Association between quadriceps fat pad edema and patellofemoral osteoarthritis: a quantitative Q-Dixon-based magnetic resonance imaging (MRI) analysis.

Background: Anterior knee pain (AKP) is a common symptom of patellofemoral osteoarthritis (PFOA). There is limited prospective evidence supporting the relationships between patellofemoral maltracking parameters, AKP, and PFOA. Thus, this prospective cross-sectional study aimed to determine the association between quadriceps fat pad (QFP) edema and patellofemoral maltracking in patients with chronic AKP and to evaluate the feasibility and diagnostic performance of a PFOA assessment using fat fraction (FF) and T2* based on Q-Dixon. Methods: This was a cross-sectional study with prospective data collection. Patients with chronic AKP were recruited from an orthopedic outpatient magnetic resonance imaging (MRI) waiting room at Shanghai Tongren Hospital between November 1, 2022, and April, 30, 2023. Exclusion criteria included age of <18 years, knee trauma, major internal derangement, prior surgery/arthroscopy, pre-existing joint diseases, and contraindications to MRI. MRI was performed using a 3.0-T instrument, and patellofemoral maltracking parameters were measured. Patellofemoral feature-relevant items, including patellar cartilage defects, patellar bone marrow lesions (BMLs), patellar osteophytes, anterior femoral osteophytes, Hoffa synovitis, and synovitis-effusion, from the semi-quantitative MRI Osteoarthritis Knee Score (MOAKS) were measured. The Anterior Knee Pain Scale (AKPS) was used to assess pain and function. FF/T2* measurement differences between groups and their associations with maltracking metrics, osteoarthritis grading based on the Iwano grading system, MOAKS, and AKPS, were investigated. Based on Iwano grading, the participants were categorized as having no-PFOA (n=40), mild PFOA (n=40), and advanced PFOA (n=40). Chi-squared and one-way analysis of variance were used to assess potential differences between the groups. Spearman's correlation test was used to analyze the correlation between the morphological parameters, AKPS, Iwano grade, MOAKS, and MRI quantitative values. Receiver operating characteristic (ROC) curves assessed the area under the curve (AUC), sensitivity, and specificity of quantitative values for distinguishing PFOA from no-PFOA. Results: Among the 120 included patients, those in the mild (86.2±8.5) and advanced (83.9±9.5) PFOA groups had significantly lower AKPS scores than those in the no-PFOA group (88.8±7.3) (P=0.03). The mean FF and T2* values of the QFP were significantly higher in the no-PFOA group than those in the mild and advanced PFOA groups (P<0.001 for FF and P=0.02 for T2*). Quantitative data on the QFP and patellofemoral maltracking parameters showed no association. FF (r=-0.686, P<0.001) and T2* (r=-0.314, P=0.008) showed a negative correlation with the Iwano grade. The AUCs for PFOA diagnosis were 0.906 [95% confidence interval (CI), 0.853-0.960] (FF) and 0.744 (95% CI, 0.657-0.831) (T2*). Conclusions: QFP FF and T2* were not associated with patellofemoral maltracking parameters but with increased PFOA in patients with AKP, suggesting that QFP abnormalities play a role in PFOA. Therefore, a quantitative QFP assessment (FF and T2*) based on Q-Dixon technology could be a convenient and reliable new imaging biomarker for PFOA severity during clinical diagnosis, treatment, and follow-up.

Histone Lactylation Is Involved in Mouse Oocyte Maturation and Embryo Development.

Numerous post-translational modifications are involved in oocyte maturation and embryo development. Recently, lactylation has emerged as a novel epigenetic modification implicated in the regulation of diverse cellular processes. However, it remains unclear whether lactylation occurs during oocyte maturation and embryo development processes. Herein, the lysine lactylation (Kla) modifications were determined during mouse oocyte maturation and early embryo development by immunofluorescence staining. Exogenous lactate was supplemented to explore the consequences of modulating histone lactylation levels on oocyte maturation and embryo development processes by transcriptomics. Results demonstrated that lactylated proteins are widely present in mice with tissue- and cell-specific distribution. During mouse oocyte maturation, immunofluorescence for H3K9la, H3K14la, H4K8la, and H4K12la was most intense at the germinal vesicle (GV) stage and subsequently weakened or disappeared. Further, supplementing the culture medium with 10 mM sodium lactate elevated both the oocyte maturation rate and the histone Kla levels in GV oocytes, and there were substantial increases in Kla levels in metaphase II (MII) oocytes. It altered the transcription of molecules involved in oxidative phosphorylation. Moreover, histone lactylation levels changed dynamically during mouse early embryogenesis. Sodium lactate at 10 mM enhanced early embryo development and significantly increased lactylation, while impacting glycolytic gene transcription. This study reveals the roles of lactylation during oocyte maturation and embryo development, providing new insights to improving oocyte maturation and embryo quality.

