Serum albumin is associated with the inherent property of acute myeloid leukemia and correlates with patient outcomes.

An accurate prognostic model for acute myeloid leukemia (AML) can guide personalized treatment. In our prospective cohort of 591 patients newly diagnosed with AML, we evaluated the prognostic significance of serum albumin levels. We recognized baseline serum albumin as a prognostic factor by univariate Cox regression analysis (albumin-high vs albumin-low: overall survival [OS]: hazard ratio [HR]: 0.679, 95% confidence interval [CI]: 0.529-0.870, P = .002; cumulative incidence of relapse [CIR]: HR: 0.705, 95% CI: 0.530-0.938, P = .017) and multivariate Cox regression analysis (OS: HR per g/L: 0.966, 95% CI: 0.940-0.993, P = .014; CIR: HR per g/L: 0.959, 95% CI: 0.927-0.993, P = .017). In the subgroup analysis, serum albumin was prognostic significant in patients who received intermediate-dose cytarabine combined with daunorubicin and omacetaxine mepesuccinate induction (albumin-high vs albumin-low: OS: HR: 0.585, 95% CI: 0.397-0.863, P = .007; CIR: HR: 0.551, 95% CI: 0.353-0.861, P = .009) rather than those receiving conventional-dose induction regimens. In addition, the impact of baseline serum albumin level was evident in patients with intermediate European LeukemiaNet risk (albumin-high vs albumin-low: OS: HR: 0.617, 95% CI: 0.424-0.896, P = .011; CIR: HR: 0.617, 95% CI: 0.388-0.979, P = .040). Gene set enrichment analysis revealed that leukemia stem cell signatures were enriched in patients with low serum albumin levels. Our study suggested that baseline serum albumin level was associated with the inherent properties of AML and correlated with patient outcomes.

Identification of red blood cell distribution width as a prognostic factor in acute myeloid leukemia.

Many prognostic factors have been identified in acute myeloid leukemia (AML). In this study, we investigated novel prognostic biomarkers using machine learning and Cox regression models in a prospective cohort of 591 patients with AML and tried to identify potential therapeutic targets based on transcriptomic data. We found that elevated red blood cell distribution width (RDW) at diagnosis was an adverse prognostic factor for AML, independent of the 2022 European LeukemiaNet (ELN2022) genetic risk. As a continuous variable, higher RDW was associated with shorter overall survival (OS) (hazard ratio [HR] 1.087, 95% confidence interval [CI] 1.036-1.139, p < 0.001) and event-free survival (EFS) (HR 1.078, 95% CI 1.033-1.124, p < 0.001). Elevated RDW returned to normal after consolidation therapy, which indicated that leukemia cells resulted in abnormal RDW. We further investigated the relationship between RDW and transcriptome in another cohort of 191 patients with AML and public datasets using gene set enrichment analysis (GSEA) and cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT). We found that patients in the high-RDW group were significantly enriched in the positive regulation of erythroid differentiation and inflammation-related pathways. Finally, we identified the inflammation-associated gene IL12RB2 and verified its prognostic relevance with patients with AML in public databases, suggesting it as a potential therapy target.

Acteoside ameliorates learning and memory impairment in APP/PS1 transgenic mice by increasing Aß degradation and inhibiting tau hyperphosphorylation.

Alzheimer's disease (AD) is a neurodegenerative disease. Senile plaques and intracellular neurofibrillary tangles are pathological hallmarks of AD. Recent studies have described the improved cognitive and neuroprotective functions of acteoside (AS). This study aimed to investigate whether the improved cognition of AS was mediated by Aß degradation and tau phosphorylation in APP/PS1 mice. The open field, Y maze, and novel object recognition tests were used to assess cognitive behavioral changes. We evaluated the levels of Aß40 and Aß42 in serum, cortex, and hippocampus, and Aß-related scavenging enzymes, phosphorylated GSK3ß and hyperphosphorylated tau in the cortex and hippocampus of APP/PS1 mice by western blotting. Our results revealed that AS treatment ameliorated anxious behaviors, spatial learning, and memory impairment in APP/PS1 mice and significantly reduced Aß deposition in their serum, cortex, and hippocampus. AS significantly increased Aß degradation, inhibited the hyperphosphorylation of tau, and significantly decreased the activity of GSK3ß, which is involved in tau phosphorylation. Altogether, these findings indicated that the beneficial effects of AS on AD-associated anxious behaviors and cognitive impairments could be attributed to promoting Aß degradation and inhibiting tau hyperphosphorylation, which might be partly mediated by GSK3ß.

