Hepatic inflammatory myofibroblastic tumor: A case report.

BACKGROUND: Hepatic inflammatory myofibroblastic tumor (HIMT) is a rare type of hepatic tumor. It is always misdiagnosed and mistreated because it is primarily found with no obvious specific manifestation, and its imaging findings are diverse. CASE SUMMARY: Here, we report a case of HIMT that was initially diagnosed as liver malignancy but was confirmed as HIMT by histopathology after hepatectomy. Mostly, HIMTs are infiltrated with plasma cells and stain positively for anaplastic lymphoma kinase on immunohistochemistry as well as for some other kinases. CONCLUSION: HIMT can be treated with single nonsteroidal anti-inflammatory drugs and without surgery when it is diagnosed accurately. Because the etiology of HIMT is unknown and the diagnosis is difficult, the pathogenesis and clinical process need to be further studied.

[Diagnosis Significance of the Levels of Cytokines IL-6, IL-10 and CXCL-13 in Cerebrospinal Fluid for Central Nervous System Infiltration of Lymphoma].

OBJECTIVE: To evaluate the diagnostic value of the expression levels of cytokines interleukin-6(IL-6), interleukin-10 (IL-10) and chemokine （C-X-C motif） ligand-13 (CXCL-13) in cerebrospinal fluid (CSF) for central nervous system infiltration of lymphoma. METHODS: Forty patients diagnosed as lymphoma or acute lymphoblastic leukemia in General Hospital of Northern Theater Command from July 2020 to July 2021 were collected and recorded their CSF indexes, including pressure, protein, Pandy test, nucleated cell count, glucose and chlorine content in CSF. The levels of cytokines IL-6, IL-10 and CXCL-13 were detected by Enzyme-linked immunosorbent assay. RESULTS: The patients were divided into CNSI (central nervous system infiltration) group and non-CNSI group, the average levels of IL-6, IL-10, CXCL-13 and IL-10/IL-6 ratio in CNSI group were higher than those in non-CNS group, but the difference of IL-10/IL-6 ratio between the two groups was statistically significant (P<0.05). Then the patients were divided into protein elevated(n=14) group and protein normal group(n=26), the levels of IL-6 ï¼» (5.78±2.69) pg/ mlï¼½ and CXCL-13 ï¼»(0.83±0.59) pg/mlï¼½ in protein elevated group were significantly higher than those in the protein normal group ï¼»IL-6: (2.41±1.16) pg/ml; CXCL-13: (0.38±0.18) pg/mlï¼½ (P<0.05). Further analysis of the expression levels of the cytokines in non-CNSI group (n=32), IL-6, IL-10, CXCL-13 level and IL-10/IL-6 ratio in the protein elevated group (n=12) were higher than those in the protein normal group (n=20), but the difference was not statistically significant. CONCLUSION: The levels of IL-6, IL-10 and CXCL-13 in CSF of lymphoma patients with CNS infiltration were higher than those in non-CNS infiltration group, and those in patients with protein elevated group are higher than those in the protein normal group.

Clinical Characteristics of Pediatric Coats' Disease With Retinal Cyst Using Wide-Angle Fluorescein Angiography.

Purpose: To assess the demographic and treatment features of pediatric patients of Coats' disease with retinal cyst using wide-angle FA. Design: A retrospective, hospital based, cross-sectional study. Participants: Pediatric patients of Coats' disease underwent wide-angle FA. Methods: A retrospective review of pediatric patients of Coats' disease who underwent wide-angle FA at a single center from January 2015 to July 2020. Demographic and treatment features were compared between patients with or without retinal cyst. Main Outcome Measures: Demographic and treatment outcomes. Results: There were 123 pediatric Coats' patients in our study, and 18.70% (23/123) of the patients developed complications with retinal cyst, 73.9% (17/23) of the retinal cysts were located in the inferior-temporal quadrant and 82.6% (19/23) of the retinal cysts were located in the peripheral retina anterior to the vortex veins. Compared with patients without retinal cyst, patients with retinal cyst had more clock-hours of telangiectasia on FA (7.32 vs. 5.41, p = 0.031), and may need more total treatments (7.47 vs. 3.53, p = 0.023) including laser photocoagulation (4.08 vs. 2.31, p = 0.019) or intravitreal anti-VEGF (3.13 vs. 2.23, p = 0.039), and also required a longer time for telangiectasia resolution (22.33 vs. 18.53 months, p = 0.043). Conclusion: Pediatric patients with Coats' disease complicated by retinal cyst presented with more clock-hours of telangiectasia on FA and needed more total treatments and longer time for telangiectasia resolution.

