New Evidence of the Impact of the National Drug Price Negotiation Policy on the Availability, Utilization, and Cost of Anticancer Medicines in China: An Interrupted Time Series Study.

Purpose: The increasing global burden of cancer has become a significant challenge for public health. The Chinese government introduced the National Drug Price Negotiation (NDPN) policy with the goal of lowering the prices of innovative drugs and enhancing their accessibility. This study aims to evaluate the impact of the 2021 NDPN policy on the availability, utilization, and cost of anticancer medicines in China. Methods: Data was gathered from 1519 hospitals between April 2021 and December 2022, with a focus on eight anticancer drugs affected by the 2021 NDPN policy. The availability, Defined Daily Doses (DDDs), and cost per Defined Daily Dose (DDDc) before and after the intervention were evaluated through interrupted time series analysis. Results: The NDPN policy resulted in a substantial 5.10% increase in the availability of anticancer drugs (p < 0.001). Utilization also experienced a significant surge, with an immediate increase of 11,254.36 DDDs (p < 0.001) and a monthly increase of 1208.28 DDDs (p < 0.001) following policy implementation. The DDDc decreased by US$ 111.00 (p < 0.001) immediately after the policy. Disparities in regional drug utilization were evident, with higher usage in the eastern region. Conclusion: The 2021 NDPN policy has notably enhanced the availability and utilization of anticancer medications in China while reducing their cost, in line with the policy's objectives. However, continuous monitoring is essential to ensure sustained access and to tackle regional disparities in drug utilization.

High-Entropy Fluorite Oxide-Modified CaO-Based Sorbent Pellets for Enhanced High-Temperature CO2 Capture.

The calcium looping technology employing CaO-based sorbents is pivotal for capturing CO2 from flue gas. However, the intrinsic low thermodynamic stability of CaO-based sorbents and the requisite molding step induce severe sintering issues, diminishing their cyclic stability. Herein, a high-entropy fluorite oxide (HEFO) inert stabilizer premised on entropy stabilization and synergistic effect strategies is introduced. HEFO-modified, CaO-based sorbent pellets are synthesized via a rapid cigarette butt-assisted combustion process (15 min) combined with the graphite molding method. Post-multiple cycles, their CO2 capture capacity reaches 0.373 g g-1, which is 2.6-fold superior to that of pure CaO, demonstrating markedly enhanced anti-sintering properties. First, the subtle morphological and crystallographic modifications suggest that the inherent entropy stability of HEFO imparts robust thermal resistance. Concurrently, the disordered structure of single-phase HEFO exhibits a high affinity for CaO, resulting in an interface binding energy of -1.83 eV, in sharp contrast to the -0.112 eV of pure CaO, thereby restricting CaO migration. Additionally, the multi-element synergistic effect of HEFO reduces the energy barrier by 0.15 eV, leading to a 40% and 140% increase in carbonation and calcination rates, respectively. This work presents highly efficient and rapidly synthesized CaO-based sorbent pellets, showcasing promising potential for industrial application.

Inhibition of inflammation and apoptosis through the cyclic GMP-AMP synthase-stimulator of interferon genes pathway by stress granules after ALKBH5 demethylase activation during diabetic myocardial ischaemia-reperfusion injury.

