CYB561 promotes HER2+ breast cancer proliferation by inhibiting H2AFY degradation.

Breast cancer (BRCA) has a high incidence and mortality rate among women. Different molecular subtypes of breast cancer have different prognoses and require personalized therapies. It is imperative to find novel therapeutic targets for different molecular subtypes of BRCA. Here, we demonstrated for the first time that Cytochromeb561 (CYB561) is highly expressed in BRCA and correlates with poor prognosis, especially in HER2-positive BRCA. Overexpression of CYB561 could upregulate macroH2A (H2AFY) expression in HER2-positive BRCA cells through inhibition of H2AFY ubiquitination, and high expression of CYB561 in HER2-positive BRCA cells could promote the proliferation and migration of cells. Furthermore, we have demonstrated that CYB561 regulates H2AFY expression, thereby influencing the expression of NF-κB, a downstream molecule of H2AFY. These findings have been validated through in vivo experiments. In conclusion, we propose that CYB561 may represent a novel therapeutic target for the treatment of HER2-positive BRCA. Graphical abstract CYB561 promotes the proliferation of HER2+ BRCA cells: CYB561 enhances the expression of H2AFY by inhibiting its ubiquitination, which leads to an increase expression of NF-κB in the nucleus. H2AFY, together with NF-κB, promotes the proliferation of HER2+ BRCA cells.

Assessing the effect of scanning parameter on the size and density of pulmonary nodules: a phantom study.

BACKGROUND: Lung cancer remains a leading cause of death among cancer patients. Computed tomography (CT) plays a key role in lung cancer screening. Previous studies have not adequately quantified the effect of scanning protocols on the detected tumor size. The aim of this study was to assess the effect of various CT scanning parameters on tumor size and densitometry based on a phantom study and to investigate the optimal energy and mA image quality for screening assessment. METHODS: We proposed a new model using the LUNGMAN N1 phantom multipurpose anthropomorphic chest phantom (diameters: 8, 10, and 12 mm; CT values: - 100, - 630, and - 800 HU) to evaluate the influence of changes in tube voltage and tube current on the size and density of pulmonary nodules. In the LUNGMAN N1 model, three types of simulated lung nodules representing solid tumors of different sizes were used. The signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were used to evaluate the image quality of each scanning combination. The consistency between the calculated results based on segmentation from two physicists was evaluated using the interclass correlation coefficient (ICC). RESULTS: In terms of nodule size, the longest diameters of ground-glass nodules (GGNs) were closest to the ground truth on the images measured at 100 kVp tube voltage, and the longest diameters of solid nodules were closest to the ground truth on the images measured at 80 kVp tube voltage. In respect to density, the CT values of GGNs and solid nodules were closest to the ground truth when measured at 80 kVp and 100 kVp tube voltage, respectively. The overall agreement demonstrates that the measurements were consistent between the two physicists. CONCLUSIONS: Our proposed model demonstrated that a combination of 80 kVp and 140 mA scans was preferred for measuring the size of the solid nodules, and a combination of 100 kVp and 100 mA scans was preferred for measuring the size of the GGNs when performing lung cancer screening. The CT values at 80 kVp and 100 kVp were preferred for the measurement of GGNs and solid nodules, respectively, which were closest to the true CT values of the nodules. Therefore, the combination of scanning parameters should be selected for different types of nodules to obtain more accurate nodal data.

Vietnamese female sex workers in rural cross-border areas of Guangxi, China: migration and HIV/STI risk behaviors.

China's HIV/AIDS epidemic continues to grow in rural and less developed areas. This consecutive cross-sectional study examines demographic and behavioral factors associated with HIV/STI infection, Hepatitis C (HCV) and other sexually transmitted infections (STIs) among Vietnamese female sex workers (FSW), a vulnerable population who cross into Guangxi, China. This study is a secondary data analysis of 303 Vietnamese and 4,348 Chinese FSWs recruited over seven years from two Chinese counties that border Vietnam. Logistic regression models compared demographics, HIV/STI status, HIV/AIDS-related knowledge, attitudes, and risk behaviors between Vietnamese FSWs and Chinese FSWs. Compared with Chinese FSWs, Vietnamese FSWs were younger, had attained lower education levels, were highly mobile, more likely to report using drugs, and were more vulnerable to HIV/STIs. Younger age, less educational attainment, shorter time in their current working location, no voluntary HIV testing in the last year, greater drug use, and not using condoms for all commercial sex in the last month were associated with higher HIV/STIs. In conclusion, several factors were associated with HIV/STI risk in Vietnamese cross-border FSWs. There is a pressing need to improve support systems for Vietnamese cross-border FSW and health system cooperation across the Chinese/Vietnamese border.

Application of low-concentration contrast agents and low-tube-voltage computed tomography to chest enhancement examinations: A multicenter prospective study.