Targeting Super-Enhancer-Driven Transcriptional Dependencies Suppresses Aberrant Hedgehog Pathway Activation and Overcomes Smoothened Inhibitor Resistance.

Aberrant activation of the Hedgehog (Hh) signaling pathway plays important roles in oncogenesis and therapeutic resistance in several types of cancer. The clinical application of FDA-approved Hh-targeted Smoothened inhibitors (SMOi) is hindered by the emergence of primary or acquired drug resistance. Epigenetic and transcriptional targeted therapies represent a promising direction for developing improved anti-Hh therapies. In this study, we integrated epigenetic/transcriptional-targeted small-molecule library screening with CRISPR/Cas9 knockout library screening and identified CDK9 and CDK12, two transcription elongation regulators, as therapeutic targets for antagonizing aberrant Hh activation and overcoming SMOi resistance. Inhibition of CDK9 or CDK12 potently suppressed Hh signaling and tumor growth in various SMOi responsive or resistant Hh-driven tumor models. Systemic epigenomic profiling elucidated the Hh-driven super-enhancer (SE) landscape and identified IRS1, encoding a critical component and cytoplasmic adaptor protein of the IGF pathway, as an oncogenic Hh-driven SE target gene and effective therapeutic target in Hh-driven tumor models. Collectively, this study identifies SE-driven transcriptional dependencies that represent promising therapeutic vulnerabilities for suppressing the Hh pathway and overcoming SMOi resistance. As CDK9 and IRS inhibitors have already entered human clinical trials for cancer treatment, these findings provide comprehensive preclinical support for developing trials for Hh-driven cancers.

Carbene Footprinting Directs Design of Genetically Encoded Proximity-Reactive Protein Binders.

Genetically encoding proximal-reactive unnatural amino acids (PrUaas), such as fluorosulfate-l-tyrosine (FSY), into natural proteins of interest (POI) confer the POI with the ability to covalently bind to its interacting proteins (IPs). The PrUaa-incorporated POIs hold promise for blocking undesirable POI-IP interactions. Selecting appropriate PrUaa anchor sites is crucial, but it remains challenging with the current methodology, which heavily relies on crystallography to identify the proximal residues between the POIs and the IPs for the PrUaa anchorage. To address the challenge, here, we propose a footprinting-directed genetically encoded covalent binder (footprinting-GECB) approach. This approach employs carbene footprinting, a structural mass spectrometry (MS) technique that quantifies the extent of labeling of the POI following the addition of its IP, and thus identifies the responsive residues. By genetically encoding PrUaa into these responsive sites, POI variants with covalent bonding ability to its IP can be produced without the need for crystallography. Using the POI-IP model, KRAS/RAF1, we showed that engineering FSY at the footprint-assigned KRAS residue resulted in a KRAS variant that can bind irreversibly to RAF1. Additionally, we inserted FSY at the responsive residue in RAF1 upon footprinting the oncogenic KRASG12D/RAF1, which lacks crystal structure, and generated a covalent binder to KRASG12D. Together, we demonstrated that by adopting carbene footprinting to direct PrUaa anchorage, we can greatly expand the opportunities for designing covalent protein binders for PPIs without relying on crystallography. This holds promise for creating effective PPI inhibitors and supports both fundamental research and biotherapeutics development.

[Clinical Analysis of Mitoxantrone Liposome in the Treatment of Children with High-Risk Acute Myeloid Leukemia].

