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Abstract Background Renal cell carcinoma (RCC) is a type of cancer that can develop at any point in adulthood, spanning the range of age-related changes that occur in the body. However, the specific molecular mechanisms underlying the connections between age and genetic mutations in RCC have not been extensively investigated. Methods Clinical and genetic data from patients diagnosed with RCC were collected from two prominent medical centers in China as well as the TCGA dataset. The patients were categorized into two groups based on their prognosticated age: young adults (YAs) and older adults (OAs). Univariate and multivariate analysis were employed to evaluate the relationships between age and genetic mutations. Furthermore, a mediation analysis was conducted to assess the association between age and overall survival, with genetic disparities serving as a mediator. Results Our analysis revealed significant differences in clinical presentation between YAs and OAs with RCC, including histopathological types, histopathological tumor stage, and sarcomatoid differentiation. YAs were found to have lower mutation burden and significantly mutated genes (SMGs) of RCC. However, we did not observe any significant differences between the two groups in terms of 10 canonical oncogenic signaling pathways-related genes mutation, telomerase-related genes (TRGs) mutation, copy number changes, and genetic mutations associated with clinically actionable targeted drugs. Importantly, we demonstrate superior survival outcomes in YAs, and we confirmed the mediating effect of genetic disparities on these survival outcome differences between YAs and OAs. Conclusion Our findings reveal previously unrecognized associations between age and the molecular underpinnings of RCC. These associations may serve as valuable insights to guide precision diagnostics and treatments for RCC.

Abstract Background Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) has been confirmed to play oncogenic role in many cancers. However, the role and mechanism of IGF2BP2 in bladder cancer (BCa) still deserves to be further revealed. Methods The mRNA and protein levels of IGF2BP2 and neuronilin-1 (NRP1) were detected by real-time quantitative PCR (RT-qPCR) and western blot. Cell proliferation, apoptosis, migration and invasion were determined using colony formation assay, EdU assay, CCK8 assay, flow cytometry and transwell assay. Xenograft tumor model was conducted to evaluate the role of IGF2BP2 in vivo. THP-1-M0 macrophages were co-cultured with the condition medium (CM) of BCa cells to induce polarization. M2 macrophage polarization was assessed by detecting the mRNA levels of M2 macrophage markers using RT-qPCR and measuring the proportion of M2 macrophage markers using flow cytometry. Moreover, MeRIP and RIP assay were performed to assess m6A level and the interaction between IGF2BP2 and NRP1. Results IGF2BP2 and NRP1 were upregulated in BCa tissues and cells. IGF2BP2 knockdown suppressed BCa cell growth and metastasis, as well as inhibited BCa tumor growth. After THP-1-M0 macrophages were co-cultured with the CM of BCa cells, the levels of M2 macrophage markers were markedly enhanced, while this effect was abolished by IGF2BP2 knockdown. IGF2BP2 level was positively correlated with NRP1 level, and it could increase NRP1 mRNA stability. NRP1 overexpression reversed the suppressive effect of IGF2BP2 knockdown on M2 macrophage polarization and BCa cell progression. Conclusion m6A-reader IGF2BP2 enhanced M2 macrophage polarization and BCa cell progression by promoting NRP1 mRNA stability.

IntroductionThis study investigates the complex relationship between economic growth, remittances (REM), export earnings (EEs), infrastructural development (IFD), and environmental sustainability (ES) in Bangladesh over the period from 1990 to 2020. Framed within the context of the Environmental Kuznets Curve (EKC) hypothesis, the research explores how these factors influence environmental outcomes and contributes to ongoing discussions on sustainable development.MethodsUtilizing advanced time-series modeling techniques, including autoregressive distributed lag (ARDL) and nonlinear ARDL (NARDL), this study applies unit root tests and co-integration analysis to examine the data. These methods allow for a detailed assessment of both short- and long-term relationships between the variables in question.ResultsThe findings confirm the EKC hypothesis, showing that economic growth initially leads to increased carbon emissions and environmental degradation, but further development contributes to environmental improvements. Remittances, however, significantly exacerbate carbon emissions and ecological degradation. On the other hand, technological innovation (TI) demonstrates a negative association with carbon emissions and ecological footprint (EF), highlighting its potential in supporting sustainable development. The impacts of export earnings and infrastructural development on environmental sustainability are mixed, with infrastructural growth in particular linked to environmental degradation.DiscussionThe study's results underscore the importance of targeted policy interventions to balance economic growth with environmental sustainability. Policymakers should focus on mitigating the environmental impacts of remittance inflows and fostering technological innovation to achieve the Sustainable Development Goals (SDGs). While export earnings and infrastructural development play critical roles in economic progress, their environmental implications require careful management to ensure long-term sustainability.

