ObjectiveTo investigate the role and underlying mechanism of the Wnt/β-catenin signaling pathway in the process of Xiaojinwan （XJW）-containing serum interfering with endothelial-mesenchymal transition （EMT） in human breast cancer MDA-MB-231 cells. MethodsXJW-containing serum was prepared by intragastric administration of XJW （4 g·kg^-1） to SD rats. MDA-MB-231 cells were cultured in vitro. β-Catenin overexpression and knockdown plasmids were constructed and transfected into MDA-MB-231 cells. The optimal XJW-containing serum （4 g·kg^-1） according to previous studies was used for β-catenin intervention and overexpression experiments. The groups for intervention/overexpression experiments included intervention/overexpression blank group， β-catenin intervention/overexpression group， intervention/overexpression blank + XJW group， and β-catenin intervention/overexpression + XJW group. Cell morphology was observed under a microscope. Flow cytometry was used to detect and record apoptosis rates. Western blot was performed to measure apoptosis-related proteins ［B-cell lymphoma 2 （Bcl-2）， Bcl-2-associated X protein （Bax）， and active-Caspase-3］ and EMT-related proteins （E-cadherin， N-cadherin， and vimentin）. Real-time polymerase chain reaction （Real-time PCR） was used to detect β-catenin mRNA expression levels in different groups. ResultsIntervention experiment results showed that compared with the intervention blank group， the β-catenin intervention group and the intervention blank + XJW group showed increased apoptosis rates （P<0.05， P<0.01）， elevated protein levels of Bax， active Caspase-3， and E-cadherin （P<0.05， P<0.01）， and decreased protein levels of Bcl-2 and Vimentin （P<0.05， P<0.01）. β-catenin mRNA expression was reduced in the β-catenin intervention group （P<0.05， 0.63 ± 0.15） and the intervention blank + XJW group （P<0.05， 0.79 ± 0.33）. Compared with the β-catenin intervention group， the β-catenin intervention + XJW group exhibited an increased apoptosis rate （P<0.01）， elevated Bax and active Caspase-3 protein levels （P<0.05， P<0.01）， and decreased Bcl-2， N-cadherin， and Vimentin protein levels （P<0.05）. β-catenin mRNA expression was further reduced in the β-catenin intervention + XJW group （P<0.01， 0.22 ± 0.08）. Compared with the intervention blank + XJW group， the β-catenin intervention + XJW group showed an increased apoptosis rate （P<0.01）， elevated Bax， active Caspase-3， and E-cadherin protein levels （P<0.05， P<0.01）， and decreased Bcl-2， N-cadherin， and vimentin protein levels （P<0.05， P<0.01）. β-catenin mRNA expression was also reduced （P<0.05）. Overexpression experiment results showed that compared with the overexpression blank group， the β-catenin overexpression group exhibited a reduced apoptosis rate （P<0.01）， while the overexpression blank + XJW group showed an increased apoptosis rate （P<0.05）. In the β-catenin overexpression and β-catenin overexpression + XJW groups， Bax and E-cadherin protein levels decreased （P<0.05， P<0.01）， while Bcl-2， N-cadherin， and vimentin levels increased （P<0.05）. In the overexpression blank + XJW group， Bax and E-cadherin levels increased （P<0.05， P<0.01）， while Bcl-2， N-cadherin， and vimentin levels decreased （P<0.05， P<0.01）. β-catenin mRNA expression increased in the β-catenin overexpression group （P<0.01， 7.26 ± 1.03） but decreased in the overexpression blank + XJW group （P<0.05， 0.73 ± 0.14）. Compared with the β-catenin overexpression group， the β-catenin overexpression + XJW group showed an increased apoptosis rate （P<0.01）， elevated Bax and E-cadherin levels （P<0.05）， and decreased N-cadherin and vimentin levels （P<0.05）. β-catenin mRNA expression was reduced （P<0.05， 4.65 ± 1.02）. Compared with the overexpression blank + XJW group， the β-catenin overexpression + XJW group exhibited a reduced apoptosis rate （P<0.01）， decreased Bax and E-cadherin levels （P<0.01）， and increased Bcl-2， N-cadherin， and Vimentin levels （P<0.05）. β-catenin mRNA expression increased （P<0.01）. ConclusionXJW-containing serum inhibits breast cancer cell proliferation by suppressing EMT， which is associated with the regulation of the Wnt/β-catenin pathway.