OBJECTIVE: To investigate the safety and efficacy of mitoxantrone liposome in the treatment of children with high-risk acute myeloid leukemia (AML). METHODS: The children with high-risk AML who received the mitoxantrone liposome regimen at Wuhan Children's Hospital from January 2022 to February 2023 were collected as the observation group, and the children with high-risk AML who received idarubicin regimen were enrolled as controls, and their clinical data were analyzed. Time to bone marrow recovery, the complete remission rate of bone marrow cytology, the clearance rate of minimal residual disease, and treatment-related adverse reactions were compared between the two groups. RESULTS: The patients treated with mitoxantrone liposome showed shorter time to recovery of leukocytes(17 vs 21 day), granulocytes(18 vs 24 day), platelets(17 vs 24 day), and hemoglobin(20 vs 26 day) compared with those treated with idarubicin, there were statistical differences (P <0.05). The effective rate and MRD turning negative rate in the observation group were 90.9% and 72.7%, respectively, while those in the control group were 94.1% and 76.4%, with no statistical difference (P >0.05). The overall response rate of the two groups of patients was similar. CONCLUSION: The efficacy of mitoxantrone liposome is not inferior to that of idarubicin in children with high-risk AML, but mitoxantrone liposome allows a significantly shorter duration of bone marrow suppression and the safety is better.

Erratum: [Corrigendum] Chloroquine potentiates the anticancer effect of sunitinib on renal cell carcinoma by inhibiting autophagy and inducing apoptosis.

[This corrects the article DOI: 10.3892/ol.2017.7635.].

E74-like ETS transcription factor 1 promotes the progression of pancreatic cancer by regulating doublecortin-like kinase 1/Janus kinase/signal transducer and activator of transcription pathway.

This study was targeted at investigating the biological functions of E74-like ETS transcription factor 1 (ELF1) in pancreatic cancer (PC) and its underlying mechanism. ELF1 expression in PC tissues was detected by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) and immunohistochemistry. Cell counting kit-8 (CCK-8) method, EdU method and flow cytometry were used to detect the cell proliferation and apoptosis of PC cell lines after transfection. A subcutaneous tumorigenesis model was constructed to validate the oncogenic role of ELF1 in vivo. PROMO database was used to predict the binding site of ELF1 on the promoter region of doublecortin-like kinase 1 (DCLK1). Dual-luciferase reporter gene assay, chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-qPCR) assay and quantitative real-time PCR were performed to detect the binding of ELF1 to the promoter region of DCLK1. The effect of ELF1 on DCLK1 expression was detected by Western blot assay. It was found that ELF1 expression in PC tissues and cells was up-regulated. ELF1 overexpression promoted the proliferation and inhibited the apoptosis of PC cells, while knocking down ELF1 had the opposite effects. ELF1 could bind to the promoter region of DCLK1 and ELF1 overexpression promoted the expression of DCLK1. Bioinformatics analysis suggested that Janus kinase (JAK) - signal transducer and activator of transcription (STAT) signaling pathway was associated to DCLK1 expression, and overexpression of ELF1 promoted the expression of Janus kinase 2 (JAK2) and signal transducer and activator of transcription 3 (STAT3). In conclusion, ELF1 promoted the malignant progression of PC via regulating DCLK1/ JAK/STAT signaling pathway.

Just give the contrast? Appraisal of guidelines on intravenous iodinated contrast media use in patients with kidney disease.

OBJECTIVE: To appraise the quality of guidelines on intravenous iodinated contrast media (ICM) use in patients with kidney disease, and to compare the recommendations among them. METHODS: We searched four literature databases, eight guideline libraries, and ten homepages of radiological societies to identify English and Chinese guidelines on intravenous ICM use in patients with kidney disease published between January 2018 and June 2023. The quality of the guidelines was assessed with the Scientific, Transparent, and Applicable Rankings (STAR) tool. RESULTS: Ten guidelines were included, with a median STAR score of 46.0 (range 28.5-61.5). The guidelines performed well in "Recommendations" domain (31/40, 78%), while poor in "Registry" (0/20, 0%) and "Protocol" domains (0/20, 0%). Nine guidelines recommended estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 as the cutoff for referring patients to discuss the risk-benefit balance of ICM administration. Three guidelines further suggested that patients with an eGFR < 45 mL/min/1.73 m2 and high-risk factors also need referring. Variable recommendations were seen in the acceptable time interval between renal function test and ICM administration, and that between scan and repeated scan. Nine guidelines recommended to use iso-osmolar or low-osmolar ICM, while no consensus has been reached for the dosing of ICM. Nine guidelines supported hydration after ICM use, but their protocols varied. Drugs or blood purification therapy were not recommended as preventative means. CONCLUSION: Guidelines on intravenous ICM use in patients with kidney disease have heterogeneous quality. The scientific societies may consider joint statements on controversial recommendations for variable timing and protocols. CRITICAL RELEVANCE STATEMENT: The heterogeneous quality of guidelines, and their controversial recommendations, leave gaps in workflow timing, dosing, and post-administration hydration protocols of contrast-enhanced CT scans for patients with kidney diseases, calling for more evidence to establish a safer and more practicable workflow. KEY POINTS: • Guidelines concerning iodinated contrast media use in kidney disease patients vary. • Controversy remains in workflow timing, contrast dosing, and post-administration hydration protocols. • Investigations are encouraged to establish a safer iodinated contrast media use workflow.

