MZ1, a BRD4 inhibitor, exerted its anti-cancer effects by suppressing SDC1 in glioblastoma.

BACKGROUND: Glioblastoma (GBM) is a relatively prevalent primary tumor of the central nervous system in children, characterized by its high malignancy and mortality rates, along with the intricate challenges of achieving complete surgical resection. Recently, an increasing number of studies have focused on the crucial role of super-enhancers (SEs) in the occurrence and development of GBM. This study embarks on the task of evaluating the effectiveness of MZ1, an inhibitor of BRD4 meticulously designed to specifically target SEs, within the intricate framework of GBM. METHODS: The clinical data of GBM patients was sourced from the Chinese Glioma Genome Atlas (CGGA) and the Gene Expression Profiling Interactive Analysis 2 (GEPIA2), and the gene expression data of tumor cell lines was derived from the Cancer Cell Line Encyclopedia (CCLE). The impact of MZ1 on GBM was assessed through CCK-8, colony formation assays, EdU incorporation analysis, flow cytometry, and xenograft mouse models. The underlying mechanism was investigated through RNA-seq and ChIP-seq analyses. RESULTS: In this investigation, we made a noteworthy observation that MZ1 exhibited a substantial reduction in the proliferation of GBM cells by effectively degrading BRD4. Additionally, MZ1 displayed a notable capability in inducing significant cell cycle arrest and apoptosis in GBM cells. These findings were in line with our in vitro outcomes. Notably, MZ1 administration resulted in a remarkable decrease in tumor size within the xenograft model with diminished toxicity. Furthermore, on a mechanistic level, the administration of MZ1 resulted in a significant suppression of pivotal genes closely associated with cell cycle regulation and epithelial-mesenchymal transition (EMT). Interestingly, our analysis of RNA-seq and ChIP-seq data unveiled the discovery of a novel prospective oncogene, SDC1, which assumed a pivotal role in the tumorigenesis and progression of GBM. CONCLUSION: In summary, our findings revealed that MZ1 effectively disrupted the aberrant transcriptional regulation of oncogenes in GBM by degradation of BRD4. This positions MZ1 as a promising candidate in the realm of therapeutic options for GBM treatment.

Reduction of renal interstitial fibrosis by targeting Tie2 in vascular endothelial cells.

BACKGROUND: Tie2, a functional angiopoietin receptor, is expressed in vascular endothelial cells and plays an important role in angiogenesis and vascular stability. This study aimed to evaluate the effects of an agonistic Tie2 signal on renal interstitial fibrosis (RIF) and elucidate the underlying mechanisms. METHODS: We established an in vivo mouse model of folic acid-induced nephropathy (FAN) and an in vitro model of lipopolysaccharide-stimulated endothelial cell injury, then an agonistic Tie2 monoclonal antibody (Tie2 mAb) was used to intervent these processes. The degree of tubulointerstitial lesions and related molecular mechanisms were determined by histological assessment, immunohistochemistry, western blotting, and qPCR. RESULTS: Tie2 mAb attenuated RIF and reduced the level of fibroblast-specific protein 1 (FSP1). Further, it suppressed vascular cell adhesion molecule-1 (VCAM-1) and increased CD31 density in FAN. In the in vitro model, Tie2 mAb was found to decrease the expression of VCAM-1, Bax, and α-smooth muscle actin (α-SMA). CONCLUSIONS: The present findings indicate that the agonistic Tie2 mAb exerted vascular protective effects and ameliorated RIF via inhibition of vascular inflammation, apoptosis, and fibrosis. Therefore, Tie2 may be a potential target for the treatment of this disease. IMPACT: This is the first report to confirm that an agonistic Tie2 monoclonal antibody can reduce renal interstitial fibrosis in folic acid-induced nephropathy in mice. This mechanism possibly involves vascular protective effects brought about by inhibition of vascular inflammation, apoptosis and fibrosis. Our data show that Tie2 signal may be a novel, endothelium-specific target for the treatment of tubulointerstitial fibrosis.

First-line Treatment Patterns and Outcomes in Advanced Non-Small Cell Lung Cancer in Sweden: A Population-based Real-world Study with Focus on Immunotherapy.

