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Objective. To investigate the efficacy and safety of the oblique supine lithotomy during percutaneous nephrolithotomy (PCNL) to treat upper urinary calculi. Methods. Clinical data were retrospectively analyzed for 371 patients with upper urinary calculi who underwent PCNL at The First Affiliated Hospital of Guangzhou University of Chinese Medicine from January 2017 to October 2020. Based on different positions, patients were divided into the observation group (oblique supine lithotomy position, 155 cases, Group 1) or control group (prone position, 216 cases, Group 2). Groups were compared for effectiveness, complications, bleeding, surgical time, clinical indicators, and hospitalization time. Results. There were no significant differences in the clinical baseline data between the two groups ( p > .05). However, the stone-free rate for patients was significantly higher in the observation than in the control group ( p < .05). Both operation time and hospital stay time were significantly lower in the observation versus the control groups ( p < .05). No significant differences were observed for complications or amount of blood loss ( p > .05). Conclusion. In patients with upper urinary calculi, percutaneous nephrolithotomy in the oblique supine lithotomy position has a higher stone-free rate than the prone position. This approach can shorten the operation and provide better comfort and quicker recovery to the patients. A further advantage is that there is no difference in safety and blood loss between the prone position and the oblique lithotomy position.

Background: Our study aimed to investigate the correlative factors influencing non-sentinel lymph node (NSLN) metastasis in Chinese breast cancer patients with 1-2 positive sentinel lymph nodes (SLNs) and to develop an intraoperative prediction model based on the least absolute shrinkage and selection operator (LASSO) algorithm to evaluate the risk of NSLN metastasis.Methods: The factors affecting NSLN status were investigated in a cohort of 714 patients with 1-2 positive SLNs treated at The First Affiliated Hospital of Chongqing Medical University between January 2013 and December 2018. A new mathematical prediction model based on the LASSO algorithm was developed and was validated in a cohort of 131 patients treated between January 2019 and December 2019.Results: In the training cohort, 266/714 (37.3%) patients had NSLN metastasis. In univariate analysis, the histologic grade (P =0.010), number of positive SLNs (P

The identification and management of malnutrition is increasingly considered as an important issue in cancer treatment. This study aimed at determining the prevalence of malnutrition among elderly inpatients with gastrointestinal cancer. Meanwhile, the exact relationship between nutrition and frailty was explored. The presence of malnutrition was determined using Mini-Nutritional Assessment Short Form (MNA-SF), Nutrition Risk Screening 2002 (NRS2002), and a batch of laboratory parameters. A cross-sectional study of 265 eligible elderly inpatients with gastrointestinal cancer was conducted. The results showed that the prevalence of malnutrition classified by MNA-SF, NRS2002, albumin, prealbumin, total protein, hemoglobin, and total lymphocyte count were 66.8%, 68.7%, 41.5%, 27.9%, 39.2%, 40.8%, and 15.5%, respectively. There was a fair agreement between MNA-SF and NRS2002 (

Gastric cancer (GC) is common in East Asia, yet its molecular and pathogenic mechanisms remain unclear. Circular RNAs (circRNAs) are differentially expressed in GC and may be promising biomarkers. Here, we investigated the role and regulatory mechanism of circTMC5 in GC. CircTMC5 expression was detected in human GC and adjacent tissues using microarray assays and qRT-PCR, while the clinicopathological characteristics of patients with GC were used to assess its diagnostic and prognostic value. The circTMC5/miR-361-3p/RABL6 axis was examined in vitro and vivo, and the immune roles of RABL6 were evaluated using bioinformatics analyses and immunohistochemistry (IHC). CircTMC5 was highly expressed in GC tissues, plasma, and cell lines, and was closely related to histological grade, pathological stage, and T classification in patients with GC. CircTMC5 expression was also an independent prognostic factor for GC and its combined detection with carcinoembryonic antigen may improve GC diagnosis. Low circTMC5 expression correlated with good prognosis, inhibited GC cell proliferation, and promoted apoptosis. Mechanistically, circTMC5 overexpression promoted GC cell proliferation, invasion, and metastasis but inhibited apoptosis by sponging miR-361-3p and up-regulating RABL6 in vitro and vivo, whereas miR-361-3p up-regulation had the opposite effects. RABL6 was highly expressed in GC and was involved in immune regulation and infiltration in GC. CircTMC5 promotes GC and sponges miR-361-3p to up-regulate RABL6 expression, thus may have diagnostic and prognostic value in GC. RABL6 also displays therapeutic promise due to its role in the immune regulation of GC.

BACKGROUND Approximately 90% of new cases of noncardiac gastric cancer (GC) are related to Helicobacter pylori (H. pylori), and cytotoxin-associated gene A (CagA) is one of the main pathogenic factors. Recent studies have shown that the pharmacological effects of cryptotanshinone (CTS) can be used to treat a variety of tumors. However, the effects of CTS on H. pylori, especially CagA+ strain-induced gastric mucosal lesions, on the development of GC is unknown. AIM To assess the role of CTS in CagA-induced proliferation and metastasis of GC cells, and determine if CagA+ H. pylori strains causes pathological changes in the gastric mucosa of mice. METHODS The effects of CTS on the proliferation of GC cells were assessed using the Cell Counting Kit-8 (CCK-8) assay, and the abnormal growth, migration and invasion caused by CagA were detected by CCK-8 and transwell assays. After transfection with pSR-HA-CagA and treatment with CTS, proliferation and metastasis were evaluated by CCK-8 and transwell assays, respectively, and the expression of Src homology 2 (SH2) domain–containing phosphatase 2 (SHP2) and phosphorylated SHP2 (p-SHP2) was detected using western blotting in AGS cells. The enzyme-linked immunosorbent assay was used to determine the immunoglobulin G (IgG) level against CagA in patient serum. Mice were divided into four groups and administered H. pylori strains (CagA+ or CagA-) and CTS (or PBS) intragastrically, and establishment of the chronic infection model was verified using polymerase chain reaction and sequencing of isolated strains. Hematoxylin and eosin staining was used to assess mucosal erosion in the stomach and toxicity to the liver and kidney. RESULTS CTS inhibited the growth of GC cells in dose- and time-dependent manners. Overexpression of CagA promoted the growth, migration, and invasion of GC cells. Importantly, we demonstrated that CTS significantly inhibited the CagA-induced abnormal proliferation, migration, and invasion of GC cells. Moreover, the expression of p-SHP2 protein in tumor tissue was related to the expression of IgG against CagA in the serum of GC patients. Additionally, CTS suppressed the protein expression levels of both SHP2 and p-SHP2 in GC cells. CTS suppressed CagA+ H. pylori strain-induced mucosal erosion in the stomach of mice but had no obvious effects on the CagA- H. pylori strain group. CONCLUSION CTS inhibited CagA-induced proliferation and the epithelial-mesenchymal transition of GC cells in vitro, and CagA+ H. pylori strains caused mucosal erosions of the stomach in vivo by decreasing the protein expression of SHP2.

