. Late apoptosis cells increased from (2.37 ± 2.8)% to (63.66 ± 1.56)%. ITF2357 induced AML1-ETO degradation by caspase-dependent pathway. 0.25 µmol/L ITF2357 induced a time- and dose-dependent increase in expression of myeloid cell surface protein CD13 and CD15. 5 µmol/L ITF2357 blocked the cells at G(0)/G(1) phase, G(0)/G(1) cells increased from (39.69 ± 6.56)% to (79.2 ± 6.51)% and s-phase cells declined from (60.12 ± 3.29)% to (18.97 ± 6.62)%. Kasumi-1 cells incubated with 0.5 µmol/L of ITF2357, AML1-ETO protein began to decrease at 24 hours and could hardly be detected at 96 hours. ITF2357 induced AML1/ETO degradation through a caspase-dependent mechanism. At the same time, acetylated H3 and H4 increased.

CONCLUSIONLow-dose HDAC inhibitor ITF2357 can effectively inhibit the AML cells proliferation, especially for AML1-ETO positive AML cells. It inhibits Kasumi-1 cells proliferation degradation of AML1-ETO protein expression, blocks the cells at G(0)/G(1) phase, and induces apoptosis and differentiation of the cells.

Acetylation ; Apoptosis ; drug effects ; Cell Differentiation ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Histone Deacetylase Inhibitors ; pharmacology ; Histones ; metabolism ; Humans ; Hydroxamic Acids ; pharmacology ; Oncogene Proteins, Fusion ; metabolism

OBJECTIVETo compare the short-term outcomes of surgical treatment for non-small cell lung cancer (NSCLC) by video-assisted thoracoscopic surgery (VATS) and open thoracotomy (OT).

METHODSData of 737 consecutive NSCLC patients who underwent surgical treatment for non-small cell lung cancer by video-assisted thoracoscopic surgery and 630 patients who underwent pulmonary resection via open thoracotomy (as controls) in Cancer Institute & Hospital, Chinese Academy of Medical Sciences between January 2009 and August 2011 were retrospectively reviewed. The risk factors after lobectomy were also analyzed.

RESULTSIn the 506 NSCLC patients who received VATS lobectomy, postoperative complications occurred in 13 patients (2.6%) and one patient died of acute respiratory distress syndrome (0.2%). In the 521 patients who received open thoracotomy (OT) lobectomy, postoperative complications occurred in 21 patients (4.0%) and one patient died of pulmonary infection (0.2%). There was no significant difference in the morbidity rate (P > 0.05) and mortality rate (P > 0.05) between the VATS group and OT group. In the 190 patients who received VATS wedge resections, postoperative complications occurred in 3 patients (1.6%). One hundred and nine patients received OT wedge resections. Postoperative complications occurred in 4 patients (3.7%). There were no significant differences for morbidity rate (P = 0.262) between these two groups, and there was no perioperative death in these two groups. Univariate and multivariate analyses demonstrated that age (OR = 1.047, 95%CI: 1.004 - 1.091), history of smoking (OR = 6.374, 95%CI: 2.588 - 15.695) and operation time (OR = 1.418, 95%CI: 1.075 - 1.871) were independent risk factors of postoperative complications.

CONCLUSIONSTo compare with the NSCLC patients who should undergo lobectomy or wedge resection via open thoracotomy, a similar short-term outcome can be achieved via VATS approach.

Age Factors ; Carcinoma, Non-Small-Cell Lung ; mortality ; pathology ; surgery ; Female ; Humans ; Length of Stay ; Lung Neoplasms ; mortality ; pathology ; surgery ; Lymphatic Metastasis ; Male ; Middle Aged ; Operative Time ; Pneumonectomy ; adverse effects ; classification ; methods ; Postoperative Complications ; etiology ; Respiratory Distress Syndrome, Adult ; etiology ; Retrospective Studies ; Smoking ; Thoracic Surgery, Video-Assisted ; adverse effects ; Thoracotomy ; adverse effects ; methods

OBJECTIVETo investigate synergistically killing effect of histone deacetylase (HDAC) inhibitor suberoylanilide hydroxamic acid (SAHA) combined with imatinib on human chronic myeloid leukemia (CML) cell line.

METHODSK562 cells were co-treated with SAHA and imatinib. Cell growth was measured by MTT assay. Apoptosis was determined using Hoechst staining apoptosis detection kit and flow cytometric analysis. Activation of Caspase pathway, expression of Bcr-Abl and its downstream target genes, and expression of anti-apoptotic proteins were detected by Western blot.

RESULTSSAHA synergized the cytotoxicity of imatinib against leukemia K562 cells, concomitantly with increased apoptosis and enhanced activation of Caspase-3, -8 and PRAP. The combination therapy resulted in significantly lower levels of Bcr-Abl,phosphorylated Bcr-Abl compared to treatment with either SAHA or imatinib alone. Furthermore,the co-treatment resulted in down-regulation of anti-apoptotic protein Mcl-1 expression. Also,marked down-regulated expression of JAK2,STAT5,and phosphorylated STAT5 was detected in the combination therapy.

CONCLUSIONCombining HDAC inhibitor SAHA with imatinib can kill CML cells synergistically by inhibiting cell growth and inducing apoptosis, which is associated with activation of Caspase pathway and regulation of anti-apoptotic proteins.

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; Benzamides ; Caspase 3 ; metabolism ; Caspase 8 ; metabolism ; Drug Synergism ; Fusion Proteins, bcr-abl ; metabolism ; Histone Deacetylase Inhibitors ; pharmacology ; Humans ; Hydroxamic Acids ; pharmacology ; Imatinib Mesylate ; Intracellular Signaling Peptides and Proteins ; metabolism ; Janus Kinase 2 ; metabolism ; K562 Cells ; Piperazines ; pharmacology ; Pyrimidines ; pharmacology ; STAT5 Transcription Factor ; metabolism