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1.
Cancers (Basel) ; 16(13)2024 Jul 03.
Article in English | MEDLINE | ID: mdl-39001511

ABSTRACT

Interobserver variations in the pathology of common astrocytic tumors impact diagnosis and subsequent treatment decisions. This study leveraged a residual neural network-50 (ResNet-50) in digital pathological images of diffuse astrocytoma, anaplastic astrocytoma, and glioblastoma to recognize characteristic pathological features and perform classification at the patch and case levels with identification of incorrect predictions. In addition, cellularity and nuclear morphological features, including axis ratio, circularity, entropy, area, irregularity, and perimeter, were quantified via a hybrid task cascade (HTC) framework and compared between different characteristic pathological features with importance weighting. A total of 95 cases, including 15 cases of diffuse astrocytoma, 11 cases of anaplastic astrocytoma, and 69 cases of glioblastoma, were collected in Taiwan Hualien Tzu Chi Hospital from January 2000 to December 2021. The results revealed that an optimized ResNet-50 model could recognize characteristic pathological features at the patch level and assist in diagnosis at the case level with accuracies of 0.916 and 0.846, respectively. Incorrect predictions were mainly due to indistinguishable morphologic overlap between anaplastic astrocytoma and glioblastoma tumor cell area, zones of scant vascular lumen with compact endothelial cells in the glioblastoma microvascular proliferation area mimicking the glioblastoma tumor cell area, and certain regions in diffuse astrocytoma with too low cellularity being misrecognized as the glioblastoma necrosis area. Significant differences were observed in cellularity and each nuclear morphological feature among different characteristic pathological features. Furthermore, using the extreme gradient boosting (XGBoost) algorithm, we found that entropy was the most important feature for classification, followed by cellularity, area, circularity, axis ratio, perimeter, and irregularity. Identifying incorrect predictions provided valuable feedback to machine learning design to further enhance accuracy and reduce errors in classification. Moreover, quantifying cellularity and nuclear morphological features with importance weighting provided the basis for developing an innovative scoring system to achieve objective classification and precision diagnosis among common astrocytic tumors.

2.
Nat Commun ; 15(1): 5792, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38987247

ABSTRACT

The construction of a large-scale quantum internet requires quantum repeaters containing multiple entangled photon sources with identical wavelengths. Semiconductor quantum dots can generate entangled photon pairs deterministically with high fidelity. However, realizing wavelength-matched quantum-dot entangled photon sources faces two difficulties: the non-uniformity of emission wavelength and exciton fine-structure splitting induced fidelity reduction. Typically, these two factors are not independently tunable, making it challenging to achieve simultaneous improvement. In this work, we demonstrate wavelength-tunable entangled photon sources based on droplet-etched GaAs quantum dots through the combined use of AC and quantum-confined Stark effects. The emission wavelength can be tuned by ~1 meV while preserving an entanglement fidelity f exceeding 0.955(1) in the entire tuning range. Based on this hybrid tuning scheme, we finally demonstrate multiple wavelength-matched entangled photon sources with f > 0.919(3), paving the way towards robust and scalable on-demand entangled photon sources for quantum internet and integrated quantum optical circuits.

