Maintenance therapy with a combination of azacitidine, danazol, and thalidomide after intensive chemotherapy in patients with acute myeloid leukemia.

OBJECTIVE: This study aimed to evaluate the efficacy of azacitidine (AZA) combined with danazol (DNZ) and thalidomide (THD) maintenance therapy after intensive chemotherapy (IC) in patients with acute myeloid leukemia (AML). METHODS: we retrospectively analyzed the clinical data of 11 patients treated with AZA combined with DNZ and THD as maintenance therapy after IC at the Baiyun Hospital were between February 2017 and March 2021. The patients' clinical features, relapse-free survival (RFS), and overall survival (OS) were analyzed. RESULTS: Eleven cases fulfilled the AML criteria per the 2016 World Health Organization classification. Of the 11 patients, five were females, and six were males, with a median age of 45 years (range, 23-65 years). Ten patients were in the first complete remission (CR1), and one patient was in the second complete remission (CR2). All patients received AZA combined with DNZ and THD maintenance therapy after IC. The median number of AZA cycles received was 7 (6-12). Until June 2022, the median follow-up period was 37 (14-63) months; one patient had a relapse, and three died. RFS at 1 year and 3 years was 100% and 71.1%, respectively, and OS at 3 years was 100%. CONCLUSION: AZA combined with DNZ and THD maintenance therapy is effective for patients with AML who are ineligible for allogeneic hematopoietic stem cell transplantation. Further studies with large sample sizes and randomized are needed to verify these findings.

Association of triglycerides to high density lipoprotein cholesterol ratio with hypertension in Chinese adults: a cross-sectional study.

BACKGROUND: It has been reported that there is a close correlation between triglycerides to high density lipoprotein cholesterol ratio (TG/HDL-C) and hypertension, but there are differences between different researches. The purpose of this study is to investigate the relationship between TG/HDL-C and hypertension in Chinese adults. METHODS: In this study, the open data for secondary analysis were obtained from DATADRYAD website (www.datadryad.org), and the raw data were from the Rich Healthcare Group Health. A total of 112 798 patients were enrolled in this study. The TG/HDL-C ratio was calculated as TG divided by HDL-C. Hypertension was defined as SBP ≥ 140 mmHg or DBP ≥ 90 mmHg. Logistic regression model was used to analyze the relationship between TG/HDL-C and hypertension. Sensitivity analysis and subgroup analysis were carried out to ensure the stability of the results. RESULTS: After adjusting for confounding factors, the increase of TG/HDL-C was independently associated with the risk of hypertension (HR, 95% CI; 1.11,1.07 ~ 1.16). Compared with the lowest quartile (Q1), the risk of hypertension increased with the increase of TG/HDL-C (Q2, Q3 and Q4) [HR, 95% CI; 1.17 (1.06-1.29); 1.25 (1.13-1.38); 1.37 (1.24-1.52)]. Moreover, the relationship between TG/HDL-C and hypertension was not linear, but showed the saturation effect, and the slope of the curve decreases with the increase of TG/HDL-C. Results of subgroup analysis showed that there was a significant correlation among BMI (>=18.5 kg/m2, <24 kg/m2) and females. CONCLUSION: TG/HDL-C is positively associated with increased risk of hypertension in Chinese adults, especially women and normal BMI.

What is known about topic:1. Identifying TG/HDL-C could help to estimate the burden of "low-risk" populations in the hypertensive population.2. Earlier screening and intervention in TG/HDL-C may lead to more effective therapeutic strategies and reduce future hypertension events.What this study adds:1. Determine the prevalence of TG/HDL-C and hypertension in a nationally representative population in China.2. Large sample size ensures powerful analysis of data.

Effects of ultrasound-guided lumbar-sciatic nerve block and epidural anesthesia on the levels of IL-6, IL-8, TNF-α and coagulation factors in peripheral blood of elderly patients after hip arthroplasty.

