Schizophrenia (SZ) stands as a severe psychiatric disorder. This study applied diffusion tensor imaging (DTI) data in conjunction with graph neural networks to distinguish SZ patients from normal controls (NCs) and showcases the superior performance of a graph neural network integrating combined fractional anisotropy and fiber number brain network features, achieving an accuracy of 73.79% in distinguishing SZ patients from NCs. Beyond mere discrimination, our study delved deeper into the advantages of utilizing white matter brain network features for identifying SZ patients through interpretable model analysis and gene expression analysis. These analyses uncovered intricate interrelationships between brain imaging markers and genetic biomarkers, providing novel insights into the neuropathological basis of SZ. In summary, our findings underscore the potential of graph neural networks applied to multimodal DTI data for enhancing SZ detection through an integrated analysis of neuroimaging and genetic features.
Humans ; Schizophrenia/pathology* ; Diffusion Tensor Imaging/methods* ; Male ; Female ; Adult ; Brain/metabolism* ; Young Adult ; Middle Aged ; White Matter/pathology* ; Gene Expression ; Nerve Net/diagnostic imaging* ; Graph Neural Networks

The key pathogenesis of coronary heart disease （CHD） is spleen deficiency and phlegm stasis， and dysfunctional high-density lipoprotein （dys-HDL） may be the biological basis for the occurrence of CHD due to spleen deficiency and phlegm stasis. Considering the biological properties and effects of high-density lipoprotein （HDL）， it is believed that the structure and components of HDL are abnormal in the state of spleen deficiency which led to dys-HDL； and dys-HDL contributes to the formation of atherosclerotic plaques through two major pathways， namely， mediating the dysfunction of endothelial cells and mediating the foaminess of macrophages and smooth muscle cells， thus triggering the development of CHD. It is also believed that dys-HDL is a microcosmic manifestation and a pathological product of spleen deficiency， and spleen deficiency makes foundation for the production of dys-HDL； dys-HDL is also an important biological basis for the phlegm-stasis interactions in CHD. The method of fortifying spleen， resolving phlegm， and dispelling stasis， is proposed as an important principle in the treatment of CHD by traditional Chinese medicine， which can achieve the therapeutic purpose by affecting the changes in the structure and components of dys-HDL， thus revealing the scientific connotation of this method， and providing ideas for the diagnosis and treatment of CHD by traditional Chinese medicine.

Lung cancer is a major cause of cancer-related mortality worldwide. Among patients with non-small cell lung cancer (NSCLC), approximately 3%-7% harbor anaplastic lymphoma kinase (ALK) gene fusions. In recent years, multiple tyrosine kinase inhibitors (TKIs) have significantly improved the survival of patients with metastatic ALK-positive NSCLC. However, disease progression due to resistance remains a challenge. This article retrospectively analyzes a case of advanced lung adenocarcinoma with the echinoderm microtubule associated protein like 4 (EML4)-ALK fusion variant 3 (V3). The patient developed resistance to Lorlatinib treatment accompanied by mesenchymal-epithelial transition factor (MET) amplification. Effective tumor control was achieved with the combined use of Crizotinib and Lorlatinib, providing a valuable reference for further exploration of treatment strategies following resistance to ALK-TKIs in clinical practice.
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Humans ; Adenocarcinoma/genetics* ; Adenocarcinoma of Lung/genetics* ; Aminopyridines/therapeutic use* ; Crizotinib/therapeutic use* ; Drug Resistance, Neoplasm/drug effects* ; Lactams/therapeutic use* ; Lung Neoplasms/genetics* ; Oncogene Proteins, Fusion/metabolism* ; Protein Kinase Inhibitors/therapeutic use* ; Proto-Oncogene Proteins c-met/metabolism* ; Pyrazoles/therapeutic use*