3.
Radiology ; 311(3): e231937, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38916510

ABSTRACT

Background Diagnosing osteoporosis is challenging due to its often asymptomatic presentation, which highlights the importance of providing screening for high-risk populations. Purpose To evaluate the effectiveness of dual-energy x-ray absorptiometry (DXA) screening in high-risk patients with osteoporosis identified by an artificial intelligence (AI) model using chest radiographs. Materials and Methods This randomized controlled trial conducted at an academic medical center included participants 40 years of age or older who had undergone chest radiography between January and December 2022 without a history of DXA examination. High-risk participants identified with the AI-enabled chest radiographs were randomly allocated to either a screening group, which was offered fully reimbursed DXA examinations between January and June 2023, or a control group, which received usual care, defined as DXA examination by a physician or patient on their own initiative without AI intervention. A logistic regression was used to test the difference in the primary outcome, new-onset osteoporosis, between the screening and control groups. Results Of the 40 658 enrolled participants, 4912 (12.1%) were identified by the AI model as high risk, with 2456 assigned to the screening group (mean age, 71.8 years ± 11.5 [SD]; 1909 female) and 2456 assigned to the control group (mean age, 72.1 years ± 11.8; 1872 female). A total of 315 of 2456 (12.8%) participants in the screening group underwent fully reimbursed DXA, and 237 of 315 (75.2%) were identified with new-onset osteoporosis. After including DXA results by means of usual care in both screening and control groups, the screening group exhibited higher rates of osteoporosis detection (272 of 2456 [11.1%] vs 27 of 2456 [1.1%]; odds ratio [OR], 11.2 [95% CI: 7.5, 16.7]; P < .001) compared with the control group. The ORs of osteoporosis diagnosis were increased in screening group participants who did not meet formalized criteria for DXA compared with those who did (OR, 23.2 [95% CI: 10.2, 53.1] vs OR, 8.0 [95% CI: 5.0, 12.6]; interactive P = .03). Conclusion Providing DXA screening to a high-risk group identified with AI-enabled chest radiographs can effectively diagnose more patients with osteoporosis. Clinical trial registration no. NCT05721157 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Smith and Rothenberg in this issue.


Subject(s)
Absorptiometry, Photon , Neural Networks, Computer , Osteoporosis , Radiography, Thoracic , Humans , Female , Osteoporosis/diagnostic imaging , Male , Radiography, Thoracic/methods , Absorptiometry, Photon/methods , Aged , Mass Screening/methods , Middle Aged
4.
Int J Cancer ; 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38924042

ABSTRACT

Several life-prolonging therapies for metastatic castration-resistant prostate cancer (mCRPC) are available, including radium-223 dichloride (223Ra), which was approved based on phase 3 data demonstrating improved overall survival (OS) and a favorable safety profile. To date, real-world evidence for 223Ra use in Taiwan is from three studies of <50 patients. This observational study (NCT04232761) enrolled male patients with histologically/cytologically confirmed mCRPC with bone metastases from centers across Taiwan. 223Ra was prescribed as part of routine practice by investigators. Patients with prior 223Ra treatment were excluded. The primary objective was to assess 223Ra safety; secondary objectives evaluated efficacy parameters, including OS. Overall, 224 patients were enrolled. Most patients had an Eastern Cooperative Oncology Group performance status of 0/1 (79.0%) and ≤20 bone metastases (69.2%); no patients had visceral metastases. 223Ra was first- or second-line therapy in 23.2% and 47.7% of patients, respectively. The total proportion of patients who received 5-6 223Ra cycles was 68.8%; this proportion was greater with first-line use (84.3%) than second- (65.7%) or third-/fourth-line use (64.1%). More chemotherapy-naïve patients (61.9%) completed the 6-cycle 223Ra treatment than chemotherapy-exposed patients (56.7%). Any-grade treatment-emergent adverse events (TEAEs) and serious TEAEs occurred in 54.0% and 28.6% of patients, respectively, while 12% experienced 223Ra-related adverse events. Median OS was 15.7 months (95% confidence interval 12.13-19.51); patients receiving 5-6 223Ra injections and earlier 223Ra use had longer OS than those receiving fewer injections and later 223Ra use. 223Ra provides a well-tolerated and effective treatment for Taiwanese patients with mCRPC and bone metastases.

5.
J Pers Med ; 14(6)2024 Jun 09.
Article in English | MEDLINE | ID: mdl-38929840

ABSTRACT

This study compared the therapeutic effects of engineered exosomes derived from RAW264.7 cells overexpressing hsa-let-7i-5p (engineered exosomes) to exosomes from human placenta-derived mesenchymal stem cells (hpMSC exosomes) against sepsis-induced acute lung injury. Adult male C57BL/6 mice were divided into lipopolysaccharide (LPS), LPS plus engineered exosome (LEExo), or LPS plus hpMSC exosome (LMExo) groups, alongside control groups. The results showed that lung injury scores (based on pathohistological characteristics) and the levels of lung function alterations, tissue edema, and leukocyte infiltration in LEExo and LMExo groups were comparable and significantly lower than in the LPS group (all p < 0.05). Furthermore, the levels of inflammation (nuclear factor-κB activation, cytokine upregulation), macrophage activation (hypoxia-inducible factor-1α activation, M1 phase polarization), oxidation, and apoptosis were diminished in LEExo and LMExo groups compared to the LPS group (all p < 0.05). Inhibition of hsa-let-7i-5p attenuated the therapeutic effects of both engineered and hpMSC exosomes. These findings underscore the potent therapeutic capacity of engineered exosomes enriched with hsa-let-7i-5p and their potential as an alternative to hpMSC exosomes for sepsis treatment. Continued research into the mechanisms of action and optimization of engineered exosomes could pave the way for their future clinical application.

