Sub-features orthogonal decoupling: Detecting bone wall absence via a small number of abnormal examples for temporal CT images.

The absence of bone wall located in the jugular bulb and sigmoid sinus of the temporal bone is one of the important reasons for pulsatile tinnitus. Automatic and accurate detection of these abnormal singes in CT slices has important theoretical significance and clinical value. Due to the shortage of abnormal samples, imbalanced samples, small inter-class differences, and low interpretability, existing deep-learning methods are greatly challenged. In this paper, we proposed a sub-features orthogonal decoupling model, which can effectively disentangle the representation features into class-specific sub-features and class-independent sub-features in a latent space. The former contains the discriminative information, while, the latter preserves information for image reconstruction. In addition, the proposed method can generate image samples using category conversion by combining the different class-specific sub-features and the class-independent sub-features, achieving corresponding mapping between deep features and images of specific classes. The proposed model improves the interpretability of the deep model and provides image synthesis methods for downstream tasks. The effectiveness of the method was verified in the detection of bone wall absence in the temporal bone jugular bulb and sigmoid sinus.

Empagliflozin alleviates the development of autoimmune myocarditis via inhibiting NF-κB-dependent cardiomyocyte pyroptosis.

Autoimmune myocarditis, which falls within the broad spectrum of myocarditis, is characterized by an excessive inflammatory response in the heart, and can progress into dilated cardiomyopathy and irreversible heart failure in all possibility. However, effective clinical therapeutics are limited due to its complex inflammatory reactions. Empagliflozin (EMPA) has been previously demonstrated to possess anti-inflammatory properties. This study aimed to determine the improvement effects of EMPA on cardiac dysfunction under the condition of autoimmune myocarditis, and to further investigate the potential mechanisms. In vivo, all male Balb/c mice were randomly divided into four groups: control, experimental autoimmune myocarditis (EAM), EAM+EMPA and EMPA. In vitro, the effects of EMPA on IL-18-stimulated H9C2 cells were explored and the underlying molecular mechanisms were further determined. EMPA treatment significantly inhibited the development of autoimmune myocarditis, and mice treated with EMPA exhibited improved cardiac function compared with that in the EAM group, potentially through modulating pyroptosis of myocardium. Specifically, the NF-κB pathway was activated in the hearts of the EAM mice, which further activated NLRP3 inflammasome-dependent pyroptosis. EMPA treatment significantly inhibited such activation, thus alleviating inflammatory reactions in the context of EAM. Moreover, in vitro, we also observed that EMPA significantly inhibited pyroptosis of IL-18-stimulated H9C2 cells, and reduced nuclear translocation of NF-κB and degradation of activated IκBα. This work provides the first direct evidence that EMPA can inhibit myocardial inflammation and improve cardiac function in EAM mice, partly attributed to the drug-induced suppression of cardiomyocyte pyroptosis via disrupting the NF-κB pathway.

The feasibility of level Ib-sparing intensity-modulated radiation therapy in patients with nasopharyngeal carcinoma and high-risk factors classified based on the International Guideline.

BACKGROUND AND PURPOSE: To examine the feasibility of level Ib-sparing intensity-modulated radiation therapy (IMRT) in patients with nasopharyngeal carcinoma (NPC) who had high-risk factors classified based on the International Guideline (IG). MATERIALS AND METHODS: We evaluated 961 non-metastatic NPC cases based on IG recommendations for prophylactic Ib irradiation. Four high-risk factors were used to categorise patients into three cohorts: A, B, and C. Propensity score matching was used to balance baseline characteristics in Cohort C, resulting in a matched Cohort C. Recurrence rates at level Ib and regional relapse-free survival (RRFS) rates were evaluated. RESULTS: Among patients with negative Ib lymph nodes (LNs), 18, 54, 420, and 444 exhibited involvement of structures that drain to level Ib as the first echelon (FES), involvement of the submandibular gland (SMG), level II LNs with radiologic extranodal extension (rENE), and level II nodes with a maximal axial diameter (MAD) ≥ 2 cm, respectively. The recurrence rate was highest in Cohort A (11.1 %). Cohort B had no level Ib recurrence. In matched Cohort C, recurrence rates were low in both groups (Ib-sparing group: 0.6 % vs. Ib-covering group: 0.6 %, P > 0.999). No significant differences were observed in 5-year RRFS rates between the two groups in cohort A (p = 0.208), cohort B (p = 0.905), and matched cohort C (p = 0.423). CONCLUSIONS: Level Ib-sparing IMRT could be performed safely for NPC patients with level II LNs who had rENE and/or MAD ≥ 2 cm. Further research should determine the necessity of level Ib prophylactic irradiation for patients with FES or SMG involvement.