BACKGROUND AND PURPOSE: The treatment landscape for patients with advanced non-small cell lung cancer (NSCLC) has evolved significantly since the introduction of immunotherapies. We here describe PD-L1 testing rates, treatment patterns, and real-world outcomes for PD-(L)1 inhibitors in Sweden. MATERIALS AND METHODS: Data were obtained from the Swedish National Lung Cancer Registry for patients with advanced NSCLC and Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-2 who initiated first-line -systemic treatment from 01 April 2017 to 30 June 2020. PD-L1 testing was available in the registry from 01 January 2018. Kaplan-Meier was used for overall survival (OS) by type treatment and histology. RESULTS: A total of 2,204 patients with pathologically confirmed unresectable stage IIIB/C or IV NSCLC initiated first-line treatment, 1,807 (82%) with nonsquamous (NSQ) and 397 (18%) with SQ. Eighty-six per cent (NSQ) or 85% (SQ) had been tested for PD-L1 expression, a proportion that increased over time. The use of platinum-based therapy as first-line treatment decreased substantially over time while there was an upward trend for PD-(L)1-based therapy. Among patients with PS 0-1 initiating a first-line PD-(L)1 inhibitor monotherapy, the median OS was 18.6 and 13.3 months for NSQ and SQ NSCLC patients, respectively, while for the PD-(L)1 inhibitor and chemotherapy combination regimen, the median OS was 24.0 months for NSQ and not evaluable for SQ patients. INTERPRETATION: The majority of advanced NSCLCs in Sweden were tested for PD-L1 expression. Real-world OS in patients with PS 0-1 receiving first-line PD-(L)1 inhibitor-based regimens was similar to what has been reported in pivotal clinical trials on PD-(L)1 inhibitors.

Necrotizing enterocolitis: current understanding of the prevention and management.

Necrotizing enterocolitis (NEC) is one of the diseases in neonates, with a high morbidity and mortality rate, especially in preterm infants. This review aimed to briefly introduce the latest epidemiology, susceptibility factors, and clinical diagnosis and presentation of NEC. We also organized new prevention strategies by risk factors according to different pathogeneses and then discussed new treatment methods based on Bell's staging and complications, and the classification of mild to high severity based on clinical and imaging manifestations. Such a generalization will help clinicians and researchers to gain a deeper understanding of the disease and to conduct more targeted classification, grading prevention, and exploration. We focused on prevention and treatment of the early and suspected stages of NEC, including the discovery of novel biomarkers and drugs to control disease progression. At the same time, we discussed its clinical application, future development, and shortcomings.

Refraction correction for deep-water three-dimensional visual measurement based on multi-objective optimization.

Refraction-induced errors affect the accuracy of three-dimensional visual measurements in deepwater environments. In this study, a binocular camera refractive imaging model was established, and a calibration method for the refraction parameters was proposed for high-accuracy shape and deformation measurements in deep-water environments. First, an initial estimate of the refractive axis was obtained using a three-dimensional calibration target. Then, the errors in the distance between the spatial point pairs and the reprojection errors are taken as the dual optimization objectives, and the Non-dominated Sorting Genetic Algorithm II is applied to optimize the refraction parameters. To efficiently calculate the reprojection error, an improved numerical computation method is proposed to accelerate the calculation of the analytical forward projection. Underwater experiments were conducted to verify the method's effectiveness. The results showed that the average error of the absolute position of the reconstructed points was less than 1.1 mm and the average error of the displacement was less than 0.04 mm. This study provides a sound solution for accurate three-dimensional visual measurement in deep-water environments.

Fast and robust calibration method of liquid-crystal spatial light modulator based on polarization multiplexing.

We propose a fast and robust method for calibrating Spatial Light Modulators (SLMs) based on polarization phase-shifting interferometry. Our method effectively calibrates the SLM by addressing both the static aberration and nonlinear phase response, utilizing specially designed gray images loaded sequentially onto the SLM. Notably, we introduce a novel kinoform that effectively eliminates the influence of tilt phase shift between two shots of the polarization camera. This results in a highly accurate phase aberration map and phase modulation curve with exceptional stability, making it an ideal method to calibrate the SLM with exceptional efficiency and precision in real applications.

Mechanical Properties of Low-Molecular-Weight Peptide Hydrogels Improved by Thiol-Ene Click Chemistry.

