Search

Dysregulated expression of microRNAs (miRNAs or miRs) has been implicated in the pathophysiology of type 2 diabetes mellitus (T2DM). However, their underlying role in the complication of detrusor fibrosis remains poorly understood. Therefore, this study aimed to examine the potential functional relevance of miR-363 in detrusor fibrosis of rats with streptozotocin (STZ)-induced T2DM through the predicted target gene collagen type I alpha 2 (Col1a2). Immunohistochemical analysis found an increase in the positive expression of collagen type III alpha 1 (Col3a1) and Col1a2 in detrusor tissues, where miR-363 expression was decreased. Next, gain- and loss-of-function experiments were performed to clarify the effects of miR-363 and Col1a2 on the activities of bladder detrusor cells. Of note, binding affinity between miR-363 and Col1a2 was verified by a dual-luciferase reporter gene assay and RNA immunoprecipitation (RIP) assay. Upregulated miR-363 inhibited Col1a2 expression, which led to increased expression of B-cell lymphoma 2 (Bcl-2) and Smad7 and accelerated cell viability, along with decreases in cell apoptosis and Col3a1, Bcl-2-associated X protein (Bax), transforming growth factor (TGF)-β1, and Smad4 expressions. In conclusion, miR-363 upregulation reduces detrusor fibrosis in rats with STZ-induced T2DM through suppression of the TGF-β1/Smad signaling pathway by targeting Col1a2. Therefore, our study provided further insights for the development of new therapeutic targets for T2DM., Graphical Abstract, miR-363 can inhibit Col1a2, which promotes viability and reduces apoptosis of detrusor cells in rats with STZ-induced T2DM through the inhibition of the TGF-β1/Smad signaling pathway, which ultimately leads to the alleviation of detrusor fibrosis. This study provides new evidence regarding the functional actions of miR-363 in T2DM.

The predation behavior of the pistol shrimp is extremely special, and the predation process will produce a huge popping sound, which has caused extensive research by scholars from all over the world. This article carried out a study on the rapid closing jet mechanism of pistol shrimp’s claws. A theoretical model, based on the hydrodynamic characteristics of seawater and the theory of fluid-structure coupling, was proposed for the interaction between the claws and seawater. A simulation model was established using the finite volume software Fluent, and the rapid closing jet mechanism of pistol shrimp’s claws was verified by using fluid dynamic grid. This article studied the influence of different fluid models on the simulation results. The effects of the claws’ closing angular velocity and angular acceleration on the interaction between the claws and seawater were analyzed, which provides a theoretical basis for the development of new underwater kinetic energy weapons.

Vinyl chloride (VC) is a confirmed human carcinogen associated with hepatocellular carcinoma and angiosarcoma. However, the role of microRNAs (miRNAs) in liver cell cycle changes under VC exposure remains unclear, which prevents research on the mechanism of VC-induced carcinogenesis. In this study, male rats were injected intraperitoneally with VC (0, 5, 25, and 125 mg/kg body weight) for 6, 8, and 12 weeks. Cell cycle analysis of liver cells, miRNA-222, miRNA-199a, miRNA-195, and miRNA-125b expression in the liver and serum, and target protein expression were performed at different time points. The results showed a higher percentage of hepatocytes in the G1/G0 and S phases at the end of 6 and 12 weeks of VC exposure, respectively. MiRNA-222 expression decreased initially and then increased, whereas miRNA-199a, miRNA-195, and miRNA-125b expression increased initially and then decreased, which corresponded with changes in cell cycle distribution and related target proteins expression (p27, cyclinA, cyclinD1, and CDK6). The corresponding expression levels of miRNAs in serum did not change. Dynamic changes in miR-222, miR-199a, miR-195, and miR-125b induced by VC can lead to cell cycle deregulation by affecting cell cycle-related proteins, and these miRNAs can serve as early biomarkers for malignant transformation caused by VC.

Objective To assess and compare the performance of fluorine-18-labeled fluorodeoxyglucose positron emission tomography (18 F-FDG-PET/ CT) and gallium-68-labeled tetraazacyclododecanetetraacetic acid-DPhe1-Tyr3-octreotate (68 Ga- DOTATATE) PET/CT in the targeted imaging of culprit tumors causing osteomalacia. Methods This was a clinical retrospective analysis. We analyzed 13 patients (five men, eight women; mean age, 49 years; range, 19-55 years) with suspicion of tumor-induced osteomalacia (TIO) between March 2017 and October 2019. All patients underwent two functional imaging methods to locate the culprittumors. Studies were performed on a PET/CT scanner. The injection doses of 18 F- FDG and 68 Ga-DOTATATE were 0.5mCi/kg and approximately 5.0mCi, respectively. In the two scans, the whole body was captured from head to toe 45 to 60 min after intravenous tracer injection. 68 Ga-DOTATATE PET/CT and 18 F-FDG PET/CT imaging results locate culprit tumors according to the following criteria: (i) abnormal foci uptake concentration was observed locally, and the uptake level was higher than the background level of the right lobe of the liver; (ii) combined CT showed or did not have obvious abnormal density changes; and (iii) non-specific ingestion lesions due to fracture, arthritis, necrosis of femoral head are excluded. Compared with the results of pathological examination and clinical follow-up, the sensitivity, specificity and accuracy of 68 Ga-DOTATATE PET/CT imaging and 18 F-FDG PET/CT imaging for TIO were analyzed. Results All patients had symptoms of osteomalacia and hypophosphatemia. The lag time (symptoms to PET diagnosis) ranged from 2 to 12 years. There were eight cases of TIO patients and five cases of non-TIO patients confirmed by surgery, pathology and follow-up. Among the eight TIO patients, there were six cases (75.0%) of PMTs, one case (12.5%) of giant cell tumor, one case (12.5%) of hemangiopericutoma. Most (n = 6, 75.0%) of the confirmed tumors in our patient population were in the lower extremities, followed by craniofacial regions (n = 1, 12.5%), and torso (n = 1, 12.5%), respectively. Among the five non-TIO patients, there were two cases of Fanconi syndrome, one case of rickets, and two cases of sporadic osteomalacia hypophosphorus. The culprit tumors could be located either in the bone (n = 5, 62.5%) or the soft tissue (n = 3, 37.5%). 18 F-FDG PET/CT was able to localize the tumor in six (6/13, 46.1%) patients. 68 Ga-DOTATATE PET/CT detected tumor in 8 (83.3%) of 13 patients. The sensitivity of 68 Ga-DOTATATE PET/CT imaging and 18 F-FDG PET/CT imaging in the evaluation of TIO in our patient population were 100% (8/8) vs 75% (6/8). The specificity of the two different methods was 80% (4/5). The overall accuracy was 92.3% (12/13) vs 76.9% (10/13). Conclusions 68 Ga-DOTATATE PET/CT is very effective in assessing hypophosphatemia patients with TIO typical symptoms compared with 18 F-FDG. Therefore, in clinically suspected cases of hypophosphatemic osteomalacia, 68 Ga-DOTATATE PET/CT should be preferred as an imaging modality investigation to avoid delay in the treatment of this disease.

Plants establish symbioses with mutualistic fungi, such as arbuscular mycorrhizal (AM) fungi, and bacteria, such as rhizobia, to exchange key nutrients and thrive. Plants and symbionts have coevolved and represent vital components of terrestrial ecosystems. Plants employ an ancestral AM signaling pathway to establish intracellular symbioses, including the legume–rhizobia symbiosis, in their roots. Nevertheless, the relationship between the AM and rhizobial symbioses in native soil is poorly understood. Here, we examined how these distinct symbioses affect root-associated bacterial communities in Medicago truncatula by performing quantitative microbiota profiling (QMP) of 16S rRNA genes. We found that M. truncatula mutants that cannot establish AM or rhizobia symbiosis have an altered microbial load (quantitative abundance) in the rhizosphere and roots, and in particular that AM symbiosis is required to assemble a normal quantitative root-associated microbiota in native soil. Moreover, quantitative microbial co-abundance network analyses revealed that AM symbiosis affects Rhizobiales hubs among plant microbiota and benefits the plant holobiont. Through QMP of rhizobial rpoB and AM fungal SSU rRNA genes, we revealed a new layer of interaction whereby AM symbiosis promotes rhizobia accumulation in the rhizosphere of M. truncatula. We further showed that AM symbiosis-conditioned microbial communities within the M. truncatula rhizosphere could promote nodulation in different legume plants in native soil. Given that the AM and rhizobial symbioses are critical for crop growth, our findings might inform strategies to improve agricultural management. Moreover, our work sheds light on the co-evolution of these intracellular symbioses during plant adaptation to native soil conditions.

