JARID2, a novel regulatory factor, promotes cell proliferation, migration, and invasion in oral squamous cell carcinoma.

BACKGROUND: Accurate regulation of gene expression is crucial for normal development and function of cells. The prognostic significance and potential carcinogenic mechanisms of the related gene JARID2 in OSCC are not yet clear, but existing research has indicated a significant association between the two. METHODS AND MATERIALS: The relationship between the expression of the JARID2 gene in tumor samples of OSCC patients and clinical pathological factors was analyzed using immunohistochemistry experiments and RT-qPCR analysis. Based on the clinical pathological data of patients, bioinformatics analysis was conducted using public databases to determine the function of JARID2 in OSCC. Knockdown OSCC cell lines were constructed, and the impact of JARID2 on the biological behavior of OSCC cell lines was assessed through CCK-8, wound healing assay, and transwell analysis. RESULTS: Immunohistochemistry experiments confirmed the correlation between JARID2 and the prognosis of OSCC patients, while RT-qPCR experiments demonstrated its expression levels in tissue and cells. CKK-8 experiments, wound healing assays, and Transwell experiments indicated that knocking down JARID2 had a negative impact on the proliferation, invasion, and migration of OSCC cells. Bioinformatics analysis results showed that the expression of JARID2 in OSCC is closely associated with patient gene co-expression, gene function enrichment, immune infiltration, and drug sensitivity. CONCLUSION: Our study indicates that JARID2 is a novel prognostic biomarker and potential therapeutic target for OSCC.

An academic achievements visualization research in the past 30 years: research on rehabilitation for head and neck cancer.

Background: Head and neck cancer acts as the sixth most common malignant tumor worldwide with an increasing incidence. The needs and methods of its rehabilitation are diverse and constantly evolving. Objective: This study aims to provide an in-depth depiction and visualization of the knowledge structure, hotspots, and emerging trends within the domain in the past 30 years through utilizing bibliometric analysis. Methods: The literature about rehabilitation for head and neck cancer in Web of Science was collected. CiteSpace and VOSviewer were used to analyze main countries, institutions, authors, journals, subject hotspots, trends, frontiers, etc. Results: A total of 1869 papers have been published since 1994. These publications were written by 874 authors from 514 institutions in 74 countries. The United States published 397 papers in this field and ranked first. Head & Neck is the most widely published journal, with Finizia, Caterina as the core author. The main keyword clustering includes terms such as #0 mandibular reconstruction (2009); #1 functional impairment (2014); #2 device lifetime (2006); #3 head and neck cancer (2003); #4 maxillofacial prosthetics (2004); #5 squamous cell carcinoma (2002); #6 readiness for return to work (2009); #7 total laryngopharyngectomy (2004). The current research frontier that has been sustained is "survivors", "reliability", and "meta analysis". Conclusion: We reveal the current status, hotspots, and trends in the field of rehabilitation for head and neck cancer. And we provided new academic insights into the characteristics and limitations of the field's development.

The Effect of Vidian Neurectomy on the Ocular Surface - The Primary Results from a Six-Month Pilot Study.

Purpose: To evaluate the effect of vidian neurectomy (VN) on the ocular surface and the possibility of dry eye in the treatment of allergic rhinitis. Methods: Twelve participants were recruited in this prospective study. Prior to and after 1 and 6 months of VN, an ocular surface disease index (OSDI) questionnaire was obtained, and the Schirmer's tear test (STT), break-up time (BUT), corneal fluorescence staining (CFS) score, and Keratograph 5M were used to evaluate the ocular surface condition. Results: Two patients (16.67%) met the dry eye diagnosis criteria one month after surgery; however, their symptoms were relieved after to 3-4 months and none of them met the diagnostic criteria for dry eye after six months. Compared with the baseline values, the STT was significantly reduced (P=0.002), while the tear meniscus height (TMH) (P=0.262), break-up time (BUT) (P=0.916), first keratographic tear film break-up time (NK-BUTfirst) (P=0.791), and average keratographic break-up time (NK-BUTave) (P=0.970) did not change significantly 6 months after surgery. The degree of STT decreased from baseline to 6-month and was related to the basic STT (ρ= 0.837, P=0.001) and sex (ρ= -0.584, P= 0.026) but not to age, OSDI score, BUT, NK-BUTfirst, NK-BUTave or CFS (all P>0.05). Among these factors, STT at baseline was confirmed to be a predictor of a decline in tear secretion after surgery (B = 0.731, P<0.001). Conclusion: In this 6-month prospective pilot study, decreased tearing was observed after VN, but this decrease did not increase the possibility of dry eyes.