[Effects and Mechanisms of Homoharringtonine on Expression of CEBPA Protein].

OBJECTIVE: To investigate the effect of homoharringtonine (HHT) on CEBPA protein and explore the mechanism of HHT in the treatment of acute myeloid leukemia (AML) with double CEBPA mutations. METHODS: The K562 cell line expressing CEBPA p30 (K562 CEBPA p30) was established. Western blot was used to determine the changes of the expression of CEBPA protein in K562 CEBPA p30, U937 and MOLM-13 cell lines before and after treatments with HHT, daunorubicin (DNR) or cytarabine (Ara-C). The effects of protease inhibitors and protein synthesis inhibitors on the expression of CEBPA protein were also determined. RNA-seq was used to analyze the difference of gene expressions and pathway enrichments between HHT group and DNR group. RESULTS: Both the endogenous CEBPA protein in U937 and MOLM-13 cell lines and the exogenous CEBPA protein in K562 CEBPA p30 were decreased by HHT (P<0.05) while were not by DNR or Ara-C. Proteasome inhibitors can increase the expression of CEBPA protein (P<0.05) while protein synthesis inhibitors can decrease the expression of CEBPA protein (P<0.05). The ribosome biogenesis related pathways in K562 CEBPA p30 were upregulated in HHT group while were not in DNR group. CONCLUSION: HHT can inhibit the synthesis of CEBPA and reduce the expression of CEBPA protein and this may be the mechanism of HHT in the treatment of CEBPA-double-mutant AML.

Comprehensive transcriptomics and metabolomics analyses reveal that hyperhomocysteinemia is a high risk factor for coronary artery disease in a chinese obese population aged 40-65: a prospective cross-sectional study.

BACKGROUND: Clinical observations suggest a complex relationship between obesity and coronary artery disease (CAD). This study aimed to characterize the intermediate metabolism phenotypes among obese patients with CAD and without CAD. METHODS: Sixty-two participants who consecutively underwent coronary angiography were enrolled in the discovery cohort. Transcriptional and untargeted metabolomics analyses were carried out to screen for key molecular changes between obese patients with CAD (CAD obese), without CAD (Non-CAD obese), and Non-CAD leans. A targeted GC-MS metabolomics approach was used to further identify differentially expressed metabolites in the validation cohorts. Regression and receiver operator curve analysis were performed to validate the risk model. RESULTS: We found common aberrantly expressed pathways both at the transcriptional and metabolomics levels. These pathways included cysteine and methionine metabolism and arginine and proline metabolism. Untargeted metabolomics revealed that S-adenosylhomocysteine (SAH), 3-hydroxybenzoic acid, 2-hydroxyhippuric acid, nicotinuric acid, and 2-arachidonoyl glycerol were significantly elevated in the CAD obese group compared to the other two groups. In the validation study, targeted cysteine and methionine metabolomics analyses showed that homocysteine (Hcy), SAH, and choline were significantly increased in the CAD obese group compared with the Non-CAD obese group, while betaine, 5-methylpropanedioic acid, S-adenosylmethionine, 4-PA, and vitamin B2 (VB2) showed no significant differences. Multivariate analyses showed that Hcy was an independent predictor of obesity with CAD (hazard ratio 1.7; 95%CI 1.2-2.6). The area under the curve based on the Hcy metabolomic (HCY-Mtb) index was 0.819, and up to 0.877 for the HCY-Mtb.index plus clinical variables. CONCLUSION: This is the first study to propose that obesity with hyperhomocysteinemia is a useful intermediate metabolism phenotype that could be used to identify obese patients at high risk for developing CAD.

Long-Wavelength Near-Infrared Divalent Nickel-Activated Double-Perovskite Ba2MgWO6 Phosphor as Imaging for Human Fingers.