Objective Riedel's thyroiditis (RT) is a very rare chronic fibrosing thyroiditis that is often associated with multifocal fibrosclerosis. Although the relationship of RT and IgG4-related disease (IgG4-RD) has been suggested, the expression of IgG and IgG4 in thyroid tissues of patients with RT has seldom been studied. Design A case series and literature review. Patients and measurements We searched our hospital's pathology database and identified five cases of RT between 2000 and 2019. The expression levels of IgG4 and IgG in thyroid tissues were detected by immunohistochemistry. We also performed a literature search of the electronic databases PubMed/MEDLINE, Web of Science and China National Knowledge Internet (CNKI). Eight papers were included in this study. Results According to immunohistochemistry, the numbers of IgG4+ plasma cells per high-power field (HPF) of the five RT patients at our hospital were 80, 8, 50, 10 and 22, and the respective IgG4+/IgG+ ratios were 76%, 80%, 43%, 19% and 28%. In the literature, 15 RT patients with confirmed IgG4 and IgG immunohistochemical findings were identified. Only seven of them fulfilled the IgG4-RD diagnostic criteria in terms of immunohistochemistry (IgG4+ > 10/HPF, IgG4+/IgG+ > 40%). In order to ensure that most RT cases can meet the IgG4 immunohistochemical criteria, an organ-specific cut-off value (≥10 IgG4+ plasma cells/HPF and ≥ an IgG4+/IgG ratio of 20%) was finally selected in our study. Conclusion Our findings of IgG4 expression in patients with RT suggest that a cut-off of 10 IgG4+ plasma cells/HPF and an IgG4+/IgG ratio of 20% are more suitable diagnostic criteria for RT in IgG4-RD.

Legumes, unlike other plants, have the ability to establish symbiosis with nitrogen-fixing rhizobia. It has been theorized that a unique property of legume root cortical cells enabled the initial establishment of rhizobial symbiosis1–3. Here we show that a SHORTROOT–SCARECROW (SHR–SCR) stem cell program in cortical cells of the legume Medicago truncatula specifies their distinct fate. Regulatory elements drive the cortical expression of SCR, and stele-expressed SHR protein accumulates in cortical cells of M. truncatula but not Arabidopsis thaliana. The cortical SHR–SCR network is conserved across legume species, responds to rhizobial signals, and initiates legume-specific cortical cell division for de novo nodule organogenesis and accommodation of rhizobia. Ectopic activation of SHR and SCR in legumes is sufficient to induce root cortical cell division. Our work suggests that acquisition of the cortical SHR–SCR module enabled cell division coupled to rhizobial infection in legumes. We propose that this event was central to the evolution of rhizobial endosymbiosis. Repurposing of an SHR–SCR stem cell program in the legume root cortex enables rhizobial symbiosis.

BACKGROUND Normal size ovarian cancer syndrome (NOCS) is a challenge for clinicians regarding timely diagnosis and management due to atypical clinical and imaging features. It is extremely rare with only a few cases reported in the literature. More data are needed to clarify its biological behavior and compare the differences with abnormal size ovarian cancer. AIM To assess the clinical and pathological features of NOCS patients treated in our institution in the last 10 years and to explore risk factors for relapse and survival. METHODS Patients who were pathologically diagnosed with NOCS between 2008 and 2018 were included. Papillary serous ovarian carcinoma (PSOC) patients were initially randomly recruited as the control group. Demographics, tumor characteristics, treatment procedures, and clinical follow-up were retrospectively collected. Risk factors for progression-free survival and overall survival were assessed. RESULTS A total of 110 NOCS patients were included; 80 (72.7%) had primary adnexal carcinoma, two (1.8%) had mesotheliomas, 18 (16.4%) had extraovarian peritoneal serous papillary carcinoma, and eight (7.3%) had metastatic tumors. Carbohydrate antigen (CA)125 and ascites quantity were lower in the NOCS cohort than in the PSOC group. The only statistically significant risk factors for worse overall survival (P < 0.05) were the levels of CA199 and having fewer than six chemotherapy cycles. The 1-year, 3-year, and 5-year survival rates were 75.5%, 27.7%, and 13.8%, respectively. CONCLUSION The clinical symptoms of the NOCS group are atypical, and the misdiagnosis rate is high. Ascites cytology and laparoscopic exploration are valuable in the early diagnosis to avoid a misdiagnosis. The level of CA199 is the most important predictor of overall survival, and more than six cycles of chemotherapy contributes to the increased survival rates of NOCS patients.

Insects employ a sensitive chemosensory system to accurately recognize external odorants, which help them to make a behavioral response quickly. Semiothisa cinerearia has caused serious damages to Sophora japonica L. in recent years, and there is still a lack of effective strategy to control the pest. Although the two type-II sex pheromones of S. cinerearia, 6Z,9Z-cis-3,4-epoxy-17:H and 3Z,6Z,9Z-17:H, have been identified for 30 years, the molecular mechanisms underlying the chemosensation of the two sex pheromones are still unknown. Here, we found that there are differences in the types of antennae sensilla between sexes, and revealed 146 putative chemosensory genes in the antennal transcriptome. Among these genes, 11 and 40 of them displayed male-biased and female-biased expression, respectively. Our findings greatly improve the chemosensory gene resources for S. cinerearia and provide a foundation for functional studies of these sex-biased genes on the chemosensation of sex pheromones and on other sex-related behaviors.

Background When the risk of lymph node metastasis (LNM) is considered minimal in patients with early gastric cancer (EGC), endoscopic submucosal dissection (ESD) is an effective alternative to radical resection. This study aims to estimate the feasibility of ESD for EGC with ulceration. Patients and Methods We retrospectively reviewed data from 691 patients who underwent gastrectomy for EGC with ulceration. Subsequently, a stratification system for lesions was created based on the expanded ESD criteria, and the associations between the subgroups and the rate of LNM were analyzed. Results LNM was confirmed in 16.5% (114/691) of patients. Univariate analysis demonstrated that age, sex, tumor size, macroscopic features, depth of invasion, tumor differentiation, Lauren type, lymphovascular invasion (LVI), and perineural invasion were associated with LNM. Multivariate analysis showed that LVI [odds ratio (OR) = 16.761, P P = 0.028), and SM2 invasion (OR = 3.230, P Conclusions Depth of invasion and LVI were strongly associated with LNM in ulcerative EGC. Endoscopic resection may be applicable for undifferentiated mucosal ulcerative EGC

Background In China, the prevalence of superficial fungal infections of the foot is high and recurrence is common. However, a prospective, large-scale and multicentre study on the aetiology of superficial fungal infections of the foot is still lacking. Objectives To study the epidemiology of aetiological agents of superficial fungal infections of the foot in urban outpatients in mainland China, as well as to understand the aetiology features of the pathogenic agent. Methods The study was designed as a multicentre, prospective epidemiological survey. A total of 1704 subjects were enrolled from seven geographical areas in mainland China. For each subject, one mycological sample and one bacterial sample were collected. KOH wet mount examination and culture were performed at local laboratories. The bacterial results were only reported in those with positive mycology. Further morphological identification and, if necessary, molecular biological identification were conducted in a central laboratory. Results Of 1704 enrolled subjects, 1327 (77.9%) subjects had positive fungal culture results. The incidence of dermatophytes, yeasts and moulds was 90.1%, 8.1% and 1.1%, respectively. The most frequently isolated aetiological agent (fungus) was Trichophyton rubrum. Moccasin form was the most commonly reported clinical diagnosis of superficial fungal infections. The most frequently isolated bacterial genus in patients was Staphylococcus. Conclusion This study prospectively investigated the clinical and mycological features of human dermatophytosis in mainland China. T rubrum was the most frequently isolated fungus, and moccasin form was the most commonly reported clinical diagnosis of superficial fungal infections.