Spinal microglia and astrocytes are both involved in neuropathic and inflammatory pain, which may display sexual dimorphism. Here, we demonstrate that the sustained activation of spinal astrocytes and astrocyte-derived interleukin (IL)-17A promotes the progression of mouse bone cancer pain without sex differences. Chemogenetic or pharmacological inhibition of spinal astrocytes effectively ameliorates bone cancer-induced pain-like behaviors. In contrast, chemogenetic or optogenetic activation of spinal astrocytes triggers pain hypersensitivity, implying that bone cancer-induced astrocytic activation is involved in the development of bone cancer pain. IL-17A expression predominantly in spinal astrocytes, whereas its receptor IL-17 receptor A (IL-17RA) was mainly detected in neurons expressing VGLUT2 and PAX2, and a few in astrocytes expressing GFAP. Specific knockdown of IL-17A in spinal astrocytes blocked and delayed the development of bone cancer pain. IL-17A overexpression in spinal astrocytes directly induced thermal hyperalgesia and mechanical allodynia, which could be rescued by CaMKIIα inhibitor. Moreover, selective knockdown IL-17RA in spinal Vglut2 ⁺ or Vgat ⁺neurons, but not in astrocytes, significantly blocked the bone cancer-induced hyperalgesia. Together, our findings provide evidence for the crucial role of sex-independent astrocytic signaling in bone cancer pain. Targeting spinal astrocytes and IL-17A/IL-17RA-CaMKIIα signaling may offer new gender-inclusive therapeutic strategies for managing bone cancer pain.

Objective To discuss the clinical value of systemic immune-inflammation index(SII)in predicting the prognosis of patients with extrahepatic cholangiocarcinoma(ECCA)treated with biliary stenting combined with 125I seeds implantation.Methods A total of 128 patients with unresectable ECCA,who received biliary stenting combined with 125I seeds implantation at the Interventional Department of the Affiliated Hospital of Xuzhou Medical University of China between August 2018 and August 2021,were enrolled in this study.The peripheral blood routine testing was performed within 3 days before operation,based on which the SII was calculated.Receiver operating characteristic(ROC)curve was applied to determine the optimal cut-off value of SII,based on which the patients were divided into high-SII group and low-SII group.Cox regression model was used to analyze the independent factors affecting patient prognosis.The Kaplan-Meier curve was plotted to analyze the one-year survival.Results The optimal cut-off value of SII was 1 050,the sensitivity was 66.0％,the specificity was 69.3％,and the area under ROC curve of SII was 0.676.The one-year survival rate of patients with ECCA in the high-SII group was significantly lower than that in the low-SII group(P＜0.05).Univariate Cox regression analysis indicated that vascular invasion,T stage,adjuvant chemotherapy,CA19-9,and preoperative SII were the important factors affecting the prognosis of patients with ECCA.Multivariate Cox regression analysis revealed that T stage,CA19-9,and preoperative SII were the independent risk factors for patient prognosis,while adjuvant chemotherapy was a protective factor.The Kaplan-Meier curves showed that the one-year survival rate in high-SII group was remarkably lower than that in the low-SII group.Conclusion Preoperative SII has an important value in evaluating the prognosis of patients with ECCA who are treated with biliary stenting combined with 125I seed implantation.(J Intervent Radiol,2023,32:1221-1225)

OBJECTIVE: To predict the learning curve of tooth preparation for all ceramic crowns of maxillary central incisors on phantom head simulators for graduate students participating in standardized dental resident training based on the modified Wright learning curve model, then to analyze and applicate the learning curve. METHODS: Twelve graduate students participating in standardized dental resident training were selected to prepare the resin maxillary central incisors on phantom head simulators for all ceramic crowns 4 times. The results of preparation were evaluated by 3 prosthetic experts with at least 10 years' experience focusing on the reduction, contour, taper, shoulder, finish line, margin placement, adjacent tooth injury, and preparation time for tooth preparation. The learning rate of tooth preparation was calculated by scores of tooth preparation of 4 times. The learning curve of tooth preparation was predicted based on the modified Wright learning curve model. According to the criteria of standardized training skill examinations for dental residents in Beijing, 80 was taken as the qualified standard score. The minimum training times for tooth preparation to satisfy the qualified standard score (80) was calculated, to analyze the characteristics of learning curve and evaluate the effectiveness of tooth preparation. RESULTS: The scores of 4 tooth preparation were 64.03±7.80, 71.40±6.13, 74.33±5.96, and 75.98±4.52, respectively. The learning rate was (106±4)%, which showed the learning curve an upward trend. There were no significant differences between the qualified standard score and the predicted scores of tooth preparation from the 5^th preparation to the 13^th preparation (P > 0.05). The predicted score of the 14^th preparation was higher than the qualified standard score (P < 0.05). CONCLUSION The trend of the learning curve of tooth preparation for all ceramic crowns of maxillary central incisors on phantom head simulators for graduate students participating in standardized dental resident training is upward, which predicts the minimum training times higher than the qualified standard score is 14 times.
Humans ; Tooth Preparation, Prosthodontic/methods* ; Incisor ; Learning Curve ; Crowns ; Tooth Preparation ; Ceramics ; Dental Porcelain ; Dental Prosthesis Design