Transmission near-infrared (NIR) imaging technology has great potential for biomedical imaging because of its lower water absorption coefficient and highly reduced photon scattering effect in biological tissues compared to visible light. The extent of biological tissue photon scattering is inversely proportional to wavelength; therefore, in principle, imaging with long-wavelength NIR helps improve the resolution of the optical image, but deep tissue high-resolution luminescence imaging is still very challenging technically. Here, we report the discovery of a Ba2MgWO6:Ni2+ double perovskite phosphor that emits broadband long-wavelength NIR (1200-2000 nm) under 365 nm near-ultraviolet (UV) excitation, with a full width at half-maximum of 255 nm. The luminescence quantum efficiency of the phosphor with optimized composition reached 16.67%. The analysis of the crystal structure of Ba2MgWO6:Ni2+ suggests that Ni2+ ions preferentially occupy the W6+ site in octahedrons with a weak crystal field, which leads to a large Stokes shift. An as-prepared long-wavelength NIR pc-LED device was built by packaging an optimized phosphor with a low-power near-UV-LED chip, which was tested to generate clear imaging of venous vessels in human fingers. These unique properties of the Ba2MgWO6:Ni2+ double perovskite phosphor makes it a promising application in the field of imaging sources for body tissue..

Activatable Mn2+-Armed nanoagonist augments antitumor immunity in colorectal cancer: A NIR-II Photonic neoadjuvant paradigm.

Postoperative recurrence frequently occurs in patients with colorectal cancer (CRC) due to residual microtumors and host cellular immune dysfunction, leading to major setbacks in clinical outcomes and CRC staging. As an increasingly prevalent therapeutic option for CRC patients, neoadjuvant chemoradiotherapy bears unmet challenges of limited tumor targeting and common side effects of gastrointestinal reaction and radiodermatitis. It is highly desirable to develop neoadjuvant treatment paradigms that impart both tumor-targeting accuracy and protection against recurrence of resectable CRC. Here we report a versatile photo-regulated nanoagonist of plasmonic gold blackbody (AuPB) with a polydopamine (PDA) coating carrying manganese ion (Mn2+) payloads (AuPB@PDA/Mn). When armed with second near-infrared (NIR-II) light, AuPB@PDA/Mn with broad-band localized surface plasmon resonance generates local hyperthermia and discharges Mn2+ ions, which evidently amplify the effects of immunogenic cell death in tumor cells and activate the cyclic GMP-AMP synthase/stimulator of interferon genes pathway in dendritic cells (DCs), hence potentiating the maturation of DC and the secretion of type I interferon in a synergistic way. Matured DCs undertake the task of tumor antigen presentation as the crosstalk to adaptive immunity. As such, the administration of AuPB@PDA/Mn coupled with NIR-II laser irradiation has eminently augmented the infiltration of CD8+ T cells as well as the development of memory CD8+ T cells in colorectal tumor models, substantiating enhanced immunomodulatory efficacy against primary and recurrent CRC. Our strategy highlights the potency of an integrated NIR-II photothermal and immunoregulatory modality by photo-activate delivery of Mn2+ ions, as a neoadjuvant paradigm for presurgical tumor debulking and against postoperative tumor recurrence.

Assessment of Instant Loss of Elbow Flexion in Children with Untreated Gartland IIA Humeral Supracondylar Fractures-A Simulation Study with Lateral Elbow Radiographs.

OBJECTIVE: The suitability of in situ cast fixation for treating Gartland IIA humeral supracondylar fractures has remained controversial due to concerns regarding loss of elbow flexion. This study aimed to assess the instant loss of elbow flexion after Gartland IIA humeral supracondylar fractures based on the relationship between the anterior marginal line of the humerus and capitellum in the lateral view. METHODS: This simulation study was conducted with normal radiographs using Adobe Photoshop 14.0, followed by verification using clinical cases. Standard lateral views of normal elbows of children were collected from January 2008 to February 2020. Adobe Photoshop was used to simulate Gartland IIA supracondylar fractures with different degrees of angulation in the sagittal plane. A formula was deduced to assess flexion loss, and this method was verified in three cases. The data were grouped by age, and the relationship between elbow flexion loss and age, as well as the angulation of the fracture, was analyzed using a one-way or multivariate ANOVA. RESULTS: There was a flexion loss of 19° (11-30°) when the anterior margin line of the humerus was tangential to the capitellum. This loss increased with age at injury (r = 0.731, P = 0.000). Moreover, the difference in angulation in the sagittal plane also influenced the extent of elbow flexion loss (r = -0.739, P = 0.000). The more horizontal the fracture line in the lateral view, the greater the loss of elbow flexion. CONCLUSION: Instant elbow flexion loss after Gartland IIA humeral supracondylar fractures increases with age at the time of injury and decreases with angulation in the sagittal plane. When the anterior margin of the humerus is tangential to the capitellum, there will be an average loss of 19° in elbow flexion. These findings provide a quantitative reference for clinical decision-making in the treatment of Gartland IIA supracondylar fractures.

