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Taken together, our results demonstrate that PI3K/Akt-mediated upregulation of DDAH2 expression plays a critical role in visfatin-promoted angiogenesis via regulating VEGF-dependent pathway.

The aim of this study was to assess the usefulness of integrated (18)F-FDG PET/CT in differentiating benign from metastatic malignant adrenal masses in patients with lung cancer. One hundred and ten adrenal masses (size range, 0.5 - 6.3 cm, mean size, 1.9 cm) were evaluated retrospectively in 87 lung cancer patients. Integrated PET/CT images were assessed. PET findings were interpreted as positive if the (18)F-FDG uptake of the adrenal mass was greater than or equal to that of the liver. PET findings were interpreted as negative if the 18F-FDG uptake of the adrenal mass was less than that of the liver. All studies were reviewed independently by 3 nuclear medicine physicians, and the results were then correlated with clinical follow-up or biopsy results when available. PET/CT findings were positive in 77 adrenal masses. Seventy-four of these were eventually considered to be metastatic adrenal disease. In the remaining 3, in the course of follow-up, two underwent percutaneous puncture, and one underwent surgery. In the end, histopathological examinations of the adrenal lesions demonstrated the presence of adenomas. PET/CT findings were negative in 33 adrenal masses, of which 31 eventually proved to be benign. The 2 adrenal masses that were false-negative, underwent PET/CT twice with a two-month interval. At the initial study, the size was 0.5cm, 0.9cm in diameter, respectively. However, at the follow-up study, PET/CT showed both positive result with the size of 1.6cm, and 2.3cm in diameter, respectively. Both adrenal masses were interpreted as metastasis. The sensitivity, specificity, and accuracy for detecting metastatic disease were 97 %( 74 of 76), 94 %( 31 of 34), and 95% (105 of 110), respectively. The positive predictive value was 95 %( 74 of 77), and the negative predictive value was 94% (31 of 33). Integrated (18)F-FDG PET-CT is an accurate, noninvasive technique for differentiating benign from metastatic adrenal lesions detected on CT or MRI in patients with lung cancer. It allows early detection and accurate localization of adrenal lesions and differentiation of metastatic nodules from benign lesions, thereby facilitating treatment planning.

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Background and Aim: HBV DNA can be reduced using antiviral drugs in patients with chronic hepatitis B (CHB); however, the rate of HBeAg seroconversion remains low. A clinical trial was conducted to assess the efficacy and safety of a de novo designed liposome-based nanoparticle lipopeptide vaccine, εPA-44, for CHB. Approach and Results: A two-stage phase 2 trial, which included a 76week, randomized, double-blind, placebo-controlled trial (stage 1) and a 68week open-label extension (stage 2), was conducted in 15 centers across China (Clinicaltrials.gov No. NCT00869778). In stage 1, 360 human leukocyte | 183 HEPATOLOGY

Background IRAK-M, negatively regulating Toll-like receptor, is shown the dual properties in the varied disease contexts. We studied the effect of IRAK-M deficiency on cigarette smoking- (CS-) induced airway inflammation under acute or subacute conditions in a mouse model. Methods A number of cellular and molecular techniques were used to detect the differences between IRAK-M knockout (KO) and wild type (WT) mice exposed to 3-day or 7-week CS. Results Airway inflammation was comparable between IRAK-M KO and WT mice under 3-day CS exposure. Upon short-term CS exposure and lipopolysaccharide (LPS) inhalation, IRAK-M KO mice demonstrated worse airway inflammation, significantly higher percentage of Th17 cells and concentrations of proinflammatory cytokines in the lungs, and significantly elevated expression of costimulatory molecules CD40 and CD86 by lung dendritic cells (DCs) or macrophages. Conversely, 7-week CS exposed IRAK-M KO mice demonstrated significantly attenuated airway inflammation, significantly lower concentrations of proinflammatory cytokines in the lungs, significantly increased percentage of Tregs, and lower expression of CD11b and CD86 by lung DCs or macrophages. Conclusions IRAK-M plays distinctive effect on CS-induced airway inflammation, and influences Treg/Th17 balance and expression of costimulatory molecules by DCs and macrophages, depending on duration and intensity of stimulus.

Background: Tenofovir amibufenamide (TMF) can provide more efficient delivery than tenofovir disoproxil fumarate (TDF).Aim: To compare the efficacy and safety of TMF and TDF for 48 weeks in patients with chronic hepatitis B (CHB). Methods:We performed a randomised, double-blind, non-inferiority study at 49 sites in China. Patients with CHB were assigned (2:1) to receive either 25 mg TMF or 300 mg TDF with matching placebo. The primary efficacy endpoint was the proportion of patients with hepatitis B virus (HBV) DNA less than 20 IU/mL at week 48. We also assessed safety, particularly bone, renal and metabolic abnormalities. Results:We randomised 1002 eligible patients. The baseline characteristics were well balanced between groups. After a median 48 weeks of treatment, the non-inferiority criterion was met in all analysis sets. In the HBeAg-positive population, 50.2% of patients receiving TMF and 53.7% receiving TDF achieved HBV DNA less than 20 IU/mL. In the HBeAgnegative population, 88.9% and 87.8%, respectively, achieved HBV DNA less than 20 IU/ mL in the TMF and TDF groups. Patients receiving TMF had significantly less decrease in bone mineral density at both hip (P < 0.001) and spine (P < 0.001), and a smaller increase in serum creatinine at week 48 (P < 0.05). Other safety results were similar between groups. Conclusion:TMF was non-inferior to TDF in terms of anti-HBV efficacy and showed better bone and renal safety. (NCT03903796).

BackgroundTo evaluate the safety and efficacy of daily somatropin (Jintropin®), a recombinant human growth hormone, in prepubertal children with ISS in China.MethodsThis study was a multicenter, randomized, controlled, open-label, phase 3 study. All subjects were randomized 3:1 to daily somatropin 0.05 mg/kg/day or no treatment for 52 weeks. A total of 481 subjects with a mean baseline age of 5.8 years were enrolled in the study. The primary endpoint was change in (△) height standard deviation score (HT-SDS) for chronological age (CA). Secondary endpoints included △height from baseline; △bone age (BA)/CA; △height velocity (HV) and △insulin-like growth factor 1 (IGF-1 SDS).Results△HT-SDS at week 52 was 1.04 ± 0.31 in the treatment group and 0.20 ± 0.33 in the control group (P &lt; 0.001). At week 52, statistical significance was observed in the treatment group compared with control for △height (10.19 ± 1.47 cm vs. 5.85 ± 1.80 cm; P &lt; 0.001), △BA/CA (0.04 ± 0.09 vs. 0.004 ± 0.01; P &lt; 0.001), △HV (5.17 ± 3.70 cm/year vs. 0.75 ± 4.34 cm/year; P &lt; 0.001), and △IGF-1 SDS (2.31 ± 1.20 vs. 0.22 ± 0.98; P &lt; 0.001). The frequencies of treatment-emergent adverse events (TEAEs) were similar for the treatment and the control groups (89.8% vs. 82.4%); most TEAEs were mild to moderate in severity and 23 AEs were considered study-drug related.ConclusionsDaily subcutaneous administration of somatropin at 0.05 mg/kg/day for 52 weeks demonstrated improvement in growth outcomes and was well tolerated with a favorable safety profile.Trial RegistrationClinicalTrials.gov (identifier: NCT03635580). URL: https://clinicaltrials.gov/ct2/show/NCT03635580