Low-molecular-weight peptide hydrogels can be formed by self-assembly through weak interactions, but the application of the hydrogel is influenced by its weak mechanical properties. Therefore, it is important to construct low-molecular-weight peptide hydrogels with excellent mechanical properties. In this work, we designed the pentapeptide molecule Fmoc-FFCKK-OH (abbreviated as FFCKK) with a sulfhydryl group, and another low-molecular-weight cross-linker N,N'-methylenebis(acrylamide) (MBA) was introduced to construct a hydrogel with excellent mechanical properties. The secondary structure change process of FFCKK and the assembly mechanism of hydrogel were analyzed using theoretical calculations and experimental characterizations. The occurrence of thiol-ene click chemistry provides covalent interaction in the hydrogel, and the synergistic effect ofcovalent interaction and hydrogen bonding improves the mechanical properties of the hydrogel by nearly 10-fold. The hydrogel was observed to be able to withstand a stress of 368 Pa and to break in a layer-by-layer manner by compression testing. The micromechanics of the hydrogels were characterized, and the excellent mechanical properties of the hydrogels were confirmed. The synergistic approach provides a new idea for the preparation of low-molecular-weight peptide hydrogels and facilitates the expansion of their potential applications in biomedical fields.

Clinical and economic impact of recurrence in early-stage non-small-cell lung cancer following complete resection.

Aim: Real-world data on outcomes for early-stage non-small-cell lung cancer (NSCLC) are needed to better understand the benefits of new therapies. Methods: In this retrospective study using the ConcertAI Patient360™ database, overall survival and healthcare resource utilization were compared among patients with recurrent and non-recurrent completely resected stage IB-IIIA NSCLC. Results: Recurrence was associated with a shorter median overall survival compared with non-recurrence (31.5 months vs 75.6 months, respectively), lower survival probability 5-years post-resection, and higher healthcare resource utilization. Patients with late recurrence had a longer restricted mean survival time versus patients with early recurrence. Conclusion: Results from this real-world study highlight the potential value of preventing or delaying recurrence in patients with early-stage NSCLC.

This study looked at how people with early-stage non-small-cell lung cancer did after surgery to completely remove the disease. It compared two groups of patients: those whose disease came back after surgery and those whose disease did not come back after surgery. The group of people whose disease came back after surgery did not live as long as those whose disease did not come back after surgery (31.5 months vs 75.6 months). Patients whose disease came back had a lower chance of living at least 5 years after surgery and they had more hospital visits and doctor's office visits. In addition, those whose disease came back within 1 year did not live as long as those whose disease came back between 1 and 5 years after surgery. Preventing or delaying the return of disease after surgery is important for improving the lives of patients with early-stage non-small-cell lung cancer.

The impact of preloaded intraocular lens implantation system (TECNIS iTec®) in routine cataract surgery in China: a time-motion analysis.

OBJECTIVE: To evaluate the impact on surgical efficiency and labor time cost of preloaded intraocular lens (IOL) implantation system compared with manual IOL implantation system in age-related cataract surgery in China. METHODS: This study was an observational, multicenter, prospective time-motion analysis. IOL preparation time, operation time, cleaning time, number and cost of cataract surgeries in eight participating hospitals were collected. The linear mixed model was used to explore factors associated with the difference in operation time between the preloaded IOL implantation system and the manual IOL implantation system. A time-motion model was constructed to convert the operation time cost saved by using preloaded IOL into economic benefits from hospital and social perspective, respectively. RESULTS: There were 2,591 cases included in the study (preloaded IOL: 1,591 cases; manual IOL: 1,000 cases). The preloaded IOL implantation system was significant time-saving in both preparation time and operation time compared to the manual IOL implantation system (25.48s vs. 47.04s, P < 0.001 and 353.84s vs. 367.46s, P = 0.004, respectively). An average total of 35.18s can be saved by using preloaded IOL per procedure. The results of linear mixed model showed that the type of IOL was the main factor leading to the difference in preparation time between preloaded IOL and manual IOL implantation system. By switching from manual IOL to preloaded IOL, the model projected additional 392 surgeries can be performed each year and an increase in revenue of $565,282 per hospital, a 9% increase from hospital perspective. And the annual productivity loss saved by using preloaded IOL was $3,006 in eight hospitals from perspective of society. CONCLUSION: Compared with manual IOL implantation system, the preloaded IOL implantation system reduces lens preparation time and operation time, which increases potential surgical volume and revenue, and reduces the loss of work productivity. This study provides real-world evidence to support the advantages of the preloaded IOL implantation system in improving efficiency of ophthalmic surgery in China.

VANet: a medical image fusion model based on attention mechanism to assist disease diagnosis.

