OBJECTIVE: Foreign studies have reported that coronary artery disease (CAD) patients with high baseline low-density lipoprotein cholesterol (LDL-C) may have a good prognosis, which is called the "cholesterol paradox". This study aimed to examine whether the "cholesterol paradox" also exists in the Chinese population. METHODS: A total of 2,056 patients who underwent the first percutaneous coronary intervention (PCI) between 2014 and 2016 were enrolled in this retrospective cohort study and classified into two groups based on baseline LDL-C = 2.6 mmol/L (100 mg/dL). The outcomes of interest included major adverse cardiovascular events (MACE), all-cause mortality, recurrent nonfatal myocardial infarction, unexpected coronary revascularization, or any nonfatal stroke. RESULTS: All-cause mortality occurred in 8 patients (0.7%) from the low-LDL-C group and 12 patients (2.4%) in the high-LDL-C group, with a significant difference between the two groups (adjusted hazard ratio: 4.030, 95% confidence interval: 1.088-14.934; P = 0.037). However, no significant differences existed for the risk of MACE or other secondary endpoints, such as unexpected revascularization, nor any nonfatal stroke in the two groups. CONCLUSION In this study, a high baseline LDL-C was not associated with a low risk of clinical outcomes in CAD patients undergoing first PCI, which suggested that the "cholesterol paradox" may be inapplicable to Chinese populations.
Humans ; Cholesterol, LDL ; Retrospective Studies ; Percutaneous Coronary Intervention/adverse effects* ; Coronary Artery Disease/surgery* ; Cholesterol ; Cholesterol, HDL ; Stroke/etiology* ; Treatment Outcome ; Risk Factors

Entinostat plus exemestane in hormone receptor-positive (HR+) advanced breast cancer (ABC) previously showed encouraging outcomes. This multicenter phase 3 trial evaluated the efficacy and safety of entinostat plus exemestane in Chinese patients with HR + ABC that relapsed/progressed after ≥1 endocrine therapy. Patients were randomized (2:1) to oral exemestane 25 mg/day plus entinostat (n = 235) or placebo (n = 119) 5 mg/week in 28-day cycles. The primary endpoint was the independent radiographic committee (IRC)-assessed progression-free survival (PFS). The median age was 52 (range, 28-75) years and 222 (62.7%) patients were postmenopausal. CDK4/6 inhibitors and fulvestrant were previously used in 23 (6.5%) and 92 (26.0%) patients, respectively. The baseline characteristics were comparable between the entinostat and placebo groups. The median PFS was 6.32 (95% CI, 5.30-9.11) and 3.72 (95% CI, 1.91-5.49) months in the entinostat and placebo groups (HR, 0.76; 95% CI, 0.58-0.98; P = 0.046), respectively. Grade ≥3 adverse events (AEs) occurred in 154 (65.5%) patients in the entinostat group versus 23 (19.3%) in the placebo group, and the most common grade ≥3 treatment-related AEs were neutropenia [103 (43.8%)], thrombocytopenia [20 (8.5%)], and leucopenia [15 (6.4%)]. Entinostat plus exemestane significantly improved PFS compared with exemestane, with generally manageable toxicities in HR + ABC (ClinicalTrials.gov #NCT03538171).

Humans ; Intestinal Polyps ; Colonic Polyps/surgery* ; Intestinal Polyposis ; Colorectal Neoplasms

Objective: More than 75% of ovarian cancer patients are diagnosed at advanced stages and die of tumor cell metastasis. This study aimed to identify new epigenetic and transcriptomic alterations associated with ovarian cancer metastasis. Methods: Two cell sublines with low- and high-metastasis potentials were derived from the ovarian cancer cell line A2780. Genome-wide DNA methylome and transcriptome profiling were carried out in these two sublines by Reduced Representation Bisulfite Sequencing and RNA-seq technologies. Cell-based assays were conducted to support the clinical findings. Results: There are distinct DNA methylation and gene expression patterns between the two cell sublines with low- and high-metastasis potentials. Integrated analysis identified 33 methylation-induced genes potentially involved in ovarian cancer metastasis. The DNA methylation patterns of two of them (i.e., SFRP1 and LIPG) were further validated in human specimens, indicating that they were hypermethylated and downregulated in peritoneal metastatic ovarian carcinoma compared to primary ovarian carcinoma. Patients with lower SFRP1 and LIPG expression tend to have a worse prognosis. Functionally, knockdown of SFRP1 and LIPG promoted cell growth and migration, whereas their overexpression resulted in the opposite effects. In particular, knockdown of SFRP1 could phosphorylate GSK3β and increase β-catenin expression, leading to deregulated activation of the Wnt/β-catenin signaling. Conclusion Many systemic and important epigenetic and transcriptomic alterations occur in the progression of ovarian cancer. In particular, epigenetic silencing of SFRP1 and LIPG is a potential driver event in ovarian cancer metastasis. They can be used as prognostic biomarkers and therapeutic targets for ovarian cancer patients.