6.
J Chin Med Assoc ; 87(7): 678-685, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38829960

ABSTRACT

BACKGROUND: Multiparametric magnetic resonance imaging (mpMRI) followed by MRI-targeted prostate biopsy is the current standard for diagnosing prostate cancer (PCa). However, studies evaluating the value of biomarkers, including prostate health index (PHI) and its derivatives using this method are limited. We aimed to investigate the efficacy of PHI density (PHID) in guiding MRI-targeted prostate biopsies to identify clinically significant PCas (csPCa). METHODS: The multicenter prospectively registered prostate biopsy database from three medical centers in Taiwan included patients with PHI and MRI-targeted and/or systematic prostate biopsies. We assessed the required values of prostate-specific antigen (PSA), prostate volume, PHI, PHID, and Prostate Imaging Reporting & Data System (PI-RADS) score using multivariable analyses, receiver operating characteristic curve analysis, and decision curve analyses (DCA). csPCa was defined as the International Society of Urological Pathology Gleason group ≥2 PCa, with an emphasis on reducing unwarranted biopsies. RESULTS: The study cohort comprised 420 individuals. Diagnoses of PCa and csPCa were confirmed in 62.4% and 47.9% of the participants, respectively. The csPCa diagnosis rates were increased with increasing PI-RADS scores (20.5%, 44.2%, and 73.1% for scores 3, 4, and 5, respectively). Independent predictors for csPCa detection included PHI, prostate volume, and PI-RADS scores of 4 and 5 in multivariable analyses. The area under the curve (AUC) for csPCa of PHID (0.815) or PHI (0.788) was superior to that of PSA density (0.746) and PSA (0.635) in the entire cohort, and the superiority of PHID (0.758) was observed in PI-RADS 3 lesions. DCA revealed that PHID achieved the best net clinical benefit in PI-RADS 3-5 and 4/5 cases. Among PI-RADS 3 lesions, cutoff values of PHID 0.70 and 0.43 could eliminate 51.8% and 30.4% of omitted biopsies, respectively. CONCLUSION: PHI-derived biomarkers, including PHID, performed better than other PSA-derived biomarkers in diagnosing PCa in MRI-detected lesions.


Subject(s)
Magnetic Resonance Imaging , Prostate , Prostatic Neoplasms , Humans , Male , Prostatic Neoplasms/pathology , Prostatic Neoplasms/diagnostic imaging , Aged , Middle Aged , Prostate/pathology , Prostate/diagnostic imaging , Magnetic Resonance Imaging/methods , Prostate-Specific Antigen/blood , Image-Guided Biopsy/methods
7.
Sci Rep ; 14(1): 14897, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38942899

ABSTRACT

In order to improve the driving ability of the explosion wave simulation equipment, reduce the erosion effect of condensed explosives on the explosion wave simulation equipment, improve the safety of the test process, and make better use of the meteorological detonation driving method, it is necessary to optimize the source of the shock wave load in the driving section. Based on the finite volume method of FLACS, a methane detonation driving model corresponding to the test is established to explore the feasibility of using methane as an explosion source to test the structure against explosion shock wave. A methane detonation drive test was carried out to verify the accuracy of the numerical model. Finally, an engineering model for attenuation of shock wave overpressure peak value in pipeline is established by dimensional analysis, and the model coefficient is determined by numerical simulation and test data. The results show that the blast pressure is the highest when the methane volume ratio reaches 9.5 vol% in the methane-air mixture. Simply increasing oxygen content has little effect on the peak overpressure and positive pressure duration of shock wave. In the pure oxygen environment, the detonation effect can be achieved when the volume ratio of methane to oxygen is 1:2, and the incident pressure of the shock wave is proportional to the volume of the gas cloud. When the gas cloud volume is constant, a reasonable selection of methane-oxygen mixture ratio can achieve a better detonation effect, which can effectively increase the peak overpressure of the shock wave in the test section. The research results can provide technical reference for the development of new explosion wave simulation equipment.

