[Safety of umeclidinium/vilanterol in Chinese patients in a real-world setting: a prospective, multicenter, single-arm, observational study].

Objective: To evaluate the safety of umeclidinium/vilanterol in Chinese participants in a real-world setting. Methods: This was a 24-week, prospective, multicenter, single-arm, observational study that enrolled participants treated with umeclidinium/vilanterol in real-world settings from 14 sites in China from 14 December 2020 to 30 January 2022. The primary outcomes were the incidence of adverse events (AEs) and serious adverse events (SAEs) at week 24. Results: A total of 887 participants on umeclidinium/vilanterol were enrolled. The mean (±SD) age of these participants was 67.5 (±9.6) years, with more men (77.7%) enrolled. The majority of the participants (98.1%) had been diagnosed with chronic obstructive pulmonary disease, and 67.6% of them reported comorbidities. More than half of the participants (52.8%) were taking concomitant medication in addition to the study treatment. AEs were reported in 59 (6.7%) participants and were predominantly mild to moderate in severity. SAEs were reported in 21 (2.4%) participants, including 9 fatal SAEs, 10 reported non-fatal SAEs, and 2 reported both non-fatal and fatal SAEs. None of the SAEs, including the fatal events, were considered by the investigators to be related to umeclidinium/vilanterol. Adverse drug reactions (ADRs) were reported in 6 (0.7%) participants with 4 preferred terms (PTs), all of which were considered mild in severity. Of these PTs, 2 were known ADRs of umeclidinium/vilanterol. Three participants (0.3%) reported AEs that were part of serious identified/potential hazards, all of which were considered by the investigators to be unrelated to umeclidinium/vilanterol. Conclusion: The results of this study showed that umeclidinium/vilanterol was well tolerated in Chinese participants in a real-world setting and no new drug-related safety signals were observed.

[Mitigating metal artifacts from cobalt-chromium alloy crowns in cone-beam CT images through deep learning techniques].

Objective: To develop and evaluate metal artifact removal systems (MARS) based on deep learning to assess their effectiveness in removing artifacts caused by different thicknesses of metals in cone-beam CT (CBCT) images. Methods: A full-mouth standard model (60 mm×75 mm×110 mm) was three-dimensional (3D) printed using photosensitive resin. The model included a removable and replaceable target tooth position where cobalt-chromium alloy crowns with varying thicknesses were inserted to generate matched CBCT images. The artifacts resulting from cobalt-chromium alloys with different thicknesses were evaluated using the structural similarity index measure (SSIM) and peak signal-to-noise ratio (PSNR). CNN-MARS and U-net-MARS were developed using a convolutional neural network and U-net architecture, respectively. The effectiveness of both MARSs were assessed through visualization and by measuring SSIM and PSNR values. The SSIM and PSNR values were statistically analyzed using one-way analysis of variance (α=0.05). Results: Significant differences were observed in the range of artifacts produced by different thicknesses of cobalt-chromium alloys (all P<0.05), with 1 mm resulting in the least artifacts. The SSIM values for specimens with thicknesses of 1.0, 1.5, and 2.0 mm were 0.916±0.019, 0.873±0.010, and 0.833±0.010, respectively (F=447.89, P<0.001). The corresponding PSNR values were 20.834±1.176, 17.002±0.427, and 14.673±0.429, respectively (F=796.51, P<0.001). After applying CNN-MARS and U-net-MARS to artifact removal, the SSIM and PSNR values significantly increased for images with the same thickness of metal (both P<0.05). When using the CNN-MARS for artifact removal, the SSIM values for 1.0, 1.5 and 2.0 mm were 0.938±0.023, 0.930±0.029, and 0.928±0.020 (F=2.22, P=0.112), while the PSNR values were 30.938±1.495, 30.578±2.154 and 30.553±2.355 (F=0.54, P=0.585). When using the U-net-MARS for artifact removal, the SSIM values for 1.0, 1.5 and 2.0 mm were 0.930±0.024, 0.932±0.017 and 0.930±0.012 (F=0.24, P=0.788), and the PSNR values were 30.291±0.934, 30.351±1.002 and 30.271±1.143 (F=0.07, P=0.929). No significant differences were found in SSIM and PSNR values after artifact removal using CNN-MARS and U-net-MARS for different thicknesses of cobalt-chromium alloys (all P>0.05). Visualization demonstrated a high degree of similarity between the images before and after artifact removal using both MARS. However, CNN-MARS displayed clearer metal edges and preserved more tissue details when compared with U-net-MARS. Conclusions: Both the CNN-MARS and U-net-MARS models developed in this study effectively remove the metal artifacts and enhance the image quality. CNN-MARS exhibited an advantage in restoring tissue structure information around the artifacts compared to U-net-MARS.

[Mitigating metal artifacts in cone-beam CT images through deep learning techniques].