IntroductionMetastatic renal cell carcinoma (mRCC) with sarcomatoid features has a poor prognosis. Cytoreductive radical nephrectomy (CRN) can improve prognosis, but patient selection is unclear. This study aimed to develop a prediction model for selecting patients suitable for CRN.Materials and methodsPatients with a diagnosis of mRCC with sarcomatoid features in the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015 were retrospectively reviewed. CRN benefit was defined as a survival time longer than the median overall survival (OS) in patients who did not receive CRN. A prediction nomogram was established and validated using the SEER cohort (training and internal validation) and an external validation cohort.ResultsOf 900 patients with sarcomatoid mRCC, 608 (67.6%) underwent CRN. OS was longer in the CRN group than in the non-CRN group (8 vs. 6 months, hazard ratio (HR) = 0.767, p = 0.0085). In the matched CRN group, 124 (57.7%) patients survived >6 months after the surgery and were considered to benefit from CRN. Age, T-stage, systematic therapy, metastatic site, and lymph nodes were identified as independent factors influencing OS after CRN, which were included in the prediction nomogram. The monogram performed well on the training set (area under the receiver operating characteristic (AUC) curve = 0.766, 95% confidence interval (CI): 0.687–0.845), internal validation set (AUC = 0.796, 95% CI: 0.684–0.908), and external validation set (AUC = 0.911, 95% CI: 0.831–0.991).ConclusionsA nomogram was constructed and validated with good accuracy for selecting patients with sarcomatoid mRCC suitable for CRN.

Abstract There is significant variability with respect to the prognosis of nonmetastatic clear cell renal cell carcinoma (ccRCC) patients with venous tumor thrombus (VTT). By applying multiregion whole‐exome sequencing on normal‐tumor‐thrombus‐metastasis quadruples from 33 ccRCC patients, we showed that metastases were mainly seeded by VTT (81.8%) rather than primary tumors (PTs). A total of 706 nonmetastatic ccRCC patients with VTT from three independent cohorts were included in this study. C‐index analysis revealed that pathological grading of VTT outperformed other indicators in risk assessment (OS: 0.663 versus 0.501–0.610, 0.667 versus 0.544–0.651, and 0.719 versus 0.511–0.700 for Training, China‐Validation, and Poland‐Validation cohorts, respectively). We constructed a risk predicting model, TT‐GPS score, based on four independent variables: VTT height, VTT grading, perinephric fat invasion, and sarcomatoid differentiation in PT. The TT‐GPS score displayed better discriminatory ability (OS, c‐index: 0.706–0.840, AUC: 0.788–0.874; DFS, c‐index: 0.691–0.717, AUC: 0.771–0.789) than previously reported models in risk assessment. In conclusion, we identified for the first‐time pathological grading of VTT as an unheeded prognostic factor. By incorporating VTT grading, the TT‐GPS score is a promising prognostic tool in predicting the survival of nonmetastatic ccRCC patients with VTT.

Abstract Background Tumorigenic phenotype of M2 tumor-associated macrophages promote tumor progression in response to exosomes cues imposed by tumor cells. However, the effect and underlying mechanisms of clear cell renal cell carcinoma (ccRCC)-derived exosomes (ccRCC-exo) on instructing macrophages phenotype remains unclear. Methods Macrophages were cocultured with ccRCC-exo and then evaluate the polarization of macrophages and migration of ccRCC cells. The effect and mechanism of lncRNA AP000439.2 overexpressed or deleted exosomes on macrophages M2 polarization were examined. Xenograft tumor mice model was used for in vivo validation. Results The ccRCC-exo significantly activated macrophages to M2 phenotype presented by increased expression of transforming growth factor-beta (TGF-β) and interleukin 10 (IL-10) at mRNA and protein levels, and these M2 macrophages in turn facilitating the migration of ccRCC cells. LncRNA AP000439.2 was highly enriched in the ccRCC-exo. Overexpression of exosomal AP000439.2 promoted M2 macrophage polarization whereas AP000439.2-deficient exosome had the opposite effects. Nuclear-localized AP000439.2 directly interacted with signal transducer and activator of transcription 3 (STAT3) proteins and phosphorylated STAT3 in macrophages. RNA-Seq results showed overexpression of AP000439.2 activated NF-κB signaling pathway. Silencing of STAT3 suppressed overexpression of AP000439.2-induced up-regulation of TGF-β and IL-10 expression, and p65 phosphorylation. AP000439.2-deleted exosome inhibited tumor growth in vivo. Conclusion Exosomes from ccRCC deliver AP000439.2 to promote M2 macrophage polarization via STAT3, thus enhancing ccRCC progression, indicating exosomal AP000439.2 might be a novel therapeutic target in ccRCC. Video Abstract