This research explores ultrastructural changes of arachnoid granulations associated with hydrocephalus after subarachnoid hemorrhage in cynomolgus monkeys. It provides a theoretical basis for further study of the etiology and prevention of hydrocephalus. Female cynomolgus monkeys about one-year-old were selected. The position range of arachnoid granulations in superior sagittal sinus and transverse sinus was determined in a randomly selected control monkey. The morphology of normal arachnoid granulations in cynomolgus monkeys was observed under a transmission electron microscope. A primate model of subarachnoid hemorrhage was established by injecting autologous blood into cisterna magna. Vomiting, movement disorder, and reduced level of consciousness were gradually observed in monkeys. Computed tomography and magnetic resonance imaging scan results confirmed subarachnoid hemorrhage and hydrocephalus, and the morphology of arachnoid granulations in hydrocephalus was observed under a transmission electron microscope. Extensive fibrosis of arachnoid granulations was observed under a transmission electron microscope in cynomolgus monkeys with hydrocephalus after subarachnoid hemorrhage.

Wrinkles are special surface corrugations in two-dimensional materials, which can be used to tune their electronic, optical, and chemical properties. There have been many studies focusing on the wr...

Background: In recent years, the efficacy of type 2 diabetes mellitus (T2DM) drugs in the treatment of Alzheimer’s disease (AD) has attracted extensive interest owing to the close associations between the two diseases. Objective: Here, we screened traditional Chinese medicine (TCM) and multi-target ingredients that may have potential therapeutic effects on both T2DM and AD from T2DM prescriptions. Methods: Network pharmacology and molecular docking were used. Results: Firstly, the top 10 frequently used herbs and corresponding 275 active ingredients were identified from 263 T2DM-related TCM prescriptions. Secondly, through the comparative analysis of 208 potential targets of ingredients, 1,740 T2DM-related targets, and 2,060 AD-related targets, 61 common targets were identified to be shared. Thirdly, by constructing pharmacological network, 26 key targets and 154 representative ingredients were identified. Further enrichment analysis showed that common targets were involved in regulating multiple pathways related to T2DM and AD, while network analysis also found that the combination of Danshen (Radix Salviae)-Gancao (Licorice)-Shanyao (Rhizoma Dioscoreae) contained the vast majority of the representative ingredients and might be potential for the cotreatment of the two diseases. Fourthly, MAPK1, PPARG, GSK3B, BACE1, and NR3C1 were selected as potential targets for virtual screening of multi-target ingredients. Further docking studies showed that multiple natural compounds, including salvianolic acid J, gancaonin H, gadelaidic acid, icos-5-enoic acid, and sigmoidin-B, exhibited high binding affinities with the five targets. Conclusion: To summarize, the present study provides a potential TCM combination that might possess the potential advantage of cotreatment of AD and T2DM.

Background: Identifying modifiable risk factors, such as obesity, to lower the prevalence of Alzheimer’s disease (AD) has gained much interest. However, whether the association is causal remains to be evaluated. Objective: The present study was designed: 1) to make a quantitative assessment of the association between obesity and AD; 2) to validate whether there was a causal association between them; and 3) to provide genetic clues for the association through a network-based analysis. Methods: Two-sample Mendelian randomization (2SMR) analysis, meta-analysis, and protein-protein interaction (PPI) network analysis, were employed. Results: Firstly, the meta-analysis based on 9 studies comprising 6,986,436 subjects indicated that midlife obesity had 33%higher AD odds than controls (OR = 1.33, 95%CI = [1.03, 1.62]), while late-life obesity were inversely associated with AD risk (OR = 0.57, 95%CI = [0.47, 0.68]). Secondly, 2SMR analysis indicated that there was no causal association between them. Thirdly, CARTPT was identified to be shared by the anti-obesity drug targets and AD susceptibility genes. Further PPI network analysis found that CARTPT interacted with CD33, a strong genetic locus linked to AD. Finally, 2SMR analysis showed that CNR1 could be a protective factor for AD. Conclusion: Multiple bioinformatic analyses indicated that midlife obesity might increase the risk of AD, while current evidence indicated that there was no causal association between them. Further, CARTPT might be an important factor linking the two disease conditions. It could help to better understand the mechanisms underlying the associations between obesity and AD.

Blood pressure variability (BPV) has been identified as an important risk factor for cardiovascular events. The white coat effect (WCE), which is measured as the first systolic blood pressure (SBP) measurement minus the mean of the second and third measurements, is a BPV indicator within a single visit. In total, 2,972 participants who had three measurements of BP within a single visit were included. The participants were divided into three groups based on their WCE percentiles: Group 1 (WCE2.5-97.5, 2.5–97.5th percentiles of WCE), Group 2 (WCE2.5, 0–2.4th percentiles of WCE), and Group 3 (WCE97.5, 97.6–100th percentiles of WCE). A multiple logistic regression model was used to analyze the relationship between WCE and stroke after adjusting for cardiovascular disease risk factors. Compared with the WCE2.5-97.5 group, the OR for stroke in the WCE2.5 group was 2.78 (95% CI: 1.22, 6.36, p = 0.015 ). After adjusting for cardiovascular factors, OR increased to 3.12 (95% CI: 1.22, 7.96, p = 0.017 ). The OR of WCE for stroke was 0.93 (95%CI: 0.87, 0.99, p = 0.036 ). BPV within a single visit is associated with stroke. The value and direction of the change may be important as well.

Emerging studies have shown that HOTAIR acts as an oncogene in gastric cancer (GC). However, its role in the extracellular matrix and in tumor immune infiltration remains unknown. HOTAIR and COL5A1 levels were analyzed by bioinformatics analysis and validated by qRT-PCR, western blotting and immunohistochemistry assays. The regulatory relationships between components of the HOTAIR/miR-1277-5p/COL5A1 axis and the role of this axis in GC were predicted by bioinformatics analysis, and validated by in vitro and in vivo experiments. The correlation between COL5A1 and GC immune infiltration was assessed by bioinformatics analysis and a COL5A1-based predictive nomogram was established using the Stomach Adenocarcinoma dataset from The Cancer Genome Atlas. We found that HOTAIR and COL5A1 were overexpressed in GC compared to normal controls, which predicted poor prognosis. The regulatory relationship of the HOTAIR/miR-1277-5p/COL5A1 axis in GC was demonstrated, and HOTAIR and COL5A1 were found to promote GC growth while miR-1277-5p exerted the reverse effects. In addition, COL5A1 was negatively associated with tumor purity but positively associated with immune infiltration, which suggested that COL5A1-mediated GC growth may be partially mediated by the regulation of immune infiltration. Additionally, the established COL5A1-based nomogram showed that COL5A1 can serve as a prognostic biomarker in GC. HOTAIR regulates GC growth by sponging miR-1277-5p and upregulating COL5A1, and COL5A1-mediated GC cell proliferation may be mediated by effects on the tumor microenvironment, which provides novel targets for GC treatment.

After brachial plexus avulsion (BPA), microglia induce inflammation, initiating and maintaining neuropathic pain. EZH2 (enhancer of zeste homolog 2) has been implicated in inflammation and neuropathic pain, but the mechanisms by which it regulates neuropathic pain remain unclear. Here, we found that EZH2 levels were markedly upregulated during BPA-induced neuropathic pain in vivo and in vitro, stimulating pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6) secretion in vivo. In rats with BPA-induced neuropathic pain, mechanical and cold hypersensitivities were induced by EZH2 upregulation and inhibited by EZH2 downregulation in the anterior cingulate cortex. Microglial autophagy was also significantly inhibited, with EZH2 inhibition activating autophagy and reducing neuroinflammation in vivo. However, this effect was impaired by inhibiting autophagy with 3-methyladenine, suggesting that the MTOR signaling pathway is a functional target of EZH2. These data suggest that EZH2 regulates neuroinflammation and neuropathic pain via a novel MTOR-mediated autophagy signaling pathway, providing a promising approach for managing neuropathic pain. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12264-020-00502-w) contains supplementary material, which is available to authorized users.

