Endobronchial ultrasound-guided transbronchial needle aspiration for diagnosing thoracic lesions: a retrospective cohort study.

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive technique for biopsy of lung, peri-pulmonary tissue and lymph nodes under real-time ultrasound-guided biopsy. It is used in the diagnosis and/or staging of benign and malignant pulmonary and non-pulmonary diseases. Our study is based on a large sample size, in a diversified population which provides a representative real-world cohort for analysis. Methods: Patients who underwent EBUS-TBNA procedure between September 2019 and August 2022 were included in this retrospective study. For cases diagnosed as benign and unclassified lesions by EBUS-TBNA, the final diagnosis was determined by further invasive surgery or a combination of therapy and clinical follow-up for at least 6 months. Results: A total of 618 patients were included in the study, including 182 females (29.4%) and 436 males (70.6%). The mean age of all patients was 61.9 ± 10.5 years. These patients were successfully punctured by EBUS-TBNA to obtain pathological results. The pathological diagnosis results of EBUS-TBNA were compared with the final clinical diagnosis results as follows: 133 cases (21.5%) of benign lesions and 485 cases (78.5%) of malignant lesions were finally diagnosed. Among them, the pathological diagnosis was obtained by EBUS-TBNA in 546 patients (88.3%) (464 malignant lesions and 82 benign conditions), while EBUS-TBNA was unable to define diagnosis in 72 patients (11.6%). 20/72 non-diagnostic EBUS-TBNA were true negative. The overall diagnostic sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of EBUS-TBNA were 91.3%, 100%, 100%, 27.8%, and 91.6% [95% confidence interval (CI): 89.1-93.6%], respectively. In this study, only one case had active bleeding without serious complications during the EBUS-TBNA procedure. Conclusion: Given its low invasiveness, high diagnostic accuracy, and safety, EBUS-TBNA is worth promoting in thoracic lesions.

Identification of HIST1H2BH as the hub gene associated with multiple myeloma using integrated bioinformatics analysis.

OBJECTIVES: Identifying the specific biomarkers and molecular signatures of MM might provide novel evidence for MM prognosis and targeted therapy. METHODS: Bioinformatic analyses were performed through GEO and TCGA datasets. The differential expression of HIST1H2BH in MM sample was validated by the qRT-PCR. And the CCK-8 assay was performed to detect the proliferation activity of HIST1H2BH on MM cell lines. RESULTS: A total of 793 DEGs were identified between bone marrow plasma cells from newly diagnosed myeloma and normal donors in GSE6477. Among them, four vital genes (HIST1H2AC, HIST1H2BH, CCND1 and TCF7L2) modeling were constructed. The increased HIST1H2BH expression was correlated with worse survival of MM based on TCGA datasets. The transcriptional expression of HIST1H2BH was significantly up-regulated in primary MM patients. And knockdown HIST1H2BH decreased the proliferation of MM cell lines. CONCLUSIONS: We have identified up-regulated HIST1H2BH in MM patients associated with poor prognosis using integrated bioinformatical methods.

UBE2C enhances temozolomide resistance by regulating the expression of p53 to induce aerobic glycolysis in glioma.

UBE2C is overexpressed in gliomas, and its overexpression has been reported to be correlated with the drug resistance of gliomas to some extent. In this study, we explore the role of UBE2C in regulating temozolomide (TMZ) resistance in glioma and investigate the underlying mechanisms involved. Twenty normal brain tissues and 100 glioma tissues from 50 TMZ-resistant patients and 50 TMZ-sensitive patients are included in this study. TMZ-resistant cell lines are constructed to explore the role of UBE2C in regulating glioma cell viability and TMZ resistance. Our results show that both the mRNA and protein levels of UBE2C are significantly elevated in the brain tissues of glioma patients, especially in those of TMZ-resistant patients. Consistently, UBE2C expression is markedly upregulated in TMZ-resistant cell lines. Overexpression of UBE2C rescues glioma cells from TMZ-mediated apoptosis and enhances cell viability. In contrast, downregulation of UBE2C expression further enhances TMZ function, increases cell apoptosis and decreases cell viability. Mechanistically, UBE2C overexpression decreases p53 expression and enhances aerobic glycolysis level by increasing ATP level, lactate production, and glucose uptake. Downregulation of p53 level abolishes the role of UBE2C downregulation in inhibiting TMZ resistance and aerobic glycolysis in glioma cells. Moreover, an animal assay confirms that downregulation of UBE2C expression further suppresses tumor growth in the context of TMZ treatment. Collectively, this study reveals that downregulation of UBE2C expression enhances the sensitivity of glioma cells to TMZ by regulating the expression of p53 to inhibit aerobic glycolysis.