BACKGROUND: Today's biomedical imaging technology has been able to present the morphological structure or functional metabolic information of organisms at different scale levels, such as organ, tissue, cell, molecule and gene. However, different imaging modes have different application scope, advantages and disadvantages. In order to improve the role of medical image in disease diagnosis, the fusion of biomedical image information at different imaging modes and scales has become an important research direction in medical image. Traditional medical image fusion methods are all designed to measure the activity level and fusion rules. They are lack of mining the context features of different modes of image, which leads to the obstruction of improving the quality of fused images. METHOD: In this paper, an attention-multiscale network medical image fusion model based on contextual features is proposed. The model selects five backbone modules in the VGG-16 network to build encoders to obtain the contextual features of medical images. It builds the attention mechanism branch to complete the fusion of global contextual features and designs the residual multiscale detail processing branch to complete the fusion of local contextual features. Finally, it completes the cascade reconstruction of features by the decoder to obtain the fused image. RESULTS: Ten sets of images related to five diseases are selected from the AANLIB database to validate the VANet model. Structural images are derived from MR images with high resolution and functional images are derived from SPECT and PET images that are good at describing organ blood flow levels and tissue metabolism. Fusion experiments are performed on twelve fusion algorithms including the VANet model. The model selects eight metrics from different aspects to build a fusion quality evaluation system to complete the performance evaluation of the fused images. Friedman's test and the post-hoc Nemenyi test are introduced to conduct professional statistical tests to demonstrate the superiority of VANet model. CONCLUSIONS: The VANet model completely captures and fuses the texture details and color information of the source images. From the fusion results, the metabolism and structural information of the model are well expressed and there is no interference of color information on the structure and texture; in terms of the objective evaluation system, the metric value of the VANet model is generally higher than that of other methods.; in terms of efficiency, the time consumption of the model is acceptable; in terms of scalability, the model is not affected by the input order of source images and can be extended to tri-modal fusion.

Long-term characterization of roadside air pollutants in urban Beijing and associated public health implications.

Road traffic constitutes a major source of air pollutants in urban Beijing, which are responsible for substantial premature mortality. A series of policies and regulations has led to appreciable traffic emission reductions in recent decades. To shed light on long-term (2014-2020) roadside air pollution and assess the efficacy of traffic control measures and their effects on public health, this study quantitatively evaluated changes in the concentrations of six key air pollutants (PM2.5, PM10, NO2, SO2, CO and O3) measured at 5 roadside and 12 urban background monitoring stations in Beijing. We found that the annual mean concentrations of these air pollutants were remarkably reduced by 47%-71% from 2014 to 2020, while the concurrent ozone concentration increased by 17.4%. In addition, we observed reductions in the roadside increments in PM2.5, NO2, SO2 and CO of 54.8%, 29.8%, 20.6%, and 59.1%, respectively, indicating the high effectiveness of new vehicle standard (China V and VI) implementation in Beijing. The premature deaths due to traffic emissions were estimated to be 8379 and 1908 cases in 2014 and 2020, respectively. The impact of NO2 from road traffic relative to PM2.5 on premature mortality was comparable to that of traffic-related PM2.5 emissions. The public health effect of SO2 originating from traffic was markedly lower than that of PM2.5. The results indicated that a reduction in traffic-related NO2 could likely yield the greatest benefits for public health.

Effect of spectral CT on tumor microvascular angiogenesis in renal cell carcinoma.