Deregulated glucose and lipid metabolism are the primary underlying manifestations associated with diabetes mellitus (DM) and non-alcoholic fatty liver disease (NAFLD). This study aims to investigate the role of Gm10804, a novel long non-coding RNA (lncRNA), in regulating hepatic glucose and lipid metabolism in DM complicated with NAFLD (DM-NAFLD). Mouse primary hepatocytes exposed to high glucose (HG) were used as a cell model. A mouse DM-NAFLD model was established by high-energy feeding combined with intraperitoneal injection of streptozotocin. The results showed that Gm10804 expression was upregulated in HG-treated hepatocytes and livers from DM-NAFLD mice. Results in hepatocytes in vitro demonstrated that Gm10804 overexpression aggravated, whereas Gm10804 silencing abrogated HG-induced increase in intracellular triglyceride (TG) content, lipid accumulation and expression of hepatic lipogenic proteins (sterol regulatory element-binding proteins 1-c [SREBP-1c] and fatty acid synthase [FAS]) and enzymes for gluconeogenesis (phosphoenolpyruvate carboxykinase [PEPCK] and glucose-6-phosphatase [G6Pase]). Further in vivo assays showed that lentivirus-mediated hepatic knockdown of Gm10804 alleviated hepatic steatosis and lipid accumulation, and decreased expression of hepatic PEPCK, G6Pase, SREBP-1c and FAS in DM-NAFLD mice. In summary, Gm10804 knockdown attenuates hepatic lipid accumulation by ameliorating disorders of hepatic glucose and lipid metabolism in DM-NAFLD. SIGNIFICANCE OF THE STUDY: We first discovered that Gm10804 knockdown attenuated hepatic lipid accumulation by ameliorating disorders of hepatic glucose and lipid metabolism in DM-NAFLD. These results help to understand the pathogenesis and development of DM-NAFLD and provide some clues for further understanding the regulation of lncRNAs in glucose and lipid metabolism.

Recent research have proved that miR-501-5p acted as a potent tumor biomarker in several cancers, excluding head and neck squamous cell carcinoma (HNSCC). The study intends to discover the potential function and mechanism of miR-501-5p in HNSCC. Data from TCGA database and qRT-PCR estimated the expression of miR-501-5p and Calcium activated Chloride Channel A4 (CLCA4). Cell proliferation, clone formation and transwell assays were performed to explore HNSCC cells biological behaviors. Luciferase assay was carried out to identify the interaction between miR-501-5p and CLCA4. miR-501-5p was profoundly up-regulated in HNSCC samples and promoted cells proliferation and metastasis. CLCA4, as a target of miR-501-5p, was connected with worse outcomes in HNSCC patients. Co-transfection assay proved that miR-501-5p/CLCA4 functioned as crucial regulators to affect HNSCC cells biological behaviors. Our study illustrated that miR-501-5p exhibited a tumor-promoting role on HNSCC by targeting CLCA4, providing a new insight for revealing the pathogenesis and treatment of HNSCC.

Background: Glioblastoma (GBM) is recognized as a malignant brain tumor with frequent mortality. Extensive evidence indicated that miR-188-3p exerts an important role in various tumors. However, the role of miR-188-3p in GBM has not been elucidated. The purpose of the present investigation was to explore the biological effect of miR-188-3p, as well as to determine its target gene in GBM.Methods: The miR-188-3p and G Protein-Coupled Receptor 26 (GPR26) expressional profiles were obtained from The Cancer Genome Atlas (TCGA) database. The proliferative ability, invasive and migratory capabilities of GBM cells were measured using Cell Counting Kit-8 and transwell assays. Bioinformatics tool and luciferase reporter gene analysis were utilized to assess the correlation between miR-188-3p and GPR26. Reverse transcription-quantitative polymerase chain reaction (RT-PCR) and western blotting were performed to detect the indicated gene expression.Results: MiR-188-3p expression was highly regulated in GBM tissue and cell lines, while GPR26 was significantly decreased in GBM. Depletion of miR-188-3p significantly retarded the cell proliferation, invasion and migration in the U-87 MG cell. Luciferase reporter gene assay showed that GPR26 was a target gene of miR-188-3p in GBM. The expression of GPR26 was negatively regulated by miR-188-3p. The inhibitory effect of miR-188-3p inhibitor on cell behaviors was further strengthened by the overexpression of GPR26 in GBM.Conclusion: These findings provided evidence for the cancer-promoting effect of miR-188-3p in GBM cells and demonstrated that GPR26 was directly targeted by miR-188-3p, which might contribute to the therapeutic therapy of GBM.

We describe a method to obtain networks of wrinkles in multilayer graphene flakes (and other layered materials) by thermal contraction of the underlying PDMS substrate they are deposited on. The exfoliated flakes on PDMS are dipped into liquid nitrogen and after removal networks of wrinkles are found. The density of wrinkles can be controlled to some degree by sequential dipping into liquid nitrogen. Atomic force microscopy shows that wrinkles form preferentially along the armchair direction of the graphene lattice in such multilayer graphene platelets. Raman spectra show that the interlayer coupling at a wrinkle in multilayer graphene differs from, and is weaker than, that in undeformed regions. High resolution transmission electron microscopy measurements show that the interlayer distance increases in strained regions, which results in the interlayer coupling being decreased in particular regions of the wrinkles in these multilayer graphenes.

Background: Acute lung injury (ALI) is a respiratory disease with high morbidity and mortality rates. Currently, there is no effective treatment to complement mechanical ventilation. Exosomes and microRNAs (miRNAs) are promising agents for the management of this disease. Methods: Exosomes were isolated from mouse bone marrow stromal stem cells (BMSCs). The levels of two miRNAs, miR-542-3P and miR-150, in exosomes were determined using RT-PCR, and miR-150 was selected for further study. ALI model was established in mice using lipopolysaccharides, and then, they were treated with saline, exosomes, miRNA agomirs, or miRNA antagomirs. The concentrations of TNF-α, IL-6, and IL-1β and the number of neutrophils and macrophages in the bronchoalveolar lavage fluid were measured. The wet/dry weight ratio of the lung tissue was calculated, and tissue pathology and apoptosis were observed using hematoxylin and eosin and terminal deoxynucleotidyl transferase dUTP nick-end labeling staining. CD34 and VE-cadherin expression was detected using immunofluorescence. Proteins associated with apoptosis and MAPK signaling were detected using Western blotting, and miR-150 expression in lung tissue was evaluated using RT-PCR. Results: We successfully isolated BMSCs and exosomes and showed that the level of miR-150 was significantly higher than that of miR-542-3p. Exosomes and miR-150 reduced inflammation and lung edema while maintaining the integrity of the alveolar structure. They also mitigated microvascular endothelial cell injury by regulating the caspase-3, Bax/Bcl-2, and MAPK signaling. Conclusions: Exosomal miR-150 attenuates lipopolysaccharide-induced ALI through the MAPK pathway.