Serum sirtuin-1 a potential marker in the diagnosis of rheumatoid arthritis.

Introduction: To explore the value of serum sirtuin-1 (SIRT1) in the diagnosis and evaluation of joint mobility of rheumatoid arthritis (RA). Materials and Methods: Serum was randomly obtained from 212 RA patients,210 non-RA patients and 58 healthy controls in a large tertiary first-class hospital in Jiangxi province from November 2021 to June 2022. The level of serum Sirt1,anti-cyclic citrulline polypeptide antibody (anti-CCP), anti-mutant citrulline vimentin antibody (anti-MCV), rheumatoid factor (RF),high-mobility group box 1 (HMGB1), collagen triple helix repeat containing 1 (CTHRC1), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were detected by ELISA, to explore the correlation between them and their value in the diagnosis and evaluation of joint range of motion of RA and statistically analyse their diagnostic efficiency. Results: ① The level of all markers was higher in the RA group than in the non-RA group and the healthy controls (p < 0.05). ② The AUC of the SIRT1 was 0.882, second only to the anti-MCV and anti-CCP. ③ The anti-CCP showed the highest sensitivity to RA diagnosis of 0.948. The specificity and positive predictive value of SIRT1 for the diagnosis of RA were the highest, which are 0.959 and 0.934 respectively. ④ In serial combination, SIRT1/anti-CCP、SIRT1/anti-MCV showed the highest specificity.SIRT1/anti-CCP in parallel combination had the highest sensitivity. ⑤ SIRT1 showed a significant correlation with other markers and DAS28 scores (p < 0.01). Conclusion: SIRT1 can be used as a new serological marker for RA diagnosis, which has a significant correlation with RA joint mobility and has a certain reference value in RA differential diagnosis, providing a new detection basis for RA differential diagnosis.

Multi-omics profiling of cholangiocytes reveals sex-specific chromatin state dynamics during hepatic cystogenesis in polycystic liver disease.

BACKGROUND & AIMS: Cholangiocytes transit from quiescence to hyperproliferation during cystogenesis in polycystic liver disease (PLD), the severity of which displays prominent sex differences. Epigenetic regulation plays important roles in cell state transition. We aimed to investigate the sex-specific epigenetic basis of hepatic cystogenesis and to develop therapeutic strategies targeting epigenetic modifications for PLD treatment. METHODS: Normal and cystic primary cholangiocytes were isolated from wild-type and PLD mice of both sexes. Chromatin states were characterized by analyzing chromatin accessibility (ATAC sequencing) and multiple histone modifications (chromatin immunoprecipitation sequencing). Differential gene expression was determined by transcriptomic analysis (RNA sequencing). Pharmacologic inhibition of epigenetic modifying enzymes was undertaken in PLD model mice. RESULTS: Through genome-wide profiling of chromatin dynamics, we revealed a profound increase of global chromatin accessibility during cystogenesis in both male and female PLD cholangiocytes. We identified a switch from H3K9me3 to H3K9ac on cis-regulatory DNA elements of cyst-associated genes and showed that inhibition of H3K9ac acetyltransferase or H3K9me3 demethylase slowed cyst growth in male, but not female, PLD mice. In contrast, we found that H3K27ac was specifically increased in female PLD mice and that genes associated with H3K27ac-gained regions were enriched for cyst-related pathways. In an integrated epigenomic and transcriptomic analysis, we identified an estrogen receptor alpha-centered transcription factor network associated with the H3K27ac-regulated cystogenic gene expression program in female PLD mice. CONCLUSIONS: Our findings highlight the multi-layered sex-specific epigenetic dynamics underlying cholangiocyte state transition and reveal a potential epigenetic therapeutic strategy for male PLD patients. IMPACT AND IMPLICATIONS: In the present study, we elucidate a sex-specific epigenetic mechanism underlying the cholangiocyte state transition during hepatic cystogenesis and identify epigenetic drugs that effectively slow cyst growth in male PLD mice. These findings underscore the importance of sex difference in the pathogenesis of PLD and may guide researchers and physicians to develop sex-specific personalized approaches for PLD treatment.