Combination of molecularly targeted therapies and immune checkpoint inhibitors in the new era of unresectable hepatocellular carcinoma treatment.

Multikinase inhibitors (MKIs) have been the only first-line treatment for advanced hepatocellular carcinoma (HCC) for more than a decade, until the approval of immune checkpoint inhibitors (ICIs). Moreover, the combination regimen of atezolizumab (anti-programmed cell death protein ligand 1 antibody) plus bevacizumab (anti-vascular endothelial growth factor monoclonal antibody) has recently been demonstrated to have superior efficacy when compared with sorafenib monotherapy. The remarkable efficacy has made this combination therapy the new standard treatment for advanced HCC. In addition to MKIs, many other molecularly targeted therapies are under investigation, some of which have shown promising results. Therefore, in the era of immuno-oncology, there is a significant rationale for testing the combinations of molecularly targeted therapies and ICIs. Indeed, numerous preclinical and clinical studies have shown the synergic antitumor efficacy of such combinations. In this review, we aim to summarize the current knowledge on the combination of molecularly targeted therapies and immune checkpoint therapies for HCC from both preclinical and clinical perspectives.

MiR-526b-3p Attenuates Breast Cancer Stem Cell Properties and Chemoresistance by Targeting HIF-2α/Notch Signaling.

Chemoresistance is a severe clinical challenge in breast cancer. Hypoxia and cancer stem cells (CSCs) contribute to the paclitaxel (PTX) resistance, but the molecular mechanisms are still elusive. MicorRNAs (miRNA) have been considered a promising therapeutic strategy in various cancers. Here, we identified the crucial function of miR-526b-3p in regulating PTX resistance and CSC properties. Our data demonstrated that miR-526b-3p mimic repressed the cell viability of breast cancer cells. The counts of Edu-positive cells were reduced by miR-526b-3p in breast cancer cells. Meanwhile, the apoptosis of breast cancer cells was induced by miR-526b-3p. Tumorigenicity analysis in the nude mice confirmed that miR-526b-3p attenuated the breast cancer cell growth in vivo. Significantly, hypoxia could enhance IC50 value of PTX in breast cancer cells. IC50 value of PTX was induced in breast cancer mammospheres. The hypoxia-inducible factor 2α (HIF-2α) expression was enhanced, but miR-526b-3p expression was repressed under hypoxia in breast cancer cells. Also, breast cancer mammospheres presented high HIF-2α expression and low miR-526b-3p expression. The inhibition of miR-526b-3p enhanced the IC50 value of PTX in breast cancer cells. MiR-526b-3p inhibitor enhanced the colony formation counts of PTX-treated breast cancer cells. The treatment of miR-526b-3p mimic suppressed the sphere formation counts of breast cancer cells and inhibited ALDH1 and Nanog expression. MiR-526b-3p was able to target HIF-2α in the cells. The overexpression enhanced but miR-526b-3p reduced the IC50 value of PTX in breast cancer cells, in which the overexpression of HIF-2α could rescue the miR-526b-3p-inhibited IC50 value of PTX. Overexpression of HIF-2α reversed miR-526b-3p-regulated apoptosis, colony formation ability, and ALDH1 and Nanog expression in the cells. Interestingly, the overexpression of HIF-2α induced but miR-526b-3p repressed the expression of HIF-2α, Hey2, and Notch in PTX-treated breast cancer cells, while HIF-2α could reverse the effect of miR-526b-3p. In conclusion, miR-526b-3p attenuated breast cancer stem cell properties and chemoresistance by targeting HIF-2α/Notch signaling. MiR-526b-3p may be utilized in the relieving chemoresistance in breast cancer.

Vascular endothelial growth factor receptor-2 and its association with tumor immune regulatory gene expression in hepatocellular carcinoma.