High-Throughput Screening of Surface Engineered Cyanine Nanodots for Active Transport of Therapeutic Antibodies into Solid Tumor.

The successful delivery of therapeutic biomacromolecules into solid tumor holds great challenge due to their high resistance to penetrate through the complex tumor microenvironments. Here, active-transporting nanoparticles are harnessed to efficiently deliver biomacromolecular drugs into solid tumors through cell transcytosis. A series of molecularly precise cyanine 5-cored polylysine G5 dendrimers (Cy5 nanodots) with different peripheral amino acids (G5-AA) is prepared. The capability of these positively charged nanodots to induce cell endocytosis, exocytosis, and transcytosis is evaluated via fluorescence-based high-throughput screen. The optimized nanodots (G5-R) are conjugated with αPD-L1 (a therapeutic monoclonal antibody binding to programmed-death ligand 1) (αPD-L1-G5-R) to demonstrate the nanoparticle-mediated tumor active transport. The αPD-L1-G5-R can greatly enhance the tumor-penetration capability through adsorption-mediated transcytosis (AMT). The effectiveness of αPD-L1-G5-R is tested in treating mice bearing partially resected CT26 tumors, mimicking the local immunotherapy of residual tumors post-surgery in clinic. The αPD-L1-G5-R embedded in fibrin gel can efficiently mediate tumor cell transcytosis, and deliver αPD-L1 throughout the tumor, thereby enhancing immune checkpoint blockade, reducing tumor recurrence, and significantly prolonging the survival time. The active-transporting nanodots are promising platforms for efficient tumor delivery of therapeutic biomacromolecules.

In Situ Deposition of Drug and Gene Nanoparticles on a Patterned Supramolecular Hydrogel to Construct a Directionally Osteochondral Plug.

The integrated repair of bone and cartilage boasts advantages for osteochondral restoration such as a long-term repair effect and less deterioration compared to repairing cartilage alone. Constructing multifactorial, spatially oriented scaffolds to stimulate osteochondral regeneration, has immense significance. Herein, targeted drugs, namely kartogenin@polydopamine (KGN@PDA) nanoparticles for cartilage repair and miRNA@calcium phosphate (miRNA@CaP) NPs for bone regeneration, were in situ deposited on a patterned supramolecular-assembled 2-ureido-4 [lH]-pyrimidinone (UPy) modified gelation hydrogel film, facilitated by the dynamic and responsive coordination and complexation of metal ions and their ligands. This hydrogel film can be rolled into a cylindrical plug, mimicking the Haversian canal structure of natural bone. The resultant hydrogel demonstrates stable mechanical properties, a self-healing ability, a high capability for reactive oxygen species capture, and controlled release of KGN and miR-26a. In vitro, KGN@PDA and miRNA@CaP promote chondrogenic and osteogenic differentiation of mesenchymal stem cells via the JNK/RUNX1 and GSK-3ß/ß-catenin pathways, respectively. In vivo, the osteochondral plug exhibits optimal subchondral bone and cartilage regeneration, evidenced by a significant increase in glycosaminoglycan and collagen accumulation in specific zones, along with the successful integration of neocartilage with subchondral bone. This biomaterial delivery approach represents a significant toward improved osteochondral repair.

A distinct circular DNA profile intersects with proteome changes in the genotoxic stress-related hSOD1G93A model of ALS.