BackgroundDifferent comprehensive care programmes (CCPs) have been developed for patients with chronic obstructive pulmonary disorder (COPD), but data regarding their effectiveness have been controversial. PubMed and Embase were searched to 1st June 2017 for articles that investigated the effects of the different types of CCPs on hospitalization or mortality rates in COPD.ResultsA total of 67 studies including 3472633 patients (mean age: 76.1±12.7 years old; 41% male) were analyzed. CCPs reduced all-cause hospitalizations (hazard ratio [HR]: 0.70, 95% confidence interval [CI]: 0.63-0.79; P2:96%) and mortality (HR: 0.69, 95% CI: 0.573-0.83; PI2:75%). Subgroup analyses for different CCP types were performed. Hospitalizations were reduced by pharmacist-led medication reviews (HR: 0.54; 95% CI: 0.37-0.78; P=0.001; I2:49%), structured care programmes (HR: 0.76; 95% CI: 0.66-0.87; PI2:88%) and self-management programmes (HR: 0.79; 95% CI: 0.64-0.99; PI2:78%), but not continuity of care programmes (HR: 0.70; 95% CI: 0.36-1.36; P=0.29; I2:100%), early support discharge or home care packages (HR: 0.97; 95% CI: 0.91-1.04; P=0.37; I2:0%) or telemonitoring (HR: 0.61; 95% CI: 0.32-1.18; P=0.14; I2:94%). Mortality was reduced by early support discharge or home care packages (HR: 0.49; 95% CI: 0.30-0.80; PI2:72%), structured care programmes (HR: 0.69; 95% CI: 0.53-0.90; PI2:61%) and telemonitoring (HR: 0.52; 95% CI: 0.31-0.89; PI2:0%), but not self-management programmes (HR: 0.79; 95% CI: 0.64-0.99; PI2:78%).ConclusionsComprehensive care programmes reduce hospitalization and mortality in COPD patients.

Complete mitochondrial genomes (mitogenomes) can provide useful information for phylogenetic relationships, gene rearrangement, and molecular evolution. In this study, the complete mitogenomes of two hermit crabs, Dardanus arrosor and Dardanus aspersus, were sequenced for the first time and compared with other published mitogenomes of Paguroidea. Each of the two mitogenomes contains an entire set of 37 genes and a putative control region, but they display different gene arrangements. The different arrangements of the two mitogenomes might be the result of transposition, reversal, and tandem duplication/random loss events from the ancestral pancrustacean pattern. Genome sequence similarity analysis reveals the gene rearrangement in 15 Paguroidea mitogenomes. After synteny analysis between the 15 Paguroidea mitogenomes, an obvious rearranged region is found in D. aspersus mitogenome. Across the 13 protein-coding genes (PCGs) tested, COI has the least and ND6 has the largest genetic distances among the 15 hermit crabs, indicating varied evolution rates of PCGs. In addition, the dN/dS ratio analysis shows that all PCGs are evolving under purifying selection. The phylogenetic analyses based on both gene order and sequence data present the monophyly of three families (Paguridae, Coenobitidae, and Pylochelidae) and the paraphyly of the family Diogenidae. Meanwhile, the phylogenetic tree based on the nucleotide sequences of 13 PCGs shows that two Dardanus species formed a sister group with five Coenobitidae species. These findings help to better understand the gene rearrangement and phylogeny of Paguroidea, as well as provide new insights into the usefulness of mitochondrial gene order as a phylogenetic marker.

BackgroundThe function and regulatory mechanism of FBXO43 in breast cancer (BC) are still unclear. Here, we intended to determine the role and mechanism of FBXO43 in BC.MethodsFBXO43 expression in BC was evaluated by analysis of The Cancer Genome Atlas (TCGA). RT-qPCR and western blotting were utilized to detect FBXO43 expression in BC cell lines. Lentivirus was applied to downregulate FBXO43 in human BC cells. Proliferation assays were performed to evaluate the proliferative ability of BC cells. The apoptosis and cell cycle analysis of BC cells were analyzed by flow cytometry. Cell migration and invasion were investigated via Transwell assays. The function of FBXO43 in vivo was evaluated by constructing a xenograft mouse model. The proteins that might interact with FBXO43 in BC were identified by mass spectrometry, bioinformatics analysis, and co-immunoprecipitation (Co-IP) assays. Finally, rescue experiments were conducted to validate the recovery effects of the proteins interacting with FBXO43.ResultsFBXO43 was highly expressed in BC and was significantly downregulated after FBXO43 knockdown. The proliferation, migration, and invasion of BC cells were inhibited, and cell apoptosis was induced by FBXO43 knockdown. In addition, an in vivo experiment indicated that FBXO43 knockdown could inhibit the cell growth of BC. The results of the Co-IP assay showed that FBXO43 interacted with PCNA. Further rescue experiments confirmed that overexpression of PCNA significantly reversed the effects of FBXO43 knockdown on BC cells.ConclusionDownregulation of FBXO43 inhibits the tumor growth of BC by limiting its interaction with PCNA. FBXO43 might be a new potential oncogene and a therapeutic target for BC.

Background:Members of the integrin β superfamily(ITGBs) have been shown to be aberrantly expressed in various human cancers and involved in tumorigenesis and progression. However, the diverse expression patterns and prognostic values of the entire ITGB family members in gastric cancer(GC) has not been systematically investigated.Methods:In the current study, Oncomine, GEPIA, Kaplan Meier plotter, TIMER, GeneMANIA, STRING and Metascape database were employed to explore the transcriptional and survival data of ITGB superfamily members in GC. Moreover, we confirmed the mRNA expression levels of ITGB superfamily members in GC cell lines by qRT-PCR.Results:The mRNA expression level of ITGB1/2/4/5/8 was upregulated in GC, while the expression level of ITGB7 was downregulated. Higher expression of ITGB2/7 was significantly associated with the tumor stage of patients with GC. However, we found that the expression level of ITGB1/2/4/5/6/7/8 was remarkably increased in GC cell lines compared to stomach normal cell lines, while ITGB3 expression was decreased in the former than in the latter. Meanwhile,higher expression levels of ITGB2/6/7 were closely correlated with better overall clinical survival (OS) and recurrence-free survival (RFS) in GC patients, while higher ITGB3/4/5 expression were strongly associated with poorer OS and RFS.We also discovered that the functions of ITGBs and their adjacent genes are mainly related to protein complexes involved in cell adhesion. the functions of ITGBs and their adjacent proteins are mainly related to focal adhesion, cell adhesion molecules, proteoglycans in cancer, small cell lung cancer, rap1 signaling pathway, IgA production by intestinal immune network, and microRNAs in cancer.In addition, the expression of ITGBs was significantly correlated with the infiltration of multiple immune cells, including B cells, CD8+ T cells, CD4+ T cells, neutrophils, macrophages, and dendritic cells.Conclusions:Our results suggested that abnormal expression of ITGBs plays a key role in the progression of GC and that ITGBs may be potential prognostic biomarkers and therapeutic targets for GC.

Nationwide prospective surveillance of all-age patients with acute respiratory infections was conducted in China between 2009‒2019. Here we report the etiological and epidemiological features of the 231,107 eligible patients enrolled in this analysis. Children, China operates a national surveillance program for acute respiratory infections and sampled over 200,000 patients between 2009–2019. Here, the authors present results from this program and describe patterns by age, pathogen type, presence of pneumonia, and season.