8.
Am J Cancer Res ; 14(4): 1561-1576, 2024.
Article in English | MEDLINE | ID: mdl-38726259

ABSTRACT

Lung squamous cell carcinoma (LUSC) remains a difficult-to-treat disease with a poor prognosis. While prominin-1 (PROM1/CD-133) is largely investigated in a variety of malignancies, the role of prominin-2 (PROM2), the other member of the prominin family, has not been studied in LUSC. Transcriptomic data derived from matched tumor and adjacent non-tumorous lung tissues of LUSC patients were employed to conduct an in-depth analysis of the genetic and epigenetic regulation of prominin genes within LUSC, utilizing bioinformatic approaches. Furthermore, cellular behavior experiments were executed to discern the biological functions of PROM2. It was observed that PROM2, in contrast to PROM1, exhibited significant upregulation and overexpression at both the mRNA and protein levels in LUSC, and this upregulation was correlated with shortened patient survival. Transcriptomic analysis unveiled DNA methylation as an epigenetic regulatory mechanism associated with PROM2 expression. Notably, two transcription factors, CBFB and NRIP1, were identified as potential regulators of PROM2 expression. Subsequent in vitro investigations demonstrated that knocking down PROM2 led to the inhibition of cancer cell migration and the epithelial-to-mesenchymal transition (EMT). In summary, the pronounced upregulation of PROM2 in LUSC patients was linked to an unfavorable prognosis, possibly attributable to its influence on cancer cell migration and EMT. These findings suggest that PROM2 could serve as a promising diagnostic biomarker and therapeutic target in the management of LUSC. Consequently, further research into the mechanistic aspects and potential therapeutic interventions targeting PROM2 is warranted in the clinical context.

9.
Life Sci Alliance ; 7(8)2024 Aug.
Article in English | MEDLINE | ID: mdl-38760173

ABSTRACT

Dynamic rearrangements of the F-actin cytoskeleton are a hallmark of tumor metastasis. Thus, proteins that govern F-actin rearrangements are of major interest for understanding metastasis and potential therapies. We hypothesized that the unique F-actin binding and bundling protein SWAP-70 contributes importantly to metastasis. Orthotopic, ectopic, and short-term tail vein injection mouse breast and lung cancer models revealed a strong positive dependence of lung and bone metastasis on SWAP-70. Breast cancer cell growth, migration, adhesion, and invasion assays revealed SWAP-70's key role in these metastasis-related cell features and the requirement for SWAP-70 to bind F-actin. Biophysical experiments showed that tumor cell stiffness and deformability are negatively modulated by SWAP-70. Together, we present a hitherto undescribed, unique F-actin modulator as an important contributor to tumor metastasis.


Subject(s)
Actins , Breast Neoplasms , Lung Neoplasms , Microfilament Proteins , Neoplasm Metastasis , Animals , Actins/metabolism , Mice , Humans , Female , Cell Line, Tumor , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Breast Neoplasms/genetics , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Lung Neoplasms/genetics , Lung Neoplasms/secondary , Microfilament Proteins/metabolism , Microfilament Proteins/genetics , Cell Movement/genetics , Actin Cytoskeleton/metabolism , Cell Proliferation/genetics , Cell Adhesion/genetics , Protein Binding
10.
Int J Mol Sci ; 25(9)2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38732143

ABSTRACT

This study explores low-intensity extracorporeal shock wave therapy (LiESWT)'s efficacy in alleviating detrusor hyperactivity with impaired contractility (DHIC) induced by ovarian hormone deficiency (OHD) in ovariectomized rats. The rats were categorized into the following four groups: sham group; OVX group, subjected to bilateral ovariectomy (OVX) for 12 months to induce OHD; OVX + SW4 group, underwent OHD for 12 months followed by 4 weeks of weekly LiESWT; and OVX + SW8 group, underwent OHD for 12 months followed by 8 weeks of weekly LiESWT. Cystometrogram studies and voiding behavior tracing were used to identify the symptoms of DHIC. Muscle strip contractility was evaluated through electrical-field, carbachol, ATP, and KCl stimulations. Western blot and immunofluorescence analyses were performed to assess the expressions of various markers related to bladder dysfunction. The OVX rats exhibited significant bladder deterioration and overactivity, alleviated by LiESWT. LiESWT modified transient receptor potential vanilloid (TRPV) channel expression, regulating calcium concentration and enhancing bladder capacity. It also elevated endoplasmic reticulum (ER) stress proteins, influencing ER-related Ca2+ channels and receptors to modulate detrusor muscle contractility. OHD after 12 months led to neuronal degeneration and reduced TRPV1 and TRPV4 channel activation. LiESWT demonstrated potential in enhancing angiogenic remodeling, neurogenesis, and receptor response, ameliorating DHIC via TRPV channels and cellular signaling in the OHD-induced DHIC rat model.