Grounded in the theory of "all marrows dominated by brain", this study explored the therapeutic mechanism of Zuogui Pills in modulating the oxytocin(OXT)/oxytocin receptor(OXTR) feed-forward loop in the treatment of postmenopausal osteoporosis(PMOP). A PMOP rat model was established using ovariectomy, and 70 Sprague-Dawley female rats were randomly divided into the following groups: sham operation group, model group, estradiol group(17β-estradiol, 0.05 mg·kg~(-1)·d~(-1)), Zuogui Pills low, medium, and high dose groups(0.2, 0.4, 0.8 g·kg~(-1)·d~(-1), respectively), and an antagonist group(atosiban 0.9 mg·kg~(-1)·d~(-1) + 17β-estradiol 0.05 mg·kg~(-1)·d~(-1) + Zuogui Pills 0.4 g·kg~(-1)·d~(-1)). After 12 weeks of model establishment, treatment was administered by gavage once daily for another 12 weeks, followed by sample collection. Enzyme-linked immunosorbent assay(ELISA) was used to measure serum levels of estrogen(E_2), OXT, tartrate-resistant acid phosphatase(TRACP-5b), and bone alkaline phosphatase(BALP). Histopathological changes in the left distal femur were observed through hematoxylin and eosin(HE) staining. Micro-computed tomography(micro-CT) was used to analyze the microstructure of the right distal femur. Western blot was employed to detect the expression levels of OXTR, small GTP-binding protein Ras, Raf1 proto-oncogene(Raf1), mitogen-activated protein kinase kinase 1/2(MEK1/2), and extracellular signal-regulated kinase 1/2(ERK1/2), and their phosphorylated forms in tibial tissues. Compared with the model group, the Zuogui Pills medium and high dose groups showed significantly increased levels of E_2, OXT, and BALP, with a notable decrease in TRACP-5b levels. Morphologically, the trabeculae in the left distal femur were more tightly arranged. The fibrous structure in the right distal femur was significantly improved in the Zuogui Pills high dose group. Additionally, the expression of OXTR, Ras, p-Raf1, p-MEK1/2, and p-ERK1/2 proteins in tibial tissues was significantly increased. The therapeutic effect of the Zuogui Pills high dose group was partially inhibited when an OXTR antagonist was administered. These findings suggest that Zuogui Pills can regulate the OXT/OXTR feed-forward loop, activate the phosphorylation of the downstream Ras/Raf1/MEK/ERK signaling pathway, and ultimately improve bone mineral density, thereby exerting therapeutic effects in PMOP.
Animals ; Rats, Sprague-Dawley ; Rats ; Female ; Drugs, Chinese Herbal/administration & dosage* ; Oxytocin/genetics* ; Receptors, Oxytocin/genetics* ; Humans ; Osteoporosis, Postmenopausal/genetics* ; Bone and Bones/drug effects* ; Brain/drug effects* ; Bone Marrow/drug effects*

OBJECTIVES: To explore the mediating role of sleep duration in the relationship between depression symptoms and myopia among middle school students. METHODS: This study was a cross-sectional research conducted using a stratified cluster random sampling method. A total of 1 728 middle school students were selected from two junior high schools and two senior high schools in certain urban areas and farms of the Xinjiang Production and Construction Corps. Questionnaire surveys and vision tests were conducted among the students. Spearman analysis was used to analyze the correlation between depression symptoms, sleep duration, and myopia. The Bootstrap method was employed to investigate the mediating effect of sleep duration between depression symptoms and myopia. RESULTS: The prevalence of myopia in the overall population was 74.02% (1 279/1 728), with an average sleep duration of (7.6±1.0) hours. The rate of insufficient sleep was 83.62% (1 445/1 728), and the proportion of students exhibiting depression symptoms was 25.29% (437/1 728). Correlation analysis showed significant negative correlations between visual acuity in both eyes and sleep duration with depressive emotions as measured by the Center for Epidemiologic Studies Depression Scale (with correlation coefficients of -0.064, -0.084, and -0.199 respectively; P<0.01), as well as with somatic symptoms and activities (with correlation coefficients of -0.104, -0.124, and -0.233 respectively; P<0.01) and interpersonal relationships (with correlation coefficients of -0.052, -0.059, and -0.071 respectively; P<0.05). The correlation coefficients for left and right eye visual acuity and sleep duration were 0.206 and 0.211 respectively (P<0.001). Sleep duration exhibited a mediating effect between depression symptoms and myopia (indirect effect=0.056, 95%CI: 0.029-0.088), with the mediating effect value for females (indirect effect=0.066, 95%CI: 0.024-0.119) being higher than that for males (indirect effect=0.042, 95%CI: 0.011-0.081). CONCLUSIONS Sleep duration serves as a partial mediator between depression symptoms and myopia in middle school students.
Humans ; Myopia/etiology* ; Male ; Female ; Depression/physiopathology* ; Cross-Sectional Studies ; Sleep ; Adolescent ; Students ; Child ; Time Factors ; Sleep Duration

[This corrects the article DOI: 10.11909/j.issn.1671-5411.2017.08.005.].