To evaluate the influence of low-concentration contrast agents and low-tube-voltage computed tomography on chest enhancement examinations, we conducted a multicenter prospective study. A total of 216 inpatients enrolled from 12 different hospitals were randomly divided into four groups: A: voltage, 120 kVp; iohexol, 350 mgI/mL; B: voltage, 100 kVp, iohexol, 350 mgI/mL; C: voltage, 120 kVp, iodixanol, 270 mgI/mL; and D: voltage, 100 kVp, iodixanol, 270 mgI/mL. Subjective image quality was assessed by two radiologists and compared by weighted kappa test. The objective image scores, scanning radiation doses, and pathological coincidence rates were analyzed. There were no significant differences in gender, age, height, weight, and body mass index between the four groups (p > 0.05). The consistency of the radiologists' ratings were good, with kappa value ranging from 0.736 (95% confidence interval: 0.54-0.933) to 0.809 (95% confidence interval: 0.65-0.968), and there was no difference in subjective image score between the four groups. The computed tomography value of group D had no difference with group A. The volume computed tomography dose index, dose length product, and effective dose of group D (6.93 ± 3.03, 241.55 ± 104.75, and 3.38 ± 1.47, respectively) were all significantly lower than those of group A (10.30 ± 4.37, 359.70 ± 152.65, and 5.04 ± 2.14, respectively). There was no significant difference in the imaging diagnosis accuracy rate between the four groups (p > 0.05). The results indicated that low-concentration contrast agents (270 mgI/mL) and low-tube-voltage (100 kVp) computed tomography can not only decrease radiation dose but also guarantee the image quality and meet the needs of imaging diagnosis in chest enhancement examinations, which make it possible for its generalization and application.

Utility of dual-energy spectral CT and low-iodine contrast medium in DIEP angiography.

OBJECTIVE: To evaluate the utility of dual-energy spectral computed tomography (CT) and low-iodine intake in CT angiography (CTA) of deep inferior epigastric perforator (DIEP) flaps. METHODS: In this prospective study, 40 patients with a BMI <28.0 kg/m(2) underwent CTA examination for breast reconstruction and were randomly assigned into two groups (n=20 for each group) as follows: Group A was submitted to dual-energy spectral CT and iodixanol (270 mg I/mL) and Group B was submitted to conventional high iodine contrast agent iohexol (350 mg I/mL). The volume CT dose index (CTDIvol ) and dose length product were recorded and the effective dose (ED) was calculated. The best mono-spectrum images of Group A were selected according to the optimal contrast to noise ratio (CNR). Both mono-spectrum images of Group A and polychromatic images of Group B were used to reconstruct maximum intensity projection (MIP) and volume rendering (VR) images of the perforating artery, respectively. Two radiologists evaluated subjective image quality using a 4-point score. The diameter of the perforating artery, CT value and SD value for the common femoral artery were measured and the CNR was calculated. The total iodine intake and radiation doses of the two groups were calculated and compared. RESULTS: The best mono-spectrum energy with the optimal CNR of the perforating artery was 63 keV. The CT value of common femoral artery in Group A (380.96±42.75HU) was 7.40% higher than in Group B (354.71±42.01 HU) but with no statistical significance (P>.05). The CNR of the common femoral artery in Group A (23.84±6.73) was 6.88% lower than in Group B (25.60±6.20), with no significant difference (P>.05). The diameters of the perforator vessels were 2.44±0.15 and 2.49±0.14 mm, respectively, with no significant difference (P>.05). Subjective image qualities for the two groups were both good for diagnostics, and the scores for Group A and Group B were (3.88±0.28) and (3.93±0.18), respectively. The scores of the two radiologists were consistent (kappa=0.634). The effective radiation dose in Group A (9.09±0 mSv) was 10.62% lower than in Group B (10.17±1.91 mSv). The total iodine intake in Group A (27 000 mg) was 22.86% lower than in Group B (35 000 mg). CONCLUSIONS: The combination of dual-energy spectral CT and low-iodine intake in CTA of DIEP flap examination with the optimal CNR technology can meet the requirements of clinical diagnostics, with a 22.86% reduction in total iodine intake and an 11.01% reduction in radiation dose.

Controlling HIV epidemics among injection drug users: eight years of Cross-Border HIV prevention interventions in Vietnam and China.

INTRODUCTION: HIV in Vietnam and Southern China is driven by injection drug use. We have implemented HIV prevention interventions for IDUs since 2002-2003 in Lang Son and Ha Giang Provinces, Vietnam and Ning Ming County (Guangxi), China. METHODS: Interventions provide peer education and needle/syringe distribution. Evaluation employed serial cross-sectional surveys of IDUs 26 waves from 2002 to 2011, including interviews and HIV testing. Outcomes were HIV risk behaviors, HIV prevalence and incidence. HIV incidence estimation used two methods: 1) among new injectors from prevalence data; and 2) a capture enzyme immunoassay (BED testing) on all HIV+ samples. RESULTS: We found significant declines in drug-related risk behaviors and sharp reductions in HIV prevalence among IDUs (Lang Son from 46% to 23% [p<0.001], Ning Ming: from 17% to 11% [p = 0.003], and Ha Giang: from 51% to 18% [p<0.001]), reductions not experienced in other provinces without such interventions. There were significant declines in HIV incidence to low levels among new injectors through 36-48 months, then some rebound, particularly in Ning Ming, but BED-based estimates revealed significant reductions in incidence through 96 months. DISCUSSION: This is one of the longest studies of HIV prevention among IDUs in Asia. The rebound in incidence among new injectors may reflect sexual transmission. BED-based estimates may overstate incidence (because of false-recent results in patients with long-term infection or on ARV treatment) but adjustment for false-recent results and survey responses on duration of infection generally confirm BED-based incidence trends. Combined trends from the two estimation methods show sharp declines in incidence to low levels. The significant downward trends in all primary outcome measures indicate that the Cross-Border interventions played an important role in bringing HIV epidemics among IDUs under control. The Cross-Border project offers a model of HIV prevention for IDUs that should be considered for large-scale replication.