First Report of Broad Bean Wilt Virus 2 Infecting Balsam (Impatiens balsamina) in China.

Balsam (Impatiens balsamina L.) is an ornamental plant cultivated extensively in China and elsewhere, but it has also been used as a medicinal plant for thousands of years (Qian et al., 2023). In 2022, an examination of 10 garden-grown I. balsamina plants in Chaoyang, Beijing, China revealed eight plants with blotches, mosaic symptoms, and deformed leaves (Fig. S1A). Total RNA was extracted from the symptomatic leaf tissue of these eight plants using the TRIzol reagent (Invitrogen, USA). Four RNA preparations (high quality and quantity) were combined for the small RNA sequencing analysis (TIANGEN Biotech Co., China). A total of 16,509,586 clean reads (18-30 nt) were obtained and assembled into larger contigs using Velvet 1.0.5. A search of the National Center for Biotechnology Information non-redundant database using BLASTX indicated 72, 24, and 19 contigs were homologous to broad bean wilt virus 2 (BBWV2), cucumber mosaic virus (CMV), and impatiens cryptic virus 1 (ICV1) sequences (Zheng et al., 2022), respectively. To verify the next-generation sequencing data, the following three sets of primer pairs were designed according to the contig sequences of these three viruses: CMV-F:5'-ATGGACAAATCTGAATCAACCAGTGC-3'/CMV-R: 5'-CCGTAAGCTGGATGGACAACC-3'; BBWV2-F:5'-CAATTTGGACAACTACAATTTGCC-3'/ BBWV2-R: 5'-GCTGAGTCTAAATCCCATCTATC-3'; and ICV1-F: 5'-CGCACAACT CTACAAT GACATGGTC-3'/ICV1-R: 5'-AGTTCCATCGTCCAGTAGGCG-3'. The primers were used to amplify CMV, BBWV2, and ICV1 sequences by reverse transcription-polymerase chain reaction (RT-PCR), with individual RNA preparations serving as the template. The CMV, BBWV2, and ICV1 target sequences were amplified from eight, four, and four samples, respectively (Fig. S1B). To evaluate virus infectivity, Nicotiana benthamiana seedlings were inoculated using a leaf tissue extract prepared from an infected I. balsamina plant. At 7 days post-inoculation, disease symptoms were detected on N. benthamiana systemic leaves (e.g., deformation and apical necrosis) (Fig. S1C). Confirmation tests involving RT-PCR indicated the N. benthamiana plants were infected with BBWV2 and CMV, but not with ICV1 (Fig. S1D). To obtain the complete BBWV2 genome sequence (RNA1 and RNA2), virus-specific PCR primers (Table S1) were designed to produce the terminal sequences via 5' and 3' rapid amplification of cDNA ends (RACE), which was completed using the SMARTer RACE 5'/3' Kit (Clontech, China). The RNA1 and RNA2 sequences comprised 5,957 nt (GenBank: OQ857921) and 3,614 nt (GenBank: OQ857922), respectively. The BLAST analyses revealed RNA1 and RNA2 were similar to sequences in other BBWV2 isolates (sequence identities of 78.88% to 95.15% and 80.83% to 91.51%, respectively). Using the neighbor-joining method and MEGA 7.0, the phylogenetic relationships between the BBWV2 isolated in this study and other isolates were determined on the basis of the full-length RNA1 and RNA2 sequences (Kumar et al., 2016). According to the RNA1 and RNA2 sequences, the BBWV2 isolated in this study was most closely related to the BBWV2 isolate from Gynura procumbens (GenBank: KX686589) and the BBWV2 isolate from Nicotiana tabacum (GenBank: KX650868), respectively (Fig. S1E). To the best of our knowledge, this is the first report of I. balsamina naturally infected with BBWV2 in China. The study findings may be useful for detecting BBWV2 in I. balsamina and for diagnosing and managing the associated disease. The authors declare no conflict of interest. Yanhong Qiu and Haijun Zhang contributed equally to this paper. Funding: This research was supported by the Beijing Academy of Agriculture and Forestry Foundation, China (KYCX202305, QNJJ202131, and KJCX20230214). References: Qian H.Q., et al. 2023. J Ethnopharmacol. 303. Zheng Y., et al. 2022. Arch Virol. 167: 2099-2102. Kumar et al. 2016. Mol Biol Evol. 33: 1870-1874.