Hypoxia predicts favorable response to carbon ion radiotherapy in non-small cell lung cancer (NSCLC) defined by 18F-FMISO positron emission tomography/computed tomography (PET/CT) imaging.

Background: Hypoxia is the bottleneck that affects the response of conventional photon radiotherapy, but it does not seem to have much effect on carbon ion radiotherapy (CIRT). This study aimed to evaluate the changes of hypoxia before and after CIRT in patients with non-small cell lung cancer (NSCLC) and whether 18F-fluoromisonidazole (18F-FMISO) positron emission tomography/computed tomography (PET/CT) imaging could predict the response to CIRT in NSCLC patients. Methods: A total of 29 patients with NSCLC who received CIRT were retrospectively included. 18F-FMISO PET/CT imaging was performed before and after treatment, and chest CT was performed after radiotherapy. Radiation response within 1 week after radiotherapy and at the initial follow-up were defined as the immediate response (IR) and early response (ER), respectively. The tumor-to-muscle ratio (TMR), hypoxia volume (HV), and the ΔTMR and ΔHV values of 18F-FMISO uptake were collected. Fisher's exact test, Mann-Whitney U test, Wilcoxon signed-rank test, and binary logistic regression were used to analyze data. Results: (I) Baseline TMR could predict the IR to CIRT with a baseline TMR cut-off value of 2.35, an area under the curve (AUC) of 0.85 [95% confidence interval (CI): 0.62-1.00], a sensitivity of 80.0%, a specificity of 87.5%, and an accuracy of 85.7%. Taking the baseline TMR =2.35 as the cut-off value of high-hypoxia and low-hypoxia group, the IR rate of the high-hypoxia group [66.7% (4/6)] and the low-hypoxia group [6.7% (1/15)] was statistically different (P=0.01). (II) ΔTMR could predict early treatment response after CIRT at initial follow-up, with a cut-off value of ΔTMR =36.6%, AUC of 0.80 (95% CI: 0.61-1.00), sensitivity of 72.7%, specificity of 90.0% and accuracy of 71.4%. Conclusions: A higher degree of tumor hypoxia may be associated with a better IR to CIRT. ΔTMR could predict early treatment response after CIRT.

Evolution and impact of molecular glue research: a bibliometric analysis from 2000 to 2023.

Background: Molecular glues, which reshape E3 ligase receptors to promote targeted protein degradation, are emerging as a promising therapeutic strategy, particularly in oncology, driven by rapidly advancing insights into their mechanisms and structural properties. Objective: This study aims to offer an insightful depiction and visualization of the knowledge structure, prevalent themes, and emerging trends within the domain since the year 2000, employing bibliometric analysis to achieve this goal. Methods: To conduct this research, a comprehensive collection of literature on molecular glues was sourced from the Web of Science database. Subsequently, the data underwent analysis utilizing CiteSpace and VOSviewer tools, enabling the identification of pivotal countries, institutions, authors, and journals, as well as the delineation of subject hotspots, trends, and the forefront of research in this evolving field. Result: Since 2000, 388 papers on molecular glues have been published, with a notable increase to an annual average of 43 articles post-2018. This research, contributed by 506 authors across 329 institutions, highlights the United States and China as leading nations in output, with 122 and 104 articles respectively. Takuzo Aida, Luc Brunsveld, and Christian Ottmann are identified as key authors. Nature emerges as the foremost publication venue, while the Chinese Academy of Sciences is the top contributing institution, underscoring the global engagement and interdisciplinary nature of molecular glue research. This study identified 19 distinct research clusters within the molecular glues domain. Conclusion: We reveal the current status, hotspots, and trends of molecular glue research since 2000, offering insights and novel scholarly perspectives on the field's prevailing limitations.

circMTO1/miR-30c-5p/SOCS3 axis alleviates oral submucous fibrosis through inhibiting fibroblast-myofibroblast transition.