BACKGROUND: Numerous genes, including SOD1, mutated in familial and sporadic amyotrophic lateral sclerosis (f/sALS) share a role in DNA damage and repair, emphasizing genome disintegration in ALS. One possible outcome of chromosomal instability and repair processes is extrachromosomal circular DNA (eccDNA) formation. Therefore, eccDNA might accumulate in f/sALS with yet unknown function. METHODS: We combined rolling circle amplification with linear DNA digestion to purify eccDNA from the cervical spinal cord of 9 co-isogenic symptomatic hSOD1G93A mutants and 10 controls, followed by deep short-read sequencing. We mapped the eccDNAs and performed differential analysis based on the split read signal of the eccDNAs, referred as DifCir, between the ALS and control specimens, to find differentially produced per gene circles (DPpGC) in the two groups. Compared were eccDNA abundances, length distributions and genic profiles. We further assessed proteome alterations in ALS by mass spectrometry, and matched the DPpGCs with differentially expressed proteins (DEPs) in ALS. Additionally, we aligned the ALS-specific DPpGCs to ALS risk gene databases. RESULTS: We found a six-fold enrichment in the number of unique eccDNAs in the genotoxic ALS-model relative to controls. We uncovered a distinct genic circulome profile characterized by 225 up-DPpGCs, i.e., genes that produced more eccDNAs from distinct gene sequences in ALS than under control conditions. The inter-sample recurrence rate was at least 89% for the top 6 up-DPpGCs. ALS proteome analyses revealed 42 corresponding DEPs, of which 19 underlying genes were itemized for an ALS risk in GWAS databases. The up-DPpGCs and their DEP tandems mainly impart neuron-specific functions, and gene set enrichment analyses indicated an overrepresentation of the adenylate cyclase modulating G protein pathway. CONCLUSIONS: We prove, for the first time, a significant enrichment of eccDNA in the ALS-affected spinal cord. Our triple circulome, proteome and genome approach provide indication for a potential importance of certain eccDNAs in ALS neurodegeneration and a yet unconsidered role as ALS biomarkers. The related functional pathways might open up new targets for therapeutic intervention.

A single-cell atlas of West African lungfish respiratory system reveals evolutionary adaptations to terrestrialization.

The six species of lungfish possess both lungs and gills and are the closest extant relatives of tetrapods. Here, we report a single-cell transcriptome atlas of the West African lungfish (Protopterus annectens). This species manifests the most extreme form of terrestrialization, a life history strategy to survive dry periods that can last for years, characterized by dormancy and reversible adaptive changes of the gills and lungs. Our atlas highlights the cell type diversity of the West African lungfish, including gene expression consistent with phenotype changes of terrestrialization. Comparison with terrestrial tetrapods and ray-finned fishes reveals broad homology between the swim bladder and lung cell types as well as shared and idiosyncratic changes of the external gills of the West African lungfish and the internal gills of Atlantic salmon. The single-cell atlas presented here provides a valuable resource for further exploration of the respiratory system evolution in vertebrates and the diversity of lungfish terrestrialization.

Mitochondria-Targeted Thymidylate Synthase Inhibitor Based on Fluorescent Molecularly Imprinted Polymers for Tumor Antimetabolic Therapy.

Antimetabolites targeting thymidylate synthase (TS), such as 5-fluorouracil and capecitabine, have been widely used in tumor therapy in the past decades. Here, we present a strategy to construct mitochondria-targeted antimetabolic therapeutic nanomedicines based on fluorescent molecularly imprinted polymers (FMIP), and the nanomedicine was denoted as Mito-FMIP. Mito-FMIP, synthesized using fluorescent dye-doped silica as the carrier and amino acid sequence containing the active center of TS as the template peptide, could specifically recognize and bind to the active site of TS, thus inhibiting the catalytic activity of TS, and therefore hindering subsequent DNA biosynthesis, ultimately inhibiting tumor growth. The imprinting factor of FMIP reached 2.9, and the modification of CTPB endowed Mito-FMIP with the ability to target mitochondria. In vitro experiments demonstrated that Mito-FMIP was able to efficiently aggregate in mitochondria and inhibit CT26 cell proliferation by 59.9%. The results of flow cytometric analysis showed that the relative mean fluorescence intensity of Mito-FMIP accumulated in the mitochondria was 3.4-fold that of FMIP. In vivo experiments showed that the tumor volume of the Mito-FMIP-treated group was only one third of that of the untreated group. In addition, Mito-FMIP exibited the maximum emission wavelength at 682 nm, which allowed it to be used for fluorescence imaging of tumors. Taken together, this study provides a new strategy for the construction of nanomedicines with antimetabolic functions based on molecularly imprinted polymers.

Biomaterials promote in vivo generation and immunotherapy of CAR-T cells.

