Background: Acute myeloid leukemia (AML) is associated with a high relapse rate and poor prognosis. This study aimed to use weighted gene coexpression network analysis (WGCNA) of gene coexpression networks to identify candidate prognostic biomarker genes in patients with AML and to investigate the expression of these genes in the human U937 cell line in vitro. Material/Methods: RNA-seq data were retrieved from the Cancer Genome Atlas (TCGA) and included bone marrow samples and survival data of patients with AML (N=151), patients who did not relapse after treatment (N=119), and patients with relapse (N=40). Differentially expressed genes were identified, WGCNA was used to detect functional modules, and survival analysis was performed. The Cell Counting Kit-8 (CCK-8) assay investigated the proliferation of U937 cells transfected with short hairpin RNAs (shRNAs), shCRIP1, shHIST1H1C, and shHIST1H1E. RNA-seq analysis identified gene expression following CRIP1 knockdown. Results: Eighty-two genes were associated with both relapse and prognosis in patients with AML. There were two prognosis-related gene modules in the coexpression network. In the coexpression network, the histone cluster 1 H1 family member gene, HIST1H1C had the maximum relapse fold change, HIST1H1E had the lowest survival p-value, and the cysteine-rich intestinal protein 1 (CRIP1) gene had the most edge numbers and was significantly associated with poor prognosis (P=0.0165786). RNA-seq data showed that there was a significant difference in gene expression after CRIP1 knockdown in U937 cells. Conclusions: WGCNA of gene coexpression networks identified CRIP1 as a potential prognostic biomarker gene in patients with AML.
Background: We introduce a minimally invasive technique for the treatment of Raynaud disease - CT-guided percutaneous thoracic sympathetic chain radiofrequency thermocoagulation. Material/Methods: Under CT guidance, the radiofrequency needle was punctured from the upper edge of the costotransverse joint to the anterior superior edge of the 4th capitulum costae and the lateral parietal pleura. After sensorial (1.5 mA, 50 Hz) and motorial (1.5 mA, 2Hz) testing to determine that there was no nerve innervation zone with muscle numbness and twitches, radiofrequency coagulation was set at 95 degrees C for 300 s. Results: A total of 17 patients were enrolled in the treatment group. All the patients underwent CT-guided percutaneous thoracic sympathetic chain puncture of the needles to the upper edge of the 4th capitulum costae on both sides. The perfusion index (PI) of the fingers began to rise 30 s after radiofrequency thermocoagulation, and the palm temperature (T) began to rise after 90 s. At the end of treatment, PI increased by an average of 4.6-fold, and the T average rose by 3.6 degrees C. Postoperative cold-water stimulation testing could no longer induce Raynaud disease. Follow-up was conducted for 1 to 15 months. Two patients were found to have recurrence at 9 months and 13 months, respectively. Conclusions: CT-guided percutaneous thoracic sympathetic nerve chain radiofrequency coagulation can effectively treat Raynaud disease.
Background: Glioblastoma, the most common and malignant glial tumor, often has poor prognosis. Tivantinib has shown its potential in treating c-Met-high carcinoma. No studies have explored whether tivantinib inhibits the development of glioblastoma. Material/Methods: The correlation between c-Met expression and clinicopathological characteristics of glioblastoma was investigated. U251 and T98MG glioblastoma cells treated with tivantinib, PI3K inhibitor (LY294002), PI3K activator (740 Y-P), and/or mammalian target of rapamycin (mTOR) inhibitor were subjected to MTT assay or colony formation assay to evaluate cell proliferation. The expression of mTOR signaling and caspase-3 in tivantinib-treated glioblastoma cells was differentially measured by western blotting. Results: In a group of Chinese patients, expression of c-Met was elevated with the size of glioblastoma, but not with the other clinicopathological characteristics, including gender, age, grade, IDH status, 1p/19q status, and Ki67 status. High dose of tivantinib (1 mu mol/L) obviously repressed the proliferation and colony formation of U251 and T98MG glioblastoma cells, but low dose (0.1 mu mol/L) of tivantinib failed to retard cell proliferation. Tivantinib blocked PI3K/Akt/mTOR signaling but did not change the expression of cleaved caspase-3. PI3K activator 740 Y-P (20 mu mol/L) significantly rescued tivantinib-induced decrease of cell proliferation. Tivantinib (1 mu mol/L) in combination with PI3K inhibitor LY294002 (0.5 mu mol/L) and mTOR inhibitor rapamycin (0.1 nmol/L) largely inhibited the proliferation of glioblastoma cells. Conclusions: c-MET inhibitor tivantinib blocks PIKE/Akt/mTOR signaling and hampers the proliferation of glioblastoma cells, which endows the drug a therapeutic effect.