AIM: Post-transcriptional modifications and their specific mechanisms are the focus of research on the regulation of myocardial damage. Stress granules (SGs) can inhibit the inflammatory response by inhibiting the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. This study investigated whether alkylation repair homologue protein 5 (ALKBH5) could affect myocardial inflammation and apoptosis during diabetic myocardial ischaemia-reperfusion injury (IRI) through the cGAS-STING pathway via SGs. METHODS: A diabetes ischaemia-reperfusion rat model and a high glucose hypoxia/reoxygenation cell model were established. Adeno-associated virus (AAV) and lentivirus (LV) were used to overexpress ALKBH5, while the SG agonist arsenite (Ars) and the SG inhibitor anisomycin were used as interventions. Then, the levels of apoptosis and related indicators in the cell and rat models were measured. RESULTS: In the in vivo experiment, compared with the normal sham group, the degree of myocardial tissue damage, creatine kinase-MB and cardiac troponin I in serum, and myocardial apoptosis, the infarcted area of myocardium, and the level of B-cell lymphoma 2 associated X protein, cGAS-STING pathway and inflammatory factors in the diabetes ischaemia-reperfusion group were significantly increased. However, the expression of SGs and the levels of ALKBH5, rat sarcoma-GTPase-activating protein-binding protein 1, T-cell intracellular antigen-1 and Bcl2 were significantly decreased. After AAV-ALKBH5 intervention, the degree of myocardial tissue damage, degree of myocardial apoptosis, and extent of myocardial infarction in myocardial tissue were significantly decreased. In the in vitro experiment, compared with those in the normal control group, the levels of lactate dehydrogenase, inflammation and apoptosis were significantly greater, and cell viability and the levels of ALKBH5 and SGs were decreased in the high glucose and hypoxia/reoxygenation groups. In the high glucose hypoxia/reoxygenation cell model, the degree of cell damage, inflammation, and apoptosis was greater than those in the high glucose and hypoxia/reoxygenation models, and the levels of ALKBH5 and SGs were further decreased. LV-ALKBH5 and Ars alleviated the degree of cell damage and inhibited inflammation and cell apoptosis. The inhibition of SGs could partly reverse the protective effect of LV-ALKBH5. The cGAS agonist G140 antagonized the inhibitory effects of the SG agonist Ars on cardiomyocyte apoptosis, inflammation and the cGAS-STING pathway. CONCLUSION: Both ALKBH5 and SGs inhibited myocardial inflammation and apoptosis during diabetic myocardial ischaemia-reperfusion. Mechanistically, ALKBH5 might inhibit the apoptosis of cardiomyocytes by promoting the expression of SGs through the cGAS-STING pathway.

SDS-Net: A lightweight 3D convolutional neural network with multi-branch attention for multimodal brain tumor accurate segmentation.

The accurate and fast segmentation method of tumor regions in brain Magnetic Resonance Imaging (MRI) is significant for clinical diagnosis, treatment and monitoring, given the aggressive and high mortality rate of brain tumors. However, due to the limitation of computational complexity, convolutional neural networks (CNNs) face challenges in being efficiently deployed on resource-limited devices, which restricts their popularity in practical medical applications. To address this issue, we propose a lightweight and efficient 3D convolutional neural network SDS-Net for multimodal brain tumor MRI image segmentation. SDS-Net combines depthwise separable convolution and traditional convolution to construct the 3D lightweight backbone blocks, lightweight feature extraction (LFE) and lightweight feature fusion (LFF) modules, which effectively utilizes the rich local features in multimodal images and enhances the segmentation performance of sub-tumor regions. In addition, 3D shuffle attention (SA) and 3D self-ensemble (SE) modules are incorporated into the encoder and decoder of the network. The SA helps to capture high-quality spatial and channel features from the modalities, and the SE acquires more refined edge features by gathering information from each layer. The proposed SDS-Net was validated on the BRATS datasets. The Dice coefficients were achieved 92.7, 80.0 and 88.9% for whole tumor (WT), enhancing tumor (ET) and tumor core (TC), respectively, on the BRTAS 2020 dataset. On the BRTAS 2021 dataset, the Dice coefficients were 91.8, 82.5 and 86.8% for WT, ET and TC, respectively. Compared with other state-of-the-art methods, SDS-Net achieved superior segmentation performance with fewer parameters and less computational cost, under the condition of 2.52 M counts and 68.18 G FLOPs.

Monte Carlo modeling of hepatic steatosis based on stereology and spatial distribution of fat droplets.

