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To estimate the variations in clinical target volumes (CTVs) and organs at risk delineation within the quality assurance (QA) program of the POTENTIAL trial, which is a multicenter, randomized phase 3 trial evaluating postmastectomy radiation therapy (RT), with or without internal mammary nodal irradiation, for patients with high-risk breast cancer.The simulating computed tomography scan data set of a benchmark case was sent to the participating centers, and the delineation of CTVs and organs at risk was required to be completed by the investigators following protocol guidelines. All submitted contours were reviewed and compared with the reference contours created by the QA team, using quantitative geometric analysis regarding volume and the Jaccard Index (JCI), Dice similarity coefficient, Geographic Miss Index, Discordance Index, and mean distance to agreement. In addition to the whole-volume analysis of all structures, the combination contour of the supraclavicular fossa and level III and II axilla (CTVsc + axIII + axII) was further analyzed on a slice-by-slice basis.The contours from 26 centers were reviewed and variations were observed between submission and reference. The variations of the CTV of the chest wall, contralateral breast, and heart were small, for which the mean JCI values were 0.62, 0.68, and 0.87, respectively. However, the mean JCI values of the CTV of the internal mammary nodal region, ipsilateral brachial plexus, left anterior descending coronary artery, and right coronary artery were 0.38, 0.21, 0.29, and 0.18, respectively, suggesting marked variations. In addition, marked under- and overoutlining variations were identified on 4 slices of CTVsc + axIII + axII on slice-by-slice analysis.There were residual contouring variations despite a detailed protocol being provided, confirming the importance of pretrial QA in RT and highlighting the need for education and consideration of a real-time central review of the target delineation before the trial participants begin RT.

Immune escape is a frequent occurrence, which limits the duration of antitumor immune responses to radiotherapy. Here, we aimed to ascertain the roles and underlying mechanisms of programmed death ligand 1 (PD-L1) in tolerance of breast cancer (BC) to radiotherapy. We first quantified microRNA-21 (miR-21) and PD-L1 expression in BC tissues and cells, followed by identification of the interactions between miR-21, PD-L1, and programmed cell death protein 4 (PDCD4). miR-21 knock-in mice were used to construct tumor-bearing models, which were then treated with anti-PD-L1 antibody and irradiation, followed by measurement of tumor growth and tumor immune escape. Finally, we evaluated the synergistic effects of radiotherapy and anti-PD-L1 antibody in vivo. The results showed increased miR-21 expression in BC tissues and cells, which was positively correlated with PD-L1 expression. The treatment with radiotherapy or anti-PD-L1 antibody in the miR-21 knock-in mice diminished tumor weight and volume, along with decreased CD3+CD8+ positive cells, serum IL-2 and IFN-γ levels, and lower PD-L1 expression, but augmented apoptosis of T and BC cells. Moreover, miR-21 significantly augmented PD-L1 expression via PI3K/Akt pathway activation by targeting PDCD4 in BC cells. Thus, radiotherapy and anti-PD-L1 antibody synergistically accelerated the therapeutic effect against BC in mice, thereby implicating a close interplay between radiotherapy, T cells, and the miR-21/PDCD4/PI3K/Akt/PD-L1 axis.

DNA G4-structures from human c-MYC promoter and telomere are considered as important drug targets; however, the developing of small-molecule-based fluorescent binding ligands that are highly selective in targeting these G4-structures over other types of nucleic acids is challenging. We herein report a new approach of designing small molecules based on a non-selective thiazole orange scaffold to provide two-directional and multi-site interactions with flanking residues and loops of the G4-motif for better selectivity. The ligands are designed to establish multi-site interactions in the G4-binding pocket. This structural feature may render the molecules higher selectivity toward c-MYC G4s than other structures. The ligand–G4 interaction studied with 1H NMR may suggest a stacking interaction with the terminal G-tetrad. Moreover, the intracellular co-localization study with BG4 and cellular competition experiments with BRACO-19 may suggest that the binding targets of the ligands in cells are most probably G4-structures. Furthermore, the ligands that either preferentially bind to c-MYC promoter or telomeric G4s are able to downregulate markedly the c-MYC and hTERT gene expression in MCF-7 cells, and induce senescence and DNA damage to cancer cells. The in vivo antitumor activity of the ligands in MCF-7 tumor-bearing mice is also demonstrated.