Effect of Arbuscular Mycorrhiza Fungus Diversispora eburnea Inoculation on Lolium perenne and Amorpha fruticosa Growth, Cadmium Uptake, and Soil Cadmium Speciation in Cadmium-Contaminated Soil.

Cadmium (Cd) pollution has become aggravated during the past decades of industrialization, severely endangering human health through its entry into the food chain. While it is well understood that arbuscular mycorrhizal fungi (AMF) have a strong ability to regulate plant growth and Cd uptake, studies investigating how they affect soil Cd speciation and influence Cd uptake are limited. We designed a pot experiment comprising two AMF-inoculant groups (inoculation with Diversispora eburnea or no inoculation), three Cd concentration levels (0, 5, and 15 mg/kg), and two plant species (Lolium perenne and Amorpha fruticosa) to study the effect of AMF Diversispora eburnea on plant growth, Cd uptake, and Cd speciation in the soil. The results revealed that L. perenne exhibited higher productivity and greater Cd uptake than A. fruticosa, regardless of AMF D. eburnea inoculation. However, AMF D. eburnea significantly altered soil Cd speciation by increasing the proportion of exchangeable Cd and decreasing residual Cd, resulting in Cd enrichment in the plant root organs and the elimination of Cd from the polluted soils. Our experiments demonstrate that inoculating plants with AMF D. eburnea is an effective alternative strategy for remediating Cd-contaminated soil.

Tumor CEMIP drives immune evasion of colorectal cancer via MHC-I internalization and degradation.

BACKGROUND: Loss of major histocompatibility complex class I (MHC-I) in tumor cells limits the use of immune checkpoint blockade (ICB) in colorectal cancer. Nevertheless, the regulatory mechanism of MHC-I downregulation in tumor cells has not been fully elucidated. Overexpression of CEMIP in tumor tissues is associated with a poor prognosis in colorectal cancer. Here, in this research, we aim to address the role of CEMIP in mediating MHC-I expression in tumor cells and investigate the underlying regulatory mechanisms. METHOD: Protein levels were analyzed by western blotting. Flow cytometry analysis was used to examine immune cells. Protein-protein interactions were investigated by co-immunoprecipitation and proximity ligation assays. The intracellular trafficking of MHC-I was revealed by an immunofluorescent technique. In addition, the effect of CEMIP on tumor growth and the antitumor efficacy of targeting CEMIP in combination with ICB therapy were evaluated in murine models of colorectal cancer. RESULTS: We reported that CEMIP specifically downregulated the expression of MHC-I on the surface of murine and human colon cancer cells, hindering the cytotoxicity of CD8+ T cells. We also demonstrated that CEMIP restricted CD8+ T-cell antitumor activities both in vitro and in vivo due to impaired MHC-I-mediated antigen presentation. Correspondingly, the combination of CEMIP inhibition and ICB impeded tumor growth and enhanced therapeutic efficacy. Mechanistically, CEMIP acted as an adaptor for the interaction betweenMHC-I and clathrin, which drove MHC-I internalization via clathrin-dependent endocytosis. Furthermore, CEMIP anchored internalized MHC-I to lysosomes for degradation, disrupting the recycling of MHC-I to the cell surface. CONCLUSION: Overall, our study unveils a novel regulatory mechanism of MHC-I on tumor cell surfaces by CEMIP-mediated internalization and degradation. Furthermore, targeting CEMIP provides an effective strategy for colorectal cancer immunotherapy.

Bacteria-mediated metformin-loaded peptide hydrogel reprograms the tumor immune microenvironment in glioblastoma.

The tumor immune microenvironment (TIME) is one of the significant hallmarks of cancer and has the important role of largely determining the malignancy level of tumors. As an approach to break through this bottleneck of tumor treatment methods, the TIME can be reprogrammed by certain nanomaterials. Here, we coated C-novyi-spores with melittin-RADA32 nanofiber hybrid peptide and loaded the immunomodulator metformin to obtain MRM-coated spores as a powerful antitumor nanodrug against glioblastoma (GBM), which is based on the activation of the TIME. MRM-coated spores exhibit extended-release profiles and an enhanced killing effect on GBM both in vitro and in vivo. Furthermore, MRM-coated spores can educate the innate and adaptive immune system by inducing sustainable CD8+ T cell responses, promoting M1 macrophage polarization, and regulating the expression of HIF1-α, PDL1, and CXCL9 in TIME. In intracranial applications, MRM-coated spores showed excellent biosafety and a strong therapeutic effect. In summary, peptide hydrogels provide a promising strategy in which advantages of different treatment methods can be incorporated to synthesize potent antitumor drugs with mild side effects from bacteria-mediated nanomaterials.