Anti-vascular endothelial growth factor (anti-VEGF) drugs have long been the only first-line treatment for advanced or unresectable hepatocellular carcinoma (HCC). Recently, the combination of bevacizumab (an anti-VEGF drug) and atezolizumab (an immune checkpoint blockade, ICB) has been proven to have superior efficacy over sorafenib. However, the complex association between VEGF signaling pathway and tumor immune microenvironment is still largely unknown. Here, we analyzed the RNA sequencing and clinical data of 365 HCC patients obtained from The Cancer Genome Atlas to investigate the potential correlation between VEGF signaling pathway and tumor immune microenvironment, including immune cell infiltration, 66 immune markers, genomic instability, and immune-related pathways. Our study revealed that VEGF signaling pathway score was positively correlated with immune cell infiltration and the expression profile of 66 immune markers. Enrichment analysis indicated that genes differentially expressed between two VEGF score subtypes were enriched in many immune-related Gene Ontology terms. Most importantly, both VEGF signaling pathway and activated CD8+ T cells were positively correlated with prognosis. Our findings suggest the co-activation of VEGF signaling pathway and tumor immune microenvironment in HCC patients, indicating the underlining mechanism of combination therapy including anti-VEGF drugs and ICBs.

MiR-19a-3p regulates the Forkhead box F2-mediated Wnt/ß-catenin signaling pathway and affects the biological functions of colorectal cancer cells.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignancies worldwide. AIM: To explore the expression of microRNA miR-19a-3p and Forkhead box F2 (FOXF2) in patients with CRC and the relevant mechanisms. METHODS: Sixty-two CRC patients admitted to the hospital were enrolled into the study group, and sixty healthy people from the same period were assigned to the control group. Elbow venous blood was sampled from the patients and healthy individuals, and blood serum was saved for later analysis. MiR-19a-3p mimics, miR-19a-3p inhibitor, miR-negative control, small interfering-FOXF2, and short hairpin-FOXF2 were transfected into HT29 and HCT116 cells. Then quantitative polymerase chain reaction was performed to quantify the expression of miR-19a-3p and FOXF2 in HT29 and HCT116 cells, and western blot (WB) analysis was conducted to evaluate the levels of FOXF2, glycogen synthase kinase 3 beta (GSK-3ß), phosphorylated GSK-3ß (p-GSK-3ß), ß-catenin, p-ß-catenin, α-catenin, N-cadherin, E-cadherin, and vimentin. The MTT, Transwell, and wound healing assays were applied to analyze cell proliferation, invasion, and migration, respectively, and the dual luciferase reporter assay was used to determine the correlation of miR-19a-3p with FOXF2. RESULTS: The patients showed high serum levels of miR-19a-3p and low levels of FOXF2, and the area under the curves of miR-19a-3p and FOXF2 were larger than 0.8. MiR-19a-3p and FOXF2 were related to sex, tumor size, age, tumor-node-metastasis staging, lymph node metastasis, and differentiation of CRC patients. Silencing of miR-19a-3p and overexpression of FOXF2 suppressed the epithelial-mesenchymal transition, invasion, migration, and proliferation of cells. WB analysis revealed that silencing of miR-19a-3p and FOXF2 overexpression significantly suppressed the expression of p-GSK-3ß, ß-catenin, N-cadherin, and vimentin; and increased the levels of GSK-3ß, p-ß-catenin, α-catenin, and E-cadherin. The dual luciferase reporter assay confirmed that there was a targeted correlation of miR-19a-3p with FOXF2. In addition, a rescue experiment revealed that there were no differences in cell proliferation, invasion, and migration in HT29 and HCT116 cells co-transfected with miR-19a-3p-mimics+sh-FOXF2 and miR-19a-3p-inhibitor+si-FOXF2 compared to the miR-negative control group. CONCLUSION: Inhibiting miR-19a-3p expression can upregulate the FOXF2-mediated Wnt/ß-catenin signaling pathway, thereby affecting the epithelial-mesenchymal transition, proliferation, invasion, and migration of cells. Thus, miR-19a-3p is likely to be a therapeutic target in CRC.

Predictors for New Native-Vessel Occlusion in Patients with Prior Coronary Bypass Surgery: A Single-Center Retrospective Research.