BACKGROUND AND OBJECTIVE: To model hepatic steatosis in adult humans with non-alcoholic fatty liver disease based on stereology and spatial distribution of fat droplets from liver biopsy specimens. METHODS: Histological analysis was performed on 30 adult human liver biopsy specimens with varying degrees of steatosis. Morphological features of fat droplets were characterized by gamma distribution function (GDF) in both two-dimensional (2D) and three-dimensional (3D) spaces from three aspects: 1) size distribution indicating non-uniformity of fat droplets in radius; 2) nearest neighbor distance distribution indicating heterogeneous accumulation (i.e., clustering) of fat droplets; 3) regional anisotropy indicating inter-regional variability in fat fraction (FF). To generalize the morphological description of hepatic steatosis to different FFs, correlation analysis was performed among the estimated GDF parameters and FFs for all specimens. Finally, Monte Carlo modeling of hepatic steatosis was developed to simulate fat droplet distribution in tissue. RESULTS: Morphological features, including size and nearest neighbor distance in 2D and 3D spaces as well as regional anisotropy, statistically captured the distribution of fat droplets by the GDF fit (R2 > 0.54). The estimated GDF parameters (i.e., scale and shape parameters) and FFs were well correlated, with R2 > 0.55. In addition, simulated 3D liver morphological models demonstrated similar sections to real histological samples both visually and quantitatively. CONCLUSIONS: The morphology of hepatic steatosis is well characterized by stereology and spatial distribution of fat droplets. Simulated models demonstrate similar appearances to real histological samples. Furthermore, the model may help understand MRI signal behavior in the presence of liver steatosis.

Cascade of Denoising and Mapping Neural Networks for MRI R2* Relaxometry of Iron-Loaded Liver.

MRI of effective transverse relaxation rate (R2*) measurement is a reliable method for liver iron concentration quantification. However, R2* mapping can be degraded by noise, especially in the case of iron overload. This study aimed to develop a deep learning method for MRI R2* relaxometry of an iron-loaded liver using a two-stage cascaded neural network. The proposed method, named CadamNet, combines two convolutional neural networks separately designed for image denoising and parameter mapping into a cascade framework, and the physics-based R2* decay model was incorporated in training the mapping network to enforce data consistency further. CadamNet was trained using simulated liver data with Rician noise, which was constructed from clinical liver data. The performance of CadamNet was quantitatively evaluated on simulated data with varying noise levels as well as clinical liver data and compared with the single-stage parameter mapping network (MappingNet) and two conventional model-based R2* mapping methods. CadamNet consistently achieved high-quality R2* maps and outperformed MappingNet at varying noise levels. Compared with conventional R2* mapping methods, CadamNet yielded R2* maps with lower errors, higher quality, and substantially increased efficiency. In conclusion, the proposed CadamNet enables accurate and efficient iron-loaded liver R2* mapping, especially in the presence of severe noise.

Evaluation of Adenosine A2A receptor gene polymorphisms as risk factors of methamphetamine use disorder susceptibility and predictors of craving degree.

The adenosine A2A receptor (ADORA2A) is highly expressed in the central nervous system and plays vital roles in drug addiction. In this study, we aimed to explore the susceptibility of ADORA2A to methamphetamine use disorder (MUD) and the craving degree based on a two-stage association analysis. A total of 3,542 (1,216 patients with MUD and 2,326 controls) and 1,740 participants (580 patients with MUD and 1,160 controls) were recruited in discovery and replication stage, respectively. Significant SNPs identified in the discovery stage were genotyped in the replication samples. Serum levels of ADORA2A were measured using enzyme-linked immunosorbent assay kits. The genetic association signal of each SNP was examined using Plink. A linear model was fitted to investigate the relationship between craving scores and genotypes of significant SNPs. SNP rs5751876 was significantly associated with MUD in the discovery samples and this association signal was then further replicated in the replication samples. Significant associations were also identified between serum levels of ADORA2A and the genotypes of rs5751876 (P = 0.0002). The craving scores in patients with MUD were strongly correlated with rs5751876 genotypes. Our results suggest that polymorphisms of the ADORA2A gene could affect the susceptibility to MUD and its craving degree.

Prior Distribution Estimation of Monitored Information in the Intensive Care Unit with the Hidden Markov Model and Decision Tree Methods.

