ObjectivePrimary liver cancer, predominantly hepatocellular carcinoma (HCC), is a significant global health issue, ranking as the sixth most diagnosed cancer and the third leading cause of cancer-related mortality. Accurate and early diagnosis of HCC is crucial for effective treatment, as HCC and non-HCC malignancies like intrahepatic cholangiocarcinoma (ICC) exhibit different prognoses and treatment responses. Traditional diagnostic methods, including liver biopsy and contrast-enhanced ultrasound (CEUS), face limitations in applicability and objectivity. The primary objective of this study was to develop an advanced, light-weighted classification network capable of distinguishing HCC from other non-HCC malignancies by leveraging the automatic analysis of brightness changes in CEUS images. The ultimate goal was to create a user-friendly and cost-efficient computer-aided diagnostic tool that could assist radiologists in making more accurate and efficient clinical decisions. MethodsThis retrospective study encompassed a total of 161 patients, comprising 131 diagnosed with HCC and 30 with non-HCC malignancies. To achieve accurate tumor detection, the YOLOX network was employed to identify the region of interest (ROI) on both B-mode ultrasound and CEUS images. A custom-developed algorithm was then utilized to extract brightness change curves from the tumor and adjacent liver parenchyma regions within the CEUS images. These curves provided critical data for the subsequent analysis and classification process. To analyze the extracted brightness change curves and classify the malignancies, we developed and compared several models. These included one-dimensional convolutional neural networks (1D-ResNet, 1D-ConvNeXt, and 1D-CNN), as well as traditional machine-learning methods such as support vector machine (SVM), ensemble learning (EL), k-nearest neighbor (KNN), and decision tree (DT). The diagnostic performance of each method in distinguishing HCC from non-HCC malignancies was rigorously evaluated using four key metrics: area under the receiver operating characteristic (AUC), accuracy (ACC), sensitivity (SE), and specificity (SP). ResultsThe evaluation of the machine-learning methods revealed AUC values of 0.70 for SVM, 0.56 for ensemble learning, 0.63 for KNN, and 0.72 for the decision tree. These results indicated moderate to fair performance in classifying the malignancies based on the brightness change curves. In contrast, the deep learning models demonstrated significantly higher AUCs, with 1D-ResNet achieving an AUC of 0.72, 1D-ConvNeXt reaching 0.82, and 1D-CNN obtaining the highest AUC of 0.84. Moreover, under the five-fold cross-validation scheme, the 1D-CNN model outperformed other models in both accuracy and specificity. Specifically, it achieved accuracy improvements of 3.8% to 10.0% and specificity enhancements of 6.6% to 43.3% over competing approaches. The superior performance of the 1D-CNN model highlighted its potential as a powerful tool for accurate classification. ConclusionThe 1D-CNN model proved to be the most effective in differentiating HCC from non-HCC malignancies, surpassing both traditional machine-learning methods and other deep learning models. This study successfully developed a user-friendly and cost-efficient computer-aided diagnostic solution that would significantly enhances radiologists’ diagnostic capabilities. By improving the accuracy and efficiency of clinical decision-making, this tool has the potential to positively impact patient care and outcomes. Future work may focus on further refining the model and exploring its integration with multimodal ultrasound data to maximize its accuracy and applicability.

Objective To explore the biomarkers and potential mechanisms of chronic restraint stress-induced myocardial injury in hyperlipidemia ApoE-/-mice.Methods The hyperlipidemia combined with the chronic stress model was established by restraining the ApoE-/-mice.Proteomics and bioinformatics techniques were used to describe the characteristic molecular changes and related regulatory mechanisms of chronic stress-induced myocardial injury in hyperlipidemia mice and to explore potential diagnostic biomarkers.Results Proteomic analysis showed that there were 43 significantly up-regulated and 58 sig-nificantly down-regulated differentially expressed proteins in hyperlipidemia combined with the restraint stress group compared with the hyperlipidemia group.Among them,GBP2,TAOK3,TFR1 and UCP1 were biomarkers with great diagnostic potential.KEGG pathway enrichment analysis indicated that fer-roptosis was a significant pathway that accelerated the myocardial injury in hyperlipidemia combined with restraint stress-induced model.The mmu_circ_0001567/miR-7a/Tfr-1 and mmu_circ_0001042/miR-7a/Tfr-1 might be important circRNA-miRNA-mRNA regulatory networks related to ferroptosis in this model.Conclusion Chronic restraint stress may aggravate myocardial injury in hyperlipidemia mice via ferrop-tosis.Four potential biomarkers are selected for myocardial injury diagnosis,providing a new direction for sudden cardiac death(SCD)caused by hyperlipidemia combined with the restraint stress.