Non-invasive evaluation of testicular torsion using ultrasound shear wave elastography: an experimental study.

PURPOSE: The goal of this study was to examine changes in testicular stiffness at various intervals after the induction of testicular torsion, as well as to assess the predictive value of testicular stiffness for testicular spermatogenesis after torsion. METHODS: Sixty healthy male rabbits were randomly assigned to one of three groups: complete testicular torsion, incomplete testicular torsion, or control. All rabbits underwent preoperative and postoperative scrotal ultrasonography, including shear wave elastography (SWE), at predetermined intervals. Changes in SWE values were analyzed and compared using repeatedmeasures analysis of variance. To assess the diagnostic performance of SWE in determining the degree of spermatogenic function impairment, the areas under the receiver operating characteristic curves (AUCs) were calculated. RESULTS: SWE measurements in both central and peripheral zones of the testicular parenchyma affected by torsion demonstrated significant negative correlations with spermatogenesis, with coefficients of r=-0.759 (P<0.001) and r=-0.696 (P<0.001), respectively. The AUCs of SWE measurements in the central or peripheral zones of the torsed testicular parenchyma were 0.886 (sensitivity, 83.3%; specificity, 100%) and 0.824 (sensitivity, 83.3%; specificity, 73.3%) for distinguishing between hypospermatogenesis and spermatogenic arrest, respectively (P=0.451, DeLong test). CONCLUSION: Variations in the stiffness of both central and peripheral regions of the testicular parenchyma correlate with the extent and duration of torsion, exhibiting a specific pattern. The "stiff ring sign" is the characteristic SWE finding associated with testicular torsion. SWE appears to aid in the non-invasive determination of the extent of spermatogenic damage in torsed testes.

Cadherin-responsive hydrogel combined with dental pulp stem cells and fibroblast growth factor 21 promotes diabetic scald repair via regulating epithelial-mesenchymal transition and necroptosis.

Diabetes causes a loss of sensation in the skin, so diabetics are prone to burns when using heating devices. Diabetic scalded skin is often difficult to heal due to the microenvironment of high glucose, high oxidation, and low blood perfusion. The treatment of diabetic scald mainly focuses on three aspects: 1) promote the formation of the epithelium; 2) promote angiogenesis; and 3) maintain intracellular homeostasis. In response to these three major repair factors, we developed a cadherin-responsive hydrogel combined with FGF21 and dental pulp stem cells (DPSCs) to accelerate epithelial formation by recruiting cadherin to the epidermis and promoting the transformation of N cadherin to E cadherin; promoting angiogenesis to increase wound blood perfusion; regulating the stability of lysosomal and activating autophagy to maintain intracellular homeostasis in order to comprehensively advance the recovery of diabetic scald.

Target and Semitarget Analysis of Advanced Glycation End Products Using a New Pair of Permanently Positively Charged Stable Isotope Labeling Agents.