This study aims to investigate the potential mechanism of curcumin in mediating interleukin-6(IL-6)/signal transducer and activator of transcription 3(STAT3) signaling pathway to repair intestinal mucosal injury induced by 5-fluorouracil(5-FU) chemotherapy for colon cancer. SD rats were intraperitoneally injected with 60 mg·kg~(-1)·d~(-1) 5-FU for 4 days to establish a model of intestinal mucosal injury. Then the rats were randomly divided into model group(equal volume of normal saline), curcumin low, medium and high dose groups(50, 100, 200 mg·kg~(-1)), and normal SD rats were used as control group(equal volume of normal saline). Each group received gavage administration for 4 consecutive days, and the changes of body weight and feces were recorded every day. After administration, blood was collected from the heart, and jejunum tissues were collected. The levels of serum interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) were detected by ELISA, and at the same time, the concentration of Evans blue(EB) in jejunum was measured. Hematoxylin-eosin(HE) staining was used to observe the pathological state of jejunum, and the length of jejunum villi and the depth of crypt were measured. The positive expression levels of claudin, occludin and ZO-1 were detected by immunohistochemistry. Western blot was used to detect the protein expression of IL-6, p-STAT3, E-cadherin, vimentin and N-cadherin in jejunum tissues. The results showed that, curcumin significantly increased body weight and fecal weight(P<0.05 or P<0.01), decreased fecal score, EB concentration, IL-1β and TNF-α levels(P<0.05 or P<0.01) in rats. In addition, curcumin maintained the integrity of mucosal surface and villi structure of jejunum to a large extent, and reduced pathological changes in a dose-dependent manner. Meanwhile, curcumin could increase the positive expression of occludin, claudin and ZO-1(P<0.05 or P<0.01), repair intestinal barrier function, downregulate the protein expression of IL-6, p-STAT3, vimentin and N-cadherin in jejunum tissues(P<0.05 or P<0.01), and upregulate the protein expression of E-cadherin(P<0.05). Therefore, curcumin could repair the intestinal mucosal injury induced by 5-FU chemotherapy for colon cancer, and the mechanism may be related to the inhibition of IL-6/STAT3 signal and the inhibition of epithelial-mesenchymal transition(EMT) process.
Animals ; Colonic Neoplasms/drug therapy* ; Curcumin ; Fluorouracil/toxicity* ; Interleukin-6/genetics* ; Intestinal Mucosa/metabolism* ; Rats ; Rats, Sprague-Dawley ; STAT3 Transcription Factor/metabolism* ; Signal Transduction

OBJECTIVE: To investigate the efficacy of eltrombopag in the treatment of refractory acquired pure red cell aplasia(PRCA). METHODS: Three patients with refractory acquired PRCA treated in the First Affiliated Hospital of Nanjing Medical University/Jiangsu Province Hospital from March 2018 to May 2019 were treated with eltrombopag(75 mg/d). The clinical data were collected for evaluating efficacy and tolerance. RESULTS: The erythrocyte count(P=0.039), hemoglobin concentration(P=0.018) and reticulocyte percentage(P=0.046) in 3 patients were significantly higher than those before treatment. The platelet count was higher than that before treatment(P=0.024). The leukocyte count and absolute neutrophil count increased in 2 patients, and decreased in 1 patient, but still remained in the normal range(P=0.924; P =0.565). Total bilirubin(TBIL) and direct bilirubin(DBIL) increased in 1 case; alanine aminotransferase(ALT), aspartate aminotransferase(AST) and serum creatinine(Scr) increased in 1 case; palpitation occurred in 1 case. All the side effects were alleviated after symptomatic treatment. CONCLUSION: Eltrombopag has certain efficacy and good tolerance in the treatment of refractory acquired PRCA, which is worthy of further exploration.

Obesity is an important risk factor for cardiovascular diseases, which can lead to a variety of cardiovascular diseases including myocardial remodeling. Obesity may induce myocardial dysfunction by affecting hemodynamics, inducing autonomic imbalance, adipose tissue dysfunction, and mitochondrial dyshomeostasis. The key necessary biochemical functions for metabolic homeostasis are performed in mitochondria, and mitochondrial homeostasis is considered as one of the key determinants for cell viability. Mitochondrial homeostasis is regulated by dynamic regulation of mitochondrial fission and fusion, as well as mitochondrial cristae remodeling, biogenesis, autophagy, and oxidative stress. The mitochondrial fission-fusion and morphological changes of mitochondrial cristae maintain the integrity of the mitochondrial structure. The mitochondria maintain a "healthy" state by balancing biogenesis and autophagy, while reactive oxygen species can act as signaling molecules to regulate intracellular signaling. The excessive accumulation of lipids and lipid metabolism disorder in obesity leads to mitochondrial dyshomeostasis, which activate the apoptotic cascade and lead to myocardial remodeling. In this review, we provide an overview of the recent research progress on obesity-induced myocardial remodeling and its possible mechanism of mitochondrial dyshomeostasis.
Humans ; Mitochondria ; pathology ; Mitochondrial Dynamics ; Myocardium ; pathology ; Obesity ; physiopathology ; Reactive Oxygen Species