In the intensive care unit, the monitored variables collected from sensors may have different behaviors among patients with different clinical basic information. Giving prior information of the monitored variables based on their specific basic information as soon as the patient is admitted will support the clinicians with better decisions during the surgery. Instead of black box models, the explainable hidden Markov model is proposed, which can estimate the possible distribution parameters of the monitored variables under different clinical basic information. A Student's t-test or correlation test is conducted further to test whether the parameters have a significant relationship with the basic variables. The specific relationship is explored by using a conditional inference tree, which is an explainable model giving deciding rules. Instead of point estimation, interval forecast is chosen as the performance metrics including coverage rate and relative interval width, which provide more reliable results. By applying the methods to an intensive care unit data set with more than 20 thousand patients, the model has good performance with an area under the ROC Curve value of 0.75, which means the hidden states can generally be correctly labelled. The significant test shows that only a few combinations of the basic and monitored variables are not significant under the 0.01 significant level. The tree model based on different quantile intervals provides different coverage and width combination choices. A coverage rate around 0.8 is suggested, which has a relative interval width of 0.77.

Research progress of stimulus-responsive antibacterial materials for bone infection.

Infection is one of the most serious complications harmful to human health, which brings a huge burden to human health. Bone infection is one of the most common and serious complications of fracture and orthopaedic surgery. Antibacterial treatment is the premise of bone defect healing. Among all the antibacterial strategies, irritant antibacterial materials have unique advantages and the ability of targeted therapy. In this review, we focus on the research progress of irritating materials, the development of antibacterial materials and their advantages and disadvantages potential applications in bone infection.

JWA suppresses proliferation in trastuzumab-resistant breast cancer by downregulating CDK12.

Breast cancer is the most common cancer worldwide. JWA is a microtubule-associated protein that has been identified as a tumor suppressor, and its downregulation in tumors is an independent adverse prognostic factor. The objective of this study was to explore the expression, regulation, and mechanism of JWA in trastuzumab-resistant breast cancers. In this study, we found that JWA expression was lower in trastuzumab-resistant breast cancers than that in trastuzumab-sensitive breast cancers. Furthermore, it was confirmed that overexpression of JWA inhibited proliferation and promoted apoptosis in trastuzumab-resistant breast cancers both in vitro and in vivo. In addition, the low expression of JWA in trastuzumab-resistant breast cancers is associated with a poor prognosis. Combining RNA-sequence datasets and next-generation sequencing, it was found that JWA negatively regulated CDK12, and was involved in the G1-to-S transition of the cell cycle. It has been reported that CDK12 drives breast cancer initiation and induces trastuzumab resistance. Taken together, high expression of JWA could inhibit the growth of trastuzumab-resistant breast cancer, and JWA is a potential predictive marker for trastuzumab resistance. In addition, targeted therapy with JWA may be a novel therapeutic strategy to improve the survival rate of trastuzumab-resistant breast cancer.

Relaxivity-iron calibration in hepatic iron overload: Reproducibility and extension of a Monte Carlo model.

The aim of this study was to reproduce relaxivity-iron calibration in hepatic iron overload using a Monte Carlo model, and further extend the model with multiple spin echo (MSE) imaging. As previously reported, relationships between relaxation rates ( R2* and single spin echo R2 ) and liver iron concentration (LIC) can be characterized by a Monte Carlo model incorporating realistic liver structure, iron distribution, and proton mobility. In this study, relaxivity-iron calibration curves at 1.5 and 3.0 T were simulated using the Monte Carlo model. Furthermore, the model was extended with MSE imaging, and iron calibrations were evaluated using two different fitting models: mononexponential with a constant offset and nonmonoexponential. Results consistent with previous empirical calibrations and Monte Carlo predictions were accurately reproduced for relaxivity-iron calibration. The predicted R2* and single spin echo R2 increased by a factor of 2.00 and 1.51, respectively, at 1.5 versus 3.0 T. MSE signals and their corresponding R2 depended strongly on LIC, interecho time, and field strength. Preliminary results showed that a nonmonoexponential model accurately characterizes the simulated MSE signals, and that strong correlations were found between predicted relaxation parameters and LIC. In conclusion, relaxivity-iron calibration is reproducible using the proposed Monte Carlo model. Furthermore, this model can be readily extended to other important applications, including predicting signal behavior for MSE imaging.