BACKGROUND: circRNAs have been shown to participate in diverse diseases; however, their role in oral submucous fibrosis (OSF), a potentially malignant disorder, remains obscure. Our preliminary experiments detected the expression of circRNA mitochondrial translation optimization 1 homologue (circMTO1) in OSF tissues (n = 20) and normal mucosa tissues (n = 20) collected from Hunan Xiangya Stomatological Hospital, and a significant decrease of circMTO1 expression was showed in OSF tissues. Therefore, we further explored circMTO1 expression in OSF. METHODS: Target molecule expression was detected using RT-qPCR and western blotting. The migration and invasion of buccal mucosal fibroblasts (BMFs) were assessed using wound healing and Transwell assays. The interaction between miR-30c-5p, circMTO1, and SOCS3 was evaluated using dual luciferase, RNA immunoprecipitation (RIP), and RNA pull-down assays. The colocalisation of circMTO1 and miR-30c-5p was observed using fluorescence in situ hybridisation (FISH). RESULTS: circMTO1 and SOCS3 expression decreased, whereas miR-30c-5p expression increased in patients with OSF and arecoline-stimulated BMFs. Overexpression of circMTO1 effectively restrained the fibroblast-myofibroblast transition (FMT), as evidenced by the increase in expression of Coll I, α-SMA, Vimentin, and the weakened migration and invasion functions in BMFs. Mechanistic studies have shown that circMTO1 suppresses FMT by enhancing SOCS3 expression by sponging miR-30c-5p and subsequently inactivating the FAK/PI3K/AKT pathway. FMT induced by SOCS3 silencing was reversed by the FAK inhibitor TAE226 or the PI3K inhibitor LY294002. CONCLUSION: circMTO1/miR-30c-5p/SOCS3 axis regulates FMT in arecoline-treated BMFs via the FAK/PI3K/AKT pathway. Expanding the sample size and in vivo validation could further elucidate their potential as therapeutic targets for OSF.

An academic achievements visualization research since the 21st century: research on salvage surgery for head and neck cancer.

Background: Head and neck cancer is the 6th most common malignancy worldwide, and its incidence is still on the rise. The salvage surgery has been considered as an important treatment strategy for persistent or recurrent head and neck cancer. Therefore, we conducted a bibliometric analysis of salvage surgery for head and neck cancer since the 21st century. Methods: The literature about salvage surgery of head and neck cancer in Web of Science was searched. CiteSpace and VOSviewer were used to analyze main countries, institutions, authors, journals, subject hotspots, trends, frontiers, etc. Results: A total of 987 papers have been published since the 21st century. These publications were written by 705 authors from 425 institutions in 54 countries. The United States published 311 papers in this field and ranked first. Head & Neck was the most widely published journal. The main keyword clustering included terms such as #0 stereotactic radiotherapy (2012); #1 randomized multicenter (2007); #2 salvage surgery (2004); #3 functional outcomes (2014); #4 transoral robotic surgery (2013); #5 neck high-resolution computed tomography (2010); #6 complications (2008); #7 image guidance (2019). The current research frontiers that have been sustained are "recurrent", "risk factors", and "reirradiation". Conclusion: The current situation of the salvage surgery for head and neck cancer in clinical treatments and basic scientific research were summarized, providing new perspectives for the development of salvage surgery for head and neck cancer in the future.

Properties of [18F]FAPI monitoring of acute radiation pneumonia versus [18F]FDG in mouse models.