Prevalence, distribution, accumulation, and risk of environmental corticosteroids and estrogens in biofilms from the Pearl River Delta.

Biofilms play a significant role in the biogeochemical processing of organic matter and the environmental fate of emerging pollutants. In this study, we investigated the occurrence and distribution of 32 endocrine-disrupting chemicals (EDCs), including 24 environmental corticosteroids (ECs) and 8 environmental estrogens (EEs), in natural biofilms from the Pearl River system. Their association between biofilms and water and environmental risk were assessed. The ECs and EEs ubiquitously occurred in the biofilms, ranging from <0.61-6.57 ng/g and <0.8-2535 ng/g, respectively. Temporally, there was no obvious variance in either ECs or EEs in the biofilms during the winter and summer, and their concentrations exhibited a spatial trend of upward to midstream, descending downstream, and then seaward attenuation at the estuary. For ECs and EEs, the similar levels of field-derived bioconcentration factors (BCFs) (logarithm values: 2.42-2.86 and 2.72-2.98, respectively) and biofilm organic carbon-normalized partitioning coefficients (Kboc) (3.39-3.69 and 3.35-3.95) suggest the comparable potential of accumulation and sorption by biofilms between these two classes of EDCs. In addition, higher values of BCF and Kboc for the EEs were found in winter and were correspondingly comparable to their distribution coefficients (Kd) and Koc derived from suspended particles and sediment, revealing that biofilms are a competitive environmental compartment for capturing EDCs, particularly during the mature period. A positive logKboc-logKow relationship suggests hydrophobic partitioning as a primary interaction mechanism between the biofilm and EEs. Moreover, high risks from biofilm-associated ECs and EEs might have posed to the fluvial ecosystem. This study provides original insights into the occurrence, fate, and risk of ECs in natural biofilms for the first time and demonstrates that biofilms may not only serve as reservoirs but also serve as sentinels for fluvial EDC contamination. These results contribute to the further understanding of the behavior and fate of EDCs in aquatic environments.

Dissimilatory manganese reduction facilitates synergistic cooperation of hydrolysis, acidogenesis, acetogenesis and methanogenesis via promoting microbial interaction during anaerobic digestion of waste activated sludge.

Anaerobic digestion (AD) of waste activated sludge (WAS) is commonly limited to poor synergistic cooperation of four stages including hydrolysis, acidogenesis, acetogenesis and methanogenesis. Dissimilatory metal reduction that induced by metal-based conductive materials is promising strategy to regulate anaerobic metabolism with the higher metabolic driving force. In this study, MnO2 as inducer of dissimilatory manganese reduction (DMnR) was added into WAS-feeding AD system for mediating complicated anaerobic metabolism. The results demonstrated that main operational performances including volatile solid (VS) degradation efficiency and cumulative CH4 production with MnO2 dosage of 60 mg/g·VS reached up to maximum 53.6 ± 3.4% and 248.2 ± 10.1 mL/g·VS while the lowest operational performances in control group (38.5 ± 2.8% and 183.5 ± 8.5 mL/g·VS) was originated from abnormal operation of four stages. Furthermore, high-throughput 16 S rRNA pyrosequencing revealed that enrichment of dissimilatory manganese-reducing contributors and methanogens such as Thermovirga, Christensenellaceae_R_7_group and Methanosaeta performed the crucial role in short-chain fatty acids (SCFAs) oxidation and final methanogenesis, which greatly optimized operational environment of hydrolysis, acidogenesis and acetogenesis. More importantly, analysis of functional genes expression proved that abundances of genes encoding enzymes participated in acetate oxidation, direct interspecies electron transfer (DIET) and CO2 reduction pathway were simultaneously up-regulated with the optimum MnO2 dosage, suggesting that DMnR with SCFAs oxidation as electron sink could benefit stable operation of four stages via triggering effective DIET-based microbial interaction mode.