Streptococcus pneumoniae(SP)is one of the common pathogens of respiratory tract infection in children, which can evolve into severe pneumonia and necrotizing pneumonia in case of severe infection.β-lactam antibiotics are the first-line treatment for SP.The resistance mechanism of SP to β-lactam antibiotics is mainly PBPs gene mutation, followed by mutations related to non-PBPs genes such as MurM, CpoA, TEM, CiaH/CiaR-TCSS and StkP-PhpP signal conjugations.Antibiotic selection pressure and vaccine-induced serotype substitution may influence SP resistance.Serotypes 19F and 19A have high resistance to β-lactam antibiotics, and promotion of PCV13 may be more beneficial than other SP vaccines in preventing SP infection in children.

Four new prenylflavonoid glycosides, namely koreanoside H-K (1-4), together with eleven known ones (5-15) were isolated from the leaves of Epimedium koreanum Nakai. Their structures were elucidated by 1D NMR, 2D NMR, HR-ESI-MS, IR and UV. The identification of the sugar moieties was carried out by means of acid hydrolysis and HPLC analysis of their derivatives. It is worth noting that compound 3 and compound 4 were elucidated to contain fucose and quinovose moieties, which were two extremely rare sugar units from the genus Epimedium. The anti-pulmonary fibrosis activity of the new compounds was evaluated using A549 cell line. Compounds 1, 2 and 4 showed significant anti-pulmonary fibrosis activities.
Chromatography, High Pressure Liquid ; Epimedium/chemistry* ; Glycosides/pharmacology* ; Plant Extracts/pharmacology* ; Plant Leaves/chemistry*

Antrodia cinnamomea is extensively used as a traditional medicine to prevention and treatment of liver cancer. However, its comprehensive chemical fingerprint is uncertain, and the mechanisms, especially the potential therapeutic target for anti-hepatocellular carcinoma (HCC) are still unclear. Using UPLC‒Q-TOF/MS, 139 chemical components were identified in A. cinnamomea dropping pills (ACDPs). Based on these chemical components, network pharmacology demonstrated that the targets of active components were significantly enriched in the pathways in cancer, which were closely related with cell proliferation regulation. Next, HCC data was downloaded from Gene Expression Omnibus database (GEO). The Cancer Genome Atlas (TCGA) and DisGeNET were analyzed by bioinformatics, and 79 biomarkers were obtained. Furtherly, nine targets of ACDP active components were revealed, and they were significantly enriched in PI3K/AKT and cell cycle signaling pathways. The affinity between these targets and their corresponding active ingredients was predicted by molecular docking. Finally, in vivo and in vitro experiments showed that ACDPs could reduce the activity of PI3K/AKT signaling pathway and downregulate the expression of cell cycle-related proteins, contributing to the decreased growth of liver cancer. Altogether, PI3K/AKT-cell cycle appears as the significant central node in anti-liver cancer of A. Cinnamomea.

【Objective】 To investigate the mechanism of pristane inducing autophagy in macrophages. 【Methods】 Pristane was used to stimulate NR8383， a rat macrophage cell line. The changes in signaling pathways of AMPK， mTOR， and endoplasmic reticulum （ER） stress pathways including eIF2α and IRE1α in the cell model， as well as the expression of transcriptional factor TFEB and its translocation to the nucleus， were detected by using Western blotting. ER stress pathways were intervened by using an inducer DTT or an inhibitor 4-PBA to determin its effect on mTOR expression and autophay. 【Results】 In pristane-stimulated NR8383 cell model， ER stress pathway eIF2α was activated at 0.5 h after stimulation， and then mTOR expression was decreased at 1 and 3 h after stimulation. There was no change for AMPK and IRE1α pathways. With 4-PBA treatment， pristane-reduced mTOR expression and increased LC3-II were reversed， while with DTT treatment， mTOR expression decreased and LC3-II expression increased even more. Pristane induced the expression and activation of TFEB in NR8383 cells. 【Conclusion】 Pristane induces ER stress and leads to autophagy enhancement in rat macrophages.