This study aimed to investigate the prognostic significance of tumor mutation burden (TMB) among patients with non-small cell lung cancer (NSCLC) who received platinum-based adjuvant chemotherapy. Tumor tissue specimens after surgical resection were collected for DNA extraction. Somatic mutation detection and TMB analysis were conducted using next-generation sequencing (NGS). Recurrence status of the patients was assessed in the hospital during the adjuvant chemotherapy period, and long-term survival data of patients were obtained by telephone follow-up. Univariate analysis between TMB status and prognosis was carried out by survival analysis. A retrospective review of 78 patients with non-squamous NSCLC who received platinum-based adjuvant chemotherapy showed a median disease-free survival of 3.6 years and median overall survival (OS) of 5.3 years. NGS analysis exhibited that the most common mutated somatic genes among the 78 patients were tumor suppressor protein p53 (TP53), epidermal growth factor receptor, low-density lipoprotein receptor related protein 1B, DNA methyltransferase 3 alpha and FAT atypical cadherin 3, and their prevalence was 56.4%, 48.7%, 37.2%, 30.7%, and 25.6%, respectively. TMB status was divided into TMB-L (≤ 4.5/Mb) and TMB-H (> 4.5/Mb) based on the median TMB threshold. Relevance of TMB to prognosis suggested that the median OS of patients with TMB-L was significantly longer than that of patients with TMB-H (NR vs. 4.6, P = 0.014). Higher TMB status conferred a worse implication on OS among patients with non-squamous NSCLC who received platinum-based adjuvant chemotherapy.

OBJECTIVE: To establish an efficient protocol for directed differentiation of human induced pluripotent stem cells (hiPSCs) into functional midbrain dopaminergic progenitor cells (DAPs) in vitro. METHODS: hiPSCs were induced to differentiate into DAPs in two developmental stages. In the first stage (the first 13 days), hiPSCs were induced into intermediate cells morphologically similar to primitive neuroepithelial cells (NECs) in neural induction medium containing a combination of small molecule compounds. In the second stage, the intermediate cells were further induced in neural differentiation medium until day 28 to obtain DAPs. After CM-DiI staining, the induced DAPs were stereotactically transplanted into the right medial forebrain bundle (MFB) of rat models of Parkinson's disease (PD). Eight weeks after transplantation, the motor behaviors of PD rats was evaluated. Immunofluorescence assay of brain sections of the rats was performed at 2 weeks after transplantation to observe the survival, migration and differentiation of the transplanted cells in the host brain microenvironment. RESULTS: hiPSCs passaged stably on Matrigel showed a normal diploid karyotype, expressed the pluripotency markers OCT4, SOX2, and Nanog, and were positive for alkaline phosphatase. The primitive neuroepithelial cells obtained on day 13 formed dense cell colonies in the form of neural rosettes and expressed the neuroepithelial markers (SOX2, Nestin, and PAX6, 91.3%-92.8%). The DAPs on day 28 highly expressed the specific markers (TH, FOXA2, LMX1A and NURR1, 93.3-96.7%). In rat models of PD, the hiPSCs-DAPs survived and differentiated into TH⁺, FOXA2⁺ and Tuj1⁺ neurons at 2 weeks after transplantation. Eight weeks after transplantation, the motor function of PD rats was significantly improved as shown by water maze test (P < 0.0001) and apomorphine-induced rotation test (P < 0.0001) compared with rats receiving vehicle injection. CONCLUSION HiPSCs can be effectively induced to differentiate into DAPs capable of differentiating into functional neurons both in vivo and in vitro. In rat models of PD, the transplanted hiPSCs-DAPs can survive for more than 8 weeks in the MFB and differentiate into multiple functional neurocytes to ameliorate neurological deficits of the rats, suggesting the potential value of hiPSCs-DAPs transplantation for treatment of neurological diseases.
Humans ; Rats ; Animals ; Induced Pluripotent Stem Cells ; Cell Differentiation/physiology* ; Neurons ; Parkinson Disease ; Mesencephalon ; Cells, Cultured