OBJECTIVE: In this study, the uptake characteristics of [18F]fibroblast activation protein inhibitor (FAPI) molecular imaging probe were investigated in acute radiation pneumonia and lung cancer xenografted mice before and after radiation to assess the future applicability of [18F]FAPI positron emission tomography/computed tomography (PET/CT) imaging in early radiotherapy response. METHODS: Initially, the biodistribution of [18F]FAPI tracer in vivo were studied in healthy mice at each time-point. A comparison of [18F]FAPI and [18F]fluorodeoxyglucose (FDG) PET/CT imaging efficacy in normal ICR, LLC tumor-bearing mice was evaluated. A radiation pneumonia model was then investigated using a gamma counter, small animal PET/CT, and autoradiography. The uptake properties of [18F]FAPI in lung cancer and acute radiation pneumonia were investigated using autoradiography and PET/CT imaging in mice. RESULTS: The tumor area was visible in [18F]FAPI imaging and the tracer was swiftly eliminated from normal tissues and organs. There was a significant increase of [18F]FDG absorption in lung tissue after radiotherapy compared to before radiotherapy, but no significant difference of [18F]FAPI uptake under the same condition. Furthermore, both the LLC tumor volume and the expression of FAP-ɑ decreased after thorax irradiation. Correspondingly, there was no notable [18F]FAPI uptake after irradiation, but there was an increase of [18F]FDG uptake in malignancies and lungs. CONCLUSIONS: The background uptake of [18F]FAPI is negligible. Moreover, the uptake of [18F]FAPI may not be affected by acute radiation pneumonitis compared to [18F]FDG, which may be used to more accurately evaluate early radiotherapy response of lung cancer with acute radiation pneumonia.

18F-FAPI PET/CT performs better in evaluating mediastinal and hilar lymph nodes in patients with lung cancer: comparison with 18F-FDG PET/CT.

BACKGROUND: The aim of this study was to evaluate the efficacy of fluorine 18 (18F) labeled fibroblast activation protein inhibitor (FAPI) in identifying mediastinal and hilar lymph node metastases and to develop a model to quantitatively and repeatedly identify lymph node status. METHODS: Twenty-seven patients with 137 lymph nodes were identified by two PET/CT images. The sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of lymph node status were analyzed, and the optimal cut-off value was identified by ROC analysis. RESULTS: The SUVmax of metastatic lymph nodes on 18F-FAPI was higher than that on 18F-FDG PET/CT (10.87 ± 7.29 vs 6.08 ± 5.37, p < 0.001). 18F-FAPI presented much greater lymph node detection sensitivity, specificity, accuracy, PPV and NPV than 18F-FDG PET/CT (84% vs. 71%; 92% vs. 67%; 90% vs. 69%, 84% vs. 52%, and 92% vs. 83%, respectively). Additionally, the diagnostic effectiveness of 18F-FAPI in small lymph nodes was greater than that of 18F-FDG PET/CT (specificity: 96% vs. 72%; accuracy: 93% vs. 73%; PPV: 77% vs. 33%, respectively). Notably, the optimal cut-off value for specificity and PPV of 18F-FAPI SUVmax was 5.3; the optimal cut-off value for sensitivity and NPV was 2.5. CONCLUSION: 18F-FAPI showed promising diagnostic efficacy in metastatic mediastinal and hilar lymph nodes from lung cancer patients, with a higher SUVmax, especially in small metastatic nodes, compared with 18F-FDG. In addition, this exploratory work recommended optimal SUVmax cutoff values to distinguish between nonmetastatic and metastatic lymph nodes, thereby advancing the development of image-guided radiation. Trial registration ClinicalTrials.gov identifier: ChiCTR2000036091.

Up modulation of dose-averaged linear energy transfer by simultaneous integrated boost in carbon-ion radiotherapy for pancreatic carcinoma.