Subject(s)
Disease Models, Animal , Extracorporeal Shockwave Therapy , Muscle Contraction , TRPV Cation Channels , Urinary Bladder , Animals , Female , Rats , TRPV Cation Channels/metabolism , TRPV Cation Channels/genetics , Extracorporeal Shockwave Therapy/methods , Urinary Bladder/physiopathology , Urinary Bladder/metabolism , Urinary Bladder, Overactive/therapy , Urinary Bladder, Overactive/metabolism , Urinary Bladder, Overactive/physiopathology , Urinary Bladder, Overactive/etiology , Ovariectomy , Rats, Sprague-Dawley , Ovary/metabolism
11.
Adv Sci (Weinh) ; 11(25): e2401685, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38664981

ABSTRACT

The redox mediated photoelectrochemical (PEC) or electrochemical (EC) alkene oxidation process is a promising method to produce high value-added epoxides. However, due to the competitive reaction of water oxidation and overoxidation of the mediator, the utilization of the electricity is far below the ideal value, where the loss of epoxidation's faradaic efficiency (FE) is ≈50%. In this study, a Br-/HOBr-mediated method is developed to achieve a near-quantitative selectivity and ≈100% FE of styrene oxide on α-Fe2O3, in which low concentration of Br- as mediator and locally generated acidic micro-environment work together to produce the higher active HOBr species. A variety of styrene derivatives are investigated with satisfied epoxidation performance. Based on the analysis of local pH-dependent epoxidation FE and products distribution, the study further verified that HOBr serves as the true active mediator to generate the bromohydrin intermediate. It is believed that this strategy can greatly overcome the limitation of epoxidation FE to enable future industrial applications.

12.
Chem Biodivers ; 21(7): e202400635, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38687253

ABSTRACT

The phytochemical investigation of the fruits of Cornus officinalis yielded a new phenolic acid derivative, neophenolic acid A (1), and a novel flavonoid glycoside, (2R)-naringenin-7-O-ß-(6''-galloyl-glucopyranoside) (2 a), along with six known flavonoid glycosides (2 b-7). Their structures were determined by 1D, 2D NMR and HRESIMS data. The absolute configuration of 1 was established by ECD analysis. Compounds 1- 7 were evaluated for their neuroprotective activities against corticosterone (CORT)-induced injury in PC-12 cells. Compounds 1, 2 a, 2 b, 5, and 6 exhibited neuroprotective activities against CORT-induced neurotoxicity in PC-12 cells. The underlying mechanism study suggested that compounds 1, 2 a, 2 b, 5, and 6 were able to attenuate CORT-induced apoptosis and damage, increase the levels of MMP and decrease Ca2+ inward flow in PC-12 cells.


Subject(s)
Apoptosis , Cornus , Fruit , Neuroprotective Agents , Cornus/chemistry , Neuroprotective Agents/pharmacology , Neuroprotective Agents/chemistry , Neuroprotective Agents/isolation & purification , Animals , Fruit/chemistry , Rats , PC12 Cells , Apoptosis/drug effects , Corticosterone/pharmacology , Cell Survival/drug effects , Molecular Structure , Flavonoids/pharmacology , Flavonoids/isolation & purification , Flavonoids/chemistry , Structure-Activity Relationship , Calcium/metabolism
13.
Cell Death Discov ; 10(1): 137, 2024 Mar 14.
Article in English | MEDLINE | ID: mdl-38485916