Background: Oxidative stress contributes to adverse atrial remodeling in diabetes mellitus. This remodeling can be prevented by the PPAR-γ agonist pioglitazone via its antioxidant and anti-inflammatory effects. In this study, we examined the molecular mechanisms underlying the protective effects of pioglitazone on atrial remodeling in a rabbit model of diabetes.Methods: Rabbits were randomly divided into control, diabetic, and pioglitazone-treated diabetic groups. Echocardiographic, hemodynamic, and electrophysiological parameters were measured. Serum PPAR-γ levels, serum and tissue oxidative stress and inflammatory markers, mitochondrial morphology, reactive oxygen species (ROS) production rate, respiratory function, and mitochondrial membrane potential (MMP) levels were measured. Protein expression of the pro-fibrotic marker TGF-β1, the PPAR-γ coactivator-1α (PGC-1α), and the mitochondrial proteins (biogenesis-, fusion-, and fission-related proteins) was measured. HL-1 cells were transfected with PGC-1α small interfering RNA (siRNA) to determine the underlying mechanisms of pioglitazone improvement of mitochondrial function under oxidative stress.Results: The diabetic group demonstrated a larger left atrial diameter and fibrosis area than the controls, which were associated with a higher incidence of inducible atrial fibrillation (AF). The lower serum PPAR-γ level was associated with lower PGC-1α and higher NF-κB and TGF-β1 expression. Lower mitochondrial biogenesis (PGC-1α, NRF1, and TFAM)-, fusion (Opa1 and Mfn1)-, and fission (Drp1)-related proteins were detected. Mitochondrial swelling, higher mitochondrial ROS, lower respiratory control rate, and lower MMP were observed. The pioglitazone group showed a reversal of structural remodeling and a lower incidence of inducible AF, which were associated with higher PPAR-γ and PGC-1α. The pioglitazone group had lower NF-κB and TGF-β1 expression levels, whereas biogenesis-, fusion-, and fission-related protein expression was higher. Further, mitochondrial structure and function were improved. In HL-1 cells, PGC-1α siRNA transfection blunted the effect of pioglitazone on Mn-SOD protein expression and MMP collapse in H2O2-treated cells.Conclusion: Diabetes mellitus induces adverse atrial structural, electrophysiological remodeling, and mitochondrial damage and dysfunction. Pioglitazone prevented these abnormalities through the PPAR-γ/PGC-1α pathway.

Frailty is emerging as an important determinant for health. Compared with Western countries, research in the field of frailty started at a later stage in China and mainly focused on older community dwellers. Little is known about frailty in Chinese cancer patients, nor the risk factors of frailty. This study aimed at investigating the prevalence of frailty and its risk factors in elderly inpatients with gastric and colorectal cancer. This cross-sectional study was conducted at a tertiary hospital in China from Mar. 2020 to Nov. 2020. The study enrolled 265 eligible inpatients aged 60 and older with gastric and colorectal cancer who underwent surgery. Demographic and clinical characteristics, biochemical laboratory parameters, and anthropometric data were collected from all patients. The Groningen Frailty Indicator was applied to assess the frailty status of patients. A multivariate logistic regression model analysis was performed to identify the risk factors of frailty and to estimate their 95% confidence intervals. The prevalence of frailty in elderly inpatients with gastric and colorectal cancer was 43.8%. A multivariate logistic regression analysis showed that older age (OR = 1.065, 95% CI: 1.001–1.132, P = 0.045), low handgrip strength (OR = 4.346, 95% CI: 1.739–10.863, P = 0.002), no regular exercise habit (OR = 3.228, 95% CI: 1.230–8.469, P = 0.017), and low MNA-SF score (OR = 11.090, 95% CI: 5.119–24.024, P

BACKGROUND: Thus far, few studies have systematically analyzed the profiles of immune cells infiltrated in the tumor microenvironment (TME) of hepatocellular carcinoma (HCC). Therefore, the purpose of our study was to comprehensively analyze the 22 tumor-infiltrating immune cells (TIICs) and the immune subtypes of HCC, as well as the factors associated with the prognosis of HCC patients. METHODS: In this study, we evaluated the abundance of 22 tumor-infiltrating immunocytes of 371 HCC patients from The Cancer Genome Atlas (TCGA) database by using the CIBERSORT algorithm, and defined immune subtypes of HCC according to unsupervised cluster analysis. The immune score of HCC patients was calculated by the prognostic regression model, while the survival analysis was evaluated by the Kaplan-Meier method. In addition, the consistency index of TIICs and principal component analysis (PCA) of immunomodulator genes were estimated. RESULTS: The results of this study showed that three distinct immune subtypes of HCC were stratified, and the C1 subtype and C3 subtype were correlated with a good prognosis. The cellular composition of three immune subtypes was different. Moreover, immunomodulator gene and programmed cell death protein 1/programmed death-ligand 1 (PD-1/PD-L1) expression in the C1 subtype was significantly higher (P

To examine the effectiveness of telemonitoring and hemodynamic monitoring devices in reducing mortality rates in heart failure. PubMed and Cochrane Library were searched to 1 May 2017 for randomized controlled trials and real-world studies investigating the effects of telemonitoring or hemodynamic monitoring on mortality in heart failure. Heart failure is associated with increased mortality. Telemonitoring and hemodynamic monitoring have been shown to reduce mortality rates in some studies but not others. Fifty-two and five publications on telemonitoring and hemodynamic monitoring were included. In 23,233 patients (mean age 70 years, mean follow-up 12 ± 10 months), telemonitoring reduced all-cause mortality by 22% (HR = 0.78; 95% confidence interval (CI), 0.74–0.83; P 0.05). Overall, telemonitoring but not hemodynamic monitoring reduced mortality in heart failure.

Background Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants formed from incomplete combustion of organic matter; some PAHs are carcinogens. Smoking, diet, and other activities contribute to exposure to PAHs. Exposure data to PAHs among combustible tobacco product users (e.g. cigarette smokers) exist; however, among non-combustible tobacco products users (e.g., e-cigarette users), such data are rather limited. Objectives We sought to evaluate exposure to PAHs among participants in Wave 1 (2013–2014) of the Population Assessment of Tobacco and Health (PATH) Study based on the type of tobacco product (combustible vs non-combustible), and frequency and intensity of product use. Methods We quantified seven PAH urinary biomarkers in 11,519 PATH Study participants. From self-reported information, we categorized 8327 participants based on their use of tobacco products as never-tobacco user (never user, n = 1700), exclusive current established combustible products user (combustible products user, n = 5767), and exclusive current established non-combustible products user (non-combustible products user, n = 860). We further classified tobacco users as exclusive cigarette user (cigarette user, n = 3964), exclusive smokeless product user (SLT user, n = 509), and exclusive e-cigarette user (e-cigarette user, n = 280). Last, we categorized frequency of product use (everyday vs some days) and time since use (last hour, within 3 days, over 3 days). We calculated geometric mean (GM) concentrations, and evaluated associations between tobacco product user categories and PAH biomarkers concentrations. Results Combustible products users had significantly higher GMs of all biomarkers than non-combustible products users and never users; non-combustible products users had significantly higher GMs than never users for four of seven biomarkers. For all biomarkers examined, cigarette users had the highest GMs compared to other tobacco-product users. Interestingly, GMs of 2-hydroxyfluorene, 3-hydroxyfluorene and ∑2,3-hydroxyphenanthrene were significantly higher in SLT users than in e-cigarette users; 3-hydroxyfluorene and 1-hydroxypyrene were also significantly higher in e-cigarette and SLT users than in never users. Everyday cigarette and SLT users had significantly higher GMs for most biomarkers than some days' users; cigarette and SLT users who used the product in the last hour had significantly higher GMs of most biomarkers than other occasional cigarette or SLT users respectively. By contrast, everyday e-cigarette users' GMs of most biomarkers did not differ significantly from those in some days' e-cigarette users; we did not observe clear trends by time of last use among e-cigarette users. Conclusions Users of tobacco products had higher PAH urinary biomarker concentrations compared to never users, and concentrations differed by type and frequency of tobacco product use.