Background Globally, colorectal cancer (CRC) affects more than 1 million people each year. In addition to non-modifiable and other environmental risk factors, Fusobacterium nucleatum infection has been linked to CRC recently. In this study, we explored mechanisms underlying the role of Fusobacterium nucleatum infection in the progression of CRC in a mouse model. Methods C57BL/6 J-Adenomatous polyposis coli (APC) Min/J mice [APC (Min/+)] were treated with Fusobacterium nucleatum (109 cfu/mL, 0.2 mL/time/day, i.g., 12 weeks), saline, or FadA knockout (FadA−/−) Fusobacterium nucleatum. The number, size, and weight of CRC tumors were determined in isolated tumor masses. The human CRC cell lines HCT29 and HT116 were treated with lentiviral vectors overexpressing chk2 or silencing β-catenin. DNA damage was determined by Comet assay and γH2AX immunofluorescence assay and flow cytometry. The mRNA expression of chk2 was determined by RT-qPCR. Protein expression of FadA, E-cadherin, β-catenin, and chk2 were determined by Western blot analysis. Results Fusobacterium nucleatum treatment promoted DNA damage in CRC in APC (Min/+) mice. Fusobacterium nucleatum also increased the number of CRC cells that were in the S phase of the cell cycle. FadA−/− reduced tumor number, size, and burden in vivo. FadA−/− also reduced DNA damage, cell proliferation, expression of E-cadherin and chk2, and cells in the S phase. Chk2 overexpression elevated DNA damage and tumor growth in APC (Min/+) mice. Conclusions In conclusion, this study provided evidence that Fusobacterium nucleatum induced DNA damage and cell growth in CRC through FadA-dependent activation of the E-cadherin/β-catenin pathway, leading to up-regulation of chk2.

Objective: Thyroglobulin antibodies (TgAb), principally comprising immunoglobulin G (IgG), are frequently found in healthy individuals. Previously, we showed that the glycosylation levels of TgAb IgG differed across various thyroid diseases, suggesting an important role of glycosylation on antibodies in the pathogenesis of thyroid diseases. Since IgG1 and IgG4 are the primary TgAb IgG subclasses, this study aimed to investigate the glycosylation of TgAb IgG1 and IgG4 subclasses in thyroid diseases. Methods: TgAb IgG was purified by affinity chromatography from the serum of patients with Hashimoto’s thyroiditis (HT) (n = 16), Graves’ disease (GD) (n = 8), papillary thyroid carcinoma (PTC) (n = 6), and PTC with histological lymphocytic thyroiditis (PTC-T) (n = 9) as well as healthy donors (n = 10). TgAb IgG1 and IgG4 concentrations were determined by enzyme-linked immunosorbent assay, and a lectin microassay was used to assess TgAb IgG1 and IgG4 glycosylation. Results: Significantly elevated mannose, sialic acid, and galactose levels on TgAb IgG1 were found in HT and PTC patients compared to GD patients and healthy controls (all p < 0.05). The mannose, sialic acid, and core fucose levels on TgAb IgG1 in PTC-T patients were higher than in healthy controls (all p < 0.05). Additionally, TgAb IgG1 from PTC-T patients exhibited lower sialylation than that from patients with PTC and higher fucosylation than that from patients with HT (both p < 0.05). However, TgAb IgG4 glycosylation did not differ among the five groups (p < 0.05). Conclusion: Our study describes different distributions of TgAb IgG1 glycosylation in various thyroid diseases. The aberrantly increased glycosylation levels of TgAb IgG1 observed in HT, PTC, and PTC-T might be indicative of immune disorders and participate in the pathogenesis of these diseases.

Here, we show that curcumin, an active hydrophobic polyphenolic compound extracted from turmeric, could reverse angiotensin II‐induced podocyte injury and apoptosis in a dose‐dependent manner. We found this protective effect of curcumin to be at least partly achieved by inhibiting endoplasmic reticulum stress. Therefore, curcumin may have potential for future development into a possible treatment for chronic kidney disease., Podocytes are an important component of the glomerular filtration barrier in the kidneys. The dysfunction and apoptosis of podocytes are important factors that can lead to the progression of chronic kidney disease (CKD). In CKD, angiotensin II is continuously elevated in circulation and is considered to have key roles in inducing podocyte injury and apoptosis. Curcumin is a hydrophobic polyphenolic compound extracted from turmeric. Increasing evidence demonstrates that curcumin has a protective effect on the kidneys in CKD. However, the mechanisms mediating this protective effect remain unclear. The aim of this study was to explore whether curcumin could protect against angiotensin II‐induced injury and apoptosis of podocytes. We performed western blotting, immunofluorescence, phalloidin staining, and terminal deoxynucleotidyl transferase nick‐end labeling staining to observe the expression level of podocyte‐specific proteins, apoptosis‐related proteins, and the arrangement of F‐actin. We found that curcumin could reverse angiotensin II‐induced podocyte injury and apoptosis in a dose‐dependent manner. In addition, curcumin dose‐dependently attenuated a pro‐apoptotic pathway, activated by angiotensin II‐induced endoplasmic reticulum stress. Conversely, the protective effects of curcumin were impaired upon addition of tunicamycin, an activator of endoplasmic reticulum stress. Thus, we speculate that curcumin protects against angiotensin II‐induced podocyte injury and apoptosis, at least partly by inhibiting endoplasmic reticulum stress.

Cumulative evidence suggests that microRNAs (miRNAs) promote gene expression in cancers. However, the pathophysiologic relevance of miRNA-mediated RNA activation in hepatocellular carcinoma (HCC) remains to be established. Our previous miRNA expression profiling in seven-paired HCC specimens revealed miR-93-5p as an HCC-related miRNA. In this study, miR-93-5p expression was assessed in HCC tissues and cell lines by quantitative real-time PCR and fluorescence in situ hybridization. The correlation of miR-93-5p expression with survival and clinicopathological features of HCC was determined by statistical analysis. The function and potential mechanism of miR-93-5p in HCC were further investigated by a series of gain- or loss-of-function experiments in vitro and in vivo. We identified that miR-93-5p, overexpressed in HCC specimens and cell lines, leads to poor outcomes in HCC cases and promotes proliferation, migration, and invasion in HCC cell lines. Mechanistically, rather than decreasing target mRNA levels as expected, miR-93-5p binds to the 3'-untranslated region (UTR) of mitogen-activated protein kinase kinase kinase 2 (MAP3K2) to directly upregulate its expression and downstream p38 and c-Jun N-terminal kinase (JNK) pathway, thereby leading to cell cycle progression in HCC. Notably, we also demonstrated that c-Jun, a downstream effector of the JNK pathway, enhances miR-93-5p transcription by targeting its promoter region. Besides, downregulation of miR-93-5p significantly retarded tumor growth, while overexpression of miR-93-5p accelerated tumor growth in the HCC xenograft mouse model. Altogether, we revealed a miR-93-5p/MAP3K2/c-Jun positive feedback loop to promote HCC progression in vivo and in vitro, representing an RNA-activating role of miR-93-5p in HCC development.

Background The low pathogenic H9N2 AIV caused the serious impact on the poultry industry and public safety. Our purpose was to investigate the molecular evolutionary characteristics of the new isolated H9N2 virus and investigate the intracellular target protein of H9N2 AIV replication in sensitive cells. Methods AIV A/chicken/Shandong/LY1/2017 (H9N2) was isolated from the cloaca of the healthy chicken in Shandong, and the full-length eight gene segments of this isolated H9N2 AIV were amplified by RT-PCR and analyzed. MDCK cells were used as the target cell model, and VOPBA assay and LC-MS/MS were carried out to identify the virus-binding protein of H9N2 AIV. MDCK cells were pre-treated with the special antibody and siRNA, and treated with H9N2 AIV to detect the virus replication. Additionally, Vimentin-pcDNA3.0 was successfully constructed, and transinfected into MDCK cells, and then H9N2 AIV mRNA was detected with RT-PCR. Results Phylogenetic analysis revealed that HA, NA, PB2, PB1, PA, NP and M seven genes of the isolated H9N2 AIV were derived from A/Chicken/Shanghai/F/98, while NS gene was derived from A/Duck/Hong Kong/Y439/97. The cleavage site sequence of HA gene of the isolated H9N2 AIV was a PARSSR G pattern, and the left side sequence (224 ~ 229) of receptor binding site was NGQQGR pattern, which were similar to that of A/Chicken/Shanghai/F/98. Following VOPBA assay, we found one protein of about 50KDa binding to H9N2 AIV, and the results of LC-MS/MS analysis proved that vimentin was the vital protein binding to H9N2 AIV. The pre-incubation of the specific antibody and siRNA decreased the viral RNA level in MDCK cells treated with H9N2 AIV. Furthermore, we found that over-expressed vimentin increased H9N2 AIV replication in MDCK cells. Conclusions These findings suggested that the isolated H9N2 AIV might be a recent clinical common H9N2 strain, and vimentin protein might be one vital factor for H9N2 AIV replication in MDCK cells, which might be a novel target for design and development of antiviral drug.