Prevalence and outcomes of transurethral resection versus radical cystectomy for muscle-infiltrating bladder cancer in the United States: A population-based cohort study.

INTRODUCTION: Although radical cystectomy is considered as the first choice for muscle-invasive bladder cancer (MIBC), there are also concerns regarding the cost of long-term morbidity, loss of body image, and compromised quality of life. Transurethral resection of bladder tumor (TURBT) is a candidate for bladder sparing treatments, but its viability as a substitute for radical cystectomy is questionable. Therefore, we conducted this population-based study to investigate the prevalence of TURBT in the treatments of T2-stage MIBC in the United States, and to compare its therapeutic efficiency with that of radical cystectomy. METHODS: Information on patients with T2-stage bladder cancer (BC) between 2000 and 2017 was extracted from the Surveillance, Epidemiology, and End Results program. The overall survival (OS) and disease-specific survival (DSS) of patients with different interventions were fitted. RESULTS: A total of 22,074 patients with T2-stage MIBC were enrolled, of whom 14,021 reached the main endpoint. Only 28% of the patients with T2-stage MIBC chose radical cystectomy as the initial surgical treatment, while TURBT was applied as the primary surgical treatment in 66.6% of the patients. The TURBT rate increased significantly with age at cancer diagnosis (40-44 years, 45.5% to > 85 years, 90.9%). The survival rate of patients undergoing TURBT was significantly lower than for those undergoing radical cystectomy (median OS: 1.5 versus 9.7 years; median DSS: 2.7 years versus not reached). Upon multivariable Cox analyses, the OS (HR: 2.34; p < 0.001) and DSS (HR: 2.68; p < 0.001) of TURBT were found to be significantly worse than those of radical cystectomy. CONCLUSION: Two-thirds of the patients with T2-stage MIBC were treated by TURBT in the United States. However, the long-term follow-up data indicate that the therapeutic efficiency of current TURBT techniques is far less effective than that of radical cystectomy. Further studies are urgently needed to devise the best management strategy for T2 stage bladder cancer.

The Integrity of Cartilage Hinge in Song 2/3 Lateral Humeral Condylar Fractures in Children: A Retrospective Radiological Study in Two Centers.

OBJECTIVE: For pediatric lateral condylar fractures (LCFs) of the humerus, it is often hard to determine the stability of the fracture based on the Song classification, especially for those categorized as Song stages 2 and 3. This study aims to define the characteristics of cartilage injury and assess the stability of LCFs classified as Song stages 2 and 3 on post-traumatic magnetic resonance imaging (MRI). METHODS: This was a retrospective study based on imaging data, conducted with a short follow-up period. From January 2016 to May 2019, data of all patients with Song 2 and Song 3 LCFs treated at two institutions were collected. Based on the inclusion criteria, a total of 62 patients with Song stage 2/3 LCF were included. All radiographs were selected for observation and classification for comparison by two observers, both experienced pediatric orthopedic surgeons. MRIs scans for comparison were analyzed in three consecutive coronal sections and cross-sections. Patients were treated conservatively with casting or surgically with closed reduction and percutaneous pinning (CRPP). RESULTS: Altogether 62 cases between 1.5 to 9 years old were included. Reliability analysis revealed poor, moderate, or good agreement between the two observers (range, 0.149-0.633). Both observers showed moderate or good consistency (range, 0.413-0.611). Among the 62 patients diagnosed with Song stages 2 and 3 fractures on initial radiographs, only two patients (3%) had complete fractures with complete disruption of the cartilage hinge as seen on MRI. The hinge was generally located in the posterior-inferior region of the distal humeral cartilage as indicated on MRI. There was no significant difference between Song stages 2 and 3 with regard to ratio of hinge to total values in any cross-sections, nor was there any significant difference in the completeness of the coronal sections (P > 0.05). Of the 62 patients treated, 50 were managed conservatively with casting and 12 underwent CRPP. Forty-nine of the remaining 60 patients (97%) with incomplete fractures were managed conservatively, while the remaining 11 patients were managed with CRPP. All patients with incomplete fractures showed bone healing and no evidence of lateral condyle displacement on follow-up radiographs. CONCLUSIONS: The Song stage 2 or 3 classification is not entirely accurate and is inadequate at guiding treatment outcomes. The cartilage hinge was most likely located posteroinferiorly within the distal humeral epiphysis. According to our findings, conservative treatment with an effective cast or splint may be sufficient for bone healing in case of incomplete cartilage fractures.