Objective:To assess common errors in head and neck CT angiography (CTA) image reports using four types of large language models (LLM), namely GPT-4, DeepSeek, ERNIE Bot and SparkDesk, and to assess the feasibility of using existing LLMs to support quality control of radiology reports in Chinese.Methods:The study was a cross-sectional study. Totally 1 000 head and neck CTA image reports were randomly selected using the simple random sampling method from Xuanwu Hospital, Capital Medical University in 2023, including 500 primary reports and 500 finalized reports. Two radiologists collaboratively identified six types of errors in the reports: description errors, writing errors, left-right confusion errors, diagnostic omissions, logical sequence errors, and other errors. The overall quality of the reports was assessed using a 5-point Likert scale. Subsequently, GPT-4, DeepSeek, ERNIE Bot and SparkDesk models were employed to detect the same six types of errors in the imaging reports and to provide overall scoring. The results from manual review were considered the gold standard for calculating F1 score to evaluate model performance. Intra-class correlation coefficients ( ICC) were used to assess the consistency between manual scores and the overall scores from the four LLMs. Results:In the primary imaging reports, the proportions of manually detected errors were as follows: descriptive errors 2.6% (13/500), writing errors 0.6% (3/500), left-right confusion errors 0, diagnostic omissions 6.4% (32/500), logical sequence errors 5.2% (26/500), and other errors 0. In the finalized imaging reports, the proportions of errors across the six categories were 0.2% (1/500), 0, 0, 0, 0, and 0.2% (1/500), respectively. For error detection in the primary imaging reports, the F1 scores of GPT-4 for the six error types were 0.992, 0.997, 0.997, 0.967, 0.980, and 0.992, respectively. DeepSeek achieved F1 scores of 0.980, 0.955, 0.981, 0.920, 0.995, and 0.960; ERNIE Bot scored 0.982, 0.990, 1.000, 0.956, 0.976, and 0.999; and SparkDesk achieved 0.985, 0.995, 1.000, 0.961, 0.982, and 1.000. In the detection of errors in finalized imaging reports, GPT-4′s F1 scores were 0.994, 0.995, 0.998, 0.973, 0.989, and 0.993; DeepSeek scored 0.968, 0.965, 0.985, 0.971, 0.991, and 0.983; ERNIE Bot achieved 0.996, 0.992, 1.000, 0.983, 0.999, and 0.997; and SparkDesk achieved 0.999, 0.999, 1.000, 1.000, 1.000, and 0.999. The consistency between GPT-4, DeepSeek, and SparkDesk models and human ratings was moderate, with ICC values of 0.514, 0.560, and 0.515 respectively (all P0.001); in contrast, the overall score of ERNIE Bot showed poor consistency with human ratings, with an ICC of 0.221 ( P0.001). Conclusion:LLMs demonstrate high accuracy in detecting errors in head and neck CTA imaging reports. The overall scoring of report quality shows moderate consistency with manual assessments, indicating a certain feasibility for automated quality control in reporting.

BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

Objective:To assess common errors in head and neck CT angiography (CTA) image reports using four types of large language models (LLM), namely GPT-4, DeepSeek, ERNIE Bot and SparkDesk, and to assess the feasibility of using existing LLMs to support quality control of radiology reports in Chinese.Methods:The study was a cross-sectional study. Totally 1 000 head and neck CTA image reports were randomly selected using the simple random sampling method from Xuanwu Hospital, Capital Medical University in 2023, including 500 primary reports and 500 finalized reports. Two radiologists collaboratively identified six types of errors in the reports: description errors, writing errors, left-right confusion errors, diagnostic omissions, logical sequence errors, and other errors. The overall quality of the reports was assessed using a 5-point Likert scale. Subsequently, GPT-4, DeepSeek, ERNIE Bot and SparkDesk models were employed to detect the same six types of errors in the imaging reports and to provide overall scoring. The results from manual review were considered the gold standard for calculating F1 score to evaluate model performance. Intra-class correlation coefficients ( ICC) were used to assess the consistency between manual scores and the overall scores from the four LLMs. Results:In the primary imaging reports, the proportions of manually detected errors were as follows: descriptive errors 2.6% (13/500), writing errors 0.6% (3/500), left-right confusion errors 0, diagnostic omissions 6.4% (32/500), logical sequence errors 5.2% (26/500), and other errors 0. In the finalized imaging reports, the proportions of errors across the six categories were 0.2% (1/500), 0, 0, 0, 0, and 0.2% (1/500), respectively. For error detection in the primary imaging reports, the F1 scores of GPT-4 for the six error types were 0.992, 0.997, 0.997, 0.967, 0.980, and 0.992, respectively. DeepSeek achieved F1 scores of 0.980, 0.955, 0.981, 0.920, 0.995, and 0.960; ERNIE Bot scored 0.982, 0.990, 1.000, 0.956, 0.976, and 0.999; and SparkDesk achieved 0.985, 0.995, 1.000, 0.961, 0.982, and 1.000. In the detection of errors in finalized imaging reports, GPT-4′s F1 scores were 0.994, 0.995, 0.998, 0.973, 0.989, and 0.993; DeepSeek scored 0.968, 0.965, 0.985, 0.971, 0.991, and 0.983; ERNIE Bot achieved 0.996, 0.992, 1.000, 0.983, 0.999, and 0.997; and SparkDesk achieved 0.999, 0.999, 1.000, 1.000, 1.000, and 0.999. The consistency between GPT-4, DeepSeek, and SparkDesk models and human ratings was moderate, with ICC values of 0.514, 0.560, and 0.515 respectively (all P0.001); in contrast, the overall score of ERNIE Bot showed poor consistency with human ratings, with an ICC of 0.221 ( P0.001). Conclusion:LLMs demonstrate high accuracy in detecting errors in head and neck CTA imaging reports. The overall scoring of report quality shows moderate consistency with manual assessments, indicating a certain feasibility for automated quality control in reporting.