Excision repair cross-complementation group 6-like (ERCC6L) is overexpressed in some malignancies; however, its role in hepatocellular carcinoma (HCC) remains to be further investigated. In the present study, we explored the expression and function of ERCC6L in HCC. We investigated the expression of ERCC6L by microarray analysis, using the Cancer Genome Atlas database, and by HCC tissue microarray. The results showed that ERCC6L expression was upregulated in tumor specimens and HCC cell lines. High ERCC6L expression in tumor tissues was significantly correlated with poor prognosis and could serve as an independent prognostic indicator for HCC patients. Results of in vitro and in vivo assays revealed that ERCC6L substantially promoted cell proliferation, and our flow cytometry analysis revealed that this was accomplished by acceleration of the G1/S transition. Finally, gene set enrichment analysis and western blotting results indicated that ERCC6L might regulate HCC proliferation by activating p53 signaling. Our study suggests that ERCC6L plays an important role in HCC proliferation and that it might serve as a promising therapeutic target in HCC.

Objective The predictive role of neutrophil-to-lymphocyte ratio (NLR) for preeclampsia (PE) has been explored in several studies and current evidence seems to be conflicting. The aim of this study is to compare the NLR values of mild and severe preeclampsia with the normotensive pregnant women, in order to explore the predictive role of NLR for preeclampsia and whether the NLR value has significant difference between severe and mild preeclampsia. Design and methods We systematically searched Pubmed, Embase, Web of Science and Cochrane database for relative literature up to May 2019. The statistical analysis was performed using Stata 12.0 software. Results Totally 15 eligible studies consisting of 3982 patients were enrolled in our meta-analysis. The NLR value is higher in preeclampsia when compared to healthy pregnant women (3270 women, MD: 1.44, 95% CI [1.04, 1.83]). Furthermore, NLR value is higher in severe preeclampsia than in mild preeclampsia (1287 women, MD: 1.12, 95% CI [0.69,1.56]). Conclusions The findings of our meta-analysis suggest that NLR value is higher in preeclampsia patients especially in severe preeclampsia. The NLR might be a useful laboratory marker for clinical prediction and disease severity evaluation of preeclampsia. However, given that the available evidence is mainly drawn from case-control studies, future cohorts are needed in this field to accurately determine optimal timing and cut-off values that may be used in the clinical setting.

Background New-onset arrhythmias and sleep disturbances are frequently observed during the postoperative period in patients undergoing thoracic surgery. Objective We evaluated the effectiveness of a single-dose stellate ganglion block (SGB) to prevent the occurrence of arrhythmias in patients undergoing thoracic surgery for cancer. Design Randomised controlled double-blind study. Setting Single university hospital. Patients Ninety patients with lung cancer or oesophagal cancer scheduled for elective video-assisted thoracoscopic surgery were randomly randomised into one of two equal groups (the SGB group and control group, n = 40 each). Interventions Patients received a single dose of 5 ml of 0.5% ropivacaine during ultrasound-guided SGB before induction of general anaesthesia in the SGB group. Main outcome measures Holter ECG was continuously monitored during the first 48 postoperative hours, and sleep state was monitored during the first two postoperative nights. Results The incidences of postoperative supraventricular tachycardias were lower in the SGB group compared with the control group during the first 48 postoperative hours; 11.6 (5/43) vs. 31.8% (14/44), respectively, P = 0.023 (odds ratio 0.28, 95% confidence interval 0.09 to 0.87). The SGB also prolonged the total sleep time and increased the sleep efficiency during the first two postoperative nights. The duration of stage N2 sleep was longer in the SGB group compared with the control group [28 (interquartile range, 14 to 58) to 94 (interquartile range, 69 to 113) min, P = 0.016] on the first postoperative night. There were no differences in the duration of stage N1 and N3 sleep (P = 0.180, 0.086, respectively) on the first postoperative night, and the duration of stage N1, N2 and N3 sleep (P = 0.194, 0.057, 0.405, respectively) on the second postoperative night between the groups. Conclusion A pre-operative SGB effectively prevented the occurrence of postoperative supraventricular tachycardias and improves the objective sleep quality in patients undergoing thoracic surgery for cancer. Trial registration number ChiCTR-1900023064.

Sorafenib, a multitargeted kinase inhibitor, has been reported to elicit a limited therapeutic effect in hepatocellular carcinoma (HCC). Currently, phototherapy, including photodynamic therapy (PDT) and photothermal therapy (PTT), is emerging as a powerful modality for cancer therapy. However, few studies have been reported the effectiveness of the combination of sorafenib with PDT and PTT in HCC. Herein, we designed and synthesized bovine serum albumin (BSA)-coated zinc phthalocyanine (ZnPc) and sorafenib (SFB) nanoparticle (ZnPc/SFB@BSA). The obtained ZnPc/SFB@BSA was able to trigger PDT, PTT, and chemotherapy. After irradiation by a 730 nm light, ZnPc/SFB@BSA significantly suppressed HCC cell proliferation and metastasis while promoted cell apoptosis in vitro. Furthermore, intravenous injection of ZnPc/SFB@BSA led to dramatically reduced tumor growth in an orthotopic xenograft HCC model. More importantly, ZnPc/SFB@BSA presented low toxicity and adequate blood compatibility. Therefore, a combination of ZnPc with sorafenib via BSA-assembled nanoparticle can markedly suppress HCC growth, representing a promising strategy for HCC patients.

This study aimed to explore the feasibility of the fractal method used in decoding disk heterogeneity, hoping to find a reliable imaging biomarker for the quantitative and continuous grading of intervertebral disks (IVDs). Totally, 180 IVDs in 65 low back pain patients (29 males, 36 female, 28–69 years) were examined with MRI. Each IVD was manually segmented on axial slice (at the mid-height layer of the disk). All disks were visually evaluated regarding degeneration grade, using Pfirrmann classification, by two experienced radiologists. Fractal dimension (FD) of the IVD was calculated from the defined regions of interest and correlated with Pfirrmann grade. Fractal dimension differed significantly between any two groups (P

The mechanistic target of rapamycin (mTOR) pathway, containing mTOR complex 1 (mTORC1) and mTORC2, is dysregulated in multiple cancers, including hepatocellular carcinoma (HCC). Mammalian lethal with sec-13 protein 8 (mLST8) is a shared constituent of both mTORC1 and mTORC2, yet little is known regarding its role in HCC development. mLST8 expression was detected in a total of 186 pairs of HCC and adjacent non-tumor specimens. The correlation between mLST8 level and clinicopathological features or prognostic significance were analyzed. The role of mLST8 on biological functions was also preliminarily studied. The study revealed that the mLST8 level was dramatically higher in HCC specimens than in adjacent non-tumor specimens. mLST8 overexpression positively correlated with tumor size, differentiation, and vessel invasion. Cases with elevated mLST8 level had more unfavorable overall survival (OS) and disease-free survival (DFS) than those with downregulated mLST8 level. Multivariate analysis demonstrated that mLST8 upregulation was an independent predictive marker for OS and DFS. Calibration curves from nomogram models indicated an excellent coherence between nomogram prediction and actual situation. Decision curve analysis proved that mLST8-based nomograms presented much higher predictive accuracy when compared with conventional clinical staging systems. Mechanistically, mLST8 enhanced cell proliferation and invasion through the AKT (protein kinase B) pathway. Our study demonstrates that mLST8 exerts an oncogenic role in HCC and may become a promising prognostic biomarker and therapeutic target for HCC patients.

Purpose Fucoidan is a natural bioactive product with broad therapeutic applications. Hepatocellular carcinoma (HCC) is a common malignancy of the liver associated with a relatively high mortality rate; thus, effective treatments are urgently needed. Here, the effects of fucoidan on HCC and the underlying mechanism were explored. Methods The proliferation and apoptosis of two HCC cell lines (BEL-7402 and LM3) treated with different concentrations of fucoidan or saline were assessed. The levels of proliferating cell nuclear antigen (PCNA) and CCK8 assay were used to determine proliferative capabilities of BEL-7402 and LM3 cells. Apoptosis of LM3 cells was assessed by Hoechst 33342 staining, Western blotting and flow cytometry. The capability of fucoidan to inhibit the growth of LM3 cells was investigated by monitoring of the p38 MAPK/ERK pathways and the upstream kinases, PI3K/Akt. LM3 xenograft tumors were used for in vivo verification. Results Cell proliferation and apoptosis assays consistently showed that fucoidan has an inhibitory effect on cell growth. Fucoidan significantly promoted apoptosis of LM3 cells through a mechanism involving activation of caspases 8, 9, and 3 accompanied by changes in B-cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax), as well as changes in the phosphorylation of p38 MAPK and ERK. Fucoidan also altered the phosphorylation of its upstream kinase, Akt. Fucoidan treatment markedly reduced the growth of LM3 xenograft tumors, consistent with the in vitro results. Conclusion Fucoidan conveys antitumor effects and, thus, should be further explored as a potential treatment option for HCC.