Background: To investigate the effects of ultrasound-guided lumbar-sciatic nerve block and epidural anesthesia on the levels of inflammatory factors such as Interleukin-6 (IL6), Interleukin-8 (IL-8), Tumor necrosis factor-a (TNF-α) and coagulation factors in peripheral blood of elderly patients after hip arthroplasty to provides reference value for the choice of intraoperative anesthesia. Methods: 96 elderly patients underwent hip arthroplasty in our hospital from March 2018 to December 2019 were selected and divided into ultrasound-guided lumbar-sciatic nerve block group (group A) and epidural anesthesia group (group B) randomly , there were 48 cases in each group. The onset time of intraoperative anesthesia, postoperative hemodynamic indexes, pain score, inflammatory factors and blood coagulation factor levels were compared between group A and group B. Results: It was proved that: (1) The onset time of sensory block and motor block in group B were shorter compared with group A, and the maintenance time of anesthesia was prolonged (P<0.05); (2) Compared with group A, visual analogue scale (VAS) score of group B patients after operation was lower (P<0.05); (3) The systolic blood pressure (SBP) and diastolic blood pressure (DBP) of group B were higher than group A (P<0.05) ) at T1 and T2, while the comparison of SBP and DBP between groups was not statistical difference at T3 and T4 (P>0.05); (3) Compared with group A, the levels of TNF, IL-8and IL-6 in peripheral blood of group B decreased after T2, T3 and T4 (P<0.05); (4) Statistical difference in plasma factor V activity (FV:C), coagulation factor VIII activity (FVIII:C) and fibrinogen (FIB) levels were showed between groups A and B at T2, T3 and T4 (P<0.05) with significantly lower values in group B compared to group A(P<0.05). (5) The half-year mortality rates of patients in two group were 5.56% and 8.33% respectively. There was no significant difference between group A and group B (P>0.05). Conclusions: Compared with epidural anesthesia, lumbarsciatic nerve block is showed significantly lower values in concentration of peripheral blood coagulation factors and inflammatory factors after surgery, thereby alleviating postoperative hypercoagulability and inflammation.

[Establishment of Drug-Resistant Cell Lines of Acute Myeloid Leukemia and Correlation of Sirt1 and PGC-1α Expression Levels with Drug Resistance].

OBJECTIVE: To construct cytarabine-resistant acute myeloid leukemia (AML) cell lines, and explore the correlation between Sirt1, PGC-1α expression levels and drug resistance. METHODS: Human acute promyelocytic leukemia Kasumi-1 cells were induced by the method of gradually increasing the concentration of Ara-C drug. The IC50 value of Kasumi-1 cells before and after drug addition was detected by CCK-8 method, so as to construct Ara-C resistant cell lines. The expression levels of Sirt1 and PGC-1α mRNA in Kasumi-1 drug-resistant cell lines and their parental cell lines were detected by real-time fluorescence quantitative PCR, and the expression levels of Sirt1 and PGC-1α protein in kasumi-1 drug-resistant cell lines and their parental cell lines were detected by Western blot. RESULTS: The constructed Kasumi-1 cell line had common morphological characteristics of drug-resistant cell lines under microscope, and the drug resistance index was greater than 5, indicating that Kasumi-1 drug-resistant cells had good drug resistance after the construction. The RT-qPCR and Western blot assays showed that the expression levels of Sirt1 and PGC-1α mRNA and protein in the drug-resistant cell lines were higher than those of the parental cell lines (P<0.001). CONCLUSION: AML cell lines resistant to Ara-C can be successfully induced by the method of gradually increasing the concentration, and the co-high expression of Sirt1 and PGC-1α may mediate the drug resistance of AML cells.

Effects of compound 21, a non­peptide angiotensin II type 2 receptor agonist, on general anesthesia­induced cerebral injury in neonatal rats.

General anesthesia has a great impact on neurodevelopment. However, the mechanisms underlying this effect and therapeutic methods to address it remain limited. The present study aimed to investigate the effects of compound (C)21, a non­peptide angiotensin II type 2 receptor agonist, on general anesthesia­induced cerebral injury in neonatal rats. Neonatal Sprague Dawley rats (postnatal day 7) were randomly divided into three groups (n=6 per group): The control, isoflurane and C21+ isoflurane (C21) group. General anesthesia was induced through inhalation of 1.3% isoflurane. Apoptosis and synaptic structure were analyzed. The levels of peroxisome proliferator­activated receptor (PPAR)­α were detected using an enzyme­linked immunosorbent assay. BCL2, apoptosis regulator (Bcl­2) expression was also measured. Compared with the control group, the cerebral cortex, hippocampus, amygdala and hypothalamus in the isoflurane group had significantly more apoptotic cells (P<0.05). The nuclei of the control group were round and transparent, while shrunken nuclei and condensed chromatin were visible in the isoflurane group. A reduction in synapse number was observed in the isoflurane group compared with the control. By contrast, nuclei shrinkage and the decrease in synaptic number was improved in the C21 group. PPAR­α and Bcl­2 expression, at the mRNA and protein levels, was significantly reduced in the isoflurane group compared with the control (P<0.05). C21 treatment reduced the decrease in PPAR­α and Bcl­2 in the cerebral cortex, hippocampus, amygdala and hypothalamus (P<0.05). Collectively, it was demonstrated that C21 prevented apoptosis and synaptic loss induced by general anesthesia in neonatal rats by enhancing the expression of PPAR­α and Bcl­2.