BACKGROUND: Local recurrence in locally advanced pancreatic cancer (LAPC) after carbon-ion radiotherapy (CIRT) may partly attribute to low dose-averaged linear energy transfer (LETd), despite high CIRT dose. PURPOSE: This study aimed to investigate the approaches to up-modulate the CIRT LETd and to evaluate the corresponding oxygen enhancement ratio (OER) reduction. METHODS: 10 LAPCs that had been irradiated by CIRT with 67.5 Gy (RBE) in 15 fractions were selected. Their original plans were taken as the control plan for the LETd and OER investigations. Our considerations for up-modulating LETd were: (1) to deliver high doses to gross tumor volume core (GTVcore), while keeping dose constraints of the gastrointestinal (GI) tract in tolerance; (2) to put more Bragg-peak (BP) within the modulated targets; (3) to increase the BP density, high doses were necessary; (4) CIRT LETd could be effectively increased to small volumes; and (5) simultaneous integrated boost technique (SIB) could achieve the aforementioned tasks. The LETd and the corresponding OER distributions of each type of SIB plan were evaluated. RESULTS: We delivered up to 100 Gy (RBE) to GTVcore using SIB. The mean LETd of GTV increased significantly by 21.3% from 47.8 to 58.0 keV/µm (p < 0.05). Meanwhile, the mean OER of GTVcore decreased by 6.6%, from 1.51 to 1.41 (p < 0.05). The GI LETdS in all modulated plans were not more than those in the original plans. CONCLUSIONS: SIB could effectively increase CIRT LETd to LAPC, thus producing reduced OER, which may effectively overcome the radioresistance of LAPCs.

Single-cell RNA sequencing reveals the complex cellular niche of pterygium.

PURPOSE: Pterygium is a vision-threatening conjunctival fibrovascular degenerated disease with a high global prevalence up to 12 %, while no absolute pharmacotherapy has been applied in clinics. In virtue of single-cell RNA sequencing (scRNA-seq) technique, our study investigated underlying pathogeneses and potential therapeutic targets of pterygium from the cellular transcriptional level. METHODS: A total of 45605 cells from pterygium of patients and conjunctiva of normal controls (NC) were conducted with scRNA-seq, and then analyzed via integrated analysis, pathway enrichment, pseudotime trajectory, and cell-cell communications. Besides, immunofluorescence and western blot were performed in vivo and in vitro to verify our findings. RESULTS: In brief, 9 major cellular types were defined, according to canonical markers. Subsequently, we further determined the subgroups of each major cell lineages. Several newly identified cell sub-clusters could promote pterygium, including immuno-fibroblasts, epithelial mesenchymal transition (EMT)-epithelial cells, and activated vascular endothelial cells (activated-vEndo). Besides, we also probed the enrichment of immune cells in pterygium. Particularly, macrophages, recruited by ACKR1+activated-vEndo, might play an important role in the development of pterygium by promoting angiogenesis, immune suppression, and inflammation. CONCLUSION: An intricate cellular niche was revealed in pterygium via scRNA-seq analysis and the interactions between macrophages and ACKR1+ activated-vEndo might be the key part in the development of pterygia.

Elevated 18 F-AIF-FAPI-04 Uptake in Hepatic Hemangioma.

ABSTRACT: A 67-year-old woman who was diagnosed with intrahepatic cholangiocellular carcinoma (CCC) by biopsy underwent 18 F-FDG and 18 F-AIF-FAPI-04 PET/CT for initial and treatment assessment. In addition to CCC, she had a history of hepatic hemangioma for 3 years. 18 F-FDG PET/CT images showed increased uptake in CCC, but no uptake in hemangiomas. However, images on 18 F-AIF-FAPI-04 PET/CT indicated negative 18 F-AIF-FAPI-04 uptake in CCC, but intense activity in hemangiomas. Our case illustrates that hepatic hemangioma demonstrated intense 18 F-AIF-FAPI-04 uptake, and final diagnosis should be made with caution.

Clinico-biological-radiomics (CBR) based machine learning for improving the diagnostic accuracy of FDG-PET false-positive lymph nodes in lung cancer.