ObjectiveTo investigate the exact age‐adjusted incidence (AAI), clinical characteristics, and survival data of collecting duct carcinoma of the kidney (CDCK) recorded in the Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute.MethodsPatients with CDCK confirmed by microscopic examination from 2004 to 2018 were selected from the SEER database. AAI rates were calculated using SEER*Stat software (version 8.3.9). The Kaplan‐Meier method was used to evaluate cancer-specific survival (CSS) rates according to tumor size, tumor stage, and treatment methods, and differences among these variables were assessed by the log‐rank test. Cox regression analysis was employed to identify variables independently related to CSS.ResultsA total of 286 patients with CDCK were identified from the database. The majority of the patients were white (69.2%), male (67.5%), and married (60.5%), and the median age was 59 years. Most patients with CDCK (74.4%) presented with stages III or IV disease. The diameter of most (59.4%) tumors was less than 7 cm, and the tumors were more commonly found on the left than on the right (55.2% vs. 44.8%). The incidence of CDCK decreased over time. The median CSS time was 17 months. In terms of the treatment modalities used, 83.9% of the patients underwent surgery; 32.9% underwent chemotherapy, and 13.6% underwent radiotherapy. The CSS rates at 1, 2, and 5 years were 57.3%, 43.2%, and 30.7%, respectively. In patients with stage IV CDCK treated with surgery alone, chemotherapy alone, and surgery plus chemotherapy, the median survival time was 5 months, 9 months, and 14 months, respectively (P =0.024). Multivariate Cox regression analysis showed surgery, chemotherapy, stage, regional lymph node metastasis, and distant metastasis were independent prognostic factors for patients with CDCK.ConclusionsCDCK is an uncommon malignant renal carcinoma, and its incidence is decreasing based on the analysis of current data. CDCK is a high stage, regional lymph-nodes positive, and metastatic disease. Compared with surgery alone or chemotherapy alone, patients with stage IV could gain survival benefit from surgery combined with chemotherapy.

Clear cell renal cell carcinoma (ccRCC) is one of the most common tumors in the urinary system. Progression in immunotherapy has provided novel options for the ccRCC treatment. However, the understanding of the ccRCC microenvironment and the potential therapeutic targets in the microenvironment is still unclear. Here, we analyzed the gene expression profile of ccRCC tumors from the Cancer Genome Atlas (TCGA) and calculated the abundance ratios of immune cells for each sample. Then, seven types of immune cells were found to be correlated to overall survival, and 3863 immune-related genes were identified by analyzing differentially expressed genes. We also found that the function of immune-related genes was mainly focused on ligand-receptor binding and signaling pathway transductions. Additionally, we identified 13 hub genes by analyzing the protein-protein interaction network, and seven of them are related to overall survival. Our study not only expands the understanding of fundamental biological features of microenvironment but also provides potential therapeutic targets.

Abstract Background Numerous recent studies indicate that the long non-coding RNAs (lncRNAs) are frequently abnormal expressed and take critical roles in many cancers. Renal cell carcinoma is the secondary malignant tumors in the urinary system and has high mortality and morbidity. Around 80% of RCCs is clear cell renal cell carcinoma (ccRCC) and is characterized by high metastasis and relapse rate. However, the clinical significances of lncRNAs in ccRCC are still unknown. Methods The human cancer lncRNA PCR array (Yingbio) was performed to detect the differentially expressed lncRNAs in human ccRCC samples. Real-time PCR (RT-PCR), dual-luciferase assay, RNA binding protein immunoprecipitation (RIP) assay, transwell assay, CCK-8 assay, and western blot were performed to explore the molecular mechanism of lncRNAs in ccRCC cell migration and invasion. Results In this study, lncRNA-H19 was high expressed and negatively correlated with miR-29a-3p in ccRCC. By bioinformatics software, dual-luciferase reporter and RIP assays, we verified that miR-29a-3p was identified as a direct target of lncRNA-H19. RT-PCR and western blot demonstrated that down-regulated lncRNA-H19 could affect the expression of miR-29a-3p targeting E2F1 with competitively binding miR-29a-3p. Furthermore, transwell assays indicated that lncRNA-H19 knockdown inhibited cells migration and invasion, but this effect was attenuated by co-transfection of lncRNA-H19 siRNA and miR-29a-3p inhibitor. Over expression of E2F1 could rescue lncRNA-H19 siRNA induced suppression on cell migration and invasion in ccRCC cells. Conclusions These results show a possible competing endogenous RNAs regulatory network involving lncRNA-H19 regulates E2F1 expression by competitively sponging endogenous miR-29a-3p in ccRCC. This mechanism may contribute to a better understanding of ccRCC pathogenesis, and lncRNA-H19 may be further considered as a potential therapeutic target for ccRCC intervention.