Therapeutic efficacy of microwave coagulation versus liver resection for hepatocellular carcinoma within the Milan criteria: A propensity score matching analysis.

INTRODUCTION: This study aimed to compare the therapeutic efficacy of resection (RES) and microwave ablation (MWA) for hepatocellular carcinoma (HCC) within the Milan criteria. MATERIALS AND METHODS: Between 2011 and 2019, 426 HCC patients within the Milan criteria were treated at our institution (RES: n = 291; MWA: n = 135). We compared overall survival (OS), disease-free survival (DFS), complications, and hospital stay in these patients using propensity score matching (PSM) and determined the prognostic factors using multivariate Cox analysis. RESULTS: Following 1:1 matching using PSM, 121 patients were matched in each group. The 1-, 3-, and 5-year OS rates were 98.3%, 84.7%, and 69.6% for the MWA group and 96.5%, 81.8%, and 78.1% for the RES group (p = 0.667). The corresponding DFS rates for the MWA and RES groups were 81.8%, 54.4%, and 42.3% and 85.4%, 67.8%, and 57.9%, respectively (p = 0.174). The MWA group had less blood loss and shorter hospital stays (both p < 0.001) than the RES group. CONCLUSION: MWA resulted in survival outcomes that were similar to those of RES for HCC within the Milan criteria. However, it had more favorable hospital stay and blood loss outcomes than RES.

Association between serum Cystatin C and renal injury in patients with chronic hepatitis B.

To explore the association between serum cystatin C (Cys-C) and renal damage in patients with chronic hepatitis B.We retrospectively analyzed the clinical data of 425 patients with chronic hepatitis B virus (HBV) infection. Liver stiffness measured by FibroScan was used to diagnosis liver fibrosis. Cys-C levels were detected via latex-enhanced immunoturbidimetric assay.A total of 425 patients were enrolled. Among them, 217 were patients with CHB with an eGFR > 90 mL/min/1.73 m and 208 with an eGFR ≤90 mL/min/1.73 m. Cys-C levels significantly differed in patients with eGFR > 90 mL/min/1.73 m compared with patients with eGFR ≤90 mL/min/1.73 m (0.81 ±â€Š0.05 vs 1.05 ±â€Š0.06 mg/L, P < .001). Moreover, the Cys-C levels were 0.82 ±â€Š0.04 mg/L in patients without liver fibrosis, 0.98 ±â€Š0.05 mg/L in patients with mild liver fibrosis, 1.05 ±â€Š0.08 mg/L in patients with advanced liver fibrosis, and 1.12 ±â€Š0.07 mg/L in patients with liver cirrhosis (P < .001). Multivariate analyses were conducted to explore the independent factors associated with a decreased eGFR. Multivariate analysis suggested that T2DM (P = .032), liver fibrosis (P = .013), and Cys-C level (P = .035) were the independent factors associated with the decreased eGFR in patients with CHB. While age (P = .020) and Cys-C level (P = .001) were the independent factors associated with the decreased eGFR in patients with CHB-related fibrosis.The fibrosis group had significantly higher Cys-C levels than those without fibrosis. Routine monitoring of Cys-C levels is of positive significance in preventing the development of renal impairment of CHB patients.

Reclassification of genus Izhakiella into the family Erwiniaceae based on phylogenetic and genomic analyses.

The genus Izhakiella was established and designated as a member of the family Enterobacteriaceae in 2016. Although the taxonomical classification of most members in this family has been relatively resolved after two reclassifications in 2016 and 2017, the classification of the genus Izhakiella remains ambiguous. In this study, a polyphasic approach was used to provide evidence supporting the fact that the genus Izhakiella should no longer be considered a member of Enterobacteriaceae and proposes its reclassification into the family Erwiniaceae. The phylogenetic tree of type species in the families Enterobacteriaceae and Erwiniaceae based on the sequences of the 16S rRNA gene, rpoB housekeeping gene, and the whole-genome comprising the 92 core genes revealed that the genus Izhakiella forms a phylogenetic lineage within the family Erwiniaceae. The average nucleotide identity (ANI) value of the type species with genus Izhakiella was found to be higher for the family Erwiniaceae than that for the family Enterobacteriaceae. Notably, 12 conserved signature indels (CSIs) that are exclusively shared among the Erwiniaceae clade members were found in the type strains of the genus Izhakiella. Based on these analyses, this study suggests the reclassification of I. capsodis and I. australiensis into the family Erwiniaceae.