Chimeric antigen receptor-T (CAR-T) cell therapy based on functional immune cell transfer is showing a booming situation. However, complex manufacturing processes, high costs, and disappointing results in the treatment of solid tumors have limited its use. Encouragingly, it has facilitated the development of new strategies that fuse immunology, cell biology, and biomaterials to overcome these obstacles. In recent years, CAR-T engineering assisted by properly designed biomaterials has improved therapeutic efficacy and reduced side effects, providing a sustainable strategy for improving cancer immunotherapy. At the same time, the low cost and diversity of biomaterials also offer the possibility of industrial production and commercialization. Here, we summarize the role of biomaterials as gene delivery vehicles in the generation of CAR-T cells and highlight the advantages of in-situ construction in vivo. Then, we focused on how biomaterials can be combined with CAR-T cells to better enable synergistic immunotherapy in the treatment of solid tumors. Finally, we describe biomaterials' potential challenges and prospects in CAR-T therapy. This review aims to provide a detailed overview of biomaterial-based CAR-T tumor immunotherapy to help investigators reference and customize biomaterials for CAR-T therapy to improve the efficacy of immunotherapy.

A Novel Hexokinases Inhibitor Based on Molecularly Imprinted Polymer for Combined Starvation and Enhanced Photothermal Therapy of Malignant Tumors.

The heat tolerance of tumor cells induced by heat shock proteins (HSPs) is the major factor that seriously hinders further application of PTT, as it can lead to tumor inflammation, invasion, and even recurrence. Therefore, new strategies to inhibit HSPs expression are essential to improve the antitumor efficacy of PTT. Here, we prepared a novel nanoparticle inhibitor by synthesizing molecularly imprinted polymers with a high imprinting factor (3.1) on the Prussian Blue surface (PB@MIP) for combined tumor starvation and photothermal therapy. Owing to using hexokinase (HK) epitopes as the template, the imprinted polymers could inhibit the catalytic activity of HK to interfere with glucose metabolism by specifically recognizing its active sites and then achieve starvation therapy by restricting ATP supply. Meanwhile, MIP-mediated starvation downregulated the ATP-dependent expression of HSPs and then sensitized tumors to hyperthermia, ultimately improving the therapeutic effect of PTT. As the inhibitory effect of PB@MIP on HK activity, more than 99% of the mice tumors were eliminated by starvation therapy and enhanced PTT.

Multimode Sensing Platform Based on Turn-On Fluorescent Silicon Nanoparticles for Monitoring of Intracellular pH and GSH.

Various physiological activities and metabolic reactions of cells need to be carried out under the corresponding pH environment. Intracellular GSH as an acid tripeptide and an important reducing substance also plays an important role in maintaining cellular acid-base balance and redox balance. Therefore, developing a method to monitor pH and GSH and their changes in cells is necessary. Herein, we developed a novel turn-on fluorescent silicon nanoparticles (SiNPs) using N-(2-aminoethyl)-3-aminopropyltrimethoxysilane as the silicon source and dithiothreitol as the reducing agent via a one-pot hydrothermal method. It was worth mentioning that the fluorescence intensity of the SiNPs increased along with the acidity increase, making the SiNPs have excellent pH and GSH sensing capability. Furthermore, the pH and GSH sensing performance of the SiNPs in the cell was verified by confocal imaging and flow cytometry experiment. Based on the above, the prepared SiNPs had the potential to be used as an intracellular pH and GSH multimode fluorescent sensing platform and exhibited the ability to distinguish between normal cells and cancer cells.

Genome-scale CRISPR-Cas9 knockout screening in nasopharyngeal carcinoma for radiosensitive and radioresistant genes.

BACKGROUND: Genome-scale CRISPR-Cas9 knockout screening may provide new insights into the mechanism underlying clinical radioresistance in nasopharyngeal carcinoma (NPC), which is remain largely unknown. Our objective was to screen the functional genes associated with radiosensitivity and radioresistance in NPC, laying a foundation for further research on its functional mechanismand. METHODS: CRISPR-Cas9 library lentivirus screening in radiation-treated NPC cells was combined with second-generation sequence technology to identify functional genes, which were further validated in radioresistant NPC cells and patient tissues. RESULTS: Eleven radiosensitive and radioresistant genes were screened. Among these genes, the expression of FBLN5, FAM3C, MUS81, and DNAJC17 were significantly lower and TOMM20, CDKN2AIP, SNX22, and SP1 were higher in the radioresistant NPC cells (C666-1R, 5-8FR) (p < 0.05). CALD1 was highly expressed in C666-1R. Furthermore, we found knockout of FBLN5, FAM3C, MUS81 and DNAJC17 promoted the proliferation of NPC cells, while CDKN2AIP and SP1 had the opposed results (p < 0.05). This result was verified in NPC patient tissues. Meanwhile, KEGG analysis showed that the Fanconi anemia pathway and the TGF-ß signaling pathway possibly contributed to radiosensitivity or radioresistance in NPC. CONCLUSIONS: Nine genes involved in the radiosensitivity or radioresistance of NPC: four genes for radiosensitivity (FBLN5, FAM3C, MUS81, and DNAJC17), two genes for radioresistance (CDKN2AIP, SP1), two potential radioresistant genes (TOMM20, SNX22), and a potential radiosensitive gene (CALD1). Genome-scale CRISPR-Cas9 knockout screening for radiosensitive and radioresistant genes in NPC may provide new insights into the mechanisms underlying clinical radioresistance to improve the efficacy of radiotherapy for NPC.