This study aims to profile dysregulated microRNA (miRNA) expression in clear cell renal cell carcinoma (ccRCC) and to identify key regulatory miRNAs in ccRCC.miRNA expression profiles in nine pairs of ccRCC tumor samples at three different stages and the adjacent, non-tumorous tissues were investigated using miRNA arrays. Eleven miRNAs were identified to be commonly dysregulated, including three up-regulated (miR-487a, miR-491-3p and miR-452) and eight down-regulated (miR-125b, miR-142-3p, miR-199a-5p, miR-22, miR-299-3p, miR-29a, miR-429, and miR-532-5p) in tumor tissues as compared with adjacent normal tissues. The 11 miRNAs and their predicted target genes were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and three key miRNAs (miR-199a-5p, miR-22 and miR-429) were identified by microRNA-gene network analysis. Dysregulation of the three key miRNAs were further validated in another cohort of 15 ccRCC samples, and the human kidney carcinoma cell line 786-O, as compared with five normal kidney samples. Further investigation showed that over-expression of miR-199a-5p significantly inhibited the invasion ability of 786-O cells. Luciferase reporter assays indicated that miR-199a-5p regulated expression of TGFBR1 and JunB by directly interacting with their 3' untranslated regions. Transfection of miR-199a-5p successfully suppressed expression of TGFBR1 and JunB in the human embryonic kidney 293T cells, further confirming the direct regulation of miR-199a-5p on these two genes.This study identified 11 commonly dysregulated miRNAs in ccRCC, three of which (miR-199a-5p, miR-22 and miR-429) may represent key miRNAs involved in the pathogenesis of ccRCC. Further studies suggested that miR-199a-5p plays an important role in inhibition of cell invasion of ccRCC cells by suppressing expression of TGFBR1 and JunB.

Telomerase, a cellular reverse transcriptase, adds telomeric repeats to chromosome ends. In normal human somatic cells, telomerase is repressed and telomeres progressively shorten, leading to proliferative senescence. Introduction of the telomerase (hTERT) cDNA is sufficient to produce telomerase activity and immortalize normal human cells, suggesting that the repression of telomerase activity is transcriptional. The telomerase transcript has been shown to have at least six alternate splicing sites (four insertion sites and two deletion sites), and variants containing both or either of the deletion sites are present during development and in a panel of cancer cell lines we surveyed. One deletion (β site) and all four insertions cause premature translation terminations, whereas the other deletion (α site) is 36 by and lies within reverse transcriptase (RT) motif A, suggesting that this deletion variant may be a candidate as a dominant-negative inhibitor of telomerase. We have cloned three alternately spliced hTERT variants that contain the α,β or both α and,β deletion sites. These alternate splicing variants along with empty vector and wild-type hTERT were introduced into normal human fibroblasts and several telomerase-positive immortal and tumor cell lines. Expression of the α site deletion variant (hTERT α−) construct was confirmed by Western blotting. We found that none of the three alternate splicing variants reconstitutes telomerase activity in fibroblasts. However, hTERT α− inhibits telomerase activities in telomerase-positive cells, causes telomere shortening and eventually cell death. This alternately spliced dominant-negative variant may be important in understanding telomerase regulation during development, differentiation and in cancer progression.

Abstract The correlation between the Cobb angle and the sagittal spinal curvature (SSC) in adolescent idiopathic scoliosis (AIS) has been reported in some previous studies, but few studies have reported on the relation of coronal wedge deformity (CWD) with sagittal curvature. This study aims to investigate the correlation between CWD and SSC in AIS patients. A retrospective analysis was conducted in 122 AIS patients treated at our hospital from January 2018 to November 2023. Correlation analysis was performed on the Cobb angle, total wedge angle(TW), apical vertebral wedge angle (APW), upper end-vertebral wedge angle (UW), lower end-vertebral wedge angle (LW), total affected structures, average wedge angle(AW), total vertebral wedge angle (TVW), average vertebral wedge angle (AVW), Vertebral Wedge Angle ratio (VWR), total disc wedge angle (TDW), average disc wedge angle (ADW), and disc wedge angle ratio (DWR). Furthermore, out of all cases which underwent lateral spinal radiographs, a correlation analysis between thoracic kyphosis (TK), lumbar lordosis (LL) and CWD was carried out on 102 patients. The Cobb angle exhibited a significant positive correlation with multiple CWD parameters (P 0.05). In mild and moderate AIS patients, CWD parameters were positively correlated with the Cobb angle and negatively correlated with thoracic SSC. This may indicate that it’s necessary to correct sagittal thoracic curvature when rectifying scoliosis in clinic. This research would not only provide new insights for clinical practice but also offer important evidence for early diagnosis and intervention.