BACKGROUND: To examine the value of energetic-spectrum computed tomography (spectral CT) quantitative parameters in renal cell carcinoma (RCC) microvascular angiogenesis. METHODS: The authors evaluated 32 patients with pathologically confirmed RCC who underwent triple-phase contrast-enhanced CT with spectral CT imaging mode from January 2017 to December 2019. Quantitative parameters include parameters derived from iodine concentration (IC) and water concentration (WC) of 120 keV monochromatic images. All specimens were evaluated including the microvascular density (MVD), microvascular area (MVA) and so on. The correlation between IC and WC (including average values and random values) with microvascular parameters were analyzed with Pearson or Spearman rank correlation coefficients. RESULTS: The MVD of all tumors was 26.00 (15.00-43.75) vessels per field at × 400 magnification. The MVD of RCC correlated positively with the mean IC, mean WC, mean NWC, mean NIC, random IC, random NIC in renal cortical phase, WCD1, WCD2, NWCD2 and ICD1 (Spearman rank correlation coefficients, r range, 0.362-0.533; all p < 0.05). The MVA of all tumors was (16.16 ± 8.98) % per field at × 400 magnification. The MVA of RCC correlated positively with the mean IC, mean WC, mean NWC, mean NIC, random IC, random NIC in renal cortical, mean WC and mean NWC in renal parenchymal phase, WCD1, WCD2, WCD3, NWCD2, and NWCD3 (Pearson or Spearman rank correlation coefficients, r range, 0.357-0.576; all p < 0.05). Microvascular grading correlated positively with the mean NWC, mean NIC and random NIC in renal cortical phase, mean NWC in renal parenchymal phase, NWCD2, WCD3, NWCD3, NICD2 and NICD3 (Spearman rank correlation coefficients, r range, 0.367-0.520; all p < 0.05). As for tumor diameter (55.19 ± 19.15), µm, only NWCD3 was associated with it (Spearman rank correlation coefficients, r = 0.388; p < 0.05). CONCLUSIONS: ICD and WCD of spectral CT have a potential for evaluating RCC microvascular angiogenesis. MVD, MVA and microvascular grade showed moderate positive correlation with ICD and WCD. ICD displayed more relevant than that of WCD. The parameters of renal cortical phase were the best in three phases. NICD and NWCD manifested stronger correlation with microvascular parameters than that of ICD and WCD.

Acyl-Coenzyme A: Cholesterol Acyltransferase-1 is Related to Hyperlipidemia in Children with Nephrotic Syndrome.

BACKGROUND: Hyperlipidemia is one of the characteristics of nephrotic syndrome, and cellular lipid accumulation in the kidney can accelerate kidney disease. ACAT1 plays important roles in cellular cholesterol homeostasis. The purpose of this study was to investigate the effect of ACAT1 on lipid metabolism in nephrotic syndrome, and its role in clinical diagnosis and efficacy evaluation. METHODS: In this case control study, 30 patients with nephrotic syndrome and 30 healthy controls were enrolled. ACAT1 mRNA was detected by qPCR, and methylation of ACAT1 promoter was assayed by sodium bisulfite sequencing. RESULTS: The expression of ACAT1 mRNA in NS group, remission group, and controls was 0.14 ± 0.06, 0.08 ± 0.03, and 0.08 ± 0.04, respectively. The methylation of ACAT1 promoter in NS group, remission group, and controls was 2.27 ± 2.71, 4.00 ± 3.15, and 4.93 ± 3.59, respectively. The AUC value of ACAT1 mRNA was 0.856 (95% CI: 0.760 - 0.951), while the AUC value of ACAT1 methylation was 0.653 (95% CI: 0.514 - 0.792). The results of Pearson's correlation suggested that the high expression of ACAT1 mRNA and the hypomethylation of ACAT1 were related to hyperlipidemia and hypoalbuminemia in nephrotic syndrome. CONCLUSIONS: This study shows that ACAT1 is related to hyperlipidemia and hypoproteinemia in nephrotic syndrome and can be a useful biomarker for the efficacy evaluation of nephrotic syndrome.

Hahn-PCNN-CNN: an end-to-end multi-modal brain medical image fusion framework useful for clinical diagnosis.

BACKGROUND: In medical diagnosis of brain, the role of multi-modal medical image fusion is becoming more prominent. Among them, there is no lack of filtering layered fusion and newly emerging deep learning algorithms. The former has a fast fusion speed but the fusion image texture is blurred; the latter has a better fusion effect but requires higher machine computing capabilities. Therefore, how to find a balanced algorithm in terms of image quality, speed and computing power is still the focus of all scholars. METHODS: We built an end-to-end Hahn-PCNN-CNN. The network is composed of feature extraction module, feature fusion module and image reconstruction module. We selected 8000 multi-modal brain medical images downloaded from the Harvard Medical School website to train the feature extraction layer and image reconstruction layer to enhance the network's ability to reconstruct brain medical images. In the feature fusion module, we use the moments of the feature map combined with the pulse-coupled neural network to reduce the information loss caused by convolution in the previous fusion module and save time. RESULTS: We choose eight sets of registered multi-modal brain medical images in four diease to verify our model. The anatomical structure images are from MRI and the functional metabolism images are SPECT and 18F-FDG. At the same time, we also selected eight representative fusion models as comparative experiments. In terms of objective quality evaluation, we select six evaluation metrics in five categories to evaluate our model. CONCLUSIONS: The fusion image obtained by our model can retain the effective information in source images to the greatest extent. In terms of image fusion evaluation metrics, our model is superior to other comparison algorithms. In terms of time computational efficiency, our model also performs well. In terms of robustness, our model is very stable and can be generalized to multi-modal image fusion of other organs.