ABSTRACT

Ferroptosis, an iron-dependent form of regulated cell death, plays a crucial role in modulating the therapeutic response in non-small cell lung cancer (NSCLC) patients. Studies have identified the signal transducer and activator of transcription 3 (STAT3) and myeloid cell leukemia-1 (MCL1) as potential targets for sorafenib, which exhibits activities in inducing ferroptosis. However, the role of STAT3-MCL1 axis in sorafenib-induced ferroptosis in NSCLC is still unclear. This study provided evidence that ferroptosis is a critical driver of sorafenib-induced cell death in NSCLC, supported by the accumulation of lipid peroxidation products, indicative of oxidative stress-induced cell death. Additionally, both in vitro and in vivo experiments showed that ferroptosis contributed to a significant portion of the anti-cancer effects elicited by sorafenib in NSCLC. The noticeable accumulation of lipid peroxidation products in sorafenib-treated mice underscored the significance of ferroptosis as a contributing factor to the therapeutic response of sorafenib in NSCLC. Furthermore, we identified the involvement of the STAT3/MCL1 axis in sorafenib-induced antitumor activity in NSCLC. Mechanistically, sorafenib inhibited endogenous STAT3 activation and downregulated MCL1 protein expression, consequently unleashing the ferroptosis driver BECN1 from the BECN1-MCL1 complex. Conversely, there is an augmented association of BECN1 with the catalytic subunit of system Xc-, SLC7A11, whose activity to import cystine and alleviate lipid peroxidation is hindered upon its binding with BECN1. Notably, we found that MCL1 upregulation correlated with ferroptosis resistance in NSCLC upon sorafenib treatment. Our findings highlight the importance of sorafenib-triggered ferroptosis in NSCLC and offer a novel strategy to treat advanced NSCLC patients: by downregulating MCL1 and, in turn, predispose NSCLC cells to ferroptosis.

14.
Oncology ; 2024 Mar 12.
Article in English | MEDLINE | ID: mdl-38471461

ABSTRACT

INTRODUCTION: The study explored the failure pattern and clinical outcomes in patients with ependymoma undergoing radiotherapy. METHODS: Between January 2004 and June 2022, we included 32 patients with ependymoma who underwent radiotherapy as part of the multimodality treatment at our institution. Of these, 27 (84.4%) underwent adjuvant radiotherapy, four received radiotherapy after local recurrence, and one received definitive CyberKnife radiotherapy (21 Gy in three fractions). The median prescribed dose was 54 Gy in patients who received conventional radiotherapy. We analyzed the local progression-free survival (LPFS), distant metastasis-free survival (DMFS), progression-free survival (PFS), overall survival (OS), and potential prognostic factors. RESULTS: The median age was 29.8 years. Approximately 28.1% were pediatric patients. Fifteen tumors (46.9%) were World Health Organization (WHO) grade II, 10 (31.3%) were WHO grade III, and seven (22.8%) were WHO grade I. Among them, 15 patients (46.9%) had posterior fossa tumors, 10 (31.3%) had supratentorial tumors, and seven (22.8%) had spinal tumors. Of the 31 patients who underwent upfront surgical resection, 19 (61.3%) underwent gross total resection or near total resection. Seventeen of 19 patients with first failures (89.5%) had isolated local recurrences. Of the 19 patients with disease progression, 11 (57.9%) were disease-free or had stable disease after salvage therapy, and five (26.3%) had disease-related mortality. Most of the first local recurrences after radiotherapy occurred in the infield (13 of 16, 81.3%). The 5-year LPFS, DMFS, PFS, and OS rates were 48.5%, 89.6%, 45.1%, and 88.4%, respectively, at a median follow-up of 6.25 years. Subtotal resection was associated with poorer LPFS and PFS in patients with intracranial ependymoma (hazard ratio = 3.69, p = 0.018 for LPFS; hazard ratio = 3.20, p = 0.029 for PFS). CONCLUSION: Incorporating radiotherapy into multimodal treatment has led to favorable outcomes in patients with ependymoma, and the extent of resection is a prognostic factor for the local control of intracranial ependymoma.