OBJECTIVES: Chronic total occlusion (CTO) is prevalent in patients with prior coronary artery bypass grafting (CABG). However, data available concerning the prevalence of new-onset CTO of native vessels in patients with prior CABG is limited. Therefore, the objective of the study is to determine predictors for new native-vessel occlusion in patients with prior coronary bypass surgery. METHODS: 354 patients with prior CABG receiving follow-up angiography are selected and analyzed in the present study, with clinical and angiographic variables being analyzed by logistic regression to determine the predictors of new native-vessel occlusion. RESULTS: The overall new occlusion rate was 35.59%, with multiple CTOs (42.06%) being the most prevalent (LAD 24.60% and RCA 18.25%, respectively). Additionally, current smoking (OR: 2.67; 95% CI: 2.60 to 2.74; p=0.01), reduced ejection fraction (OR: 1.76; 95% CI: 1.04 to 2.97; p=0.04), severe stenosis (OR: 3.65; 95% CI: 2.55 to 5.24; p=0.01), and diabetes mellitus (OR: 1.86; 95% CI: 1.34 to 2.97; p=0.04) serve as the independent predictors for new native-vessel occlusion. CONCLUSION: As to high incidence of postoperative CTO, appropriate revascularization strategies and postoperative management should be taken into careful consideration.

Outcomes of secondary sulcus intraocular lens implantation in unilateral anterior persistent fetal vasculature.

AIM: To evaluate the surgical results of sulcus intraocular lens (IOL) implantation in children with unilateral anterior persistent fetal vasculature (PFV) underwent primary vitrectomy combined with lensectomy and preservation of the peripheral anterior capsule. METHODS: Twenty-two eyes of 22 children with unilateral anterior PFV who underwent sulcus secondary IOL implantation were analyzed. Main outcome measures were preoperative and postoperative visual acuity, and complications both intraoperatively and postoperatively. RESULTS: Review of 22 consecutive patients identified best-corrected visual acuity (BCVA) improvement from 1.37±0.84 to 0.73±0.57 logarithm of the minimal angle of resolution (logMAR) after IOL implantation (P<0.001) with a mean follow-up was 16.55±5.86mo. Average age at secondary IOL implantation was 41.05±15.41mo. Three eyes (13.64%) achieved BCVA of 0.3 logMAR at the final visit. Transient intraocular pressure rise (4 eyes; 18.18%), postoperative increased inflammation (3 eyes; 13.64%) and postoperative hypotony (2 eyes; 9.09%) were common complications. CONCLUSION: Properly preservation of the anterior lens capsule during the primary surgery facilitated secondary sulcus IOL implantation in pediatric patients with anterior PFV, with favorable postoperative visual outcomes and compatible percentage of complications.

Case Report: Focal Choroidal Excavation Underlying Combined Hamartoma of the Retina and Retinal Pigment Epithelium.

SIGNIFICANCE: There are few reports of focal choroidal excavation (FCE) in combined hamartoma of the retina and retinal pigment epithelium (CHRRPE). This report documents a case of this rare condition and suggests that there might be a relationship between FCE and CHRRPE. PURPOSE: The purpose of this study was to describe a case of FCE underlying CHRRPE. CASE REPORT: A 6-year-old Chinese boy presented with a 2-month history of decreased vision in his left eye. Fundus examination of the left eye showed an elevated fibrotic mass in the macular area with pigment disturbance. Optical coherence tomography revealed a cup-shaped FCE in the macula with thickening and disorganization of multiple retinal layers and overlying epiretinal proliferation in the left eye. A diagnosis of FCE within CHRRPE was made, and periodic review was recommended. CONCLUSIONS: There may be an association or a causal relationship between CHRRPE and FCE. It is plausible that FCE in the setting of CHRRPE is a developmental abnormality that occurs after birth because of a weakening of the retinal pigment epithelium and thinning of the choroid beneath the tumor. Continued monitoring for FCE progression and potential choroidal neovascularization is indicated.

Outcomes of small gauge pars plicata vitrectomy for patients with persistent fetal vasculature: a report of 105 cases.

AIM: To evaluate the surgical outcomes in eyes with persistent fetal vasculatures (PFV) managed by small gauge pars plicata vitrectomy. METHODS: Consecutive patients with PFV treated by small gauge pars plicata vitrectomy at Beijing Tongren Eye Center between January 2010 and January 2013 were retrospectively reviewed. RESULTS: A total of 118 eyes of 105 patients with PFV were included and undergone small gauge pars plicata vitrectomy, of which 84 (71.2%) eyes had lensectomy and 16 (13.6%) eyes had lens aspiration and immediate intraocular lens implantation. The percentage of sutured scleral incision of 23 gauge vitrectomy (71.7%, 33/46) was higher than that of the 25 gauge vitrectomy (18.1%, 13/72). At last follow-up, visual acuity remained stable in 34 eyes (28.8%) and improved in 84 eyes (71.2%). Age at surgery (less than 2y), anterior type of PFV, and immediate IOL implantation were associated with postoperative improved visual acuity. Sixty five (55.1%) eyes had retinal detachment preoperatively, among which 33 (50.8%, 33/65) eyes had retinal reattachment or partial retinal reattachment. CONCLUSION: The results suggest that cases with PFV have a potential for developing good visual acuity after small gauge pars plicata vitrectomy with favorable anatomic outcomes and acceptable rate of serious surgical complications.