Th cytokine profile in childhood-onset systemic lupus erythematosus.

BACKGROUND: Childhood-onset systemic lupus erythematosus (cSLE) is a kind of chronic inflammatory disease characterized by a highly abnormal immune system. This study aimed to detect the serum levels of Th (T helper) cytokines (IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-13, IL-17A, IL-17F, IL-21, IL-22, IFN-γ and TNF-α) in cSLE and healthy controls, and then to elucidate their association with clinical manifestations, disease activity and laboratory parameters. In order to provide clues for early diagnosis and timely intervention treatment of cSLE patients. METHODS: A total of 33 children with cSLE and 30 healthy children were enrolled in this study. Children in the cSLE group were classified into the inactive or active cSLE group according to their SLE disease activity index 2000 (SLEDAI-2 K) score. Th cytokine profiles in the peripheral blood were detected and analysed. RESULTS: Levels of IL-2, IL-10 and IL-21 in the cSLE group were significantly higher than those in the healthy control group (P < 0.05, P < 0.01 and P < 0.01, respectively). Expression of IL-2, IL-10 and IL-21 in the active cSLE group was significantly higher than that in the healthy control group (P < 0.05, P < 0.01 and P < 0.05, respectively), but that of IL-22 expression was markedly lower in the active cSLE group than in the healthy control group (P < 0.001). IL-21 in the inactive SLE group was significantly higher than that in the healthy control group (P < 0.05), and levels of IL-2 and IL-10 in the active cSLE group were significantly higher than those in the inactive cSLE group (P < 0.01 and P < 0.05). In-depth analysis showed that after excluding age, gender and drug interference, the levels of IL-2 (P < 0.05), IL-6 (P < 0.05) and IL-10 (P < 0.05) were still positively correlated with SLEDAI-2 K scores. However, the levels of IL-6 (P < 0.05) and IFN- γ (P < 0.05) were still negatively correlated with CD4+/CD8+, and the concentration of IL-6 (P < 0.05) was still positively correlated with the occurrence of nephritis. CONCLUSION: This study provides a theoretical basis for the discovery of effective methods to regulate imbalance in T lymphocyte subsets in cSLE, which may lead to new approaches for the diagnosis of cSLE.

Femoral nerve compression caused by a hibernoma in the right thigh: a case report and literature review.

BACKGROUND: A hibernoma, also known as a brown fat tumor, is a rare benign soft tissue tumor, which originates from brown adipose tissue remaining in the fetus after the gestational period. It is often detected in adult men, presenting as a painless slow-growing mass. Hibernomas of the thigh have been reported; however, motor and sensory disorders caused by the tumors compressing the femoral nerve have not been reported. We report a case of a histopathologically proven hibernoma that induced femoral mononeuropathy. CASE PRESENTATION: A 26-year-old man was admitted to the hospital due to a mass, approximately 11.0 × 9.0 × 4.0 cm in size, that had developed 5 years ago in the anterolateral aspect of the proximal thigh. Furthermore, he had a history of hypoesthesia 1 month prior to his admission. He had signs and symptoms of both a motor and sensory disorder, involving the anterior aspect of the right thigh and the medial aspect of the calf, along the distribution of the femoral nerve. During surgery, the femoral nerve was found to be compressed by the giant tumor. The resultant symptoms probably caused the patient to seek medical care. Marginal resection of the mass was performed by careful dissection, and the branches of the femoral nerve were spared. Histopathology examination showed findings suggestive of a hibernoma. At the 4-month follow-up, no femoral nerve compression was evident, and local tumor recurrence or metastasis was not found. CONCLUSIONS: Asymptomatic hibernomas do not require treatment; however, in cases of hibernomas with apparent symptoms, complete marginal surgical excision at an early stage is a treatment option because it is associated with a low risk of postoperative tumor recurrence.

Design, Synthesis, and Antitumor Activity of Olmutinib Derivatives Containing Acrylamide Moiety.