Background: Serine hydroxymethyltransferase (SHMT) is the enzyme that catalyzes the reversible conversion of serine to glycine and tetrahydrofolate-bound one-carbon unit. Upregulation of SHMT2 has been observed in a variety of cancers, but the expression profile and clinical value of SHMT2 in gastric cancer (GC) are still unknown. Material/Methods: In this study, SHMT2 expression was assessed in 130 patients with GC by immunohistochemistry (IHC). mRNA of SHMT2 in GC tissues and normal gastric epithelium was compared with qRT-PCR results. The correlations between SHMT2 and the clinicopathologic factors were analyzed with the chi-square test. Univariate analysis with Kaplan-Meier method was used to estimate the correlations between survival rate and clinicopathologic factors, including SHMT2. The independent prognostic biomarkers were confirmed by multivariate analysis using the Cox-regression hazard model. The function of SHMT2 in progression of GC was assessed by in vitro experiments. Results: The percentages of low and high expression of SHMT2 were 46.92% and 53.08%, respectively. SHMT2 mRNA in GC tissue was significantly higher than mRNA in the patient-paired adjacent tissues. In the clinical analysis, SHMT2 expression was notably associated with positive lymphatic invasion. High SHMT2 was also demonstrated to independently predict poor prognosis of GC. After silencing SHMT2, we proved that SHMT2 can promote proliferation and invasion of GC cells. Conclusions: High SHMT2 promoted progression and was an independent prognostic biomarker of GC, suggesting that SHMT2 detection would be helpful for stratification of high-risk patients and thus directing personalized treatment.
Background: Primary intramedullary spinal cord lymphoma (PISCL) is a rare cause of myelopathies. Considering its poor prog-nosis, it is essential to determine the appropriate treatment strategies and to develop nomograms to predict survival outcome for PISCL patients. Material/Methods: Data were collected from the Surveillance, Epidemiology and End Results (SEER) database. We used 364 patients to investigate overall survival (OS) and 289 patients for cancer-specific survival (CSS). Kaplan-Meier method was to evaluate correlations of survival with different treatment strategies and clinicopathologic factors. Univariate and multivariable analyses were conducted to assess OS and CSS based on different variables. Risk factors were integrated to build nomograms. Results: Most of the 414 PISCL patients diagnosed with positive histology had diffuse B cell lymphoma, were under 60 years old, were male, were of white race, had 1 primary tumor, were married, were low stage, and had previously undergone chemotherapy. We found that radiation therapy had no effect on patient OS and CSS, and patients receiving chemotherapy alone tended to have better OS and CSS in comparison with other groups. In addition, we showed that clinicopathologic factors, including histologic type, age, stage, and marital status, could serve as independent prognostic factors for PISCL patient OS and CSS. These factors were utilized to construct nomograms. The calibration curves demonstrated good agreement. The concordance indexes for OS and CSS were 0.672 (P=0.024) and 0.683 (P=0.029), respectively. Conclusions: Practical nomograms were established for patients' OS and CSS. Besides, this study can guild clinician to make the right decision for appropriate treatment of PISCL patients.