Assessment of Liver Fibrosis Using Real-time Shear-wave Elastography for Patients with Hepatitis B e Antigen-negative Chronic Hepatitis B and Alanine Transaminase <2 Times the Upper Limit of Normal.

BACKGROUND: We assessed liver fibrosis using real-time shear-wave elastography (SWE) combined with liver biopsy (LB) for patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) and alanine transaminase < 2 times the upper limit of normal and hepatitis B virus DNA < 2000 IU/ml. METHODS: A total of 107 patients met the inclusion criteria. Real- ime SWE and ultrasoundassisted liver biopsies were consecutively performed. Fibrosis was staged according to the METAVIR scoring system. Analyses of receiver operating characteristic curve were performed to calculate the optimal area under the receiver operating characteristic curve for F0-F1 versus F2-F4, F0-F2 versus F3-F4, and F0-F3 versus F4 for real-time SWE. RESULTS: The most concurrent liver fibrosis degrees were between F1 and F2 for these HBeAg-negative CHB patients. Liver stiffness increased in parallel with the degree of liver fibrosis using SWE measurements. The area under the receiver operating characteristic curves was 0.881 (95% confidence interval [CI]: 0.704-1.000) for SWE (p = 0.004); 0.912 (95% CI: 0.836-0.987) for SWE (p = 0.000); 0.981 (95% CI: 0.956-1.000) for SWE (p = 0.000); 0.974 (95% CI: 0.936-1.000) for SWE (p = 0.000) when comparing F0 versus F1-F4, F0-F1 versus F2-F4, F0-F2 versus F3-F4, and F0-F3 versus F4, respectively. CONCLUSIONS: SWE has the advantage of providing an image of liver stiffness in real-time. As an alternative to LB, the development of all these noninvasive methods for dynamic evaluation of liver fibrosis will decrease the need for LB, making clinical care safer and more convenient for patients with liver diseases.

The importance of genetic counseling and genetic screening: a case report of a 16-year-old boy with resistant hypertension and severe hypokalemia.

Liddle's syndrome, an autosomal dominant form of monogenic hypertension, is characterized by salt-sensitive hypertension with early penetrance, hypokalemia, metabolic alkalosis, suppression of plasma rennin activity and aldosterone secretion, and a clear-cut response to epithelial sodium channel blockers but not spironolactone therapy. Here, we describe the case of a 16-year-old boy patient with resistant hypertension (maintain 170-180/100-110 mm Hg after administration four kinds of antiypertensive drugs) and severe hypokalemia. After a series of checks, we exclude primary aldosteronism and renal artery stenosis and other diseases. Finally, the Liddle syndrome was diagnosed because of the DNA sequencing found that the proband's mother and himself had mutations P616L (c.1847 C>T) in the SCNN1B gene. Liddle syndrome should be considered as a cause of hypertension in children or adolescents particularly with suppressed renin activity. Early diagnosis and appropriately tailored treatment avoid complications of long-term unrecognized or inappropriately managed hypertension. Genetic testing has made it possible to make accurate diagnoses and develop tailored therapies for mutation carriers. The role of genetic testing and genetic counseling in establishing the early diagnosis of Liddle's syndrome is important.

In vivo synthesis of nano-selenium by Tetrahymena thermophila SB210.

Nano-selenium has a great potential to be used in chemical, biological, medical and environmental fields. Biological methods for nano-selenium synthesis have attracted wide interests, because they can be operated at ambient temperature and pressure without complicated equipments. In this work, a protozoa, Tetrahymena thermophila (T. thermophila) SB210, was used to in vivo synthesize nano-selenium. The biosynthesized nano-selenium was characterized using transmission electron microscopy, energy dispersive X-ray spectroscopy and Raman spectroscopy. The synthesized amorphous spherical selenium nanoparticles had diameters of 50-500nm with the coexistence of irregular nano-selenium. The expressions of glutathione (GSH) synthesis related gene glutathione synthase, cysteine-rich protein metallothionein related gene metallothionein-1 and [2Fe-2S] cluster-binding protein related gene were up-regulated in the nano-selenium producing group. Also, the subsequent GSH detection and in vitro synthesis experimental results suggest the three proteins were likely to be involved in the nano-selenium synthesis process.