Identifying modifiable risk factors for Parkinson's disease (PD) to help prevent this disease has attracted increasing interest in recent years for the limited effective drugs at present. Despite many studies indicated that infection acts as a risk factor for PD, there is no quantitative assessment of the impact of viral and bacterial infections on the risk of developing PD. The present study performed a meta-analysis on the basis of 38 datasets from 13 studies covering 287,773 PD cases and 7,102,901 controls to ascertain the association between PD and infection and the differences in the strength of the viral and bacterial infections. The overall meta-analytic results indicated that individuals with infection had a 20% increased risk of PD compared with controls (OR 1.20, 95%CI 1.07-1.32). The subgroup analysis according to the type of infection found that bacterial infection had a significant impact on increased risk of PD (OR 1.40, 95%CI 1.32-1.48). The present analysis indicated that infection could increase the risk of developing PD, and physician should be aware of the risk of developing PD in subjects with infection.

There is increasing evidence from molecular studies to support the role of inflammation and increased oxidative stress that produce structural and electrical atrial remodeling to produce Atrial Fbrillation (AF). Oxidative damage to cardiomyocytes yields chemical substances that are secreted in urine. These substances can serve as biomarkers that can be measured, potentially allowing clinicians to quantify oxidative damage to the heart.

National-based prospective surveillance of all-age patients with acute diarrhea was conducted in China between 2009‒2018. Here we report the etiological, epidemiological, and clinical features of the 152,792 eligible patients enrolled in this analysis. Rotavirus A and norovirus are the two leading viral pathogens detected in the patients, followed by adenovirus and astrovirus. Diarrheagenic Escherichia coli and nontyphoidal Salmonella are the two leading bacterial pathogens, followed by Shigella and Vibrio parahaemolyticus. Patients aged, Diarrhoea is a major cause of morbidity and mortality in China. Here, the authors present results from a large sentinel surveillance scheme from 217 hospitals in all 31 provinces in mainland China, including ~150,000 patients with acute diarrhoea and covering years 2009-2018.

Background The prognosis of colon cancer (CC) is challenging to predict due to its highly heterogeneous nature. Ferroptosis, an iron-dependent form of cell death, has roles in various cancers; however, the correlation between ferroptosis-related genes (FRGs) and prognosis in CC remains unclear. Methods The expression profiles of FRGs and relevant clinical information were retrieved from the Cancer Genome Atlas (TCGA) database. Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) regression model were performed to build a prognostic model in TCGA cohort. Results Ten FRGs, five of which had mutation rates ≥ 3%, were found to be related to the overall survival (OS) of patients with CC. Patients were divided into high- and low-risk groups based on the results of Cox regression and LASSO analysis. Patients in the low-risk group had a significantly longer survival time than patients in the high-risk group (P < 0.001). Enrichment analyses in different risk groups showed that the altered genes were associated with the extracellular matrix, fatty acid metabolism, and peroxisome. Age, risk score, T stage, N stage, and M stage were independent predictors of patient OS based on the results of Cox analysis. Finally, a nomogram was constructed to predict 1-, 3-, and 5-year OS of patients with CC based on the above five independent factors. Conclusion A novel FRG model can be used for prognostic prediction in CC and may be helpful for individualized treatment.

Background Mosquitoes host and transmit numerous arthropod-borne viruses (arboviruses) that cause disease in both humans and animals. Effective surveillance of virome profiles in mosquitoes is vital to the prevention and control of mosquito-borne diseases in northwestern China, where epidemics occur frequently. Methods Mosquitoes were collected in the Shaanxi-Gansu-Ningxia region (Shaanxi Province, Gansu Province, and Ningxia Hui Autonomous Region) of China from June to August 2019. Morphological methods were used for taxonomic identification of mosquito species. High-throughput sequencing and metagenomic analysis were used to characterize mosquito viromes. Results A total of 22,959 mosquitoes were collected, including Culex pipiens (45.7%), Culex tritaeniorhynchus (40.6%), Anopheles sinensis (8.4%), Aedes (5.2%), and Armigeres subalbatus (0.1%). In total, 3,014,183 (0.95% of clean reads) viral sequences were identified and assigned to 116 viral species (including pathogens such as Japanese encephalitis virus and Getah virus) in 31 viral families, including Flaviviridae, Togaviridae, Phasmaviridae, Phenuiviridae, and some unclassified viruses. Mosquitoes collected in July (86 species in 26 families) showed greater viral diversity than those from June and August. Culex pipiens (69 species in 25 families) and Culex tritaeniorhynchus (73 species in 24 families) carried more viral species than Anopheles sinensis (50 species in 19 families) or Aedes (38 species in 20 families) mosquitoes. Conclusion Viral diversity and abundance were affected by mosquito species and collection time. The present study elucidates the virome compositions of various mosquito species in northwestern China, improving the understanding of virus transmission dynamics for comparison with those of disease outbreaks., Author summary Most traditional viral research methods are limited to screening for a few types of viruses with low throughput. Here, we relied on metagenomic sequencing, which is a broadly non-specific screen for any virus, for monitoring of mosquito-borne viruses in the Shaanxi-Gansu-Ningxia region of China in 2019. The baseline of viral abundance and diversity in local Culex pipiens, Culex tritaeniorhynchus, Anopheles sinensis, and Aedes mosquitoes were investigated, with 116 viral species identified in 31 viral families, including Flaviviridae, Togaviridae, Phasmaviridae, Phenuiviridae, and some unclassified viruses. This study provides a baseline survey of the viromes of mosquitoes in the study area, highlighting the necessity of strengthened monitoring of mosquito-borne pathogens.

Alzheimer disease (AD) is the most common form of neurodegenerative disease in older adults and has a complicated etiology. Recently, the roles of short-chain fatty acids (SCFAs), the main metabolites generated by fermentation of dietary fiber by gut microbiota, in the pathogenesis of AD have attracted considerable interest. This study analyzed the multiple roles of SCFAs in AD pathogenesis from five aspects, including: 1) epigenetic regulation; 2) modulation of neuroinflammation; 3) maintenance of the blood-brain barrier (BBB); 4) regulation of brain metabolism; and 5) interference in amyloid protein formation. According to the currently available evidence, SCFAs, particularly butyrate, cause important biological effects that interfere with the development of AD. However, the effect of other SCFAs, such as propionate, on AD might be either beneficial or harmful to different pathways, indicating that the role of SCFAs in the pathogenesis of AD is rather complicated and warrants further investigations.