BACKGROUND: The main problem of positron emission tomography/computed tomography (PET/CT) for lymph node (LN) staging is the high false positive rate (FPR). Thus, we aimed to explore a clinico-biological-radiomics (CBR) model via machine learning (ML) to reduce FPR and improve the accuracy for predicting the hypermetabolic mediastinal-hilar LNs status in lung cancer than conventional PET/CT. METHODS: A total of 260 lung cancer patients with hypermetabolic mediastinal-hilar LNs (SUVmax ≥ 2.5) were retrospectively reviewed. Patients were treated with surgery with systematic LN resection and pathologically divided into the LN negative (LN-) and positive (LN +) groups, and randomly assigned into the training (n = 182) and test (n = 78) sets. Preoperative CBR dataset containing 1738 multi-scale features was constructed for all patients. Prediction models for hypermetabolic LNs status were developed using the features selected by the supervised ML algorithms, and evaluated using the classical diagnostic indicators. Then, a nomogram was developed based on the model with the highest area under the curve (AUC) and the lowest FPR, and validated by the calibration plots. RESULTS: In total, 109 LN- and 151 LN + patients were enrolled in this study. 6 independent prediction models were developed to differentiate LN- from LN + patients using the selected features from clinico-biological-image dataset, radiomics dataset, and their combined CBR dataset, respectively. The DeLong test showed that the CBR Model containing all-scale features held the highest predictive efficiency and the lowest FPR among all of established models (p < 0.05) in both the training and test sets (AUCs of 0.90 and 0.89, FPRs of 12.82% and 6.45%, respectively) (p < 0.05). The quantitative nomogram based on CBR Model was validated to have a good consistency with actual observations. CONCLUSION: This study presents an integrated CBR nomogram that can further reduce the FPR and improve the accuracy of hypermetabolic mediastinal-hilar LNs evaluation than conventional PET/CT in lung cancer, thereby greatly reducing the risk of overestimation and assisting for precision treatment.

Extraction and Application of Hydraulic Support Safety Valve Characteristic Parameters Based on Roof Pressure Data.

The safety valves of powered supports control the maximum working resistance, and their statuses must be known to ensure the safety of both the support and the overlying strata. However, the inspection of powered support valves involves manual or semiautomated operations, the costs of which are high. In this study, an extreme point extraction method was developed for the determination of the characteristic parameters of safety valves using roof pressure data, and a safety valve state monitoring module was constructed. Using the longwall face of 0116306 with top coal caving in the Mindong Mine as an example, the characteristic parameters of the safety valves were extracted, including the peak, reseating, and blowdown pressures, as well as the recovery and unloading durations. The results of the field tests showed the following: (1) The amplitude threshold method based on extreme points can be used to accurately extract characteristic parameters, and the distribution of the characteristic parameters of the safety valves follows either a Gaussian or an exponential distribution. (2) The mining pressure analysis results, derived from the characteristic parameters, closely align with the in situ mining pressure observations. This method can be used for the online monitoring of safety valve conditions, increasing the operational efficiency and quality of safety valve inspections.

The mechanism of IL-13 targeting IL-13Rα2 in regulating oral mucosal FBs through PI3K/AKT/mTOR.

OBJECTIVE: The objective of this investigation was to examine the presence of interleukin (IL)-13 and its receptor IL-13Rα2 in the tissues of oral submucous fibrosis (OSF), investigate their biological functions, and explore the underlying mechanisms involved in the development of OSF. MATERIALS AND METHODS: The expression of IL-13 and IL-13Rα2 in the oral mucosa of patients with OSF and normal individuals was determined through immunohistochemistry and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Primary fibroblasts (FBs) were extracted through enzymatic digestion and then cultured. Immunofluorescence was employed to identify the FB cultures and the location of IL-13Rα2. The effects of IL-13/IL-13Rα2/PI3K/AKT/mTOR on the migration, proliferation, and secretion of fiber-related proteins of FBs were explored via the wound healing assay, CCK-8 assay, EDU assay, and RT-qPCR. The impact of IL-13Rα2 silencing and PI3K/AKT inhibition on the effect of IL-13 on FBs was analyzed by RT-qPCR and Western blotting. RESULTS: IL-13 and IL-13Rα2 were highly expressed in OSF. Primary FBs were successfully extracted and cultured. IL-13Rα2 was found to be localized in myofibroblasts. IL-13 promoted the proliferation, migration, and secretion of fibril-associated proteins in FBs. The proliferation, migration, and secretion of fibril-associated proteins of FBs were decreased following IL-13Rα2 silencing and inhibition of the PI3K/AKT/mTOR pathway. CONCLUSION: IL-13 may promote the proliferation, migration, and secretion of fiber-related proteins of FBs through the PI3K/AKT/mTOR pathway by targeting IL-13Rα2.