Modified kyphoplasty with controllable balloon dilatation for treatment of thoracolumbar osteoporotic vertebral compression fractures.

PURPOSE: To investigate the surgical effects of modified kyphoplasty with controllable balloon dilatation for treatment of thoracolumbar osteoporotic vertebral compression fractures (OVCF). METHODS: From April 2013 to October 2017, a total of 53 patients with thoracolumbar OVCF were treated with controllable balloon percutaneous kyphoplasty (C-PKP). Peri-operative parameters including days from injury to operation, operation time, injected cement volume, cement leakage and complications were collected. Visual analogue scale (VAS) and Cobb angle before and after operation were applied to evaluate surgical effects. Moreover, a total of 53 cases treated with traditional balloon of percutaneous kyphoplasty were retrospectively analyzed and compared with C-PKP in above parameters. RESULTS: C-PKP achieved significant fewer events of cement leakage (type C) than that of traditional PKP (5/53 vs 13/53, p < 0.01). The patients were followed up for 10.8 ± 4.2 months; VAS and Cobb angle of the injured vertebra in both two groups at three days and final follow-up were significantly improved compared with that before surgery (p < 0.05), while there were no significant differences between the two groups regarding the VAS and Cobb angle at corresponding time points (p > 0.05). CONCLUSIONS: C-PKP technology is a safe and efficient way for the treatment of thoracolumbar OVCF, and it can reduce cement leakage.

Weak magnetic field significantly enhances methane production from a digester supplemented with zero valent iron.

Weak magnetic field (WMF) provided by a magnet was proposed to enhance CH4 production from a swine manure-fed digester supplemented with micron-sized zero valent iron (ZVI). Compared to the control without ZVI addition and WMF application (RControl), treatments that included ZVI only (RZVI) and coupled WMF with ZVI (RZVI/WMF) increased the CH4 production by 77.0% and 124.5%, respectively. As evidenced by the elevated levels of total soluble iron, WMF apparently promoted the corrosion of ZVI, providing extra H2 for hydrogenotrophic methanogenesis and creating a more reductive environment to reduce propionic-type fermentation. Microbial analysis results revealed that the relative abundance of Methanothrix (capable of accepting electrons) in RZVI/WMF were 75.1% higher than that in RZVI. Essentially, WMF application promoted the direct interspecies electron transfer-based methanogenesis by (1) providing more electrons as the direct substrate, and (2) inducing Lorentz force to facilitate the mass transfer between the released electrons and the methanogens.

Adsorption Mechanism of Oil-in-Water on a TiO2/Al2O3-Polyvinylidene Fluoride (PVDF) Ultrafiltration Membrane.

For the sake of gaining a clear idea of the adsorption mechanism involved with an oil emulsion-membrane system, Daqing crude oil emulsion and two types of polyvinylidene fluoride (PVDF) ultrafiltration membranes made in our laboratory were used as the objects to pursue the adsorption characteristics in this system. Several isotherm and kinetics models were used here to simulate the adsorption process; the effect of variables such as time, initial concentration, temperature, as well as scanning electron microscopy (SEM) and attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectra were investigated to assist in understanding the mechanism. The results show that the Redlich-Peterson model and the pseudo-first-order kinetic model are the best fitting models, with all of the models exhibiting correlation coefficient ( R2) values of >0.98, suggesting an endothermic adsorption process that involves a combination of chemical and physical mechanisms. Moreover, the thermodynamic parameters, such as Δr Gmθ, Δr Hmθ, and Δr Smθ were also calculated from the temperature dependence, indicating a nonspontaneous process, and increases in temperature had a negative effect on the oil-in-water (o/w) adsorption. Ultimately, further evidence is obtained from the microstructural and infrared spectral analyses.