A genome and single-nucleus cerebral cortex transcriptome atlas of the short-finned pilot whale Globicephala macrorhynchus.

Cetaceans (dolphins, whales, and porpoises) have large and anatomically sophisticated brains. To expand our understanding of the cellular makeup of cetacean brains and the similarities and divergence between the brains of cetaceans and terrestrial mammals, we report a short-finned pilot whale (Globicephala macrorhynchus) single-nucleus transcriptome atlas. To achieve this goal, we assembled a chromosome-scale reference genome spanning 2.25 Gb on 22 chromosomes and profiled the gene expression of five major anatomical cortical regions of the short-finned pilot whale by single-nucleus RNA-sequencing (snRNA-seq). We identified six major cell lineages in the cerebral cortex (excitatory neurons, inhibitory neurons, oligodendrocytes, oligodendrocyte precursor cells, astrocytes, and endothelial cells), eight molecularly distinct subclusters of excitatory neurons, and four subclusters of inhibitory neurons. Finally, a comparison of snRNA-seq data from the short-finned pilot whale, human, and rhesus macaque revealed a broadly conserved cellular makeup of brain cell types. Our study provides genomic resources and molecular insights into cetacean brain evolution.

Type I interferon signaling facilitates resolution of acute liver injury by priming macrophage polarization.

Due to their broad functional plasticity, myeloid cells contribute to both liver injury and recovery during acetaminophen overdose-induced acute liver injury (APAP-ALI). A comprehensive understanding of cellular diversity and intercellular crosstalk is essential to elucidate the mechanisms and to develop therapeutic strategies for APAP-ALI treatment. Here, we identified the function of IFN-I in the myeloid compartment during APAP-ALI. Utilizing single-cell RNA sequencing, we characterized the cellular atlas and dynamic progression of liver CD11b+ cells post APAP-ALI in WT and STAT2 T403A mice, which was further validated by immunofluorescence staining, bulk RNA-seq, and functional experiments in vitro and in vivo. We identified IFN-I-dependent transcriptional programs in a three-way communication pathway that involved IFN-I synthesis in intermediate restorative macrophages, leading to CSF-1 production in aging neutrophils that ultimately enabled Trem2+ restorative macrophage maturation, contributing to efficient liver repair. Overall, we uncovered the heterogeneity of hepatic myeloid cells in APAP-ALI at single-cell resolution and the therapeutic potential of IFN-I in the treatment of APAP-ALI.

Unraveling the Plasma Protein Corona by Ultrasonic Cavitation Augments Active-Transporting of Liposome in Solid Tumor.

Ligand/receptor-mediated targeted drug delivery has been widely recognized as a promising strategy for improving the clinical efficacy of nanomedicines but is attenuated by the binding of plasma protein on the surface of nanoparticles to form a protein corona. Here, it is shown that ultrasonic cavitation can be used to unravel surface plasma coronas on liposomal nanoparticles through ultrasound (US)-induced liposomal reassembly. To demonstrate the feasibility and effectiveness of the method, transcytosis-targeting-peptide-decorated reconfigurable liposomes (LPGLs) loaded with gemcitabine (GEM) and perfluoropentane (PFP) are developed for cancer-targeted therapy. In the blood circulation, the targeting peptides are deactivated by the plasma corona and lose their targeting capability. Once they reach tumor blood vessels, US irradiation induces transformation of the LPGLs from nanodrops into microbubbles via liquid-gas phase transition and decorticate the surface corona by reassembly of the lipid membrane. The activated liposomes regain the capability to recognize the receptors on tumor neovascularization, initiate ligand/receptor-mediated transcytosis, achieve efficient tumor accumulation and penetration, and lead to potent antitumor activity in multiple tumor models of patient-derived tumor xenografts. This study presents an effective strategy to tackle the fluid biological barriers of the protein corona and develop transcytosis-targeting liposomes for active tumor transport and efficient cancer therapy.