Background: The initiation of atherosclerosis (AS) is attributed to the dysfunction of endothelial cells (ECs) via the inhibition of g protein-coupled estrogen receptor (GPER). In the current study, we assessed the potential of Ginsenoside Rb1 (Rb1) to attenuate the dysfunction of ECs via GPER-mediated PI3K/Akt pathway. Material/Methods: AS was induced in rabbits and then the AS rabbits were treated with Rb1. Thereafter, the ECs were isolated from AS and healthy rabbits, and treated with Rb1. The effect of Rb1 on blood lipid levels in AS rabbits and on apoptosis, inflammatory response, and GPER/PI3K/Akt axis activity in ECs was detected. Furthermore, the activities of GPER and PI3K were modulated to verify the key role of the axis in the anti-AS effect of Rb1. Results: The levels of total cholesterol, low-density lipoprotein (LDL), and triglyceride in AS rabbits were suppressed by Rb1 while the high-density lipoprotein (HDL) level was increased. In in vitro assays, Rb1 administration inhibited apoptosis process and the production of pro-inflammation cytokines in AS ECs. The expression levels of GPER, p-PI3K, and p-Akt were upregulated by Rb1, associated with the increased level of BcI-2 and reduced level of Bax. When the activity of GPER was inhibited by GP-15 in AS ECs, the treatment effect of Rb1 was blocked. However, the activation of PI3K could restore the protective effect of Rb1 after the inhibition of GPER. Conclusions: The anti-AS potential of Rb1 was exerted by restoring the regular function of ECs via the activation of GPER-mediated PI3K/Akt signaling.
Background: Curcumin is a polyphenol compound extracted from the root of the herb Curcuma longa, which is used in traditional Chinese medicine (TCM). Worldwide, colorectal carcinoma (CRC) is an increasing cause of morbidity and mortality. This study aimed to investigate the effects of increasing concentrations of curcumin on cell viability, proliferation, and apoptosis of SW620 human colonic adenocarcinoma cells cultured in vitro, and the signaling pathways involved. Material/Methods: SW620 human colonic adenocarcinoma cells were cultured in curcumin at concentrations of 0, 4, 8, 16, and 32 mu mol/l for 48 hours. Specific small interfering RNA (siRNA) was transfected into SW620 cells to silence the expression of caudal type homeobox-2 (CDX2). Cell viability was measured using the MTT assay. Flow cytometry evaluated cell apoptosis. Western blot and reverse transcriptase-polymerase chain reaction (RT-PCR) were used to assess the nuclear translocation of beta-catenin and the activation of Wnt signaling. Results: Curcumin reduced cell viability and increased apoptosis of SW620 human colonic adenocarcinoma cells in a dose-dependent way, and increased the expression of CDX2 but decreased beta-catenin nuclear translocation and the expression of Wnt3a, c-Myc, survivin, and cyclin D1. CDX2 silencing significantly reduced the effects of curcumin on SW620 human colonic adenocarcinoma cells. The nuclear translocation of beta-catenin, and expression levels of Wnt3a, c-Myc, survivin, and cyclin D1 were significantly higher in CDX2-silenced SW620 cells. Conclusions: Curcumin reduced cell viability and increased apoptosis in SW620 human colonic adenocarcinoma cells by re- storing CDX2, which inhibited the Wnt/beta-catenin signaling pathway.