Tenofovir decrease hepatocellular carcinoma recurrence in chronic hepatitis B patients after liver resection.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are recommended as the first-line choices regarding the treatment of chronic hepatits B. The impact of the two antiviral agents on prognosis of Chronic hepatitis B (CHB) related hepatocellular carcinoma (HCC) remains to be explored. We aim to investigate whether CHB-related HCC patients receiving TDF and ETV have a different prognosis. METHODS: 233 CHB-related compensated cirrhosis patients were divided into groups according to the nucleut(s)ide patients received. The results of TDF and ETV groups were reviewed and compared. The disease-free survival (DFS) and overall survival (OS) of both groups were analyzed and compared. RESULTS: 233 CHB-related compensated cirrhosis patients from 2013 October to 2014 November were included in our study. 107 and 126 patients received TDF and ETV monotherapy, respectively. Child-Pugh score, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin level, status of hepatitis B e antigen (HBeAg) and serum HBV DNA level were compared between groups. DFS in TDF-treatment group were significantly longer than it in ETV-treatment group (p < 0.05). multi-variant analysis indicated that TDF duration was significantly associated with lower probability of HCC development, (hazard ratio, 0.35; 95% confidence interval range, 0.33-0.84, p < 0.05). CONCLUSION: Anti-virus regimen containing TDF benefits for the prognosis of CHB-related liver cirrhosis patients.

[Research progress on pathogenesis of temporary osteoporosis in hip].

Transient osteoporosis of the hip(TOH) is classified as a type of bone marrow edema syndrome. TOH is lack of previous study and there is still controversy about his pathogenesis. In recent years, with the development of multi-discipline, such as imaging, pathology, molecular biology, the study has found that the pathological mechanism is complex, while its mechanism is still not clear, which need further research. This paper summarizes the research progress on the pathogenesis of TOH from neurogenic, osteonecrosis, abnormal vascular function, subchondral fracture, heredity and regional acceleration and son on.

Predictors for advanced liver fibrosis in chronic hepatitis B virus infection with persistently normal or mildly elevated alanine aminotransferase.

The aim of the present study was to evaluate the predictors for advanced liver fibrosis in patients with chronic hepatitis B virus (HBV) infection with persistently normal alanine aminotransferase (PNALT), or persistently or intermittently mildly elevated ALT (PIEALT). A total of 305 patients were included in the present study. Liver biopsies were evaluated using the METAVIR scoring system. Liver stiffness (LS) was measured using Fibroscan. Multivariate logistic regression and the area under the receiver operating characteristic curve (AUROC) were used to examine the diagnostic value of the predictors for advanced liver fibrosis. HBV DNA viral load in the PNALT group was significantly lower compared with the PIEALT group (4.57±1.68 vs. 5.71±1.69 log10 IU/ml; P<0.001). Body mass index and LS were also significantly lower in the PNALT group compared with the PIEALT group (P<0.001). The proportion of patients with liver fibrosis was significantly higher in the PIEALT group compared with the PNATL group (P=0.001). High ALT levels were an independent predictor for liver fibrosis, with an odds ratio (OR) of 2.69 (P=0.002). Male sex (OR=0.34, P=0.007), high ALT levels (OR=2.37, P=0.029) and a high HBV DNA load (OR=1.39, P=0.005) were independent predictors for advanced liver fibrosis. The AUROC was 0.65 (P=0.003) when using ALT levels to predict advanced liver fibrosis. ALT levels at ≥0.88 upper limit of normal (ULN; 35 IU/l) were considered as positive for advanced liver fibrosis, the sensitivity and specificity were 87.8 and 47.4%, respectively. The AUROC was 0.64 (P=0.004) when using the HBV DNA value to predict advanced liver fibrosis. When an HBV DNA value of ≥4.99 log10 IU/ml was considered as positive for advanced liver fibrosis, the sensitivity and specificity were 78.0 and 49.5%, respectively. The AUROC was 0.72 (P<0.001) when combining ALT, HBV DNA load and sex into a formulation to predict advanced liver fibrosis. When the formulation score at >-2.22 was considered as positive for advanced liver fibrosis, the sensitivity and specificity were 61.5 and 70.7%, respectively. Therefore, normal ALT levels do not always indicate the absence of hepatic fibrosis. A combination of ALT levels, sex and serum HBV DNA load may more effectively identify patients with CHB at high risk of developing fibrosis. These patients may benefit from liver biopsy.

miR-138 promotes migration and tube formation of human cytomegalovirus-infected endothelial cells through the SIRT1/p-STAT3 pathway.