miR­23b inhibits proliferation of SMMC­7721 cells by directly targeting IL­11.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer­associated mortality in the 21st century. microRNA (miR)­23b has been shown to be involved in the pathogenesis of many cancers, including breast and prostate cancer. However, the role of miR­23b in HCC remains unclear. The present study revealed a negative correlation between miR­23b expression in HCC tissues and progression of carcinomas. Compared to normal tissues, miR­23b expression was significantly downregulated in HCC tissues, whereas the expression of interleukin (IL)­11 and IL­11 receptor α (IL­11Rα) was significantly upregulated, indicating that miR­23b expression is negatively correlated with IL­11 and IL­11Rα expression. In addition, miR­23b inhibited proliferation and promoted apoptosis of SMMC­7721 cells. This effect was mediated by IL­11, which was found to be the direct target of miR­23b in this study. These results indicated that miR­23b regulates IL­11 and IL­11Rα expression, and might act as an anti­oncogenic agent in the progression of HCC by directly downregulating IL­11 expression.

Shikonin Inhibites Migration and Invasion of Thyroid Cancer Cells by Downregulating DNMT1.

BACKGROUND Shikonin is a component of Chinese herbal medicine. The aim of this study was to investigate the effects of shikonin on cell migration of papillary thyroid cancer cells of the TPC-1 cell line in vitro and expression levels of the phosphate and tensin homolog deleted on chromosome 10 (PTEN) and DNA methyltransferase 1 (DNMT1) genes. MATERIAL AND METHODS The Cell Counting Kit-8 (CCK-8) assay was performed to evaluate the proliferation of TPC-1 papillary thyroid cancer cells, and the normal thyroid cells, HTori-3, in vitro. A transwell motility assay was used to analyze the migration of TPC-1 cells. Western blot was performed to determine the expression levels of PTEN and DNMT1 genes. A methylation-specific polymerase chain reaction (PCR) (MSP) assay was used to evaluate the methylation of PTEN. RESULTS Following treatment with shikonin, the cell survival rate of TPC-1 cells decreased in a dose-dependent manner; the inhibitory effects on HTori-3 cells were less marked. Shikonin inhibited TPC-1 cell migration and invasion in a dose-dependent manner. The methylation of PTEN was suppressed by shikonin, which also reduced the expression of DNMT1 in a dose-dependent manner, and increased the expression of PTEN. Overexpression of DNMT1 promoted the migration of TPC-1 cells and the methylation of PTEN. Levels of protein expression of PTEN in TPC-1 cells treated with shikonin decreased, and were increased by DNMT1 knockdown. CONCLUSIONS Shikonin suppressed the expression of DNMT1, reduced PTEN gene methylation, and increased PTEN protein expression, leading to the inhibition of TPC-1 cell migration.

MiR-29b expression is associated with a dexmedetomidine-mediated protective effect against oxygen-glucose deprivation-induced injury to SK-N-SH cells in vitro.

Ischemic cerebral stroke is a leading cause of death and long-term disability world-wide. Neuronal injury following cerebral ischemia initiates a complex series of signaling cascades that lead to neuronal cell death. MicroRNA 29b (miR-29b) has reported involvement in the pathogenic process of ischemic brain injury. Dexmedetomidine (Dex) is a highly selective α2 adrenergic receptor stimulant that exerts a protective effect on brain tissue. To determine whether Dex might directly influence miR-29b expression after an ischemic injury, human neuroblastoma SK-N-SH cells were subjected to oxygen-glucose deprivation (OGD) for the purpose of creating a neuronal injury model that mimics the effects of brain ischemia in vitro. Next, the association of miR-29b with the protective effect of Dex against ischemic brain injury was studied through the enhancement or inhibition of miR-29b expression by transfection with an miR-29b mimic or inhibitor. We demonstrated that Dex treatment could reduce miR-29b expression, increase cell viability, and inhibit cell apoptosis in the OGD-induced neuronal injury model in vitro. Furthermore, down-regulation of miR-29b expression produced effects on OGD-induced neuronal injuries that were similar to those produced by Dex treatment. Moreover, up-regulation of miR-29b reversed the protective effect of Dex treatment against OGD-induced neuronal injury. Therefore, down-regulation of miR-29b expression might play a role in anti-apoptotic signaling similar to that played by Dex. Elucidation of the role played by miR-29b in ischemia, and identification of a definite association between Dex and miR-29b may lead to the development of new strategies for treating ischemic brain injuries.