Single-cell-resolution transcriptome map revealed novel genes involved in testicular germ cell progression and somatic cells specification in Chinese tongue sole with sex reversal.

Female-to-male sex reversals (pseudomales) are common in lower vertebrates and have been found in natural populations, which is a concern under rapid changes in environmental conditions. Pseudomales can exhibit altered spermatogenesis. However, the regulatory mechanisms underlying pseudomale spermatogenesis remain unclear. Here, we characterized spermatogenesis in Chinese tongue sole (Cynoglossus semilaevis), a species with genetic and environmental sex determination, based on a high-resolution single-cell RNA-seq atlas of cells derived from the testes of genotypic males and pseudomales. We identified five germ cell types and six somatic cell types and obtained a single-cell atlas of dynamic changes in gene expression during spermatogenesis in Chinese tongue sole, including alterations in pseudomales. We detected decreased levels of Ca2+ signaling pathway-related genes in spermatogonia, insufficient meiotic initiation in spermatocytes, and a malfunction of somatic niche cells in pseudomales. However, a cluster of CaSR genes and MAPK signaling factors were upregulated in undifferentiated spermatogonia of pseudomales. Additionally, we revealed that Z chromosome-specific genes, such as piwil2, dhx37, and ehmt1, were important for spermatogenesis. These results improve our understanding of reproduction after female-to-male sex-reversal and provide new insights into the adaptability of reproductive strategies in lower vertebrates.

Efficacy of concurrent chemoradiotherapy plus Endostar compared with concurrent chemoradiotherapy in the treatment of locally advanced nasopharyngeal carcinoma: a retrospective study.

BACKGROUND: To retrospectively analyze the efficacy and safety of concurrent chemoradiotherapy (CCRT) plus recombinant human endostatin (Endostar, CCRT + E) versus CCRT alone in locally advanced nasopharyngeal carcinoma (LANPC). METHODS: A retrospective analysis of patients initially treated for LANPC from November 2016 to March 2019 was performed: trial group received CCRT + E and control group received CCRT. Prognoses and adverse effects were evaluated. RESULTS: Eighty-eight patients were included: 43 received CCRT + E and 45 received CCRT. The median follow-up time was 54.0 (range: 8.0-64.0) months. The survival data of the CCRT + E and CCRT groups were as follows: 3-year progression-free survival (PFS) rates, 81.4% and 63.6% (hazard ratio [HR] 0.418, 95%CI 0.181-0.963, P = 0.034); 3-year distant metastasis-free survival (DMFS) rates, 88.3% and 77.3% (HR 0.370, 95%CI 0.132-1.039, P = 0.049); 3-year overall survival rates, 88.2% and 81.9% (HR 0.437, 95%CI 0.151-1.260, P = 0.114); and 3-year locoregional failure-free survival rates, 87.8% and 86.9% (HR 0.795, 95%CI 0.242-2.616, P = 0.705). Three months after radiotherapy, the complete response (CR) rates of cervical lymph node regression were 97.7% and 82.2% for the CCRT + E and CCRT groups (P = 0.041). The corresponding CR rates were 100% and 80.0% for lymph node necrosis (P = 0.001) and 100% and 85.2% for extranodal extension (P = 0.041). The CCRT + E group had higher incidence of grade 3/4 leukopenia (32.6% vs. 13.3%, P = 0.031), with similar results for late toxicity. CONCLUSIONS: CCRT + E significantly prolonged 3-year PFS and DMFS in LANPC, and patients had better lymph node regression.

A geometric alignment for human temporal bone CT images via lateral semicircular canals segmentation.

PURPOSE: Due to the different posture of the subject and settings of CT scanners, the CT images of the human temporal bone should be geometrically aligned with multiplanar reconstruction to ensure the symmetry of the bilateral anatomical structure. Manual alignment is a time-consuming task for radiologists and an important preprocessing step for further computer-aided CT analysis. We propose a fully automatic alignment algorithm for temporal bone CT images via lateral semicircular canals (LSCs) segmentation. METHODS: The LSCs are segmented with our proposed multifeature fusion network as anchors at first. Then, we define a standard 3D coordinate system and propose an alignment procedure. RESULTS: The experimental results show that our LSC segmentation network achieved a higher segmentation accuracy. The acceptable rate is achieved 85% over 910 raw temporal bone CT sequences. The alignment speed is reduced from 10 min by manual to 60s. CONCLUSIONS: Aiming at the problem of bilateral asymmetry in the raw temporal bone CT images, we propose an automatic geometric alignment method. Our proposed method can help to perform alignment of temporal bone CT images efficiently.