A pair of positively charged stable isotope labeling (SIL) agents, (4-carbonochloridoylphenyl)-trimethylazanium iodide (d0-CCPTA) and d6-CCPTA, were designed and synthesized. These agents were employed in the precolumn labeling of advanced glycation end products (AGEs) within 5 min under mild conditions. Through derivatization, the mass spectrometry response of the AGEs was enhanced by approximately 2 orders of magnitude. The detection and quantitation limits were in the ranges of 3.1-7.1 and 10.0-23.7 ng/kg, respectively. The recoveries were in the range of 90.1-94.3%, and the matrix effect ranged from -6.6 to -3.5%. CCPTA produced "CCPTA-specific production ions", and all analytes were analyzed by common multiple reaction monitoring (MRM) parameters. The common MRM parameters were applied to the semitarget analysis of 41 types of AGE candidates in the absence of standards, with 13 AGEs identified.

Vanadate-based Fe-MOFs as promising negative electrode for hybrid supercapacitor device.

In the supercapacitor field, negative electrodes are mainly concentrated in carbon-based materials, such as activated carbon, carbon nanotubes, graphene, and so forth. However, materials based on metal-organic frameworks (MOFs) as negative active components are relatively rare. Herein, a series of composite materials based on graphene oxide (GO) and vanadate-based Fe-organic frameworks have been prepared by hydrothermal method namely GO/Fe-VO4-BIPY. The deposition amount of polyoxometalate-based metal-organic frameworks (POMOFs) on the surface of graphene is adjusted by changing the content of POMOFs. Through the deposition, it can effectively reduce the accumulation between graphene, and increase the dispersion of POMOFs. As a result, the charge storage performance of the as-obtained materials is greatly improved. Among these materials, GO/Fe-VO4-BIPY-1 has the most prominent performance, with a specific capacitance of 190 F g-1at 0.5 A g-1, which is attributed to the excellent synergistic effect between the Faraday chemical reaction and electric double-layer capacitance. In comparison with pristine Fe-VO4-BIPY, GO/Fe-VO4-BIPY-1 delivers more excellent surface area and therefore exhibits abundant redox reaction sites, achieving better electrochemical performance the best. After assembly with the positive Ni(OH)2electrode, the maximum energy density of 46.84 W h kg-1at a power density of 850 W kg-1is achieved.

Incidence and Risk Factors for the Development of Axial Symptoms Following Posterior Single-Door Laminoplasty: A Retrospective Analysis.

OBJECTIVE: Posterior single-door laminoplasty is a widely practiced clinical procedure, but the occurrence of postoperative axial syndrome (AS) remains a significant concern. The aim of this study was to identify risk factors associated with AS and develop a risk prediction model. METHODS: Clinical data from 226 patients who underwent posterior single-door laminoplasty between June 2017 and June 2022 were collected. Through Logistic model analysis, the risk factors of AS are clarified and the intensity of each risk factor is explained in the form of forest plot. Subsequently, we constructed a predictive model and plotted receiver operating characteristic curves to assess the model's predictive value. RESULTS: In the end, 87 cases were diagnosed with AS, resulting in an incidence rate of 38.5%. Logistic regression analysis revealed that preoperative encroachment rate of anterior spinal canal (pre-op ERASC), intraoperative facet joints destruction, intraoperative open-door angle, postoperative loss of cervical curvature, and postoperative loss of cervical range of motion were independent risk factors for AS. Conversely, preoperative cervical curvature (pre-op CC) and postoperation early function training were protective factors against AS. The Youden index indicated that the cutoff values for pre-op ERASC and pre-op CC were 26.6°and 16.5, respectively. The risk prediction model for AS was constructed and a nomogram was plotted. The model has high clinical value. CONCLUSIONS: Pre-op ERASC, pre-op CC, intraoperative facet joints destruction, intraoperative open-door angle, postoperative loss of cervical curvature, postoperative loss of cervical range of motion, and postoperation early function training are independent influencing factors for AS occurrence. The risk model has good practicability.

Association between short-term exposure to ambient air pollution and upper respiratory tract infection in Kunshan.