OBJECTIVE: To analyze the characteristics and prognosis of acute leukemia(AL) with SET-NUP214 fusion gene. METHODS: The clinical data of 17 patients over 14 years old newly diagnosed with SET-NUP214 positive AL admitted in Institute of Hematology and Blood Diseases Hospital from August 2017 to May 2021 were analyzed retrospectively. RESULTS: Among the 17 SET-NUP214 positive patients, 13 cases were diagnosed as T-ALL (ETP 3 cases, Pro-T-ALL 6 cases, Pre-T-ALL 3 cases, Medullary-T-ALL 1 case), AML 3 cases (2 cases M5, 1 case M0) and ALAL 1 case. Thirteen patients presented extramedullary infiltration at initial diagnosis. All 17 patients received treatment, and a total of 16 cases achieved complete remission (CR), including 12 cases in patients with T-ALL. The total median OS and RFS time were 23 (3-50) months and 21 (0-48) months, respectively. Eleven patients received allogeneic hematopoietic stem cell transplantation(allo-HSCT), with median OS time of 37.5 (5-50) months and median RFS time of 29.5 (5-48) months. The median OS time of 6 patients in chemotherapy-only group was 10.5 (3-41) months, and median RFS time of 6.5 (3-39) months. The OS and RFS of patients with transplantation group were better than those of chemotherapy-only group (P=0.038). Among the 4 patients who relapsed or refractory after allo-HSCT, the SET-NUP214 fusion gene did not turn negative before transplantation. While, in the group of 7 patients who have not relapsed after allo-HSCT till now, the SET-NUP214 fusion gene expression of 5 patients turned negative before transplantation and other 2 of them were still positive. CONCLUSION The fusion site of SET-NUP214 fusion gene is relatively fixed in AL patients, often accompanied by extramedullary infiltration. The chemotherapy effect of this disease is poor, and allo-HSCT may improve its prognosis.
Humans ; Adolescent ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; Retrospective Studies ; Leukemia, Myeloid, Acute/therapy* ; Hematopoietic Stem Cell Transplantation ; Acute Disease ; Prognosis ; Leukemia-Lymphoma, Adult T-Cell/therapy* ; Nuclear Pore Complex Proteins

Four new sesquiterpene quinone meroterpenoids, dysideanones F-G (1-2) and dysiherbols D-E (3-4), were isolated from the marine sponge Dysidea avara collected from the South China Sea. The new structures were elucidated by extensive analysis of spectroscopic data including HR-MS and 1D and 2D NMR spectra, and their absolute configurations were assigned by single-crystal X-ray diffraction and ECD calculations. Anti-inflammatory evaluation showed that dysiherbols D-E (3-4) exhibited moderate inhibitory activity on TNF-α-induced NF-κB activation in human HEK-293T cells with IC₅₀ values of 10.2 and 8.6 μmol·L^-1, respectively.
Animals ; Dysidea/chemistry* ; Porifera ; Quinones/pharmacology* ; Sesquiterpenes/pharmacology* ; Skeleton

Objective:To explore the influencing factors for postoperative delirium in General Ward of Neurosurgery and evaluate the influence of serum acetylcholinesterase level in it.Methods:A retrospective study was performed. Two hundred and ninety-eight patients accepted surgery and diverted into General Ward of Neurosurgery in our hospital from January 2021 to July 2021 were chosen in our study. The 4AT delirium scoring tool was used to evaluate whether the patients had delirium, and these patients were, then, divided into non-delirium group and delirium group. The preoperative general data, history of deseases and laboratory results (serum acetylcholinesterase level) were collected. Univariate analysis and multivariate Logistic regression analysis were used to determine the independent factors affecting the occurrence of postoperative delirium, especially the relation between preoperative serum acetylcholinesterase level and postoperative delirium. Receiver operating characteristics (ROC) curve was drawn to evaluate the predictive value of serum acetylcholinesterase in postoperative delirium.Results:The incidence of postoperative delirium in 298 patients in General Ward of Neurosurgery was 24%, including 225 patients into the non-delirium group and 73 patients into the delirium group. There were significant differences between the two groups in the proportions of patients having resuscitation in anesthesia ICU, using postoperative analgesic pump and having alcoholism history, surgical duration, intraoperative bleeding, proportion of patients accepting skull base surgery, proportion of patients remaining awake 2 h after surgery, and incidence of bilateral frontal lobe pneumatosis after surgery ( P<0.05). Preoperative serum acetylcholinesterase level in delirium group ([2.35±0.49] U/mL) was significantly lower than that in non-delirium group ([2.78±0.48] U/mL, P<0.05). Preoperative serum acetylcholinesterase level ( OR=0.116, 95%CI: 0.034-0.394, P=0.001), postoperative resuscitation in anesthesia ICU ( OR=0.043, 95%CI: 0.002-0.878, P=0.041), keeping awake 2 h after surgery ( OR=7.641, 95%CI: 1.675-34.858, P=0.009), surgical duration ( OR=1.887, 95%CI: 1.192-2.987, P=0.007), intraoperative bleeding ( OR=1.010, 95%CI: 1.006-1.014, P<0.001), and skull base surgery ( OR=6.700, 95%CI: 1.907-23.547, P=0.003) were all independent influencing factors for postoperative delirium in patients in General Ward of Neurosurgery. The area under ROC curve for serum AchE level to predict the occurrence of postoperative delirium was 0.735(95%CI: 0.679-0.800, P<0.001); when the cut-off value was 2.67 U/mL, the sensitivity and specificity were 64% and 75%. Conclusions:Skull base surgery, keeping awake 2 h after surgery, long surgical duration and large amount of intraoperative bleeding can promote the occurrence of postoperative delirium; admission to anesthesia ICU after surgery can reduce the occurrence of delirium. When the preoperative serum AchE level is less than 2.67 U/mL, the possibility of postoperative delirium should be warned.