Graphical abstract, Highlights • It is the first study to identify neoandrographolide as a novel inhibitor of Rab5. • Neoandrographolide can occupy the surface groove of Rab5 for inhibiting its activity. • Neoandrographolide exhibits anticancer effect on lung cancer by targeting Rab5., Rab5 is a small GTPase that plays a crucial role in oncogenic signal transduction, which was considered as an attractive target for cancer therapy. Rapid GDP/GTP exchange in the packet of Rab5 sustains its high activity for promoting cancer progression. However, Rab5 currently remains undruggable due to the lack of specific inhibitor. Herein, we reported the discovery of a novel Rab5 inhibitor, neoandrographolide (NAP), by using high-throughput virtual screening with a natural product library containing 7459 compounds, which can occupy the surface groove of Rab5, competing with GDP/GTP for the binding. Ser34 is the most important residue in the groove of Rab5, as it forms most hydrogen-bond interactions with GDP/GTP or NAP, and in silico mutation of Ser34 decreased the stabilization of Rab5. Moreover, fluorescence titration experiment and isothermal titration calorimetry (ITC) assay revealed a direct binding between NAP and Rab5. Biochemical and cell-based assays showed that NAP treatment not only diminished the activity of Rab5, but also suppressed cell growth of cancer cell. This finding firstly identifies NAP as a novel inhibitor of Rab5, which directly binds with Rab5 by occupying the GDP/GTP binding groove to suppress its functions, highlighting a great potential of NAP to be developed as a chemotherapeutic agent in cancer therapy.

Background According to the latest American Joint Committee on Cancer and Union for International Cancer Control manuals, cystic duct cancer (CC) is categorized as a type of gallbladder cancer (GC), which has the worst prognosis among all types of biliary cancers. We hypothesized that this categorization could be verified by using taxonomic methods. Aim To investigate the categorization of CC based on population-level data. Methods Cases of biliary cancers were identified from the Surveillance, Epidemiology, and End Results 18 registries database. Together with routinely used statistical methods, three taxonomic methods, including Fisher's discriminant, binary logistics and artificial neuron network (ANN) models, were used to clarify the categorizing problem of CC. Results The T staging system of perihilar cholangiocarcinoma [a type of extrahepatic cholangiocarcinoma (EC)] better discriminated CC prognosis than that of GC. After adjusting other covariates, the hazard ratio of CC tended to be closer to that of EC, although not reaching statistical significance. To differentiate EC from GC, three taxonomic models were built and all showed good accuracies. The ANN model had an area under the receiver operating characteristic curve of 0.902. Using the three models, the majority (75.0%-77.8%) of CC cases were categorized as EC. Conclusion Our study suggested that CC should be categorized as a type of EC, not GC. Aggressive surgical attitude might be considered in CC cases, to see whether long-term prognosis could be immensely improved like the situation in EC.

Previous evidence has shown that the increased expression of aurora kinase is closely related to melanoma progression and is an important therapeutic target in melanoma. Danusertib is an inhibitor of aurora kinase, and recent studies have shown that danusertib treatment induces autophagy in several types of cancer. Interestingly, autophagy plays a dual function in cancer as a pro-survival and anti-survival factor. In this study, we investigated the role of danusertib on the induction of autophagy in melanoma and determined the impact of autophagy induction on its anticancer activity against melanoma. Our results showed that danusertib can significantly inhibit melanoma growth by inducing cell cycle arrest and apoptosis. In addition, we demonstrated that danusertib treatment significantly inhibits the oncogenic Akt/mTOR signaling pathway and induces autophagy in melanoma cells. Furthermore, we identified that the inhibition of autophagy can enhance the inhibitory effects of danusertib on melanoma growth. Thus, the induction of autophagy by danusertib appears to be a survival mechanism in melanoma cells that may counteract its anticancer effects. These findings suggest a novel strategy to enhance the anticancer efficacy of danusertib in melanoma by blocking autophagy.

Rationale and Objectives To compare upper abdominal computed tomography (CT) image quality of new model-based iterative reconstruction (MBIR) with low-contrast resolution preference (MBIRNR40), conventional MBIR (MBIRc), and adaptive statistical iterative reconstruction (ASIR) at low dose with ASIR at routine-dose. Materials and Methods Study included phantom and 60 patients who had initial and follow-up CT scans. For patients, the delay phase was acquired at routine-dose (noise index = 10 HU) for the initial scan and low dose (noise index = 20 HU) for the follow-up. The low-dose CT was reconstructed with 40% and 60% ASIR, MBIRc, and MBIRNR40, while routine-dose CT was reconstructed with 40% ASIR. CT value and noise measurements of the subcutaneous fat, back muscle, liver, and spleen parenchyma were compared using one-way ANOVA. Two radiologists used semiquantitative 7-scale (−3 to +3) to rate image quality and artifacts. Results The phantom study revealed superior low-contrast resolution with MBIRNR40. For patient scans, the CT dose index for the low-dose CT was 3.00 ± 1.32 mGy, 75% lower than the 11.90 ± 4.75 mGy for the routine-dose CT. Image noise for the low-dose MBIRNR40 images was significantly lower than the low-dose MBIRc and ASIR images, and routine-dose ASIR images (p Conclusion MBIRNR40 with low-contrast resolution preference provides significantly lower noise and better image quality than MBIRc and ASIR in low-dose abdominal CT; significantly better objective and subjective image quality than the routine-dose ASIR with 75% dose reduction.

Background Acute respiratory infections (ARI) cause considerable morbidity and mortality worldwide, especially in children. Unfortunately, there are limited multi-center data on common viral respiratory infections in south China. Methods A total of 4403 nasal swabs were collected from children in 10 cities in Guangdong, China in 2019. Seven respiratory viruses, influenza A virus (IFA), influenza B virus (IFB), respiratory syncytial virus (RSV), adenoviruses (ADV) and parainfluenza virus types 1–3 (PIV1, PIV2 and PIV3), were detected by direct immunofluorescence antibody assay. The personal information and clinical characteristics were recorded and analyzed. Results The results showed that at least one virus was detected in 1099 (24.96 %) samples. The detection rates of RSV, IFA, ADV, PIV3, PIV1 and PIV2 were 7.13 % (314/4403), 5.31 % (234/4403), 4.02 % (177/4403), 3.04 % (134/4403), 1.70 % (75/4403) and 1.16 % (51/4403), respectively. The detection rate of RSV was highest in 0–6-month-old children at 18.18 % (106/583), while the detection rate of IFA was highest in 12–18-year-old children at 20.48 % (17/83). The total detection rates in winter and spring were 35.67 % (219/614) and 34.56 % (403/1166), higher than those in summer, 17.41 % (284/1631), and autumn, 19.46 % (193/992). Conclusions RSV and IFA were the main respiratory viruses in children. With increasing age the detection rate of RSV decreased in children, but the trends for the detection rates of IFA and IFB were the opposite. This study provided the viral etiology and epidemiology of pediatric patients with ARI in Guangdong, China.

BackgroundSarcopenia is a poor prognostic factor in patients with esophageal cancer (EC). It can be aggravated by neoadjuvant therapy (NAT) that improves the prognosis of patients with EC. Until now, the impact of preoperative sarcopenia on survival prognosis in patients receiving NAT for EC remains unclear.MethodsWe systematically researched relevant studies in the PubMed, EMBASE, Web of Science, the Cochrane Library databases up to March 8, 2020. Prevalence of sarcopenia before and after NAT, overall survival (OS) and disease-free survival (DFS) were collected for analysis. Finally, eleven cohort studies were included.ResultsPooled analysis indicated that preoperative sarcopenia was negatively associated with OS. (HR = 1.290; 95% CI [1.078–1.543]; P = 0.005; I2 = 0.0%) and DFS (HR = 1.554; 95% CI [1.177–2.052]; P = 0.002; I2 = 0.0%) in the patients with EC receiving NAT. The prevalence of sarcopenia increased by 15.4% following NAT (95%CI [12.9%-17.9%]). Further subgroup analysis indicated that sarcopenia diagnosed following NAT (HR = 1.359; 95% CI [1.036–1.739]; P = 0.015; I2 = 6.9%) and age >65 years (HR = 1.381; 95% CI [1.090– 1.749]; P = 0.007; I2 = 0.0%) were the independent risk factors for decreased OS.ConclusionsClinicians should strengthen the screening of preoperative sarcopenia in patients of EC both receiving NAT and older than 65 years and give active nutritional support to improve the prognosis of patients.Systematic Review RegistrationInternational Platform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY), identifier INPLASY202050057.