Background: Knee stability has an important role in the gait of hemiplegic stroke patients. However, factors affecting knee stability have not been assessed concerning gait. The purpose of this study was to explore whether co-contraction of the lower limb muscles contributes to the knee stability during the stance phase of the gait cycle in hemiplegic stroke patients. Material/Methods: A total of 30 hemiplegic stroke patients, ages 36-79 years, were instructed to walk at their natural speed. The root mean square of surface electromyography was used to measure activities of the biceps femoris and rectus femoris muscles, white the co-contraction ratio was computed based on the root mean squares. The peak angle of knee extension was acquired in the stance phase by 3D kinematic analyses. Lower limb function was evaluated using the Fugl-Meyer scale for lower limb motor assessment. Results: A statistically significant increase of the muscle co-contraction ratio of the involved extremity was observed compared with that of the uninvolved extremity (t=-4.066, P<0.05). The muscle co-contraction ratio was significantly correlated with the peak angle of knee extension (r=0.387, P=0.035), Fugl-Meyer scale (r=-0.522, P=0.003), and Modified Ashworth Scale (r=0.404, P=0.027) during the stance phase of the gait cycle. Conclusions: Our results showed that co-contraction of the rectus femoris muscle contributes to the stability of the knee and lower limb function in hemiplegic stroke patients, and suggests that co-contraction should be considered in the rehabilitation of knee stability during gait in hemiplegic stroke patients. Appropriate rehabilitation assessment planning with hemiplegic stroke patients, such as muscle co-contraction or knee stability of, might be created based on our results.
Background: This study aimed to identify the risk factors of complications after small-intestinal polypectomy by single-balloon enteroscopy (SBE), and to assess the value of serum C-reactive protein (CRP) and the max polyp diameter (Dmax) in predicting postoperative complications of small-intestinal polypectomy. Material/Methods: Between April 2017 and April 2018, clinical data from 37 patients who underwent small-intestinal polypecto- my were retrospectively analyzed. Results: Thirty-seven small-intestinal polypectomy procedures (18 oral and 19 anal) were carried out in 37 patients (M: F 20: 17; age 35.6 +/- 13.0 years). A total of 1081 small-intestine polyps were removed. Three patients (8.1%) had bleeding and 3 patients (8.1%) had perforation after small-intestinal polypectomy. Based on multivariate logistic analysis, CRP [1.104 (95% CI 1.022-1.191)] was the only risk factor for complications among the patients. According to the area under the receiver operating characteristic (AUROC) curve, CRP (27.5 mg/L), Dmax (3.5 cm), and the combination of CRP + Dmax appear to be predictive factors for complications after small-intestinal polypectomy. Conclusions: SBE is an effective endoscopic tool for patients with small-intestinal polyps. CRP, Dmax, and the combination of CRP+Dmax may be potential predictors of complications from small-intestinal polypectomy.
Background: Depressive symptoms are a pervasive mental health problem in Chinese adolescents. The aim of this article was to systematically assess the trend of depressive symptoms in China among adolescents (1988 to 2018). Material/Methods: A systematic and comprehensive Literature search was conducted in both English and Chinese databases, includ- ing PubMed, EMBASE, Cochrane CENTRAL, CNKI, and Wan Fang Database, to identify relevant studies published between 1988 and 2018. Batteries of analyses in this meta-analysis were undertaken using Stata version 12.0 statistical software. Results: Sixty-two related reports involving 232 586 participants finally met our inclusion and exclusion criteria. The re- sults suggest the prevalence of depressive symptoms has generally increased over time. The prevalence estimates before 2000 were 18.4% (95% CI, 14.5-22.3%), and were 26.3% (95% CI, 21.9-30.8%) after 2016. The pooled prevalence of depressive symptoms among children and adolescents was 22.2% (95% CI: 19.924.6%, 1 2 =99.6%, p<0.001). More subgroup analyses classified by screening instrument, gender, and region were carried out in this meta-analysis. Conclusions: Results of our meta-analysis suggest that depressive symptoms have become more prevalent among Chinese adolescents. This trend emphasizes the need for effective prevention strategies and greater availability of screening tools for this vulnerable population.