Background Frailty is emerging as an important determinant for health, while researches in the field of frailty start at a later stage in China and mainly focuses on community elderly dwellers. Little is known about frailty in cancer patients in China, nor the risk factors of frailty. This study aimed to investigate the prevalence of frailty and its risk factors in elderly inpatients with gastrointestinal cancer. Methods This cross-sectional study was performed at a tertiary hospital in China from Mar. 2020 to Nov. 2020. The study enrolled 265 inpatients aged 60 and older with gastrointestinal cancer who successfully underwent surgery. The demographic and clinical characteristics, biochemical laboratory parameters, and anthropometric data were collected from all patients. The Groningen Frailty Indicator was applied to assess patients’ frailty status. Multivariate logistic regression model analysis was carried out to identify risk factors of frailty and estimate their 95% confidence intervals. Results The prevalence of frailty in elderly inpatients with gastrointestinal cancer was 43.8%. A multivariate logistic regression analysis showed that older age (OR = 1.065, 95% CI: 1.001–1.132, P = 0.045), low handgrip strength (OR = 4.346, 95% CI: 1.739–10.863, P = 0.002), no regular exercise habit (OR = 3.228, 95% CI: 1.230–8.469, P = 0.017), and low MNA-SF score (OR = 11.090, 95% CI: 5.119–24.024, P

Background:Papillary Thyroid Carcinoma (PTC) represents the most common thyroid cancer. Until recently, treatment options for PTC patients are limited. Nilotinib is the second-generation tyrosine kinase inhibitor, and has been widely used in the treatment of Chronic Myeloid Leukemia (CML).Objectives:We aimed to explore whether nilotinib is effective for the suppression PTC cancer progression and the underlying mechanisms.Results:In this study, the three human PTC cell lines (KTC-1, BCPAP, and TPC1) were used to verify the effects of nilotinib on cell growth. The half maximal inhibitory concentration (IC50) was calculated according to the growth curve post nilotinib treatment at different concentrations. Cell counting kit-8 and colony formation analysis were used to monitor cell growth after nilotinib treatment. Cell apoptosis and autophagy related proteins and phosphorylation of PI3K/Akt/mTOR were detected by Western blotting analysis.Methods:Nilotinib treatment could effectively inhibit PTC cell growth, which was accompanied by an increase in apoptosis and induction of autophagy. Mechanistically, nilotinib treatment repressed the phosphorylation of the PI3K/Akt/mTOR pathway.Conclusion:Collectively, our results demonstrated that nilotinib may display anti-tumor effect against PTC via inhibiting PI3K/Akt/mTOR pathway and inducing apoptosis and autophagy.

Aberrant alternative splicing (AS) has been highly involved in the tumorigenesis and progression of most cancers. The potential role of AS in invasive breast cancer (IBC) remains largely unknown. In this study, RNA sequencing of IBC samples from The Cancer Genome Atlas was acquired. AS events were screened by conducting univariate and multivariate Cox analysis and least absolute shrinkage and selection operator regression. In total, 2146 survival-related AS events were identified from 1551 parental genes, of which 93 were related to prognosis, and a prognostic marker model containing 14 AS events was constructed. We also constructed the regulatory network of splicing factors (SFs) and AS events, and identified DDX39B as the node SF gene, and verified the accuracy of the network through experiments. Next, we performed quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) in triple negative breast cancer patients with different responses to neoadjuvant chemotherapy, and found that the exon-specific expression of EPHX2, C6orf141, and HERC4 was associated with the different status of patients that received neoadjuvant chemotherapy. In conclusion, this study found that DDX39B, EPHX2 (exo7), and HERC4 (exo23) can be used as potential targets for the treatment of breast cancer, which provides a new idea for the treatment of breast cancer.

In view of great difficulties in the pathogenesis analysis of Alzheimer’s disease (AD) presently, profiling the modifiable risk factors is crucial for early detection and intervention of AD. However, the causal associations among them have yet to be identified, and the effective integration and application of these data also remain considerable challenges due to the lack of efficient collection and analysis procedures. To address this issue, we performed comprehensive analyses by two-sample Mendelian randomization (2SMR) and established the AlzRiskMR database (https://github.com/SDBMC/RiskFactors2AD). Four 2SMR analysis methods, including inverse variance weighted (IVW), MR-Egger, weighted median, and weighted mode, were used for the complementary calculation to test the reliability of the results. The database currently comprises 1870 sets of data of Genome-Wide Association Studies (GWAS) from the MR-Base and NHGRI-EBI GWAS Catalog database. AlzRiskMR database not only estimates causal associations between modifiable risk factors and AD but also offers a useful and timely resource for early intervention of AD development incidence.

Purpose of Review: Excessive supraventricular ectopic activity (ESVEA), in the form of frequent premature atrial contractions (PACs) and runs of PACs, is commonly observed in clinical practice and is frequently considered to be benign. Yet, recent studies have demonstrated a link between ESVEA and adverse cardiovascular outcomes. The aim of this meta-analysis was to examine the association between ESVEA and the risk of atrial fibrillation (AF), stroke, and mortality. Recent Findings: A systematic search was performed in PubMed, EMBASE, and the Cochrane Library up to December 2017 to identify studies assessing adverse cardiovascular outcomes in patients with ESVEA, recorded on ambulatory electrocardiography. ESVEA was defined as a burden of PACs > 30 PACs/h or any runs of ≥20 PACs. The risk estimates for EVSEA and each clinical endpoint were pooled and analyzed separately. Results: Five studies comprising 7545 participants were included in this meta-analysis. The pooled analysis showed that ESVEA doubled the risk of AF (HR 2.19, 95% CI 1.70–2.82). ESVEA was also associated with a higher incidence of stroke (HR 2.23, 95% CI 1.24–4.02). Finally, ESVEA was associated with higher all-cause mortality (HR 1.61, 95% CI 1.25–2.07). Summary: Our meta-analysis found that ESVEA is closely associated with AF, stroke, and all-cause mortality. Further studies are required to examine the implication of therapeutic strategies in patients with ESVEA, in order to prevent potential subsequent adverse cardiovascular outcomes.

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies, which ranks the third leading cause of cancer-related death worldwide. The screening of anti-HCC drug with high efficiency and low toxicity from traditional Chinese medicine (TCM) has attracted more and more attention. As a TCM, Chinese dragon's blood has been used for the treatment of cardiovascular illness, gynecological illness, skin disorder, otorhinolaryngological illness, and diabetes mellitus complications for many years. However, the anti-tumor effect and underlying mechanisms of Chinese dragon's blood remain ill-defined. Herein we have revealed that Chinese dragon's blood EtOAc extract (CDBEE) obviously suppressed the growth of human hepatoma HepG2 and SK-HEP-1 cells. Moreover, CDBEE inhibited the migration and invasion of HepG2 and SK-HEP-1 cells. Additionally, CDBEE displayed good in vitro anti-angiogenic activity. Importantly, CDBEE treatment significantly blunted the oncogenic capability of HepG2 cells in nude mice. Mechanistically, CDBEE inhibited Smad3 expression in human hepatoma cells and tumor tissues from nude mice. Using RNA interference, we demonstrated that CDBEE exerted anti-hepatoma activity partially through down-regulation of Smad3, one of major members in TGF-β/Smad signaling pathway. Therefore, CDBEE may be a promising candidate drug for HCC treatment, especially for liver cancer with aberrant TGF-β/Smad signaling pathway.