The health effects of air pollution have become a major public health problem. Studies on the relationship between short-term exposure to air pollutants and upper respiratory tract infection (URTI) related clinic visits and expenditures were scarce. From January 1, 2019, to December 31, 2021, we included all the URTI cases that turned to 11 public hospitals in Kunshan, and summarized individual medical cost. Daily meteorological factors and 24-h mean concentrations of four common air pollutants, including particulate matter with an aerodynamic diameter less than 2.5 µm (PM2.5) and 10 µm (PM10), sulfur dioxide (SO2), and nitrogen dioxide (NO2), were consecutively recorded. Generalized additive regression model was adopted to quantify the associations between each air pollutant and the daily clinic visits of URTI cases. We further calculated attributable number (AN) and attributable fraction, and performed sensitivity analysis by gender, age, and season. A total of 934,180 cases were retrieved during the study period. PM2.5, PM10, SO2, and NO2 showed significant associations with hospital visits and expenditures due to URTI. Relative risks for them were 1.065 (95% confidence interval [CI] 1.055, 1.076), 1.045 (95% CI 1.037, 1.052), 1.098 (95% CI 1.038, 1.163), and 1.098 (95% CI 1.085, 1.111) on lag 0-5 days, respectively. Thirty-one thousand four hundred fifty-five (95% CI 27,457, 35,436) cases could be ascribed to increased NO2 and accounted for 3.37% (95% CI 2.94%, 3.79%) of all clinic visits. Sensitivity analyses indicated that the effects of air pollution were generally consistent for male and female. PM2.5, PM10, and NO2 had stronger associations among people aged ≤ 18 years, followed by those aged 19-64 years and ≥ 65 years. The association strengths of air pollution varied seasonally. Short-term exposure to ambient air pollutants had significant associations with clinic visits and expenditures owing to URTI. Children and adolescents appeared to be more susceptible to adverse health effects of air pollution. NO2 may be a priority when formulating pollution control measures.

Recent progress on phytoremediation of urban air pollution.

The rapid growth of population and economy has led to an increase in urban air pollutants, greenhouse gases, energy shortages, environmental degradation, and species extinction, all of which affect ecosystems, biodiversity, and human health. Atmospheric pollution sources are divided into direct and indirect pollutants. Through analysis of the sources of pollutants, the self-functioning of different plants can be utilized to purify the air quality more effectively. Here, we explore the absorption of greenhouse gases and particulate matter in cities as well as the reduction of urban temperatures by plants based on international scientific literature on plant air pollution mitigation, according to the adsorption, dust retention, and transpiration functions of plants. At the same time, it can also reduce the occurrence of extreme weather. It is necessary to select suitable tree species for planting according to different plant functions and environmental needs. In the context of tight urban land use, the combination of vertical greening and urban architecture, through the rational use of plants, has comprehensively addressed urban air pollution. In the future, in urban construction, attention should be paid to the use of heavy plants and the protection and development of green spaces. Our review provides necessary references for future urban planning and research.

Transgenerational hormesis and sublethal effects of five key insecticides for controlling Spodoptera frugiperda on its endoparasitoid Cotesia marginiventris.

BACKGROUND: The endoparasitoid Cotesia marginiventris (Cresson) is a promising biological control agent of the fall armyworm (FAW) Spodoptera frugiperda (Smith). Because the application of insecticides is one of the prime choices in pest management, we evaluated the sublethal and transgenerational effects of the five key insecticides-chlorantraniliprole, emamectin benzoate, spinetoram, Bacillus thuringiensis (Bt), and Mamestra brassicae nucleopolyhedrovirus (MbNPV)-on the parasitoid. RESULTS: Exposure to five insecticides at a concentration causing 10% mortality (LC10 ) caused hormetic effects in the parent generation (F0 ) by increasing the parasitism and reducing the immature duration. Interestingly, the hormetic response was also observed in the offspring generation indirectly exposed to the insecticides. Furthermore, insecticides increased the parasitism rate by 6.32-14.73% in the F1 generation, which was similar to that of the F0 generation (3.96-11.81%) compared with the control. No significant adverse effect was observed on the number of emerged parasitoids of the F1 and F2 generations. However, insecticides had a detrimental impact on body size and fecundity in the F1 and F2 generations, which showed a small body size with shorter hind tibiae and a significant reduction in the female ratio compared with the control; the exception was that chlorantraniliprole significantly improved the female ratio in the F2 generation. CONCLUSIONS: Five insecticides at LC10 induced transgenerational hormetic and sublethal effects on C. marginiventris. Our results provide a scientific basis for a better understanding of the long-term impacts of insecticides at sublethal doses on parasitoids, facilitating the development of improved integrated pest management programs for FAW control. © 2023 Society of Chemical Industry.