Inflammatory modulation of the associations between prenatal maternal depression and neonatal brain.

Inflammatory signaling has a role in sensing intrauterine environment, which may be moderators in altering fetal brain development upon maternal environment. This study integrated cytokine transcriptome of post-mortem fetal brains, neonatal brain imaging and genetic variants (n = 161) to examine whether cytokines are candidates for modulating the relationship between prenatal maternal depression and fetal brain development. This study obtained the transcriptome data of 208 cytokine genes in 12 fetal brain regions from the BrainSpan database. We also included 161 mother-child dyads with prenatal maternal depressive symptoms assessed at 26 weeks of gestation, cytokine genotype data extracted from umbilical cord specimens, and neonatal brain images from a longitudinal prospective birth cohort. We revealed that 22 cytokine genes are expressed in specific brain regions in utero, whose variants have roles in modulating the effects of the prenatal environment on the accelerated fetal development of the hippocampus, auditory, parietal, orbitofrontal, and dorsal prefrontal cortex. Neonates high in the genetic expression score (GES) of TNFRSF19 and IL17RB showed a larger right hippocampal volume, high in the GES of BMPR1B showed the thicker thickness of the sensorimotor cortex, and high in the GES of IL1RAP and CXCR4 demonstrated the thicker thickness of the dorsal and orbital prefrontal cortex in relation with greater prenatal maternal depressive symptoms. Our findings suggest that in humans, the cytokine genes are expressed in a brain region-specific manner in utero and may have potential roles in modulating the fetal development of the corresponding brain regions in response to the maternal environment.

Extent of breast cancer type 1 promoter methylation correlates with clinicopathological features in breast cancers.

AIM OF STUDY: The current meta-analysis investigated the correlation between breast cancer type 1 (BRCA1) promoter methylation and the clinicopathological features of breast cancer (BC). MATERIALS AND METHODS: An electronic literature search was performed to identify and select cohort studies, by employing stringent inclusion and exclusion criteria, for data relevant to promoter methylation of BRCA1 and BC. Statistical analysis of the extracted data was performed using comprehensive meta-analysis 2.0 software (CMA 2.0) (Biostat Inc., Englewood, New Jersey, USA). RESULTS: A total of 125 published studies were retrieved from the literature search, and finally, 18 cohort studies meeting our inclusion criteria were incorporated into our meta-analysis. The 18 studies contained a total of 3213 BC patients. Meta-analysis results revealed that BRCA1 promoter methylation in BC patients with high and moderately differentiated tumors (I-II) was significantly lower than patients with poorly-differentiation tumors (III) (odds ratio [OR] =0.450, 95% confidence interval [95% CI] =0.241-0.838, P = 0.012). BRCA1 promoter methylation in BC patients with lymph node (LN) metastasis was significantly higher than patients without LN metastasis (OR = 2.244, 95% CI = 1.278-3.940, P = 0.005). The results of ethnicity-based subgroup analysis showed a significant difference in histological grade of BC on Asians, LN metastasis of BC in Asians and Caucasians, subtypes of BC in Caucasians, and age at diagnosis of BC patients in Caucasians (all P < 0.05). CONCLUSIONS: Our meta-analysis revealed that BRCA1 promoter methylation status is linked to tumor grade and LN metastasis of BC.

Multicenter cross-sectional screening of the BRCA gene for Chinese high hereditary risk breast cancer populations.