18F-FES and 18F-FDG PET/CT imaging as a predictive biomarkers for metastatic breast cancer patients undergoing cyclin-dependent 4/6 kinase inhibitors with endocrine treatment.

OBJECTIVE: The aim of this study was to investigate the potential value of dual tracers 18F-FDG and 18F-FES PET/CT in predicting response to Cyclin-Dependent 4/6 Kinase (CDK4/6) inhibitors combined with endocrine therapy for metastatic estrogen receptor (ER)-positive breast cancer patients. METHODS: This retrospective study enrolled 38 ER-positive metastatic breast cancer patients from our center who underwent both 18F-FDG and 18F-FES PET/CT scans within 1 month before CDK4/6 inhibitors combined with endocrine therapy. The extracted parameters comprised the maximum standardized uptake value (SUVmax) for both FDG and FES PET, as well as the ratio between FES and FDG SUVmax. Each parameter was dichotomized based on its median threshold. The primary endpoint was progression-free survival (PFS), which was estimated using the Kaplan-Meier method and compared by the log-rank test. RESULTS: After a median follow-up of 15.6 months, progressive disease was observed in 23 out of 38 patients, and the median PFS for the whole cohort was 21.0 months [95% confidence interval (CI) 12.7-29.3]. FES and FDG PET identified 6 patients (15.8%) with FES-negative lesions, suggesting ER heterogeneity in metastatic lesions. The median PFS of these patients was only 5.3 months (95% CI 1.7-8.9), which was substantially shorter than that of patients with 100% FES-positive lesions (median PFS 22.9 months, 95% CI 17.1-28.7, P < 0.001). Patients with 100% FES-positive lesions who had high FES/FDG showed significantly shorter PFS compared to those with low FES/FDG (14.9 vs. 30.5 months, P = 0.003). CONCLUSIONS: This study shows that FDG and FES PET imaging may serve as valuable tools for patient selection in the context of CDK4/6 inhibitor therapy combined with endocrine treatment, and have the potential to function as prognostic biomarkers.

Automated Stratum Interface Detection Using the Optimized Drilling Specific Energy through Self-Adaptive Logistic Function.

The precise detection of stratum interfaces holds significant importance in geological discontinuity recognition and roadway support optimization. In this study, the model for locating rock interfaces through change point detection was proposed, and a drilling test on composite strength mortar specimens was conducted. With the logistic function and the particle swarm optimization algorithm, the drilling specific energy was modulated to detect the stratum interface. The results indicate that the drilling specific energy after the modulation of the logistic function showed a good anti-interference quality under stable drilling and sensitivity under interface drilling, and its average recognition error was 2.83 mm, which was lower than the error of 6.56 mm before modulation. The particle swarm optimization algorithm facilitated the adaptive matching of drive parameters to drilling data features, yielding a substantial 50.88% decrease in the recognition error rate. This study contributes to enhancing the perception accuracy of stratum interfaces and eliminating the potential danger of roof collapse.

Definitive carbon ion re-irradiation with pencil beam scanning in the treatment of unresectable locally recurrent rectal cancer.

This study aimed to evaluate the oncological outcomes and safety of carbon ion re-irradiation with pencil beam scanning (PBS) delivery technique for previously irradiated and unresectable locally recurrent rectal cancer (LRRC). Between June 2017 and September 2021, 24 patients of unresectable LRRC with prior pelvic photon radiotherapy who underwent carbon ion re-irradiation at our institute were retrospectively analyzed. Carbon ion radiotherapy was delivered by raster scanning with a median relative biological effectiveness-weighted dose of 72 Gy in 20 fractions. Weekly CT reviews were carried out, and offline adaptive replanning was performed whenever required. The median follow-up duration was 23.8 months (range, 6.2-47.1 months). At the last follow-up, two patients had a local disease progression, and 11 patients developed distant metastases. The 1- and 2-year local control, progression-free survival and overall survival rates were 100 and 93.3%, 70.8 and 45.0% and 86.7 and 81.3%, respectively. There were no Grade 3 or higher acute toxicities observed. Three patients developed Grade 3 late toxicities, one each with gastrointestinal toxicity, skin reaction and pelvic infection. In conclusion, definitive carbon ion re-irradiation with PBS provided superior oncologic results with tolerable toxicities and may be served as a curative treatment strategy in unresectable LRRC.