Background: Type 2 diabetes impairs the healing process and induces apoptosis of fibroblasts, which are thought to be involved in this process. We investigated the possible mechanisms involved in AGEs-induced apoptosis of human dermal fibroblasts. Material/Methods: e examined the expression of apoptosis-related proteins in fibroblasts isolated from human diabetic wounds. Human dermal fibroblasts exposed to AGEs were used to study the links among apoptosis, ROS, and NLRP3 inflammasome activation. Signaling mechanisms were evaluated by preincubating the cells with appropriate inhibitors. Cleaved caspase-8, cleaved caspase-3, BAX, Bcl-2, and NLRP3 inflammasome expression were measured by Western blot analysis. ROS generation, cell viability, and cell apoptosis were assessed. Results: We observed a higher level of cleaved caspase-8 and cleaved caspase-3 expression in fibroblasts isolated from human diabetic wounds compared with controls. AGEs decreased the proliferation of cells in a concentration-dependent and time-dependent manner. The exposure of fibroblasts to AGEs significantly increased the number of cells in early and late apoptosis stages. AGES-induced human dermal fibroblasts showed high expressions of cleaved caspase3, cleaved caspase8, and Bax. Treatment with AGEs induced the expression of NLRP3, caspase-1, and ASC. AGES-induced apoptosis was blocked by BAY 11-7082, an inhibitor of the NLRP3 inflammasome. AGEs increased the production of ROS in fibroblasts, and its apoptogenic effect was blocked by NAC. Conclusions: AGEs cause apoptosis of fibroblasts by inducing the generation of ROS and activating the NLRP3 inflammasome. In vivo experiments are needed to confirm these results.
Background: Osteoarthritis (OA) is a joint disease characterized by articular cartilage degeneration and inflammation. We have previously clarified that a xanthan gum (XG) preparation exerts ameliorating effect on a rabbit OA model by regulating matrix metalloproteinase (MMP)-1 and MMP-3, which are critical proteins in the Wnt3a/beta-catenin pathway. Thus, it is reasonable to predict that the Wnt3a/beta-catenin pathway is involved in the treatment of OA with XG. Material/Methods: The effect of XG in OA model animals were observed by hematoxylin and eosin staining (HE), Safranin O staining, and Fast Green staining. Articular cartilage degradation on the medial plateau sides was quantified using the modified Pritzker OARSI score. The levels of IL-6, TNF-alpha, and IL-1 beta in synovial fluid were determined with ELISA. The protective effect of XG in rat chondrocytes was assessed by CCK8 assay. Moreover, activation of the Wnt3a/beta-catenin pathway and the expression of MMP13, ADAMTS5, aggrecan, and collagen II under the influence of XG was measured by Western blot and qRT-PCR. Results: Our results showed that XG reduced the OARSI score and the concentration of inflammatory cytokines in OA after intra-articular injection. XG acted on Wnt3a/beta-catenin in ATDC5 cells in a dose-dependent manner and exhibited a protective effect. XG also decreased the expression of MMP13 and ADAMTS5 and rescued the inhibition of aggrecan and collagen II expression in SNP-stimulated chondrocytes. Conclusions: These results indicate that the effects of XG are related to the Wnt3a/beta-catenin pathway and XG suppresses matrix degradation by inhibiting the expression of MMPs and ADAMTS and promotes aggrecan and collagen II content in the ECM, indicating its favorable potential for use in OA therapy.
Background: The choice of optimal internal fixation device for distal tibial fractures remains controversial. The purpose of our study was to evaluate the effectiveness and safety of open reduction and internal fixation, minimally invasive percutaneous osteosynthesis, and intramedullary nailing of distal tibial fractures in adults using network meta-analysis of data from clinical trials. Material/Methods: The studies were abstracted from MEDLINE, EMBASE, CNKI, and the Cochrane Central Register of Controlled Trials. Randomized controlled trials meeting inclusion and exclusion criteria were selected. Statistical analyses were conducted using Stata software, version 13.0 (Stata Corporation, College Station, Texas, USA). Results: Eleven randomized controlled trials were included. The total number of participants was 710 and the studies were published between 2005 and 2017. There were no significant differences in rates of delayed union, nonunion, or malunion among the various treatments (all p>0.05). The intramedullary nailing group had a lower incidence of wound complications than did the open reduction and internal fixation group and minimally invasive percutaneous osteosynthesis technique group. The SUCRA probabilities were 28.6% for ORIF, 98.4% for IMN, and 22.9% for MIPPO. Conclusions: Given the superior results for intramedullary nailing in terms of wound complications, we recommend this procedure for treatment of distal tibial fractures. More RCTs focused on distal tibial fractures are needed to support the current evidence.