Objective To study antioxidant role and mechanism of Rg1 in rats with cerebral ischemia reperfusion injury (IRI).Methods One hundred and twenty healthy male rats were randomly divided into six groups: control group, sham operation group, model group, different concentration (30,60,90 mg/kg) of Rg1 treatment group.MCAO SD rats model was established by suture－occluded method;the Rg1 treatment groups were given Rg1 i.p. in advance, after 24 hours of reperfusion, neurobehavioral scores of all groups were examined by Longa’s standard;The expression of Nrf2 and HO－1 were analyzed by western blot;The content of SOD and MDA was detected by kit.Results The score of model group rats are significantly higher than control group,compared with the model group, the score of different concentration of Rg1 treatment group was decreased (P＜0.05) . The Nrf2 and HO－1 expression in model group was mildly higher than the control or sham group (P＜0.05) . Both of them in every Rg1 treatment group was higher than model group. Compared with control or sham group, SOD content was observably depressed but MDA content was dramatically increased in model group,interestingly,SOD content was enhanced, MDA content was attenuated in different concentration of Rg1 treatment group (P＜0.05). Conclusion Rg1 increases Nrf2 and HO－1 protein expression and SOD content, reduces MDA content,improves neurofunctional performance of rats after MCAO,and alleviates cerebral cerebral IRI.

Graft-versus-host disease (GVHD) is a major complication of allo-hematopoietic stem cell transplantation. It is reported that IL-2R, TNFR1, elafin (for skin GVHD) and REG-3α (for gastrointestinal GVHD) can be used in the early diagnosis of acute GVHD, but they cannot predict the response to therapy independently. Therefore, it is urgent to find a biomarker to predict GVHD and glucocorticoid resistance. ST2 is a member of IL-1 receptor family and specially binds to IL-33. Researchers have found that higher ST2 level is associated with increased GVHD risk, glucocorticoid resistance and transplantation-related mortality. This review focuses on the structure, function, signal transduction pathway of ST2/IL-33, and its roles in diagnosis and treatment of autoimmune diseases and GVHD.
Autoimmune Diseases ; Biomarkers ; Early Diagnosis ; Graft vs Host Disease ; diagnosis ; therapy ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Receptors, Interleukin-1 ; metabolism ; Transplantation, Homologous

OBJECTIVETo study the clinical characteristics of ecotopic viral integration site-1 (EVI1) and BCR/ABL positive childhood leukemia.

METHODSClinical data of four children with EVI1 and BCR/ABL positive leukemia and eight children with BCR/ABL positive but EVI1 negative chronic myeloid leukemia (CML) were retrospectively analyzed.

RESULTSIn the four children with EVI1 and BCR/ABL positive leukemia, two were initially diagnosed with chronic phase of CML, one with accelerated phase of CML and one with high-risk acute lymphoblastic leukemia (ALL). There were no significant differences in clinical characteristics at diagnosis between the patients with EVI1 and BCR/ABL positive leukemia and BCR/ABL positive but EVI1 negative leukemia. CD33 and CD38 were highly expressed and t(9;22) abnormality was present in all patients with EVI1 and BCR/ABL positive leukemia. Two of the 3 children with EVI1 and BCR/ABL positive CML achieved complete remission one or three months after treatment. Acquired negative status conversion occurred for EVI1 but not BCR/ABL in one CML case. The 3 children with EVI1 and BCR/ABL positive CML survived 20, 13 and 14 months, respectively, without recurrence. The child with EVI1 and BCR/ABL positive ALL failed to achieve complete remission after the first course of treatment and discontinued further treatment.

CONCLUSIONSCo-expression of EVI1 and BCR/ABL fusion gene can be found in childhood CML and ALL. The relatively rare leukemia has not significant difference respect to clinical characteristics. Prognosis of the disease needs to be determined by clinical studies with a larger sample size.

Child ; DNA-Binding Proteins ; genetics ; Female ; Genes, abl ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; genetics ; MDS1 and EVI1 Complex Locus Protein ; Male ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; Prognosis ; Proto-Oncogenes ; genetics ; Retrospective Studies ; Transcription Factors ; genetics