Adipose tissue macrophages (ATMs) represent the most abundant leukocytes in adipose tissue (AT). An increase in number and a phenotypical switch of ATMs during the development of obesity contribute to chronic inflammation and metabolic disorders, which have been regarded as potential therapeutic targets to restore AT homeostasis. Emodin has been shown to exert strong anti-inflammatory property via acting on macrophages in a range of disease models. However, whether emodin exerts a beneficial effect on obesity via modulating ATMs has not been reported. In high-fat diet (HFD)-induced obese mice, emodin significantly inhibited the increase of body weight and lipid accumulation in ATs. Emodin apparently reduced glucose and insulin levels and ameliorated serum lipid profiles in HFD-fed mice. Moreover, the local and systemic inflammation was dramatically alleviated by emodin. We next discovered that M2 macrophage percentage was greatly increased by emodin although total ATMs was not altered, which resulted in a net increase of M2 macrophages in AT. In vitro studies confirmed that emodin promoted the polarization of macrophages towards M2. Gene ontology (GO) analysis showed that myeloid leukocyte differentiation and activation were among the most significant biological processes in emodin-treated ATMs. We further identified that TREM2 was the most dramatically upregulated molecule by emodin and emodin-induced M2 macrophage polarization was dependent on TREM2. Furthermore, silencing TREM2 apparently abrogated the effect of emodin on AT inflammation and adipogenesis. We, for the first time, disclosed that emodin inhibited obesity by promoting M2 macrophage polarization via TREM2, suggesting that emodin may be explored as a clinical and translational candidate in preventing obesity and its related metabolic diseases.

Psoriasis affects more than 125 million people worldwide, and the diagnosis and treatment efficacy evaluation of the disease mainly rely on clinical assessments that could be subjective. Our previous study showed that the skin erythema level could be quantified using diffuse reflectance spectroscopy (DRS), and the hemoglobin concentration of most psoriatic lesion was higher than that of its adjacent uninvolved skin. While the compromised epidermal barrier function has been taken as the major cause of clinical manifestation of skin dryness and inflammation of psoriasis, very few methods can be used to effectively evaluate this function. In this study, we investigate the near infrared spectroscopic features of psoriatic (n = 21) and normal (n = 21) skin that could link to the epidermal barrier function. From the DRS measurements, it was found that the water bonding status and light scattering properties of psoriasis are significantly different from those of uninvolved or normal skin. The connection between these parameters to the epidermal barrier function and morphology will be discussed. Our results suggest that objective evaluation of epidermal barrier function of psoriasis could be achieved using a simple DRS system.

Total endovascular repair remains challenging for Kommerell diverticulum with chronic type A aortic dissection. We reported the first total endovascular repair for a Kommerell diverticulum with chronic retrograde type A aortic dissection. We conducted total endovascular repair with a unibody, single-branched, stent-graft combined with the chimney technique for reconstruction of both subclavian arteries. Completion angiography showed complete exclusion of the primary entry tear without endoleak and patency of all stent-grafts, and computed tomographic angiography at follow-up showed significant remodeling of the false lumen. In this case we show that total endovascular repair is feasible and safe in selective patients of this kind.

A cross-sectional survey that reached 21 out of 34 provinces of China was conducted during the coronavirus disease 2019 (COVID-19) outbreak in China. The study discovered different patterns of sour...

BACKGROUND Endoscopic submucosal dissection (ESD) has been routinely performed in applicable early gastric cancer (EGC) patients as an alternative to conventional surgical operations that involve lymph node dissection. The indications for ESD have been recently expanded to include larger, ulcerated, and undifferentiated mucosal lesions, and differentiated lesions with slight submucosal invasion. The risk of lymph node metastasis (LNM) is the most important consideration when deciding on a treatment strategy for EGC. Despite the advantages over surgical procedures, lymph nodes cannot be removed by ESD. In addition, whether patients who meet the expanded indications for ESD can be managed safely remains controversial. AIM To determine whether the ESD indications are applicable to Chinese patients and to investigate the predictors of LNM in EGC. METHODS We retrospectively analyzed 12552 patients who underwent surgery for gastric cancer between June 2007 and December 2018 at the Affiliated Hospital of Qingdao University. A total of 1262 (10.1%) EGC patients were eligible for inclusion in this study. Data on the patients’ clinical, endoscopic, and histopathological characteristics were collected. The absolute and expanded indications for ESD were validated by regrouping the enrolled patients and determining the positive LNM results in each subgroup. Predictors of LNM in patients were evaluated by univariate and multivariate analyses. RESULTS LNM was observed in 182 (14.4%) patients. No LNM was detected in the patients who met the absolute indications (0/90). LNM occurred in 4/311 (1.3%) patients who met the expanded indications. According to univariate analysis, LNM was significantly associated with positive tumor marker status, medium (20-30 mm) and large (>30 mm) lesion sizes, excavated macroscopic-type tumors, ulcer presence, submucosal invasion (SM1 and SM2), poor differentiation, lymphovascular invasion (LVI), perineural invasion, and diffuse and mixed Lauren’s types. Multivariate analysis demonstrated SM1 invasion (odds ration [OR] = 2.285, P = 0.03), SM2 invasion (OR = 3.230, P < 0.001), LVI (OR = 15.702, P < 0.001), mucinous adenocarcinoma (OR = 2.823, P = 0.015), and large lesion size (OR = 1.900, P = 0.006) to be independent risk factors. CONCLUSION The absolute indications for ESD are reasonable, and the feasibility of expanding the indications for ESD requires further investigation. The predictors of LNM include invasion depth, LVI, mucinous adenocarcinoma, and lesion size.

With the improvement of internet technology in health applications, the utilization of internet and social media as new survey methodologies and recruitment source for research participants have been encouraged, yet evidence of the feasibility in people living with HIV (PLHIV) study is still lacking. We conducted a cross-sectional survey to determine whether there are differences among PLHIV recruited from social media networks and health-care systems using an HIV stigma and discrimination questionnaire. The result revealed that PLHIV recruited from social media networks were younger, more sexually active, and had higher educational status and awareness of the country's HIV rights protection laws than those recruited from hospitals. By contrast, participants recruited from hospitals were more diverse regarding key population compositions, had lived with HIV for a longer duration, had a higher prevalence of concomitant physical disabilities than those recruited from social media networks, and fit Taiwan PLHIV characteristics described by 2016 census from Taiwan Centres for Disease Control. We conclude that sampling bias exists when utilizing social media networks for PLHIV studies.

OBJECTIVE To test the feasibility of the clot volume and right ventricular dysfunction for risk stratification of acute pulmonary embolism (APE) patients. METHODS CT pulmonary angiography (CTPA) images of 158 APE patients were collected. After excluding 38 (24.1%) patients due to unsatisfactory quality, 120 APE patients (61 males and 59 females) were divided into high-risk (n = 37) and non-high-risk (n = 83) groups. Clot burden was measured by an automated programme (clot volume) and by two semi-quantitative systems (Qanadli and Mastora scores). The ratios of the right ventricular diameter to left ventricular diameter (RVd/LVd) and area (RVa/LVa) were obtained. The correlations amongst the above parameters were analysed. Receiver operating characteristic (ROC) curves were calculated to determine the efficacy of high-risk APE. Multivariate analyses were used to identify the independent predictors. RESULTS Strong positive correlations were found between the clot volume and both Qanadli score (r2 = 0.696, P

Background Growing evidence suggests that the ubiquitin-proteasome system is involved in the pathogenesis and recurrence of hepatocellular carcinoma (HCC); yet, little is known about the role of ubiquitin-conjugating enzyme E2T (UBE2T) in HCC. Materials and methods UBE2T levels were detected in HCC tissues and hepatoma cell lines using quantitative reserve transcriptase-polymerase chain reaction and Western blot analysis. Next, the changes of phenotypes after UBE2T knockdown or overexpression were evaluated using in vitro methods. Finally, the mechanism of UBE2T in HCC was tested using ex vivo and in vivo methods. Results In the present study, we reported that UBE2T mRNA and protein levels were significantly upregulated in HCC tissues compared to adjacent non-tumor tissues. Additionally, suppression of UBE2T expression inhibited proliferation, colony formation, tumorigenesis, migration, and invasion of hepatoma cells, whereas UBE2T overexpression led to the opposite outcomes. Moreover, suppression of UBE2T expression resulted in an increase in G2/M phase and a decrease in the percentage of cells in G1 phase, which indicated a cell cycle arrest at the G2/M phase. In contrast, the percentage of cells in G2/M phase decreased following UBE2T overexpression. Further study indicated that UBE2T regulated the G2/M transition by modulating cyclin B1 and cyclin-dependent kinase 1. Conclusion Taken together, the findings of the present study uncover biological functions of UBE2T in hepatoma cells, and delineate preliminary molecular mechanisms of UBE2T in modulating HCC development and progression.