Abstract In prior investigations, a correlation was established between patient outcomes in locally advanced non-small cell lung cancer (LA-NSCLC) following thoracic irradiation and parameters, such as pre/post-treatment neutrophil-to-lymphocyte ratio (NLR) and NLR change (ΔNLR). However, these parameters could potentially be influenced by radiation-related variables, such as gross tumor volume (GTV). The primary aim of this study was to elucidate the factors impacting post-treatment NLR and ΔNLR and to further assess their prognostic relevance. In this retrospective study, a cohort of 188 LA-NSCLC patients who underwent thoracic radiation between 2012 and 2017 was assessed. The calculation of pre/post-treatment NLR involved the use of absolute neutrophil and lymphocyte counts. ΔNLR was defined as the difference between post- and pre-treatment NLR values. To assess the relationships between various variables and overall survival (OS), local progression-free survival (LPFS), and distant metastasis-free survival (DMFS), the Kaplan–Meier technique and Cox proportional hazards regression were employed. Additionally, Spearman’s rank correlation analysis was carried out to investigate correlations between the variables. The analysis revealed that both post-treatment NLR (r = 0.315, P 67.41 cm3 group (P = 0.028 and P = 0.042, respectively), highlighting ΔNLR as the sole independent predictive factor for survival and metastasis, irrespective of GTV.

Abstract Purpose The duration of type 2 diabetes mellitus (T2DM) and blood glucose levels have a significant impact on the development of T2DM complications. However, currently known risk factors are not good predictors of the onset or progression of diabetic retinopathy (DR). Therefore, we aimed to investigate the differences in the serum lipid composition in patients with T2DM, without and with DR, and search for potential serological indicators associated with the development of DR. Methods A total of 622 patients with T2DM hospitalized in the Department of Endocrinology of the First Affiliated Hospital of Xi’an JiaoTong University were selected as the discovery set. One-to-one case–control matching was performed according to the traditional risk factors for DR (i.e., age, duration of diabetes, HbA1c level, and hypertension). All cases with comorbid chronic kidney disease were excluded to eliminate confounding factors. A total of 42 pairs were successfully matched. T2DM patients with DR (DR group) were the case group, and T2DM patients without DR (NDR group) served as control subjects. Ultra-performance liquid chromatography–mass spectrometry (LC–MS/MS) was used for untargeted lipidomics analysis on serum, and a partial least squares discriminant analysis (PLS-DA) model was established to screen differential lipid molecules based on variable importance in the projection (VIP) > 1. An additional 531 T2DM patients were selected as the validation set. Next, 1:1 propensity score matching (PSM) was performed for the traditional risk factors for DR, and a combined 95 pairings in the NDR and DR groups were successfully matched. The screened differential lipid molecules were validated by multiple reaction monitoring (MRM) quantification based on mass spectrometry. Results The discovery set showed no differences in traditional risk factors associated with the development of DR (i.e., age, disease duration, HbA1c, blood pressure, and glomerular filtration rate). In the DR group compared with the NDR group, the levels of three ceramides (Cer) and seven sphingomyelins (SM) were significantly lower, and one phosphatidylcholine (PC), two lysophosphatidylcholines (LPC), and two SMs were significantly higher. Furthermore, evaluation of these 15 differential lipid molecules in the validation sample set showed that three Cer and SM(d18:1/24:1) molecules were substantially lower in the DR group. After excluding other confounding factors (e.g., sex, BMI, lipid-lowering drug therapy, and lipid levels), multifactorial logistic regression analysis revealed that a lower abundance of two ceramides, i.e., Cer(d18:0/22:0) and Cer(d18:0/24:0), was an independent risk factor for the occurrence of DR in T2DM patients. Conclusion Disturbances in lipid metabolism are closely associated with the occurrence of DR in patients with T2DM, especially in ceramides. Our study revealed for the first time that Cer(d18:0/22:0) and Cer(d18:0/24:0) might be potential serological markers for the diagnosis of DR occurrence in T2DM patients, providing new ideas for the early diagnosis of DR.

Abstract The correlation between scoliosis and sagittal curvature of the cervical, thoracic, and lumbar spine have already been reported in previous studies. However, as a part of the spine, the change in coccygeal morphology in AIS patients has not yet been studied. In this study, a retrospective analysis was performed on 400 patients who were divided into a non-scoliotic group (206 patients) and an AIS group (194 patients). The Postacchini coccygeal radiological classification that was modified by Nathan was used to observe and compare the sagittal coccygeal morphology between the two groups. The results showed that the non-scoliotic group had the highest percentage (52.4%) of patients with type I and the lowest (3.4%) proportion of patients with type V; moreover, the AIS group had the highest percentage (69.1%) of patients with type I and the lowest (1.5%) proportion of patients with type V. The coccygeal morphology was significantly different between the non-scoliotic group and the AIS group (P = 0.001). No significant differences in coccygeal morphology were found between the males and females in the two groups (mild and moderate scoliosis and different segmental scoliosis). In addition, a significant correlation between coccygeal morphology and scoliosis (P = 0.035) was found. In conclusion, coccygeal morphology significantly differs between AIS patients and non-scoliotic adolescents. There was a smaller proportion of patients with a type I coccyx and a larger proportion of patients with a type II or type III coccyx in the AIS group than in the non-scoliotic group. In other words, the presence of a more pronounced coccygeal curve in AIS patients may be caused by an incorrect sitting position and an imbalance in the contraction of the pelvic muscles. It should be further studied whether correcting the sitting position and muscular imbalances could change coccygeal morphology and subsequently affect the development of AIS.