Background: Lung cancer is the leading cause of cancer deaths in the world. Its major histopathological subtype is non-small cell lung cancer (NSCLC). Xiaoai Jiedu recipe (XJR) is a traditional Chinese medicine formula that can suppress growth and invasion of tumor cells. Here, we assessed the antitumor effect of XJR on NSCLC explored the underlying mechanisms. Material/Methods: Three concentrations of XJR (low, middle, and high) were used to treat A549 cells. Cell Counting Kit-8 and colony formation assay were used to measure proliferation of A549 cells. Apoptosis was evaluated by Hoechst 33342 staining and flow cytometry. The expression of apoptosis-associated proteins was measured by Western blot analysis. Transwell and scratch wound healing assay were used to assess invasion and migration, respectively, of A549 cells. The expression of p38 MAPK pathway-associated proteins were measured using Western blot analysis. Results: XJR suppressed proliferation and promoted apoptosis of A549 cells, especially in the high-dose group. The expression of Bcl-2 was reduced with increasing expression of Bax, cleaved caspase-3, and cleaved caspase-9. Invasion and migration abilities of A549 cells were inhibited after XJR treatment. XJR treatment decreased the expression levels of phosphorylated p38 (p-p38), p-ERK, and p-JNK in a dose-dependent manner. Conclusions: The results demonstrated that XJR can inhibit proliferation, invasion, and migration, and induce apoptosis of NSCLC by blocking the p38 MAPK pathway, which shows the potential of XJR as a new treatment of NSCLC.
Background: Osteosarcoma (OS) is a highly aggressive, metastatic bone tumor with a poor prognosis, and occurs more commonly in children and adolescents. Therefore, new drugs and treatments are urgently needed. In this study, we investigated the effect and potential mechanisms of C18H17NO6 on osteosarcoma cells. Material/Methods: Human MNNG osteosarcoma cells were treated with different concentrations of C18H17NO6. The proliferation of the MNNG cells was examined via CCK-8 assay. Cell migration and invasion were tested via wound-healing assay and Transwell migration and invasion assays. ELISA was used to detect MMP-2, MMP-9, and VEGF secretion. Finally, Western blotting and qRT-PCR were used to detect protein and mRNA expressions, respectively. Results: C18H17NO6 inhibited MNNG proliferation in a dose- and time-dependent manner and inhibited MMP-2, MMP-9, and VEGF secretion. C18H17NO6 treatment significantly downregulated N-cadherin and Vimentin expression levels and upregulated E-cadherin expression levels in vitro and in vivo. C18H17NO6 inhibited tumor growth in a MNNG xenograft. We also found that C18H17NO6 6 can significantly reduce the phosphorylation of the PI3K/AKT signaling pathway in vivo and in vitro. However, 740Y-P (a PI3K agonist) had the opposite effect on proliferation, migration and invasion of MNNG cells treated with C18H17NO6. LY294002 (a PI3K inhibitor) downregulated p-PI3K and p-AKT could mimic the inhibitory effect of C18H17NO6. Conclusions: Our results suggest that C(18)H(17)NO(6 )can inhibit human MNNG osteosarcoma cell invasion and migration via the PI3K/AKT signaling pathway both in vivo and in vitro. C(18)H(17)NO(6 )may be a highly effective and low-toxicity natural drug for the prevention or treatment of OS.