[Clinical Analysis of Infants with Acute Lymphoblastic Leukemia (18 cases)].

OBJECTIVE: To investigate the clinical features and outcomes of infants (<1 year old) with acute lymphoblastic leukemia (IALL). METHODS: The clinical manifestations, laboratory examination results, treatment and prognosis of 18 infants diagnosed with ALL at our department between January 1, 2014 and August 31, 2022 were retrospectively analyzed. RESULTS: Among the 18 cases of IALL, there were 10 males and 8 females. The median age of patients was 6.5 months old (3 months-11 months old). The median white blood cell count (WBC) was 33.63×109/L ï¼»(3.92-470)×109/Lï¼½ at initial diagnosis, including 2 patients with WBC≥300×109/L. Flow cytometric immunophenotyping showed a B-lineage infant ALL in all the 18 patients. Eight of the 18 children had abnormal chromosome karyotype analysis. Fusion gene detection showed 12 KMT2A-rearrangement of 18 patients. 15 patients underwent leukemia related mutation gene screening, among which KRAS, NRAS and FLT3 were the most common mutation genes. 4 patients underwent allogeneic hematopoietic stem cell transplantation and two survived. 14 patients received chemotherapy only and ten survived. The 3-year OS rate was (65.5±11.5)%, while the EFS rate was (46.9±12.3)%. CONCLUSION: B-cell ALL and KMT2A rearrangement are prevalent in IALL. The therapeutic effect of IALL with standard childhood ALL protocal is similer to international infant specific protocal.

Apolipoprotein E (ApoE) orchestrates adipose tissue inflammation and metabolic disorders through NLRP3 inflammasome.

Obesity is a metabolic disorder characterized by the hypertrophy expansion of adipose tissue, resulting in dysregulated energy metabolism, and accompanied by chronic low-grade inflammation. Adipose tissue macrophages (ATMs), a principal component of inflammation, respond to microenvironment signals and modulate adipose tissue remodeling and metabolic processes situation-specific. However, the mechanisms governing how the organism maintains equilibrium between its chronic inflammation and metabolism still need to be understood. Here, we describe a novel role of apolipoprotein E (ApoE), which associated with lipid particles, in maintaining fat deposition and system metabolic inflammation. Using human samples and mouse models, we show that ApoE is robustly downregulated in obese individuals, db/db mice, and mice of high-fat diet (HFD) feeding and increased in obese subjects with diabetes. Furthermore, we found that ApoE deficiency mice globally prevented obesity by restraining adipose tissue expansion and improved systemic glucose tolerance and insulin sensitivity. However, macrophage contributed to metabolic inflammation due to increased IL-1ß production in adipose tissue from ApoE-/- mice induced by HFD. Our results suggest that the role of ApoE in regulating obesity and obesity-associated glucose dysregulation is inconsistent. Mechanistically, ApoE modulates of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome priming and activation step. Thus, our studies might provide new sights into ApoE, which is required for obesity-induced hyperglycemia, hyperinsulinism, and adaptive inflammation responses but diminishes the tolerance towards a subsequent metabolic inflammatory challenge. Our study shed new light on the integral role of apolipoprotein APOE in immunometabolism and adipose tissue homeostasis.

Analysis of risk factors for axial symptoms after posterior cervical open-door laminoplasty.