BACKGROUND:The development of calcium phosphate bone cement is limited due to its poor mechanical properties and weak osteogenic ability.Silicate bioactive glass is highly favored due to its excellent biological activity and osteogenic ability.Simultaneously,fiber structures can enhance the mechanical strength of materials.OBJECTIVE:To investigate the mechanical properties,biocompatibility,and osteogenic effect of silicate bioactive glass fiber composite calcium phosphate bone cement.METHODS:Different mass percentages(0％,10％,and 20％)of silicate bioactive glass fiber were added to the solid phase of calcium phosphate bone cement,mixed with the liquid phase and cured for 48 hours to obtain silicate bioactive glass fiber composite calcium phosphate bone cement.The mechanical properties,setting time,and ion precipitation of the cement were characterized.The three groups of bone cement extracts were co-cultured with MC3T3-E1 cells.The cell compatibility of the materials was evaluated by CCK-8 assay,live/dead staining,and phalloidin staining.After osteogenic induction,the osteogenic induction ability of the materials was evaluated by alkaline phosphatase staining,alizarin red staining,RUNX2 immunofluorescence staining,and RT-PCR.RESULTS AND CONCLUSION:(1)With the increase of silicate bioactive glass fiber content,the compressive strength and flexural strength of bone cement increased,and the setting time was prolonged.When bone cement was immersed in simulated body fluid,the precipitation of silicon ions,calcium ions,and phosphorus ions could be detected.Moreover,with the increase of silicate bioactive glass fiber content,the mass concentration of silicon ions and phosphorus ions released by bone cement increased,and the mass concentration of calcium ions decreased.(2)Live/dead staining and phalloidin staining results exhibited that silicate bioactive glass fiber composite calcium phosphate bone cement had no toxic effect on MC3T3-E1 cells.CCK-8 assay results showed that silicate bioactive glass fiber composite calcium phosphate bone cement could promote the proliferation of MC3T3-E1 cells.(3)With the increase of silicate bioactive glass fiber content in bone cement,the alkaline phosphatase activity and extracellular calcium deposition of MC3T3-E1 cells increased,the expression of RUNX2 protein increased,and the expression of alkaline phosphatase,osteocalcin,osteopontin,and RUNX2 mRNA expression increased.(4)The results indicate that silicate bioactive glass fibers can enhance the mechanical properties and osteogenic induction ability of calcium phosphate bone cement,among which 20％silicate bioactive glass fibers have a more obvious effect.

Convergence insufficiency intermittent exotropia (CI-IXT) is a subtype of intermittent exotropia.Surgery remains the most commonly used treatment.Improved unilateral lateral rectus recession-medial rectus resection (I-RR), slanted or nonslanted bilateral medial rectus resection (BMRs) and bilateral slanted lateral rectus recession (S-BLRc) are the commonly used modalities for surgical treatment.These treatment modalities have been able to correct distance and near exotropia and simultaneously reduce the near-distance difference.The clinical application of slanted or nonslanted BMRs is limited due to exodrift over time.I-RR and S-BLRc are widely used in clinics for patients with CI-IXT because of better long-term outcomes.A good knowledge of the different indications of each procedure and its appropriate application can lead to good clinical results.This article reviews recent advances in the surgical management of CI-IXT.