15.
Am J Cancer Res ; 14(2): 854-868, 2024.
Article in English | MEDLINE | ID: mdl-38455397

ABSTRACT

The poor outcome of patients with lung adenocarcinoma (LUAD) highlights the importance to identify novel effective prognostic markers and therapeutic targets. Long noncoding RNAs (lncRNAs) have generally been considered to serve important roles in tumorigenesis and the development of various types of cancer, including LUAD. Here, we aimed to investigate the role of ENTPD3-AS1 (ENTPD3 Antisense RNA 1) in LUAD and to explore its potential mechanisms by performing comprehensive bioinformatic analyses. The regulatory effect of ENTPD3-AS1 on the expression of NR3C1 was validated by siRNA-based silencing. The effect of miR-421 on the modulation of NR3C1 was determined by miRNA mimics and inhibitors transfection. ENTPD3-AS1 was expressed at lower levels in tumor parts and negatively correlated with unfavorable prognosis in LUAD patients. It exerted functions as a tumor suppressor gene by competitively binding to oncomir, miR-421, thereby attenuating NR3C1 expression. Transfection of lung cancer A549 cells with miR-421 mimics decreased the expression of NR3C1. Transfection of lung cancer A549 cells with miR-421 inhibitors increased the expression of NR3C1 with lower cellular functions as proliferation and migration via epithelial-mesenchymal transition. In addition, inhibition of ENTPD3-AS1 by siRNA transfection decreased the levels of NR3C1, supporting the ENTPD3-AS1/miR-421/NR3C1 cascade. Moreover, the bioinformatic analysis also showed that ENTPD3-AS1 could interact with the RNA-binding proteins (RBPs), CELF2 and QKI, consequently regulating RNA expression and processing. Taken together, we identified that ENTPD3-AS1 and its indirect target NR3C1 can act as novel biomarkers for determining the prognosis of patients with LUAD, and further study is required.

17.
Am J Cancer Res ; 14(1): 169-181, 2024.
Article in English | MEDLINE | ID: mdl-38323273

ABSTRACT

One-carbon metabolism plays a crucial role in tumorigenesis as it supplies the one-carbon units necessary for nucleotide synthesis, epigenetic regulation, and redox metabolism, ensuring the rapid proliferation of cancer cells. However, their roles in prostate cancer progression remain poorly understood. In this study, we investigated the association between genetic variants in the one-carbon metabolism pathway and clinical outcomes in patients receiving androgen deprivation therapy for prostate cancer. The associations of 130 single-nucleotide polymorphisms located within 14 genes involved in the one-carbon metabolism pathway with cancer-specific survival (CSS), overall survival, and progression-free survival were assessed using Cox regression in 630 patients with prostate cancer. Subsequently, functional studies were performed using prostate cancer cell lines. After adjusting for covariates and multiple testing, MTHFD1L rs2073190 was found to be significantly associated with CSS (P = 0.000184). Further pooled analysis of multiple datasets demonstrated that MTHFD1L was upregulated in prostate cancer and increased MTHFD1L expression was positively correlated with tumor aggressiveness and poor patient prognosis. Functionally, MTHFD1L knockdown suppressed prostate cancer cell proliferation and colony formation. RNA sequencing and pathway analysis revealed that differentially expressed genes were predominantly enriched in the cell cycle pathway. In conclusion, genetic variants in MTHFD1L of one-carbon metabolism may serve as promising predictors, and our findings offer valuable insights into the underlying genetic mechanisms of prostate cancer progression.

18.
Heliyon ; 10(3): e25176, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38327404

ABSTRACT

Purpose: Foot drop still occurs in clinical practice, including in our case. Treatments for foot drop vary based on its etiology and severity of symptoms. Hence, in intractable foot drop cases, an invasive surgical intervention is needed. Here, we introduce a special noninvasive technique to treat our patient's foot drop. In this approach, we applied STIMPOD NMS460 neuromuscular stimulator device (STIMPOD NMS460), which is a low-frequency (10 Hz or less) transcutaneous electrical nerve stimulation (TENS) device with a pulsed radiofrequency (PRF) component. We are eager to know how effective the device is in treating foot drop, and we compared it with two kinds of surgical interventions. Materials and methods: The device settings are 5 Hz in frequency and 30mA in current amplitude. The device was applied on her left side at the L4 and L5 regions and at the fibular head. Each therapy session consists of individual 15-min treatments on these two body areas, and it only takes a total of 30 minutes. We recorded the change in ankle dorsiflexion degrees and muscle strength of our patient. Results and Conclusions: To our surprise, our patient's actual treatment status through STIMPOD NMS460 showed more effective recovery and no specific side effects than surgical interventions in similar conditions. Besides, after a three-month intervention, her affected ankle dorsiflexion recovered to almost her usual status. The reason why this device has such an effect may be that it has the benefits of TENS and PRF. Besides, some studies have revealed the nerve-repair effect of TENS and PRF. In conclusion, we believe that this device is fairly promising and may be qualified to be used in other patients with foot drop.