Abstract Objective The objective of this study was to investigate the safety and effectiveness of high-dose-rate brachytherapy as a treatment modality for recurrent or residual neck metastatic lymph nodes following external radiotherapy. Methods 38 patients with 52 metastatic lymph nodes recurring or residual after previous external radiotherapy was completed to metastatic lymph nodes in the neck were collected from January 2019 to February 2022. High-dose-rate brachytherapy with 192Ir was performed with a prescribed dose of 20–30 Gy/1f (effective biological dose of 60–120 Gy), and imaging was performed at 1, 3, and 6 months after treatment to assess the local control rate and adverse effects of treatment. Results All 38 patients received completed treatment, and they were followed up for 6 months. 52 patients with neck lymph node metastases had an objective response rate. (Complete response, CR + Partial response, PR) of 76.9%, which comprised 89.5% (34/38) for lymph nodes ≤ 3 cm and 42.9% (4/14) for > 3 cm, P = 0.028. P > 0.05 for CR + PR versus stable disease, SD + progressive disease, PD for lymph nodes between different subdivisions of the neck. Using the Radiation Therapy Oncology Group (RTOG) Acute Toxicity Scoring System, there were 6 cases of acute radioskin injuries of degree I and 4 cases of degree II with a 60% symptomatic relief rate. Conclusions High-dose-rate brachytherapy serves as a safe and effective method in treating recurrent residual neck metastatic lymph nodes in the field after external radiotherapy, exerting tolerable adverse effects.

Abstract Background The effectiveness of selective COX-2 inhibitors in preventing colorectal cancer recurrence has been demonstrated, however it is unknown how safe and successful they will be over the long term. As a result, we looked at the efficacy, safety, and consequences of adding COX-2 inhibitors to the treatment plan afterward. Methods In patients with advanced colorectal cancer, we compared the efficacy of celecoxib at two different doses (200 mg twice day and 400 mg twice daily) with placebo. To evaluate the impacts of post-treatment, several datasets from inception to June 2022 were searched. Response rate, illness control rate, and 3-year survival were the main results. And evaluated several safety outcomes, particularly those that were susceptible to adverse events. Results The study comprised a total of 9 randomized controlled trials (3206 participants). Celecoxib and rofecoxib doidn’t significantly improved the 1–3 year remission rate (OR, 1.57 [95% CI: 0.95–2.57]) and disease control rate (OR, 1.08 [95% CI: 0.99–1.17]). Subgroup analysis of different doses showed that 400 mg of celecoxib significantly improved the response rate (OR, 2.82 [95%CI: 1.20–6.61]). 200 mg celecoxib was not significant (OR, 1.28 [95% CI: 0.66–2.49]). Rofecoxib also did not fully improve disease response rates. Celecoxib at any dose improved 3-year survival (OR, 1.21 [95% CI: 1.02–1.45]). It is important to note that COX-2 inhibitors did not significantly enhance the likelihood of adverse events including gastrointestinal or cardiovascular side effects at any dose. Conclusions For patients with advanced colorectal cancer, a reasonable chemoprevention regimen can include celecoxib 400 mg twice daily.

The present study aims to investigate the therapeutic value of third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) combined with cranial radiotherapy (RT) in patients with EGFR-positive non-small cell lung cancer (NSCLC) and brain metastases (BMs).MethodologyThis is a retrospective study that involved 213 patients with EGFR-NSCLC and BMs, with the patients divided into two groups: the upfront cranial RT (ucRT) group (n = 96) and the non-ucRT group (n = 117). All patients were administered with osimertinib, and those in the ucRT group also underwent RT. The overall survival (OS), progression-free survival (PFS) and intracranial PFS (IPFS) of the two groups were compared.ResultsThe ucRT group manifested a markedly higher IPFS than the non-ucRT group (29.65 months vs 21.8 months; P < 0.0001). The subgroup analysis revealed that patients with oligometastases (OLOGO-BMs; 1–3 BMs) demonstrated a notably longer OS (44.5 months vs 37.3 months; P < 0.0001), PFS (32.3 months vs 20.8 months; P = 0.6884) and IPFS (37.8 months vs 22.1 months; P < 0.0001) in the ucRT group than in the non-ucRT group. However, for patients with multiple BMs, there was no significant difference in OS (27.3 months vs 34.4 months; P = 0.0710) and PFS (13.7 months vs 13.2 months; P = 0.0516) between the ucRT group and the non-ucRT group; the ucRT group exhibited a higher IPFS (26.4 months vs 21.35 months; P = 0.0028). Cox’s multivariate analysis of patients with OLOGO-BM indicated that the use of ucRT was linked to a better OS (heart rate [HR] = 0.392; 95% confidence interval [CI]: 0.178–0.863; P = 0.020) and PFS (HR = 0.558; 95% CI: 0.316–0.986; P = 0.044).ConclusionUpfront cerebral cranial stereotactic radiosurgery can improve outcomes in EGFR-positive patients with NSCLC and OLOGO-BM. However, for patients with multiple BMs, the preferable strategy may be pre-treatment with EGFR-TKIs.