Due to lack of systematic reviews, BRCA, DNA Repair Associated (BRCA) mutations in the Chinese population are not completely understood. The following study investigates the prevalence and type of BRCA mutations in Chinese patients with high hereditary risk of breast cancer (BC). Patients Drwere recruited from 14 cities between October 2015 and February 2016, and were selected based on family and personal medical history. BRCA mutations were analyzed by collecting blood samples from all participants. 437 BC patients were included. A total of seventy-six (17.4%) mutation carriers were identified with no geographic difference. The mutation rate in the early-onset BC patients was lower compared to family history of breast/ovarian cancer (OC), bilateral BC, male BC, BC&OC or meeting ≥2 criteria (9.2 vs. 21.7, 24.0, 22.2, 16.7 and 24.3%, respectively, P=0.007). A total of 61 mutation sites were identified (BRCA1 32, BRCA2 29) including 47.5% novel sites and extra 10 variants of uncertain significance. A total of five sites were repeated in more than one unrelated patient. A total of 11 sites were associated with hereditary breast and ovarian cancer syndrome, two of which were confirmed by family pedigrees. Compared with BRCA- patients, patients with BRCA1 mutation tended to be triple-negative BC (P<0.001), whereas patients with BRCA2 mutation were more likely to be hormone receptor positive BC (P=0.02). The present study provides a general BRCA mutation profile in the Chinese population. The prevalence of BRCA mutation in BC patients with high hereditary risk is lower compared with Western populations. Chinese mutation type is different with Western people, without obvious founder mutation.

Primate-specific miRNA-637 inhibited tumorigenesis in human pancreatic ductal adenocarcinoma cells by suppressing Akt1 expression.

As a primate-specific microRNA, miR-637 has been discovered for nearly 10 years. Our previous study demonstrated that miR-637 acted as a suppressor in hepatocellular carcinoma. However, its biomedical significance in pancreatic cancer remains obscure. In the present study, miR-637 was found to be significantly downregulated in pancreatic ductal adenocarcinoma (PDAC) cell lines and most of the PDAC specimens. Furthermore, the enforced overexpression of miR-637 dramatically inhibited cell proliferation and induced apoptosis of PDAC cells. Akt1, as a serine/threonine-protein kinase, has been identified as an oncogene in multiple cancers including pancreatic cancer. Our data confirmed that Akt1 was a novel target for miR-637, and its knockdown also induced cell growth inhibition and apoptosis in PDAC cells. In conclusion, our data indicated that miR-637 acted as a tumor-suppressor in PDAC, and the suppressive effect was mediated, at least partially, by suppressing Akt1 expression.

Rapid look-up table method for noise-corrected curve fitting in the R2* mapping of iron loaded liver.

PURPOSE: Fitting the measured decay signal to the first moment in the presence of noncentral chi noise (M(1) NCM) can correctly address the effect of noise on the effective transverse relaxation rate (R2*) relaxometry of iron loaded liver. However, this method requires intensive computation, which restricts its application to R2* mapping. This work aims to develop a rapid implementation of the M(1) NCM method for R2* mapping. METHODS: The computation of the confluent hypergeometric function in the M(1) NCM model was approximated using cubic spline interpolation with breakpoints and coefficients precalculated and stored in a look-up table (M(1) NCM-LUT). The performance of the proposed M(1) NCM-LUT method was evaluated through simulation and based on in vivo liver R2* relaxometry data. RESULTS: In both simulation and in vivo studies, the maximum absolute difference between R2* maps generated by the M(1) NCM and M(1) NCM-LUT methods was nearly 10(-3) s(-1) or less, and the M(1) NCM-LUT method obtained a R2* map in approximately 1 s and achieved an acceleration of approximately five orders of magnitude. CONCLUSION: The proposed M(1) NCM-LUT method can significantly increase the speed of the liver R2* mapping using the M(1) NCM model. This development is important in promoting application of this R2* mapping technique for tissue iron quantification.

Laparoscopy-Assisted D2 Radical Gastrectomy for Advanced Gastric Cancer.