Endoscopic excision as a viable alternative to major resection for early duodenal cancers: A population-based cohort study.

BACKGROUND: Duodenal cancer presents an elusive therapeutic challenge for clinicians to treat because of its highly malignant behavior and anatomical complexity. Endoscopic excision has been administered to treat early-stage cancers of upper gastrointestinal tract, especially esophagus and stomach cancer. There is currently a scarcity of data regarding the application and efficacy of endoscopic resection for early duodenal cancer due to its rarity. This study aimed at exploring the prevalence and efficacy of endoscopic excision in treatment for early duodenal cancer in comparison with major surgery. METHODS: This cohort study retrospectively collected patients with primary Tis/T1-N0-M0 duodenal cancer in the Surveillance, Epidemiology, and End Results database from 2004 to 2017. Prevalence of endoscopic excision in duodenal cancer treatment, overall survival (OS) and disease-specific survival (DSS) of patients who received different tumor-resection procedures were estimated. RESULTS: A total of 1354 patients with Tis/T1-stage duodenal cancer were identified. Most patients (69.4%) underwent tumor resection as initial treatments. Among them, 65.7% underwent endoscopic excision, while 34.3% underwent major surgery. The multivariable Cox analyses revealed that endoscopic excision was associated with a significantly favorable OS (HR: 0.70; 95% CI: 0.52-0.95, p = 0.02) and DSS (HR: 0.32; 95% CI: 0.17-0.60, p < 0.001), compared to major surgery, for Tis/T1-stage cancer patients. In addition to cancer-related deaths (p < 0.001), endoscopic resection manifested significantly lower cumulative mortality rate of post-operative infectious diseases (p = 0.03). CONCLUSION: Endoscopic resection currently accounted for approximately two-thirds of all procedures to resect Tis/T1-stage duodenal tumor. Endoscopic resection represents a viable therapeutic option in the management of Tis/T1-stage duodenal cancer for its oncological superiorities to major surgery and its capacity to reduce operative traumas and morbidities.

White tea alleviates non-alcoholic fatty liver disease by regulating energy expenditure and lipid metabolism.

Non-alcoholic fatty liver disease (NAFLD) is one of the leading causes of liver disease, which lacks effective treatments. Abnormal lipid metabolism and inflammation are the most prominent pathological manifestations of NAFLD. Recently, it has been reported that white tea extract (WTE) can regulate lipid metabolism in human adipocytes and liver cancer cells in vitro. However, its beneficial effects on NAFLD and the underlying mechanisms remain largely unknown. Here, we showed that WTE alleviated obesity, lipid accumulation, hepatic steatosis, and liver injury in a mouse model of NAFLD. Mechanistically, we demonstrated that WTE exerted the anti-NAFLD effect by decreasing the expression of genes involved in lipid transport and synthesis processes while activating genes associated with energy expenditure. In addition, a comparison of the transcriptional responses of WTE with that of green tea extract (GTE) revealed that WTE can not only regulate lipid metabolism and stress response like GTE but also regulate antioxidant and inflammatory pathways more effectively. Taken together, our findings demonstrate that WTE inhibits the progression of NAFLD in a mouse model and indicate that WTE can be a potential dietary intervention for NAFLD.

The prognostic factors in acute myeloid leukaemia with double-mutated CCAAT/enhancer-binding protein alpha (CEBPAdm).