Two series of olmutinib derivatives containing an acrylamide moiety were designed and synthesized, and their IC50 values against cancer cell lines (A549, H1975, NCI-H460, LO2, and MCF-7) were evaluated. Most of the compounds exhibited moderate cytotoxic activity against the five cancer cell lines. The most promising compound, H10, showed not only excellent activity against EGFR kinase but also positive biological activity against PI3K kinase. The structure-activity relationship (SAR) suggested that the introduction of dimethylamine scaffolds with smaller spatial structures was more favorable for antitumor activity. Additionally, the substitution of different acrylamide side chains had different effects on the activity of compounds. Generally, compounds H7 and H10 were confirmed as promising antitumor agents.

A privacy protection method for health care big data management based on risk access control.

With the rapid development of modern information technology, the health care industry is entering a critical stage of intelligence. Faced with the growing health care big data, information security issues are becoming more and more prominent in the management of smart health care, especially the problem of patient privacy leakage is the most serious. Therefore, strengthening the information management of intelligent health care in the era of big data is an important part of the long-term sustainable development of hospitals. This paper first identified the key indicators affecting the privacy disclosure of big data in health management, and then established the risk access control model based on the fuzzy theory, which was used for the management of big data in intelligent medical treatment, and solves the problem of inaccurate experimental results due to the lack of real data when dealing with actual problems. Finally, the model is compared with the results calculated by the fuzzy tool set in Matlab. The results verify that the model is effective in assessing the current safety risks and predicting the range of different risk factors, and the prediction accuracy can reach more than 90%.

Trends in the Price per Median and Mean Life-Year Gained Among Newly Approved Cancer Therapies 1995 to 2017.

BACKGROUND: The prices of newly approved cancer drugs have risen over the past decades. A key policy question is whether the clinical gains offered by these drugs in treating specific cancer indications justify the price increases. OBJECTIVES: To evaluate the price per median and mean life year gained among newly approved cancer therapies from 1995 to 2017. METHODS: We collected data on the price (in 2017 USD) per life-year gained among cancer drug-indication pairs approved by the US Food and Drug Administration (FDA) between 1995 and 2017. We modeled trends using fractional polynomial and linear spline regression models that controlled for route of administration and cancer type fixed effects. RESULTS: We found that between 1995 and 2012, price increases outstripped median survival gains, a finding consistent with previous literature. Nevertheless, price per mean life-year gained increased at a considerably slower rate, suggesting that new drugs have been more effective in achieving longer-term survival. Between 2013 and 2017, price increases reflected equally large gains in median and mean survival, resulting in a flat profile for benefit-adjusted launch prices in recent years. CONCLUSIONS: Although drug costs have been rising more rapidly than median survival gains, they have been rising at about the same rate as mean survival gains. This suggests that when accounting for longer-term survival gains, the benefits of new drugs are roughly keeping pace with their costs, despite rapid cost growth.

G protein pathway suppressor 2 enhanced the renal large-conductance Ca2+-activated potassium channel expression via inhibiting ERK1/2 signaling pathway.

G protein pathway suppressor 2 (GPS2) is a multifunctional protein and transcriptional regulation factor that is involved in the G protein MAPK signaling pathway. It has been shown that the MAPK signaling pathway plays an important role in the regulation of renal large-conductance Ca2+-activated potassium (BK) channels. In this study, we investigated the effects of GPS2 on BK channel activity and protein expression. In human embryonic kidney (HEK) BK stably expressing cells transfected with either GPS2 or its vector control, a single-cell recording showed that GPS2 significantly increased BK channel activity ( NPo), increasing BK open probability ( Po), and channel number ( N) compared with the control. In Cos-7 cells and HEK 293 T cells, GPS2 overexpression significantly enhanced the total protein expression of BK in a dose-dependent manner. Knockdown of GPS2 expression significantly decreased BK protein expression, while increasing ERK1/2 phosphorylation. Knockdown of ERK1/2 expression reversed the GPS2 siRNA-mediated inhibition of BK protein expression in Cos-7 cells. Pretreatments of Cos-7 cells with either the lysosomal inhibitor bafilomycin A1 or the proteasomal inhibitor MG132 partially reversed the inhibitory effects of GPS2 siRNA on BK protein expression. In addition, feeding a high-potassium diet significantly increased both GPS2 and BK protein abundance in mice. These data suggest that GPS2 enhances BK channel activity and its protein expression by reducing ERK1/2 signaling-mediated degradation of the channel.