R-(+)-WIN55212-2 protects pericytes from ischemic damage and restores retinal microcirculatory patency after ischemia/reperfusion injury.

BACKGROUND AND PURPOSE: Cannabinoids are vasoactive substances that act as key regulators of arterial tone in the blood vessels supplying peripheral tissues and the central nervous system. This study aimed to investigate the potential of R-(+)-WIN55212-2 (WIN), a cannabinoid receptor 1 agonist (CB1), as a treatment for retinal ischemia/reperfusion (I/R) injury. EXPERIMENTAL APPROACH: Male Wistar rats were subjected to retinal I/R injury by increasing intraocular pressure in the anterior chamber. The rats were randomly divided into four groups: normal control, I/R, vehicle (pre-treated with dimethyl sulfoxide [DMSO] via intraperitoneal injection), and experimental (pre-treated with WIN at a dose of 1 ml/kg via intraperitoneal injection). The rats were sacrificed at different time points of reperfusion (1 hour, 3 hours, 6 hours, and 1 day) after inducing retinal I/R injury, and their retinas were collected for analysis. Oxygen-glucose deprived/reperfusion (OGD/R) was performed by initially perfusing the retinas with oxygenated artificial cerebrospinal fluid (ACSF), then switching to an OGD solution to simulate ischemia, followed by another perfusion with ACSF. Pericyte contraction and the "no-reflow" phenomenon were observed using infrared differential interference contrast (IR-DIC) microscopy and immunohistochemistry. Western blot, enzyme-linked immunosorbent assay (ELISA), and nitric oxide (NO) detection were used to explore the potential mechanism. KEY RESULTS: In both the OGD/R and I/R models, retinal pericytes exhibited persistent contraction even after reperfusion. The ability of WIN to regulate the tone of retinal pericytes and capillaries was specifically blocked by the BKCa inhibitor iberiotoxin (100 nM). WIN demonstrated a protective effect against retinal I/R injury by preserving blood flow in vessels containing pericytes. Pretreatment with WIN alleviated the persistent contraction and apoptosis of retinal pericytes in I/R-induced rats, accompanied by a reduction in intracellular calcium ion (Ca2+) concentration. The expression of CB1 decreased in a time-dependent manner in the I/R group. After I/R injury, endothelium-derived nitric oxide (eNOS) levels were reduced at all time points, which was successfully reversed by WIN therapy except for the 1 day group. Additionally, the downregulation of cyclic guanosine monophosphate (cGMP) and BKCa expression at 3 hours, 6 hours, and 1 day after I/R injury was restored by pretreatment of WIN. CONCLUSIONS & IMPLICATIONS: WIN exerted its protective effects on retinal I/R injury by inhibiting the contraction and apoptosis of pericytes through the CB1-eNOS-cGMP-BKCa signaling pathway, thus ameliorated the occlusion of retinal capillaries.

Factors that impacted mobile-payment adoption in China during the COVID-19 pandemic.

The Unified Theory of Acceptance and Use of Technology (UTAUT) is a potential paradigm for explaining technology adoption and can be applied to a wide range of scenarios. During the COVID-19 (C-19) outbreak in China, mobile-payment platforms (Mpayment) were used extensively in everyday life because they allowed people to avoid direct and indirect connections during transactions, adhere to social-distancing guidelines, and support social-economic stabilization. By exploring the technological and psychological variables that influenced user Mpayment-adoption intentions during the C-19 pandemic, this study broadens the literature on technology adoption in emergency circumstances and expands the UTAUT. A total of 593 complete samples were collected online, with SPSS used for data analysis. The empirical findings reveal that performance expectancy, trust, perceived security, and social influence all had a significant influence on Mpayment acceptance during the C-19 outbreak, with social distancing having the greatest impact, followed by fear of C-19. Interestingly, perceived-effort expectancy had a negative influence on payment acceptance. These findings suggest that future studies should apply the expanded model to different countries and areas to investigate the impact of the C-19 pandemic on Mpayment acceptance.