BACKGROUND/AIMS: The aim of this study was to investigate the efficacy and advantages of laparoscopy-assisted gastrectomy (LAG) with D2 lymphadenectomy versus conventional open D2 gastrectomy (ODG) in advanced gastric cancer (AGC) patients. METHODOLOGY: From June 2009 to June 2014, 233 patients who were treated by conventional radical ODG and 188 cases who underwent radical LAG for AGC at our department were enrolled in this study. Clinical data recorded in hospital database was retrospectively reviewed and analyzed. RESULTS: There were no significant differences in age, gender or preoperative laboratory tests distribution between the LAG group and the ODG group. Two (1%) of the patients who underwent LAG required conversion to ODG. The advantages of minimally invasive surgery including earlier recovery of bowel movements and shorter postoperative hospitalization time were observed in LAG group. The number of harvested lymph nodes was 24.3 ± 3.3 in the LAG group and 25.0 ± 2.8 in ODG (p = 0.110). CONCLUSIONS: Although prospective randomized trials with long follow-up period are needed to identify the feasibility, we have shown the safety and advantages of LAG with D2 lymphadenectomy for treating AGC patients in this study.

Stability of the recombinant anti­erbB2 scFv­Fc­interleukin­2 fusion protein and its inhibition of HER2­overexpressing tumor cells.

The anti­erbB2 scFv­Fc­IL­2 fusion protein (HFI) is the basis for development of a novel targeted anticancer drug, in particular for the treatment of HER2­positive cancer patients. HFI was fused with the anti­erbB2 antibody and human IL­2 by genetic engineering technology and by antibody targeting characteristics of HFI. IL­2 was recruited to target cells to block HER2 signaling, inhibit or kill tumor cells, improve the immune capacity, reduce the dose of antibody and IL­2 synergy. In order to analyse HFI drug ability, HFI plasmid stability was verified by HFI expression of the trend of volume changes. Additionally, HFI could easily precipitate and had progressive characteristics and thus, the buffer system of the additive phosphate­citric acid buffer, arginine, Triton X­100 or Tween­80, the establishment of a microfiltration, ion exchange, affinity chromatography and gel filtration chromatography­based purification process were explored. HFI samples were obtained according to the requirements of purity, activity and homogeneity. In vivo, HFI significantly delayed HER2 overexpression of non­small cell lung cancer (Calu­3) in human non­small cell lung cancer xenografts in nude mice, and the inhibition rate was more than 60% (P<0.05) in the group treated with 1 mg/kg the HFI dose; HFI significantly inhibited HER2 expression of breast cancer (FVB/neu) transgenic mouse tumor growth in 1 mg/kg of the HFI dose group, and in the following treatment the 400 mm3 tumors disappeared completely. Combined with other HFI test data analysis, HFI not only has good prospects, but also laid the foundation for the development of antibody­cytokine fusion protein­like drugs.

NEDD9 is a positive regulator of epithelial-mesenchymal transition and promotes invasion in aggressive breast cancer.

Epithelial to mesenchymal transition (EMT) plays an important role in many biological processes. The latest studies revealed that aggressive breast cancer, especially the triple-negative breast cancer (TNBC) subtype was frequently associated with apparent EMT, but the mechanisms are still unclear. NEDD9/HEF1/Cas-L is a member of the Cas protein family and was identified as a metastasis marker in multiple cancer types. In this study, we wished to discern the role of NEDD9 in breast cancer progression and to investigate the molecular mechanism by which NEDD9 regulates EMT and promotes invasion in triple-negative breast cancer. We showed that expression of NEDD9 was frequently upregulated in TNBC cell lines, and in aggressive breast tumors, especially in TNBC subtype. Knockdown of endogenous NEDD9 reduced the migration, invasion and proliferation of TNBC cells. Moreover, ectopic overexpression of NEDD9 in mammary epithelial cells led to a string of events including the trigger of EMT, activation of ERK signaling, increase of several EMT-inducing transcription factors and promotion of their interactions with the E-cadherin promoter. Data presented in this report contribute to the understanding of the mechanisms by which NEDD9 promotes EMT, and provide useful clues to the evaluation of the potential of NEDD9 as a responsive molecular target for TNBC chemotherapy.