19.
Front Surg ; 11: 1327028, 2024.
Article in English | MEDLINE | ID: mdl-38327545

ABSTRACT

Avulsion fracture of the anterior superior iliac crest (ASIC) following autogenous bone grafting for anterior lumbar fusion (ALF) is an extremely rare complication. We describe a very rare case of avulsion fracture of the ASIC following autograft for ALF in a revision surgery for treating lumbar tuberculosis. A 68-year-old woman with lumbar tuberculosis underwent posterior debridement and posterior iliac crest bone graft fusion; however, her lumbar tuberculosis recurred 9 months after surgery. She then underwent a lumbar revision surgery, including removal of the posterior instrumentation and debridement, followed by anterior L2 corpectomy, debridement, anterior left iliac crest bone graft fusion, and internal fixation. When walking for the first time on postoperative day 3, she experienced a sharp, sudden-onset pain in the anterior iliac crest harvest area. X-ray revealed an avulsion fracture of the ASIC. Considering her failure to respond to conservative treatment for one week and large displacement of the fracture ends, an open reduction and internal fixation surgery was scheduled. Her pain symptoms were significantly relieved after the operation. Although rare, fracture of the ASIC following autograft for ALF should not be ignored. Fracture of the ASIC is usually treated conservatively. Additional surgical treatment is required only when intractable pain fails to respond to conservative treatment or when there is a large displacement of fracture ends that are not expected to heal spontaneously.

20.
Brain Pathol ; : e13244, 2024 Feb 02.
Article in English | MEDLINE | ID: mdl-38308041

ABSTRACT

Intracerebral hemorrhage (ICH) induces a complex sequence of apoptotic cascades and inflammatory responses, leading to neurological impairment. Transient receptor potential vanilloid 1 (TRPV1), a nonselective cation channel with high calcium permeability, has been implicated in neuronal apoptosis and inflammatory responses. This study used a mouse ICH model and neuronal cultures to examine whether TRPV1 activation exacerbates brain damage and neurological deficits by promoting neuronal apoptosis and neuroinflammation. ICH was induced by injecting collagenase in both wild-type (WT) C57BL/6 mice and TRPV1-/- mice. Capsaicin (CAP; a TRPV1 agonist) or capsazepine (a TRPV1 antagonist) was administered by intracerebroventricular injection 30 min before ICH induction in WT mice. The effects of genetic deletion or pharmacological inhibition of TRPV1 using CAP or capsazepine on motor deficits, histological damage, apoptotic responses, blood-brain barrier (BBB) permeability, and neuroinflammatory reactions were explored. The antiapoptotic mechanisms and calcium influx induced by TRPV1 inactivation were investigated in cultured hemin-stimulated neurons. TRPV1 expression was upregulated in the hemorrhagic brain, and TRPV1 was expressed in neurons, microglia, and astrocytes after ICH. Genetic deletion of TRPV1 significantly attenuated motor deficits and brain atrophy for up to 28 days. Deletion of TRPV1 also reduced brain damage, neurodegeneration, microglial activation, cytokine expression, and cell apoptosis at 1 day post-ICH. Similarly, the administration of CAP ameliorated brain damage, neurodegeneration, brain edema, BBB permeability, and cytokine expression at 1 day post-ICH. In primary neuronal cultures, pharmacological inactivation of TRPV1 by CAP attenuated neuronal vulnerability to hemin-induced injury, suppressed apoptosis, and preserved mitochondrial integrity in vitro. Mechanistically, CAP reduced hemin-stimulated calcium influx and prevented the phosphorylation of CaMKII in cultured neurons, which was associated with reduced activation of P38 and c-Jun NH2 -terminal kinase mitogen-activated protein kinase signaling. Our results suggest that TRPV1 inhibition may be a potential therapy for ICH by suppressing mitochondria-related neuronal apoptosis.

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