Demographics and Economic Burden of Nasopharyngeal Carcinoma Inpatients.

Objective: Nasopharyngeal carcinoma is particularly prevalent in Guangdong and Guangxi (southern China); the economic burden of nasopharyngeal cancer patients is heavy in China. This study is aimed at retrospectively analyzing the basic features and economic burden of newly diagnosed nasopharyngeal carcinoma patients admitted to the First Affiliated Hospital of Guangxi Medical University and at providing a scientific basis for nasopharyngeal carcinoma prevention and control strategies. Methods: The data of 3,727 nasopharyngeal carcinoma inpatients diagnosed from January 2012 to December 2020 were extracted from the Guangxi Nasopharyngeal Carcinoma Healthcare Big Data Management Information Platform. Basic demographic characteristics, duration of hospital stay, and hospitalization cost of nasopharyngeal carcinoma patients were collected and analyzed statistically. Results: The incidence period of nasopharyngeal carcinoma was primarily from 30 to 69 years of age, with the 40-49-year age group comprising the largest proportion of nasopharyngeal carcinoma patients, accounting for 34.18% of the patients with newly diagnosed nasopharyngeal carcinoma in the hospital. The male-to-female ratio was 2.87 : 1. There were 2,223 cases from rural areas, 2,153 from the Han ethnic group, and 1,460 from the Zhuang ethnic group, accounting for 59.65%, 55.77%, and 39.17% of the total number of cases, respectively. The average duration of hospitalization decreased whereas the average hospitalization cost increased annually. Multivariate analysis of hospitalization cost showed that the duration of hospital stay, rural/urban, and ethnicity was the main influencing factors: the longer the duration of hospital stay, the higher the hospitalization cost; patients from rural incurred lower costs than from urban; ethnic Zhuang patients incurred significantly lower costs than patients from other ethnicities. Conclusion: Early diagnosis and treatment should be actively carried out to reduce the incidence of nasopharyngeal carcinoma, especially for rural, ethnic Zhuang, and males in the 40-49-year age group patients. The future research on nasopharyngeal carcinoma will focus on exploring the pathogenesis of nasopharyngeal carcinoma, improving the screening system, and reducing the burden on patients, in order to further improve the survival rate and quality of life of patients with nasopharyngeal carcinoma.

Protective Effect of Qiliqiangxin against Doxorubicin-Induced Cardiomyopathy by Suppressing Excessive Autophagy and Apoptosis.

BACKGROUND: Doxorubicin (DOX) is one of the most potent and widely prescribed antitumor agents; however, its clinical use is limited by cardiac side effects. In this study, we aimed to clarify the protective effects of Qiliqiangxin (QL), a traditional Chinese medicine formulation, on DOX-induced cardiotoxicity and to explore the underlying mechanisms in a rat model. METHODS: Male Sprague-Dawley rats were randomly assigned to three groups with different interventions (control, DOX, and DOX plus QL) for 31 days. Cardiac function was monitored. The levels of oxidative stress in plasm were detected, the activities of autophagy and apoptosis in rat hearts were determined, and then, the related PI3K/AKT/mTOR signal pathway regulating apoptosis and autophagy was investigated. RESULTS: QL improved cardiac dysfunction and decreased the increased level of cardiac enzymes in plasm caused by DOX. Moreover, DOX exposure resulted in oxidative stress enhancement, which was suppressed by QL treatment. Then, we discovered that DOX intervention caused the apoptosis of cardiomyocytes by activating the mitochondrial-dependent apoptotic pathway which was strongly inhibited by QL treatment. Furthermore, there was a significant increase in autophagic activities in the DOX-stimulated myocardium. Administration of QL substantially inhibited the enhanced autophagic activities, which might be attributed to the activation of PI3K/AKT/mTOR cascade, followed by suppression of ULK1 activity. CONCLUSIONS: QL exhibited protective roles against DOX-induced cardiotoxicity possibly via mediating the PI3K/AKT/mTOR pathway, leading to inhibition of autophagy and subsequent apoptosis activities.