Effect of fibulin-5 on adhesion, migration and invasion of hepatocellular carcinoma cells via an integrin-dependent mechanism.

AIM: To elucidate the role of fibulin-5 (FBLN-5) as a suppressor of hepatocellular carcinoma (HCC) cell metastasis via integrin. METHODS: The expression of FBLN-5 was determined by immunohistochemistry in 140 HCC samples and matched normal tissues, and was further confirmed by RT-PCR and Western blot analyses in various cell lines. Recombinant FBLN-5 was expressed in Escherichia coli BL21(DE3), purified and used in cell attachment assays. Expression of a specific plasmid or a specific siRNA in HCC cells resulted in the overexpression or knockdown of FBLN-5, respectively. Further, the migration and invasion of HCC cells were investigated using the Boyden chamber and transwell assays. The concentration of secreted matrix metalloproteinase 7 (MMP-7) was determined using ELISA. RESULTS: FBLN-5 expression was found to be downregulated in HCC. Its expression was significantly correlated with advanced tumor metastasis; this was indicative of poor 5-year overall survival. Recombinant full-length human FBLN-5 promoted the attachment of HCC cells via integrins: it inhibited HCC cell adhesion and migration to fibronectin in a concentration-dependent manner. It also inhibited HCC cell migration and invasion through an integrin-binding arginine-glycine-aspartic acid (RGD) motif by downregulating MMP-7. CONCLUSION: These results suggest that lower FBLN-5 expression is an important indicator of poor survival and that FBLN-5 inhibits HCC motility via an integrin-dependent mechanism. RGD-dependent suppression of MMP-7 by FBLN-5 might contribute to the development of new therapeutic strategies for HCC.

Myeloid-related protein 8 induces self-tolerance and cross-tolerance to bacterial infection via TLR4- and TLR2-mediated signal pathways.

Myeloid-related protein 8 (Mrp8) is the active component of Mrp8/14 protein complex released by phagocytes at the site of infection and stimulates inflammatory responses. However, it is unclear whether Mrp8 could induce self-tolerance and cross-tolerance to bacterial infection. Here we report that Mrp8 triggered TNF-α and IL-6 release via a Toll-like receptor 4 (TLR4)-dependent manner. Pre-stimulation of murine macrophages and human monocytes with Mrp8 induced self-tolerance to Mrp8 re-stimulation and cross-tolerance to lipopolysaccharide (LPS), bacterial lipoprotein (BLP), gram-negative and gram-positive bacterial challenges, with substantially attenuated TNF-α and IL-6 release. Moreover, Mrp8 tolerisation significantly reduced serum TNF-α and IL-6, increased polymorphonuclear neutrophil (PMN) recruitment and accelerated bacterial clearance, thus protecting mice against LPS-induced lethality and cecal ligation and puncture (CLP)-induced polymicrobial sepsis. In addition to TLR4, TLR2 also contributed to Mrp8-induced inflammatory response and tolerance. Down-regulation of phosphorylated p38 by Mrp8 pre-stimulation was predominantly responsible for the intracellular mechanism of Mrp8-induced tolerance. Thus, our findings of Mrp8-induced self-tolerance and cross-tolerance may provide a potential strategy for attenuating an overwhelming proinflammatory cascade and enhancing antimicrobial responses during microbial sepsis.

Predictive Ability of the SYNergy Between Percutaneous Coronary Intervention with TAXus and Cardiac Surgery Score II for Long-term Mortality in Patients with Three-vessel Coronary Artery Disease Undergoing Percutaneous Coronary Intervention Treated with Second-generation Drug-eluting Stents.