Branchial Region ; Branchioma/diagnosis* ; Humans ; Sleep ; Snoring

Brucea javanica oil emulsion (BJOE) has been used to treat tumor in China for more than 40 years. However, its components and effectiveness in the treatment of acute lymphocytic leukemia (ALL) and its mechanism of anti-cancer activity remain unknown. In the current study, high-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) was used to analyze the components of BJOE. Then, the anti-leukemia effects of BJOE were examined both in vitro and in vivo using ALL Jurkat cells and the p388 mouse leukemia transplant model, respectively. The primary ALL leukemia cells were also used to confirm the anti-leukemia effects of BJOE. The apoptotic-related results indicated that BJOE induced apoptosis in Jurkat cells and were suggestive of intrinsic apoptotic induction. Moreover, BJOE inhibited Akt (protein kinase B) activation and upregulated its downstream targets p53 and FoxO1 (forkhead box gene, group O-1) to initiate apoptosis. The activation of GSK3β was also involved. Our findings demonstrate that BJOE has anti-leukemia effects on ALL cells and can induce apoptosis in Jurkat cells through the phosphoinositide3-kinase (PI3K) /Akt signaling pathway.
Animals ; Apoptosis ; Brucea/chemistry* ; Glycogen Synthase Kinase 3 ; Humans ; Jurkat Cells ; Mice ; Phosphatidylinositol 3-Kinases/genetics* ; Plant Oils/pharmacology* ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy* ; Proto-Oncogene Proteins c-akt/genetics* ; Seeds/chemistry* ; Signal Transduction

Objective:To investigate the effect and mechanism of Chaihu Jia Longgu Mulitang （CJLM） on hippocampal NOD-like receptor protein 3 （NLRP3）inflammasome pathway in rats with depression. Method:Sixty male SD rats were randomly divided into a normal group，a model group， a MCC950 （1 mg·kg^-1） group， and high- （13 g·kg^-1）， medium- （6.5 g·kg^-1）， and low-dose （3.25 g·kg^-1） Chaihu Jia Longgu Mulitang groups， with 10 rats in each group．The depression model was induced by isolation combined with chronic unpredictable mild stimulation（CUMS） in rats except for those in the normal group. Rats were treated correspondingly for 21 days by intraperitoneal injection in the MCC950 group and gavage in other groups. The normal group and the model group received an equal volume of normal saline. The depression-like behaviors of rats were observed by sucrose preference test （SPT） and novelty-suppressed feeding test. Enzyme-linked immunosorbent assay （ELISA） was used to determine the levels of interleukin-1β （IL-1β） and IL-18 in the hippocampus of depressed rats. Western blot was used to detect the protein levels of NLRP3， apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain （ASC）， and Caspase-1. Result:Compared with the normal group， the model group showed decreased sucrose preference rate （P<0.01）， prolonged novelty-suppressed feeding time （P<0.01）， enhanced protein expression of NLRP3，ASC， and caspase-1 （P<0.05， P<0.01）， and elevated expression of IL-1β and IL-18 （P<0.01）. Conclusion:CJLM can alleviate depression-like behaviors in CUMS-induced model rats， and the underlying mechanism is related to the inhibition of the NLRP3 inflammasome pathway．