Background: MicroRNAs (miRNAs) act as pivotal functions in gastric cancer (GC) carcinogenesis and progression. MiR-559 has been defined as a potential cancer suppressor gene in a few cancers. Nevertheless, the biological effect of miR-559 in human GC and the underlying molecular mechanism still unclear and need to be further illuminated. Methods: Quantitative real-time PCR (qRT-PCR) was fulfilled for measuring the miR-559 expression level in GC. The dual-luciferase reporter was used to verify that tripartite motif-containing 14 (TRIM14) is a target gene of miR-559. The expression levels of TRIM14 were examined by qRT-PCR and Western blot in GC tissue specimens and cell lines. The effects of miR-559 on GC cell growth were detected with MTT and cell counting assays. Cell cycle and apoptosis were examined by using flow cytometry. Overexpression and siRNA further demonstrated the role of TRIM14 in GC. Results: Our results revealed that miR-559 expression was dramatically downregulated in human GC tissue specimens and cell lines. MiR-559 overexpression restrained GC cell growth, and induced cell cycle G1-S phase arrest and apoptosis. MiR-559 inhibitors promoted cell multiplication and cell cycle G1-S transition, and inhibited apoptosis. MiR-559 level was negatively related to TRIM14 mRNA level in GC. The results showed that TRIM14 was affirmed to be a target gene of miR-559. MiR-559 overexpression downregulated the TRIM14 expression, and miR-559 inhibitors upregulated the TRIM14 expression. Particularly, knockdown of TRIM14 gave rise to the semblable cellular effects observed upon miR-559 overexpression. TRIM14 overexpression recapitulated the revulsive cellular and molecular effects by suppression of miR-559. Furthermore, both miR-559 overexpression and TRIM14 silencing led to the inhibition of the AKT signaling pathway. On the contrary, miR-559 suppression and TRIM14 overexpression activated the AKT signaling pathway, and inhibited Bax/Bcl-2 pathway. Conclusions: The findings illustrate that miR-559 restrains cell multiplication via suppressing the AKT signaling pathway in human GC and induces cell apoptosis through the suppression of Bax/Bcl-2 signaling pathway via targeting TRIM14. The findings imply that miR-559 acts as a pivotal function in human GC and represents a latent novel target in GC therapy.

Mitochondrial dysfunction and oxidative stress play an important role in the pathogenesis of both atrial fibrillation (AF) and diabetes mellitus (DM). Wenxin Keli (WXKL), an antiarrhythmic traditional Chinese medicine, has been shown to prevent cardiac arrhythmias through modulation of cardiac ion channels. This study tested the hypothesis that WXKL can improve atrial remodeling in diabetic rats by restoring mitochondrial function. Primary atrial fibroblasts of neonatal SD rats were divided into four groups: control, hydrogen peroxide (H2O2), H2O2+WXKL 1 g/L, and H2O2+WXKL 3 g/L groups. Intracellular mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and mitochondrial oxygen consumption were measured. SD male rats were randomly divided into three groups: control, DM, and DM+WXKL groups. Rats in the DM+WXKL group were treated with daily gavage of WXKL at 3 g/kg. After eight weeks, echocardiography, hemodynamic examination, histology, electrophysiology study, mitochondrial respiratory function, and western blots were assessed. H2O2 treatment led to increased ROS and decreased intracellular MMP and mitochondrial oxygen consumption in primary atrial fibroblasts. WXKL improved the above changes. DM rats showed increased atrial fibrosis, greater left atrial diameter, lower atrial conduction velocity, higher conduction heterogeneity, higher AF inducibility, and lower mitochondrial protein expression, and all these abnormal changes except for left atrial diameter were improved in the DM+WXKL group. WXKL improves atrial remodeling by regulating mitochondrial function and homeostasis and reducing mitochondrial ROS in diabetic rats.

Mitochondrial oxidative stress and dysfunction play an important role of atrial remodeling and atrial fibrillation (AF) in diabetes mellitus. Endoplasmic reticulum (ER) stress has been linked to both physiological and pathological states including diabetes. The aim of this project is to explore the roles of ER stress in hyperglycemia-induced mitochondrial dysfunction and cell death of atrial cardiomyocytes. High glucose upregulated ER stress, mitochondrial oxidative stress, and mitochondria-associated ER membrane (MAM)- enriched proteins (such as glucose-regulated protein 75 (GRP75) and mitofusin-2 (Mfn2)) of primary cardiomyocytes in vitro. Sodium phenylbutyrate (4-PBA) prevented the above changes. Silencing of Mfn2 in HL-1 cells decreased the Ca2+ transfer from ER to mitochondria under ER stress conditions, which were induced by the ER stress agonist, tunicamycin (TM). Electron microscopy data suggested that Mfn2 siRNA significantly disrupted ER-mitochondria tethering in ER stress-injured HL-1 cells. Mfn2 silencing attenuated mitochondrial oxidative stress and Ca2+ overload, increased mitochondrial membrane potential and mitochondrial oxygen consumption, and protected cells from TM-induced apoptosis. In summary, Mfn2 plays an important role in high glucose-induced ER stress in atrial cardiomyocytes, and Mfn2 silencing prevents mitochondrial Ca2+ overload-mediated mitochondrial dysfunction, thereby decreasing ER stress-mediated cardiomyocyte cell death.

Background Sepsis is one of the common death factors in intensive care unit, which refers to the systemic inflammatory response syndrome caused by infection. It has many complications such as acute renal injury, shock, multiple organ dysfunction, and failure. The mortality of acute renal injury is the highest among the complications, which is a serious threat to the safety of patients and affects the quality of life. This study aimed to observe the changes in autophagy-related protein expressions in patients with acute kidney injury (AKI) after continuous renal replacement therapy (CRRT) and their impacts on prognosis. Methods 207 AKI patients visiting the Emergency Department of The First People’s Hospital of Xuzhou from January 2014 to February 2018 were recruited and treated with CRRT. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was applied to detect the expression of autophagy-related genes, including light chain 3 type II (LC3-II), autophagy-related 5 (Atg-5) and Beclin-1, in the monocytes of the patient’s peripheral blood before and after treatment. The levels of inflammatory mediators interleukin (IL)-1β and IL-6 were determined via enzyme-linked immunosorbent assay before and after treatment. The patient’s serum creatinine (Scr) level before and after treatment was measured using a full-automatic biochemistry analyser. Moreover, the treatment effect was graded after CRRT, and the relationship between the prognosis of patients and the autophagy-related proteins was observed. Results The Scr levels in the patients were significantly decreased after treatment with CRRT. Before treatment, the IL-1β and IL-6 blood levels were high in the patients, while the amounts were significantly reduced after CRTT. The expressions of LC3-II, Atg-5 and Beclin-1 in the monocytes of patients after treatment were significantly decreased compared with those before treatment. Compared with those in survived patients, the expression of autophagy-related proteins was significantly elevated in in patients died after one to three weeks after the treatment. IL-1β, IL-6, LC3-II and Beclin-1, but not Atg-5 values were significantly correlated with Scr. Conclusion The expression of LC3-II, Atg-5 and Beclin-1 in the monocytes of patients may change prominently after treatment with CRRT, so they are expected to be regarded as new prognostic indicators for AKI patients.