BACKGROUND: The SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery Score II (SS-II) can well predict 4-year mortality in patients with complex coronary artery disease (CAD), and guide decision-making between coronary artery bypass graft surgery and percutaneous coronary intervention (PCI). However, there is lack of data regarding the utility of the SS-II in patients with three-vessel CAD undergoing PCI treated with second-generation drug-eluting stents (DES). The purpose of the present study was to evaluate the ability of the SS-II to predict long-term mortality in patients with three-vessel CAD undergoing PCI with second-generation DES. METHODS: Totally, 573 consecutive patients with de novo three-vessel CAD who underwent PCI with second-generation DES were retrospectively studied. According to the tertiles of the SS-II, the patients were divided into three groups: The lowest SS-II tertile (SS-II ≤20), intermediate SS-II tertile (SS-II of 21-31), and the highest SS-II tertile (SS-II ≥32). The survival curves of the different groups were estimated by the Kaplan-Meier method. Univariate and multivariate Cox proportional hazard regression analyses were performed to evaluate the relationship between the SS-II and 5-year mortality. The performance of the SS-II with respect to predicting the rate of mortality was studied by calculating the area under the receiver operator characteristic (ROC) curve. The predictive ability of the SS-II for 5-year mortality was evaluated and compared with the SS alone. RESULTS: The overall SS-II was 27.6 ± 9.0. Among patients in the lowest, intermediate and the highest SS-II tertiles, the 5-year rates of mortality were 1.6%, 3.2%, and 8.6%, respectively (P = 0.003); the cardiac mortality rates were 0.5%, 1.9%, and 5.2%, respectively (P = 0.014). By multivariable analysis, adjusting for the potential confounders, the SS-II was an independent predictor of 5-year mortality (hazard ratio: 2.45, 95% confidence interval: 1.38-4.36; P = 0.002). The SS-II demonstrated a higher predictive accuracy for 5-year mortality compared with the SS alone (the area under the ROC curve was 0.705 and 0.598, respectively). CONCLUSION: The SS-II is an independent predictor of 5-year mortality in patients with three-vessel CAD undergoing PCI treated with second-generation DES, and demonstrates a superior predictive ability over the SS alone.

[α-GalCer reduces Acute Graft-versus-Host Disease by Altering Donor T Cells Migration].

OBJECTIVE: This study was aimed to explore the new mechanism of α-Galactosyleramide (α-GalCer), a synthetic glycolipid, and a well-known activator of natural killer T cells (NKT) for improving acute graft-versus-host disease(aGVHD). METHODS: Murine allogeneic bone marrow transplantation (allo-BMT) model was established. Recipient mice were injected intraperitoneally with α-GalCer immediately after allo-BMT, whereas mice from the vehicle groups received the diluent (DMSO) only. The severity degree of aGVHD was estimated by survival, aGVHD clinical score and pathology. The mechanism of aGVHD reduced by α-GalCer was explored by detecting T cells migration in vivo and in vitro. RESULTS: Mice in α-GalCer group survived longer than in control group, and their clinical and pathological status of aGVHD were lighter. α-GalCer reduced aGVHD by altering donors T cell migration. CONCLUSION: After allo-BMT α-GalCer reduces aGVHD by altering donor T cells migration.

Blockade of autophagy aggravates endoplasmic reticulum stress and improves Paclitaxel cytotoxicity in human cervical cancer cells.

PURPOSE: Autophagy is one of the ways to degrade unfolded proteins after endoplasmic reticulum (ER) stress. The purpose of this study is to determine whether a blockade of autophagy leads to aggravated endoplasmic reticulum stress, which then induces cells apoptosis in HeLa cells treated with paclitaxel. MATERIALS AND METHODS: Autophagy activation and the proapoptotic effects were characterized using monodansylcadaverine labeling and Hoechest staining, respectively. A Western blot analysis was used to detect the expression of apoptotic and autophagy-related genes. A flow cytometry was used to assess the cell apoptosis ratio. RESULTS: Paclitaxel exposure induced the aggregation of autophagosomes in the cytoplasms of cervical cancer HeLa cells. The expression of Beclin 1 and LC3 II were upregulated, but p62 was downregulated, which suggests that autophagy was promoted by paclitaxel. On the other hand, the expression of GRP78 obviously increased, suggesting that ER stress was induced after paclitaxel treatment. The cell proliferation assay indicated that a knockdown of Beclin 1 sensitized HeLa cells to paclitaxel. Furthermore, paclitaxel-mediated apoptotic cell death was further potentiated by the pretreatment with autophagy inhibitor chloroquine or small interfering RNA against Beclin 1. These results suggest that an induction of autophagy by paclitaxel may induce cell survival rather than cell death in HeLa cells; moreover, inhibition of autophagy led to an aggravated ER stress and an induction of downstream apoptosis. CONCLUSION: Our results reveal autophagy induced by paclitaxel conferred protection of tumor cells against apoptosis, and blockade of autophagy subsequently aggravated ER stress, enhancing the apoptosis associated with paclitaxel treatment in HeLa cells.