The prognostic factors to stratify acute myeloid leukaemia (AML) with double-mutated CCAAT/enhancer-binding protein alpha (CEBPAdm) into different risk groups remains to be determined. In this retrospective study, we evaluated 171 consecutive patients with newly diagnosed AML with CEBPAdm by a Cox proportional hazards regression model. In univariate analyses, colony stimulating factor 3 receptor (CSF3R) and Wilms tumour 1 (WT1) mutations were associated with poor relapse-free survival (RFS). The induction regimens including homoharringtonine (omacetaxine mepesuccinate) or intermediate-dose cytarabine was associated with favourable RFS and overall survival (OS). The induction regimen including both homoharringtonine and intermediate-dose cytarabine was associated with the most favourable RFS (3-year RFS 84.7%) and OS (3-year OS 92.8%) compared to the conventional cytarabine and daunorubicin regimen (3-year RFS 27.7%, hazard ratio [HR] 0.126, 95% confidence interval [CI] 0.051-0.313, Wald p < 0.001; and 3-year OS 56.4%, HR 0.179, 95% CI 0.055-0.586, Wald p = 0.005). In multivariate analyses, the induction regimen including intermediate-dose cytarabine (HR 0.364, 95% CI 0.205-0.646, Wald p < 0.001) and CSF3R mutations (HR 2.667, 95% CI 1.276-5.572, Wald p = 0.009) were independently associated with RFS. Taken together, we found that induction regimen and CSF3R mutations were independent prognostic factors for AML with CEBPAdm.

KIAA1199 drives immune suppression to promote colorectal cancer liver metastasis by modulating neutrophil infiltration.

BACKGROUND AND AIMS: Metastasis is the primary cause of cancer mortality, and colorectal cancer (CRC) frequently metastasizes to the liver. Our previous studies demonstrated the critical role of KIAA1199 in tumor invasion and metastasis in CRC. In the present study, we described an immune regulatory effect of KIAA1199 that creates a permissive environment for metastasis. APPROACH AND RESULTS: Flow cytometry was used to examine the effects of KIAA1199 on the infiltration of tumor immune cells. Neutrophils and T cells were isolated, stimulated, and/or cultured for in vitro function assays. In the patients with CRC, high expression levels of KIAA1199 were associated with an increased neutrophil infiltration into the liver. This result was further validated in mouse metastasis models. The increased influx of neutrophils contributed to the KIAA1199-driven CRC liver metastasis. Mechanistically, KIAA1199 activated the TGFß signaling pathway by interacting with the TGFBR1/2 to stimulate CXCL1 and CXCL3 production, thereby driving the aggregation of immunosuppressive neutrophils. Genetic blockade or pharmacologic inhibition of KIAA1199 restored tumor immune infiltration, impeded tumor progression, and potentiated response to immune checkpoint blockade (ICB). CONCLUSIONS: These findings indicated that KIAA1199 could facilitate the liver infiltration of immunosuppressive neutrophils via the TGFß-chemokine (C-X-C motif) ligand (CXCL)3/1-CXCR2 axis, which might be clinically targeted for the treatment of hepatic metastasis.

Localized Degradation of Neutrophil Extracellular Traps by Photoregulated Enzyme Delivery for Cancer Immunotherapy and Metastasis Suppression.

Extrusion of neutrophil extracellular traps (NETs), a fundamental host innate immune defense against pathogens, has recently been linked to cancer resistance to immunotherapy and distant metastasis. These findings highlight interesting areas of cancer-elicited inflammation and potential therapeutic strategies. Disrupting existing NETs with DNase I has been proved to enhance the therapeutic efficacy of tumor immunotherapy and attenuate metastatic spread. However, systemic biodistribution of DNase I raises safety issues, potentially impairing host defense against infection. Hence, tumor-specific delivery and metastatic niche-targeted effects are attractive options for localized degradation of NETs. We have engineered a nanoplatform with a plasmonic gold blackbody (AuPB) core with broad-spectrum photo activity and a mesoporous polydopamine (mPDA) shell for efficient loading and photoregulated release of DNase I. The on-demand released DNase I triggered by the second near-infrared (NIR-II) light irradiation breaks the "NET-mediated physical barrier", thereby increasing the contact of immune cytotoxic cells with tumor cells in living mice and sensitizing immune checkpoint therapy of primary colorectal cancer (CRC). Moreover, the deposition and light-controlled cargo release from systemically delivered AuPB@mPDA carriers in liver, the most frequent site of CRC metastasis, abolished NET-mediated capture of circulating tumor cells and hence metastatic seeding. Our findings indicate that the localized, light-regulated release of DNase I by photoactive carriers in the NIR-II window represent a translational route for immune-mediated tumor regression and metastasis inhibition.