Human cytomegalovirus (HCMV) has been reported to be linked to vascular disease through the induction of neovessel formation. We have previously reported that microRNA (miR)-217 and miR-199a-5p enhance endothelial angiogenesis via inhibition of sirtuin 1 (SIRT1) in HCMV-infected human umbilical vein endothelial cells (HUVECs). Here, we found that miR-138 also suppressed the expression of the SIRT1 protein and stimulated phosphorylation of signal transducer and activator of transcription 3 (p-STAT3). Moreover, the regulation of p-STAT3 expression mediated by SIRT1 was found to promote HCMV-induced angiogenesis. These findings revealed that miR-138 might promote angiogenesis of HCMV-infected HUVECs by activating the SIRT1-mediated p-STAT3 pathway, and this could provide novel insights into HCMV-induced angiogenesis.

MicroRNA-217 promotes angiogenesis of human cytomegalovirus-infected endothelial cells through downregulation of SIRT1 and FOXO3A.

Human cytomegalovirus(HCMV) infection has been shown to contribute to vascular disease through the induction of angiogenesis. However, the role of microRNA in angiogenesis induced by HCMV infection remains unclear. The present study was thus designed to explore the potential effect of miR-1217 on angiogenesis and to disclose the underlying mechanism in endothelial cells. We found that HCMV infection of endothelial cells(ECs) enhanced expression of miR-217 and reduced SIRT1 and FOXO3A protein level in 24 hours post infection(hpi). Transfection of miR-217 inhibitor not only depressed cellular migration and tube formation induced by HCMV infection, but also enhanced SIRT1 and FOXO3A protein expression. Additionally, luciferase assay confirmed that miR-217 directly targeted FOXO3A mRNA 3`UTR. Furthermore, pretreatment with resveratrol depressed motility and tube formation of HCMV-infected ECs, which could be reversed by SIRT1 siRNA. Similarly, delivery of FOXO3A overexpression lentivirus suppressed proliferative rate, migration and tube formation of HCMV-infected ECs, which reversed by transfection of FOXO3A siRNA. In summary, HCMV infection of endothelial cells induces angiogenesis by both of miR-217/SIRT1 and miR-217/FOXO3A axis.

Insulin alleviates posttrauma cardiac dysfunction by inhibiting tumor necrosis factor-α-mediated reactive oxygen species production.

OBJECTIVE: Clinical evidence indicates that intensive insulin treatment prevents the incidence of multiple organ failures in surgical operation and severe trauma, but the mechanisms involved remain elusive. This study was designed to test the hypothesis that insulin may exert anti-inflammatory and antioxidative effects and thus alleviate cardiac dysfunction after trauma. DESIGN: Prospective, randomized experimental study. SETTING: Animal research laboratory. SUBJECTS: Sprague Dawley rats. INTERVENTIONS: Anesthetized rats were subjected to 200 revolutions at a rate of 35 rpm in Noble-Collip drum to induce a nonlethal mechanical trauma and were randomized to receive vehicle, insulin, and insulin + wortmannin treatments. An in vitro study was performed on cultured cardiomyocytes subjected to sham-traumatic serum (SS), traumatic serum (TS), SS + tumor necrosis factor (TNF)-α, SS + H2O2, TS + neutralizing anti-TNF-α antibody, or TS + tempol treatments. MEASUREMENTS AND MAIN RESULTS: Immediate cardiac dysfunction occurred 0.5 hr after trauma without significant cardiomyocyte necrosis and apoptosis, while serum TNF-α and cardiac reactive oxygen species (ROS) production was increased. Importantly, incubation of cardiomyocytes with TS or SS + TNF-α significantly increased ROS generation together with dampened cardiomyocyte contractility and Ca transient, all of which were rescued by TNF-α antibody. Administration of insulin inhibited TNF-α and ROS overproduction and alleviated cardiac dysfunction 2 hours after trauma. Scavenging ROS with tempol also attenuated cardiac dysfunction after trauma, whereas insulin combined with tempol failed to further improve cardiac functional recovery compared with insulin treatment alone. Moreover, the aforementioned anti-TNF-α, antioxidative, and cardioprotective effects afforded by insulin were almost abolished by the phosphatidylinositol 3-kinase inhibitor wortmannin. CONCLUSIONS: These results demonstrate for the first time that mechanical trauma induces a significant increase in TNF-α and ROS production, resulting in immediate cardiac dysfunction. Early posttrauma insulin treatment alleviates cardiac dysfunction by inhibiting TNF-α-mediated ROS production via a phosphatidylinositol 3-kinase/Akt-dependent mechanism.