Inconel 718 is widely used in aeroengine hot end parts, such as turbine disks, blades, drive shafts and so on. Its excellent mechanical and thermal properties also lead to the poor machinability, poor surface integrity, thus affecting the fatigue life of the machined part. This paper proposes an ultrasonic peening milling (UPM) technology which can introduce ultrasonic impact to the machined surface during end milling by applying ultrasonic vibration perpendicular to the machined surface. The effects of vibration on the surface integrity and fatigue life of this material were investigated in comparison with conventional milling (CM). The results showed that the best fatigue life of 2.20 × 106 cycles was achieved by UPM. Compared to the CM process, UPM improved the fatigue life by 16.1 times due to better surface quality with fewer surface defects, thicker stress-affecting layers, and the reinforced machined surface achieved in UPM. The results and findings of this study could contribute to the development of new effective and anti-fatigue machining methods for Inconel 718 in the future.

Context Dehydroandrographolide succinate (DAS) is mainly used in the clinical treatment of various infectious diseases. Its potential effects on platelet aggregation and blood coagulation systems have not been reported systematically. Objective To explore whether DAS exerts an antithrombotic effect and its internal mechanism. Materials and methods Human blood samples and Sprague-Dawley (SD) rats divided into control, aspirin (30 mg/kg), and DAS groups (200, 400 and 600 mg/kg) were used to measure the platelet aggregation rate, coagulation function, coagulation factor activity, and contents of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1α (6-keto-PGF1α). The histopathology of the SD rat gastric mucosa was also observed. All rats were administered intragastric or intraperitoneal injections once a day for 3 consecutive days. Results Compared to control group, DAS significantly inhibited the platelet aggregation rate (ED50 = 386.9 mg/kg) by decreasing TXB2 levels (1531.95 ± 649.90 pg/mL to 511.08 ± 411.82 pg/mL) and activating antithrombin III (AT-III) (103.22 ± 16.22% to 146.46 ± 8.96%) (p

Objective: To investigate the effects of IMR, iDose4 and FBP reconstruction algorithms on the image quality of multi-row spiral CT in the chest before costal cartilage rhinoplasty. Methods: A total of 60 patients who met the inclusion criteria and planned to receive autogenous costal cartilage rhinoplasty were collected. All patients underwent chest CT examination before operation and completed relevant 3D reconstruction based on images generated by IMR, iDose4 and FBP reconstruction algorithms, and the image quality of the three reconstruction algorithms was analyzed. The subjective evaluation score and objective evaluation indexes of image quality in each group were recorded and compared including costal cartilage CT value, noise, signal-to-noise ratio and contrast noise ratio. Results: The CT reconstruction images obtained by the three algorithms could all accurately assess the degree of costal cartilage calcification. Subjective evaluation of image quality showed that the IMR group obtained higher score and held obvious advantages, mainly reflected in the IMR reconstruction algorithm compared with iDose4 and FBP two algorithms in the costal cartilage calcification spot edge display and inhibition of liver, gastrointestinal content and weakened heart beating artifacts. Objective evaluation of costal cartilage CT value, SNR, contrast noise ratio and statistical analysis, the final statistical results showed that IMR, iDose4 and FBP reconstruction algorithm group showed significant statistical differences, IMR group showed obviously the best image quality. Conclusion: All three reconstruction algorithms of IMR, idose4 and FBP can accurately evaluate the presence and degree of calcification of autologous costal cartilage. Under the same scanning conditions, compared with the reconstruction algorithms of FBP and iDose4, IMR reconstruction algorithms can reducecan significantly reduce image noise, improve CNR and SNR, and improve the subjective image quality of costal cartilage. It is more acceptable to clinical surgeons and can be used as the preferred algorithm reconstruction technique for costal cartilage CT examination, which is most worthy of promotion.