Objective: To develop and evaluate metal artifact removal systems (MARSs) based on deep learning to assess their effectiveness in removing artifacts caused by different thicknesses of metals in cone-beam CT (CBCT) images. Methods: A full-mouth standard model (60 mm×75 mm×110 mm) was three-dimensional (3D) printed using photosensitive resin. The model included a removable and replaceable target tooth position where cobalt-chromium alloy crowns with varying thicknesses were inserted to generate matched CBCT images. The artifacts resulting from cobalt-chromium alloys with different thicknesses were evaluated using the structural similarity index measure (SSIM) and peak signal-to-noise ratio (PSNR). CNN-MARS and U-net-MARS were developed using a convolutional neural network and U-net architecture, respectively. The effectiveness of both MARSs were assessed through visualization and by measuring SSIM and PSNR values. The SSIM and PSNR values were statistically analyzed using one-way analysis of variance (α=0.05). Results: Significant differences were observed in the range of artifacts produced by different thicknesses of cobalt-chromium alloys (all P<0.05), with 1 mm resulting in the least artifacts. The SSIM values for specimens with thicknesses of 1.0 mm, 1.5 mm, and 2.0 mm were 0.916±0.019, 0.873±0.010, and 0.833±0.010, respectively (F=447.89, P<0.001). The corresponding PSNR values were 20.834±1.176, 17.002±0.427, and 14.673±0.429, respectively (F=796.51, P<0.001). After applying CNN-MARS and U-net-MARS to artifact removal, the SSIM and PSNR values significantly increased for images with the same thickness of metal (both P<0.05). When using the CNN-MARS for artifact removal, the SSIM values for 1.0, 1.5 and 2.0 mm were 0.938±0.023, 0.930±0.029, and 0.928±0.020 (F=2.22, P=0.112), while the PSNR values were 30.938±1.495, 30.578±2.154 and 30.553±2.355 (F=0.54, P=0.585). When using the U-net-MARS for artifact removal, the SSIM values for 1.0, 1.5 and 2.0 mm were 0.930±0.024, 0.932±0.017 and 0.930±0.012 (F=0.24, P=0.788), and the PSNR values were 30.291±0.934, 30.351±1.002 and 30.271±1.143 (F=0.07, P=0.929). No significant differences were found in SSIM and PSNR values after artifact removal using CNN-MARS and U-net-MARS for different thicknesses of cobalt-chromium alloys (all P>0.05). Visualization demonstrated a high degree of similarity between the images before and after artifact removal using both MARSs. However, CNN-MARS displayed clearer metal edges and preserved more tissue details when compared with U-net-MARS. Conclusions: Both the CNN-MARS and U-net-MARS models developed in this study effectively remove the metal artifacts and enhance the image quality. CNN-MARS exhibited an advantage in restoring tissue structure information around the artifacts compared to U-net-MARS.

[Analysis of video-urodynamic and clinical features of non-neuropathic lower urinary tract dysfunction in children].

Objective: To analyze the video-urodynamic(VUDS) and clinical features of non-neuropathic lower urinary tract dysfunction (NNLUTD) in children. Methods: Children diagnosed with NNLUTD in the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2020 were included. Children with neurological, rectal dysfunction and anatomical abnormalities were excluded. VUDS and urinalysis were performed in all children who were divided into 4 groups accordingly: normal group (Normal group), detrusor overactivity group(DO group), detrusor sphincter dyssynergia group (DSD group) and detrusor underactivity group (DU group). VUDS and clinical features, vesicoureteral reflux (VUR) and urinary tract infections (UTI) were analyzed. Results: A total of 173 children were included in this study, including 103 males and 70 females, aged (7.2±3.3) years. VUDS showed that 46 cases (26.6%) were in Normal group, 63 cases (36.4%) in DO group, 39 cases (22.5%) in DSD group and 25 cases (14.5%) in DU group. Compared with Normal group and DO group, the proportion of VUR in DSD group and DU group was significantly higher [18(46.2%) and 11(44.0%) vs 7(15.0%) and 14(22.2%), all P<0.05],and the proportion of male children was significantly higher than that of female children with VUR only in DO group [12(32.4%) vs 2(7.7%), P=0.020 ]; Compared with DO group, the proportion of UTI in DSD group and DU group was significantly higher [16(41.0%) and 12(48.0%) vs 12(19.0%), all P<0.05], and the proportion of female children was significantly higher than that of male children with UTI in normal group, DO group and DU group [9(45.0%) vs 4(15.4%), 8(30.8%) vs 4(10.8%)and 7(87.5%) vs 5(29.4%), all P<0.05]. The maximum detrusor pressure in DSD group was significantly higher than that in Normal group, DO group and DU group [(95±47) vs (43±18), (56±18) and (12±9)cmH2O, all P<0.05, 1 cmH2O=0.098 kPa).Compared with Normal group and DO group, post void residual in DSD group and DU group was significantly increased [(58±38) and (70±62) vs (8±8) and (8±7)ml, all P<0.05], and the proportion of lower bladder compliance was significantly increased [(15(38.5%) and 11(44%) vs 1(2.2%) and 10(15.9%), all P<0.05]. Compared with normal group, the maximum bladder capacity of DO, DSD and DU group were all significantly decreased [(178±61), (184±81) and (194±93) vs (256±92)ml, all P<0.05]. The proportion of urgency had significant difference in the four groups [13(28.3%) in Normal group, 41(65.1%) in DO group, 22(56.4%) in DSD group and 11(44.0%) in DU group, P=0.001], and the proportion of dysuria had significant difference too [5(10.9%) in Normal group, 18(28.6%) in DO group, 20(51.3%) in DSD group and 15(60.0%) in DU group, P<0.001]. Conclusions: Children with 4 different conditions of NNLUTD have distinct video-urodynamic features. The higher ratio of VUR and UTI in DSD and DU children may be associated with reduced bladder compliance and increased post void residual. VUDS is useful for the diagnosis and treatment of refractory children with NNLUTD.