BACKGROUND: Laminoplasty (LP), a procedure commonly used to treat cervical spondylotic myelopathy (CSM), often results in the development of axial symptoms (AS) postoperatively. This study aims to analyze the risk factors associated with the occurrence of AS after LP. METHODS: We collected and evaluated clinical data from 264 patients with CSM who underwent LP treatment at our institution from January 2018 to January 2022 through a single-center retrospective study. Of the patients, 153 were male and 111 were female, with an average age of 58.1 ± 6.7 years. All patients underwent C3-7 posterior laminoplasty. Based on the occurrence of postoperative axial symptoms, the patients were divided into an AS group and a non-AS group. General information, including age, gender, disease duration, Japanese Orthopaedic Association (JOA) score, postoperation early function training, and collar-wearing time, was recorded and compared between the two groups. Surgical-related data, such as operative segments, surgical time, intraoperative blood loss, intraoperative facet joint destruction, and destruction of the C7 spinous process muscle insertion, were also compared. Imaging data, including preoperative cervical curvature, cervical range of motion, preoperative encroachment rate of the anterior spinal canal, and angle of laminar opening, were collected. Univariate and multivariate logistic regression analyses were used to identify risk factors for the development of AS after LP, and receiver operator characteristic (ROC) curves were utilized to explore the optimal preoperative parameters. RESULTS: All 264 patients successfully underwent surgery and were followed up for an average of 19.5 ± 6.8 months. At the 6-month follow-up, 117 patients were diagnosed with AS, resulting in an incidence rate of 40.2%. The multivariate logistic regression analysis identified that preoperative encroachment rate of anterior spinal canal (Pre-op ERASC), intraoperative facet joints destruction (Intra-op FJD), intraoperative open-door angle (Intra-op OA), destroy the C7 spinous process muscle insertion (Destroy C7 SPMI), postoperative loss of cervical curvature (Post-op LCC), and postoperative loss of cervical range of motion (Post-op LCROM) were independent risk factors for AS. Conversely, preoperative cervical curvature (Pre-op CC) and postoperation early function training (Post-op EFT) were protective factors against AS. According to the ROC curve, the cutoff values for preoperative anterior spinal canal occupation rate and preoperative cervical curvature were 28.5% and 16.5°, respectively. When the preoperative anterior spinal canal occupation rate was greater than 28.5% or the preoperative cervical curvature was less than 16.5°, AS was more likely to occur after surgery. CONCLUSION: High preoperative anterior spinal canal occupation rate, facet joint damage during surgery, C7 spinous process muscle stop point damage, larger angle of laminar opening, and greater postoperative cervical curvature loss and cervical range of motion loss are associated with an increased risk of developing AS after cervical laminoplasty. Conversely, a larger preoperative cervical curvature and early postoperative functional exercises can help reduce the occurrence of AS.

Robustness of Quantitative Diffusion Metrics from Four Models: A Prospective Study on the Influence of Scan-Rescans, Voxel Size, Coils, and Observers.

BACKGROUND: Quantitative diffusion metrics provide additional microstructural information of diseases. The robustness of quantitative diffusion metrics should be established before clinical application. PURPOSE: To evaluate the variability and reproducibility of quantitative diffusion MRI metrics. STUDY TYPE: Prospective. POPULATION: 14 volunteers (7 men; median age, range, 28, 26-59 years). FIELD STRENGTH/SEQUENCE: 3.0-T/Diffusion spectrum imaging. ASSESSMENT: Brain MRI studies were performed four times per subject: involving different combinations of coil types and voxel sizes. Regions of interest of 13 brain anatomical sites were drawn by one observer twice and another observer once to allow interobserver and intraobserver reproducibility assessment. Twenty-five quantitative metrics were calculated using four diffusion models. STATISTICAL TESTS: The variability was evaluated with coefficients of variation (CV), and quartile coefficient of dispersion (QCD). The reproducibility was assessed with intraclass correlation coefficient (ICC), and concordance correlation coefficient (CCC). Wilcoxon signed rank test was used to compare the influence of factors on robustness of quantitative diffusion metrics. A two-tailed P < 0.05 was considered statistically significant. RESULTS: The variability of quantitative diffusion metrics showed CV of 2.4%-68.2%, and QCD of 0.6%-48.2%, respectively. The reproducibility of scans using 20-channel coils with voxels of 2 × 2 × 2 mm3 and 3 × 3 × 3 mm3 , respectively (ICC 0.03-0.84, CCC 0.03-0.84) was significantly worse than that of repeated scans using a 20-channel coil with a voxel size of 2 × 2 × 2 mm3 (ICC of 0.74-0.97, CCC 0.74-0.97) and that of scans using 20- and 64-channel coils, respectively, with a voxel size of 2 × 2 × 2 mm3 (ICC 0.59-0.95, CCC 0.59-0.95). The intraobserver reproducibility (ICC 0.49-0.94, CCC 0.49-0.94) was significantly better than the interobserver reproducibility (ICC 0.28-0.91, CCC 0.28-0.91). DATA CONCLUSION: Our study indicated that the voxel size has a greater influence on the reproducibility of quantitative diffusion metrics than scan-rescans and coils. The reproducibility within one observer was higher than that between two observers. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.