There is conflicting results on whether prior antiplatelet therapy (APT) is associated with poor outcome in spontaneous intracerebral haemorrhage (ICH) patients. To determine whether prior APT is associated with spontaneous ICH, and whether there is a difference between the different types of APT, including cyclooxygenase inhibitor (COX-I), adenosine diphosphate receptor inhibitor (ADP-I) and phosphodiesterase inhibitor (PDE-I). A retrospective study of patients with ICH diagnosed between 2001 and 2013 in the National Health Insurance Research Database. Baseline unbalance between APT and non-APT groups was solved by multivariable adjustment (primary analysis) and propensity score matching (sensitivity analysis). Patients with prior APT had a higher rate of in-hospital death (odds ratio [OR], 1.16; 95% confidence interval [CI], 1.09-1.23) compared to non-APT group. Compared to non-APT group, there was a greater rate of in-hospital death with spontaneous ICH with ADP-I (OR, 1.49; 95% CI, 1.24-1.79) and COX-I (OR, 1.17; 95% CI, 1.09-1.25). PDE-I exhibited no difference in in-hospital death with spontaneous ICH (OR, 1.03; 95% CI, 0.91-1.16) compared to non-APT group. Remarkably, the in-hospital mortality rate was significantly higher in the ADP-I group than in the PDE-I group (hazard ratio, 1.45; 95% CI, 1.17-1.80). In this study, ADP-I and COX-1, but not PDE-I, are the most likely contributors to the association of APT with poor outcome with spontaneous ICH patients. These findings suggest that the complexity of the different mechanism of actions of prior APT can alter the outcome in spontaneous ICH.

Objective The impact of antithrombotic agents on patients with primary intracerebral hemorrhage (ICH) remains controversial, especially patients who require emergent craniotomy. This study was undertaken to evaluate clinical outcomes in operated patients with ICH with and without previous antithrombotic agents. Methods This is a retrospective cohort study. Between January 2001 and December 2013, all patients with ICH who received emergent craniotomy and who were present in Taiwan's National Health Insurance Research Database were screened and divided into those with previous antiplatelet therapy, anticoagulant therapy, and nonantithrombotic therapy according to their health care claims data within 3 months of index admission. The primary end points included in-hospital mortality and complications and short-term outcome. Results Of 18,872 eligible patients, 16,251 (87.1%) did not receive any antithrombotic therapy, 2267 patients had antiplatelet therapy, and 354 patients had anticoagulation therapy. After propensity score matching, significantly more blood transfusions and craniectomies were identified in the patients with previous antithrombotic treatment compared with those undergoing nonantithrombotic therapy. Compared with the nonantithrombotic treatment cohort, patients under previous anticoagulant treatment had significantly higher in-hospital mortality (odds ratio, 2.12; 95% confidence interval, 1.45–3.10). Furthermore, during the 6-month follow-up period, previous anticoagulant therapy was independently associated with a greater risk of all-cause mortality (P = 0.001). The in-hospital and 6-month all-cause mortality of patients with previous antiplatelet treatment was not significantly different from patients with nonantithrombotic treatment. Conclusions These findings suggested an increased risk of in-hospital mortality and poor short-term outcome among operated patients with ICH with previous antithrombotic therapy, particularly anticoagulant therapy, but not with antiplatelet therapy.

Macrophages have been recognized as a vital factor that can promote renal fibrosis. Previously we reported that the EGFR mimotope could alleviate the macrophage infiltration in the Sjögren's syndrome-like animal model. In current study, we sought to observe whether the active immunization induced by the EGFR mimotope could ameliorate renal fibrosis in the murine Unilateral Ureteral Obstruction (UUO) model. A series of experiments showed the EGFR mimotope immunization could ameliorate renal fibrosis, reduce the expressions of fibronectin, α-SMA and collagen I and alleviate the infiltrations of F4/80+ macrophages in UUO model. Meanwhile, the EGFR mimotope immunization could inhibit the EGFR downstream signaling. Additionally, the frequency of and F4/80+CD9+/FAS+ macrophages significantly increased in spleen after the EGFR mimotope immunization. These evidence suggested that the EGFR mimotope could alleviate renal fibrosis by both inhibiting EGFR signaling and promoting macrophages apoptosis.

Long non‑coding RNAs (lncRNAs) have been shown to contribute to progression and prognosis of hepatocellular carcinoma (HCC). However, expression profiling and interaction of lncRNAs with messenger RNAs (mRNAs) and microRNAs (miRNAs) remain largely unknown in HCC. The expression profiling of lncRNAs, mRNA and miRNAs was obtained using microarray. The Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analysis were used to characterize potential functions of differentially expressed mRNAs. Cytoscape was applied to construct an lncRNA‑miRNA‑mRNA co‑expression network and candidate lncRNAs were validated via quantitative PCR in 30 pairs of HCC and adjacent tumor‑free tissues. In this study, 1,056 upregulated and 1,288 downregulated lncRNAs were identified, while 2,687 mRNAs and 6 miRNAs were aberrantly expressed in HCC compared with adjacent tumor‑free tissues. Potential functions of differentially expressed mRNAs were demonstrated to significantly participate in modulating critical genes in the cell cycle, such as cyclin E1 and cyclin B2. After screening, 95 lncRNAs, 5 miRNAs and 36 mRNAs were recruited for construction of lncRNA‑mRNA‑miRNA co‑expression network in the cell cycle pathway. Subsequently, the top 5 lncRNAs that potentially modulate critical genes in the cell cycle were selected as the candidates for further verification. Kaplan‑Meier curves using the Cancer Genome Atlas database showed that 13 targeted mRNAs were associated with overall survival of HCC patients. Finally, three lncRNAs, including ENST00000522221, lnc‑HACE1‑6:1 and lnc‑ICOSLG‑11:1, are significantly upregulated in HCC tissues compared with adjacent tumor‑free tissues. These findings suggest that lncRNAs play essential roles in the pathogenesis of HCC via regulating coding genes and miRNAs, and may be important targets for diagnosis and treatment of this disease.

To investigate the influence of virtual monochromatic spectral (VMS) CT images at different energy levels on the effectiveness of a motion correction technique (SSF) in dual-energy Spectral coronary CT angiography (CCTA). 29 cases suspected of or diagnosed with coronary artery disease underwent Spectral CCTA using a prospective ECG triggering with 250 ms padding time. SSF was applied to the determined least-motion phase to generate 6 additional sets of VMS images with energy levels from 40 to 100 keV. CT value and standard deviation (SD) in the aortic root and epicardial adipose tissue were measured. Image quality of the RCA, LAD and LCX was evaluated on a per-vessel basis in each patient. Two reviewers evaluated the artery using the score of the segment. The low energy VMS images increased CT value and image noise compared with higher-energy VMS images, except 90 keV and 100 keV. The CNR of 40–70 keV were higher than those of 80–100 keV (P

Purpose To investigate the value of dual-energy spectral computed tomography (CT) imaging in the differential diagnosis of small bowel adenocarcinoma (SBA) from primary small intestinal lymphoma (PSIL). Materials and Methods We retrospectively analyzed the images of 27 SBA cases and 15 PSIL cases. These patients underwent spectral CT imaging in the arterial phase (AP) and venous phase (VP). CT attenuation values of tumors at different energy levels were measured to generate spectral attenuation curve and to calculate curve slope (λHU). Iodine concentration (IC) in tumors at AP and VP were measured and normalized to that of aorta as normalized iodine concentration (NIC). Independent samples t test was used to analyze the spectral CT parameters; Receiver operating characteristic curves were generated to evaluate the diagnostic efficacy of each parameter. Results There were significant differences between SBA and PSIL in IC (2.09 ± 0.71 vs 1.33 ± 0.15 mg/ml), NIC (0.20 ± 0.06 vs 0.13 ± 0.02) and slope (λHU) (2.78 ± 1.06 vs 1.86 ± 0.30) in AP and (1.86 ± 0.68 vs 1.37 ± 0.18 mg/ml for IC; 0.47 ± 0.13 vs 0.33 ± 0.02 for NIC and 2.00 ± 0.56 vs 1.50 ± 0.26 for λHU) in VP (all p 0.05). Using 1.38 mg/ml as a threshold value for iodine concentration at AP, one could obtain the area-under-curve of 0.93 for receiver operating characteristic study and sensitivity of 94% and specificity of 85% for differentiating SBA from PSIL. The sensitivity and specificity values were significantly higher than the respective values of 62% and 60% with the conventional CT numbers at 70keV. Conclusion Quantitative parameters obtained in spectral CT, especially iodine concentration in AP, provide high accuracy for differentiating SBA from PSIL.