Cytochrome C suppresses renal accumulation and nephrotoxicity of polymyxin B.

The receptor megalin plays an important role in the accumulation of polymyxin B (PMB) in renal cells in vitro. This study aimed to examine the effects of cytochrome c (cyto c), a typical megalin ligand, on renal accumulation and nephrotoxicity of PMB in vivo. Thirty Sprague-Dawley rats were randomly divided into the vehicle control group, PMB group, PMB + cyto c 50, 100, or 200 mg/kg group, respectively, and were treated with intravenous cyto c 30 min before the administration of PMB 4.0 mg/kg once a day for consecutive 5 days. On the 4th day after administration, 24 h urine was collected to determine N-acetyl-ß-D-glucosaminidase excretion. Six hours after the last injection on the 5th day, kidneys were harvested to assay PMB concentration and observe pathological alterations, and blood samples were collected to assay serum creatinine (SCr), blood urea nitrogen (BUN), and blood ß2-microglobulin (ß2-MG) levels. Cyto c 50, 100, and 200 mg/kg decreased the accumulation of PMB in the kidney by 18.5%, 39.1% ( p < 0.01), and 36.8% ( p < 0.01), respectively, and reduced 24 h N-acetyl-ß-D- glucosaminidase excretion by 22.5% ( p < 0.05), 40.4% ( p < 0.01), and 40.4% ( p < 0.01), respectively. Kidney pathological damage induced by PMB was markedly reduced by cyto c 100 mg/kg and 200 mg/kg. However, there were no significant differences in SCr, BUN, and blood ß2-MG levels among the groups. These results indicated that cyto c may inhibit the renal accumulation and nephrotoxicity of PMB in a rat model, further proving the role of megalin in the accumulation of PMB.

Sorafenib in combination with transarterial chemoembolization for hepatocellular carcinoma: a meta-analysis.

OBJECTIVE: This meta-analysis aimed to analyze the efficacy of sorafenib in combination with transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Electronic data bases were searched for studies (1) enrolled HCC patients undergoing TACE; (2) with sorafenib therapy and control arm of no sorafenib therapy were included for meta-analysis and meta-regression; (3) studies without control arm were included for data review and (4) had time to progression (TTP) and overall survival (OS) or relative outcome of HCC as the endpoint. Meta-analysis and meta-regression were performed according to Cochrane guidelines. RESULTS: Five studies (3 randomized trials, 1 cohort study and 1 prospective non- randomized controlled trial, totally 899 patients) were eligible for meta-analysis. The hazard ratio (HR) for TTP was 0.75 (95% CI: 0.48-1.03, p = 0.003) with significant heterogeneity (I2 = 82.7%) and for OS was 0.76 (95% CI: 0.47-1.05, p = 0.147) with slight heterogeneity (I2 = 47.9%). However, no covariate was found as independent predictor for better treatment efficacy. Hand-foot skin reaction, alopecia, rash/desquamation, diarrhea, hypertension, fatigue, anorexia, nausea and vomiting were common adverse events. CONCLUSIONS: TACE combined with sorafenib has potential efficacy for HCC.

Magnetic studies of a syn-anti triatomic carboxylate-bridging chainlike copper(II) complex exhibiting ferromagnetic exchange.

The magnetic properties of triatomic syn-anti carboxylate bridging copper(II) complex, {[Cu(2,2'-bipydine)(maleate)].2H2O}infinity (complex 1), were investigated experimentally and theoretically, suggesting weak ferromagnetic intrachain interaction. The magnetic data were analyzed and interpreted in terms of Heisenberg chain model corrected by a mean molecular field. Fitting parameters obtained for J, g, and zJ' are 3.14 cm(-1), 2.08, and -0.13, respectively. Density functional theory with generalized gradient approximation was applied to calculate the electronic structure and spin distribution of the present complex. The structural and electronic factors controlling the magnetic interactions were also determined. Ferromagnetic intrachain interactions through triatomic syn-anti carboxylate bridge result from nonplanarity of the bridging network, the exchange pathway involving both the sigma and pi orbitals of the carboxylate bridge and the spin delocalization of each magnetic orbital on the atoms of the carboxylate bridge from the copper(II) centers.