Objective: To investigate the optimal dosage of contrast agent in three-dimensional dynamic enhanced magnetic resonance angiography (3D CE-MRA) in the imaging of arterial lesions of both lower limbs. Methods: 45 patients who underwent 3D CE-MRA angiography of lower extremity arteries in our hospital were randomly divided into three groups A, B and C. The gadolinium dosages of the three groups were respectively 0.1 mmol/kg, 0.2 mmol/kg and 0.3 mmol/kg. They were injected intravenously with saline at the ratio of 1:1. The images of different dose scanning schemes were scored subjectively and objectively. Subjective scoring: the lower limb arteries were divided into femoral artery, popliteal artery and calf artery (posterior tibial artery, anterior tibial artery and common peroneal artery). The quality of MIP reconstruction images was evaluated, and the overall venous overlap scoring of calf and foot vessels was also carried out. Finally, the differences of the three scanning schemes were compared by Wilcoxon test.The objective scoring is to measure and calculate the signal intensity Si, signal-to-noise ratio SNR and contrast-to-noise ratio of the original enhanced images of the three groups, compare the horizontal signal intensity differences of femoral artery, popliteal artery and calf artery, and compare the differences of the three scanning schemes by t-test. Results: When the contrast medium dosage was 0.1 mmol/kg, the image quality scores of femoral artery, popliteal artery and calf artery were (3.35±0.25), (2.97±0.25), (2.35±1.15) respectively; When the dosage of contrast agent was 0.2 mmol/kg, the scores of the above parts were (3.75±0.35), (3.55±0.32), (2.97±0.70) respectively; When the dosage of contrast agent was 0.3 mmol/kg, the scores of the above parts were (3.90±0.41), (3.83±0.52), (3.10±0.75) respectively. 33.33% of the images in group A did not meet the diagnostic needs, while all the images in group B and C met the diagnostic needs. There was significant difference between group A and group B, and there was no significant difference between group B and group C. B The Si, SNR and CNR of femoral artery and popliteal artery in group C were significantly higher than those in group A, and there was no significant difference between group B and C. The images of group B and C were better than those of group A. Conclusion: Appropriate increase of the contrast medium dosage is helpful to improve the 3D CE-MRA imaging quality of both lower limb arteries. The contrast medium dosage of 0.2 mmol/kg is reliable and accurate for the evaluation of blood vessels, and can provide accurate and reliable imaging basis for the formulation of treatment plan for patients with peripheral artery diseases.

Background: Individual metals have been linked to sex hormones disruption, but the associations of metals mixture are rarely examined among children. Methods: A total of 1060 participants of 6–19-year-old who participated in the National Health and Nutrition Examination Survey (2013–2016) were included. Eighteen metals were quantified in the whole blood and urine. Sex hormones were measured in serum, including total testosterone (TT), estradiol (E2), and sex hormone binding globulin (SHBG). In addition, free androgen index (FAI) and the ratio of TT to E2 were calculated. Bayesian kernel machine regression and latent class analysis were performed to assess the associations of metals mixture and exposure patterns of metals at varied levels with sex hormones while adjusting for selected covariates. All analyses were conducted by sex-age and sex-puberty groups to explore the potential sex-dimorphic effects. Results: Exposure to metals mixture was associated with elevated levels of FAI and E2 among 12–19 years old girls. Moreover, the exposure pattern of metals that was characterized by high levels of blood and urinary cadmium, blood manganese, and urinary cobalt was associated with elevated E2 and reduced TT/E2 levels among girls of 12–19 years old. However, the associations of metals mixture with sex hormones were overall nonsignificant among boys. Nevertheless, metals exposure pattern that was characterized by high levels of blood lead, urinary barium, strontium, and lead but comparatively low levels of the other metals was consistently associated with reduced levels of FAI and E2 but elevated levels of TT/E2 and SHBG among boys of 12–19 years old. Conclusion: Metals mixture and exposure patterns that were dominated by high levels of certain metals were associated with sex hormones imbalance among 12–19 years old children in a sex-dimorphic pattern, with the identified individual metals that drove the associations of metals mixture varied by sex.

Abscisic acid (ABA) hydroxylation is an important pathway for ABA inactivation and homeostasis maintenance. Here, we discover a new downstream catabolite of neophaseic acid (neoPA) in the ABA 9′-hydroxyl pathway and identify it as epi-neodihydrophaseic acid (epi-neoDPA) by comparing its accurate mass, retention time, and MSn spectra with those of our chemically synthesized epi-neoDPA. Analyses of Arabidopsis seed germination and ABA-related gene expression reveal that neoPA rather than epi-neoDPA possesses ABA-like hormonal activity. In vitro enzyme activity tests of prokaryotic recombinant protein reveal that NeoPAR1 (neoPA reductase 1) identified from Arabidopsis converts neoPA into epi-neoDPA. Site-directed mutation at Tyr163 in the conserved motif of NeoPAR1 abolishes the catalytic activity of NeoPAR1. Accelerated seed germination was observed in NeoPAR1 knockdown and knockout mutants, whereas retarded seed germination and the accumulation of epi-neoDPA and ABA were observed in NeoPAR1 overexpression lines, suggesting that NeoPAR1 is involved in seed germination and maintenance of ABA homeostasis.