BACKGROUND Gastric adenocarcinoma of fundic gland type (GA-FG) has recently been proposed as a novel histological type of gastric cancer. CASE SUMMARY We report a case of GA-FG in a 77-year-old Chinese woman with epigastric distention who was referred to endoscopy for the management of an incidentally found submucosal tumor-like elevated lesion in the lower part of the gastric body. The tumor occurred after Helicobacter pylori (H. pylori) eradication therapy without long-term use of proton pump inhibitors. Complete and curable removal of the tumor was performed by endoscopic submucosal dissection. Histopathological findings showed numerous cells with basophilic cytoplasm and mildly atypical nuclei-like chief cells of the fundic gland. The tumor was observed to have the so-called “endless glands” pattern of the well-differentiated mixed phenotype. A safe resection margin without lymphatic and venous invasion was observed. As the tumor occurred after H. pylori eradication therapy, it is unknown whether there was a relationship with H. pylori eradication. The patient will be followed up by periodic gastroscopic observation. CONCLUSION In conclusion, we report a case of GA-FG after H. pylori eradication therapy without long-term proton pump inhibitors use. Further analysis of similar cases will reveal the clinical behavior of GA-FG.

Background Increasing attention is now focused on the role of the small airways in asthma. Patients with small airway asthma typically have a preserved forced expiratory volume in 1 second, with disproportionate small airway dysfunction. Objective The aim of this study was to determine whether there are structural changes in the large airways in patients with small airway asthma. Methods Nine patients with small airway asthma and 20 healthy controls underwent high-resolution computed tomography (HRCT) scan. The apicoposterior segmental bronchus in the left upper lobe (LB1+2) and the posterior basal segmental bronchus in the left lower lobe (LB10) were identified on HRCT images. The luminal area (LA), wall area (WA), and wall area percentage (WA%) of each bronchus were measured from the 2nd (lobar) to the 6th generation and compared between the patients with small airway asthma and the healthy controls. Results The WA% of the 6th generation in the patients with small airway asthma was higher than that in the healthy controls; the difference was statistically significant (LB1 + 2, P = .040; LB10, P = .033). Conclusion Structural changes in the large airways of patients with small airway asthma may represent an early stage of asthma.

Background: Aberrant expression of pepsinogen C (PGC) has been observed in human cancers. However, its role in hepatocellular carcinoma (HCC) remains to be established. The goal of this study is to illustrate PGC expression and to evaluate its clinical relevance in HCC. Materials and methods: PGC expression was examined in 75 pairs of HCC and adjacent non-tumor tissues using tissue microarray. The correlations between its expression and clinical parameters were also analyzed. Results: PGC overexpression was significantly associated with larger tumor size (≥5 cm; P=0.017) and incomplete encapsulation (P

The mechanistic target of rapamycin (mTOR) pathway coordinates organismal growth and homeostasis in response to growth factors, nutrients, and cellular energy stage. The pathway regulates several major cellular processes and is implicated in various pathological conditions, including hepatocellular carcinoma (HCC). This review summarizes recent advances of the mTOR pathway, highlights the potential of the mTOR pathway as a therapeutic target, and explores clinical trials targeting the mTOR pathway in HCC. Although the review focuses on the mTOR pathway involved in HCC, more comprehensive discussions (eg, developing a rational design for future trials targeting the mTOR pathway) are also applicable to other tumors.

Glioma is one of the most common brain tumors, suggesting the importance of investigating the molecular mechanism of gliomas. We studied the roles of Ribonucleotide Reductase Regulatory Subunit M2 (RRM2) in glioma. Expressions of RRM2 are higher in glioma tissues evidenced by TCGA data, western blot and immunohistochemistry. RRM2 is negatively correlated with glioma patient's survival. RNA-seq showed that genes involved in apoptosis, proliferation, cell adhesion and negative regulation of signaling were up-regulated upon RNAi-mediated knock-down of RRM2. Cell phenotypes specific for stably knocking down RRM2 were determined using stable transfection in vitro. In an in vivo model, knock-down of RRM2 inhibited tumor growth and caused suppression of AKT and ERK1/2 signalings. Interfering RRM2 also down-regulated the expression of cyclin A, cyclin B1, cyclin D1, Vimentin, and N-cadherin, and elevated E-cadherin expression. Moreover, overexpression of RRM2 failed to increase the expression of cyclin B1, cyclin D1, and N-cadherin when phosphorylation of AKT and ERK1/2 was suppressed by LY294002 or PD98059. These findings indicated that RRM2 is a positive regulator of glioma progression which contributes to the migration and proliferation of glioma cells through ERK1/2 and AKT signalings and might be a novel prognostic indicator for glioma patients.

Neonatal Fc receptor (FcRn) is down-regulated in Hashimoto's thyroiditis (HT) thyrocytes and mediates IgG endocytosis in thyrocytes. The serum distribution of IgG subclasses (of TgAb and TPOAb) differs between HT patients and normal individuals. We aimed to explore the direction and regulation of FcRn-mediated IgG transport in thyrocyte monolayers and the difference between various IgG subclass transport. IgG was transported by FcRn from the basolateral to apical side in the thyrocyte monolayers grown on Transwell filters and the transport was inhibited by IFN-γ and TNF-α. Stimulation by T3 and TSH down-regulated FcRn expression in thyrocytes. IgG1 was transported preferentially over IgG2 and IgG4, which might be related to the differences in FcRn-binding affinities as shown by SPR. FcRn mediates unidirectional IgG transport in thyrocytes in a tissue-specific manner. Down-regulation of FcRn is speculated to play a protective role in HT pathogenesis by mainly reducing IgG1 transport in thyrocytes.

Objective We aimed to evaluate a new model-based iterative reconstruction (MBIRn) algorithm either with spatial resolution and noise reduction balance (MBIRSTND) or spatial resolution preference (MBIRRP20) for quantitative analysis of airway in low-dose chest computed tomography (CT) with a computer-aided detection (CAD) software, in comparison to adaptive statistical iterative reconstruction (ASIR) in routine-dose CT. Methods Thirty patients who underwent both the routine-dose (noise index [NI] = 14 HU) and low-dose (at 30% level with NI = 28 HU) CT examination for pulmonary disease were included. Image acquisition was performed with 120 kVp tube voltage and automatic tube current modulation. Routine-dose scans were reconstructed with ASIR, whereas low-dose scans were reconstructed with ASIR, MBIRSTND, and MBIRRP20. Airway dimensions of the right middle lobe bronchus from the four reconstructions were measured using CAD software. Two radiologists used a semiquantitative 5 scoring criteria (−2, inferior to; +2, superior to; −1 slightly inferior to; +1, slightly superior to; and 0, equal to ASIR in routine-dose CT) to rate the subjective image quality of MBIRSTND and MBIRRP20 of airway trees. The paired t test and Wilcoxon signed-rank test were used for statistical comparison. Results The low-dose CT provided 70.76% dose reduction compared to the routine-dose CT (0.88 ± 0.83 mSv vs 3.01 ± 1.89 mSv). MBIRSTND and MBIRRP20 with low-dose CT provided longer bronchial length measurements and were better in measurement variability and continuity and completeness of bronchial walls than ASIR in routine-dose CT (P Conclusions MBIRSTND and MBIRRP20 algorithms provide better airway quantification at 30% of the radiation dose, compared to ASIR at routine-dose CT.