Purpose: In advanced or high-grade prostate cancer (PCa), prostate-specific antigen (PSA) is usually elevated, however, some patients may present with low initial PSA (iPSA) levels. The objective of this study was to evaluate whether different iPSA levels were associated with dissimilar clinical outcomes among men with high-grade PCa and advanced disease after robot-assisted laparoscopic radical prostatectomy (RaLRP). Methods: This study enrolled 69 PCa patients with initial Gleason score ≥8 and pathologic T-stage ≥3a from April 2012 to December 2018. Patients were stratified into 3 groups based on iPSA levels at diagnosis

Aurora A kinase is a cell cycle regulator that is dysregulated in several different malignancies. Nevertheless, its regulatory mechanisms are still not fully understood. Here, we report that ubiquitin specific peptidase 3 (USP3) promotes proliferation and metastasis of esophageal squamous cell carcinoma (ESCC) cells by mediating deubiquitination of Aurora A. Analysis of human clinical samples indicated that USP3 and Aurora A are highly expressed in ESCC. Cellular experiments confirmed that high expression of USP3 and Aurora A in ESCC cells promoted malignant cell proliferation and invasion. In this mechanism, USP3 leads to suppression of Aurora A ubiquitination, resulting less proteasome degradation. We constructed the deubiquitinated mimetic K143R of Aurora A and found that K143R significantly promoted the proliferation and invasion of ESCC cells and was not regulated by the deubiquitination of USP3. Moreover, Aurora A K143R potentiated the kinase activity of Aurora A in ESCC cells. Thus, our findings demonstrate that the tumorigenic feature of ESCC is in part mediated by USP3-facilitated deubiquitination of Aurora A.

OBJECTIVES The role of thoracic endovascular aortic replacement (TEVAR) in patients with concomitant blunt thoracic aortic injury (BTAI) and blunt abdomen trauma (BAT) was evaluated using nationwide real-world data. The risk of post-TEVAR abdominal haemorrhage was studied. METHODS Patients with BTAI and BAT in the National Trauma Data Bank were retrospectively studied. Propensity score matching was used to evaluate the effect of TEVAR in delayed abdominal surgeries for haemostasis and the delayed need for blood transfusion. A multivariable logistic regression analysis was used to evaluate the independent risk factors for delayed intra-abdominal haemorrhage in these patients. RESULTS A total of 928 concomitant BTAI and BAT patients were studied (TEVAR versus non-TEVAR, 206 vs 722). After a well-balanced propensity score matching analysis, patients who received TEVAR had significantly more delayed abdominal surgeries for haemostasis (7.7% vs 4.5%, standardized mean difference = 0.316) and delayed need for blood transfusion (11.6% vs 7.1%, standardized mean difference = 0.299) than those who did not. The multivariable logistic regression analysis showed that TEVAR increased the need for delayed abdominal surgeries (odds ratio = 2.026, P = 0.034). Among the patients who underwent TEVAR, the patients with delayed abdominal surgeries for haemostasis had a significantly higher proportion of severe abdominal injury (abdominal Abbreviated Injury Scale score of 4 or 5) than patients without delayed abdominal surgeries for haemostasis (31.6% vs 15.5%, P = 0.038). CONCLUSIONS Patients with concomitant BTAI and BAT had a higher risk of intra-abdominal haemorrhage after TEVAR, especially patients with severe abdominal trauma.

The purpose of this study was to explore the correlations between patients’ opioid-taking self-efficacy, social support, and their pain management satisfaction, and to evaluate the effect of social support and opioid-taking self-efficacy in explaining the variance in pain management satisfaction. We used a cross-sectional and correlational research design and recruited 123 cancer patients via convenience sampling. We used the following instruments: the Opioid-Taking Self-Efficacy Scale, the Inventory of Socially Supportive Behavior, and the Chinese version of the Pain Treatment Satisfaction Scale. There were significant and negative correlations between opioid-taking self-efficacy and pain management satisfaction (r = − .43, p

Idiopathic pulmonary fibrosis (IPF) is defined as a specific form of chronic, progressive fibrosing interstitial pneumonia. It is unknown why fibrosis in IPF distributes in the peripheral or named sub-pleural area. Migration of pleural mesothelial cells (PMC) should contribute to sub-pleural fibrosis. Calpain is known to be involved in cell migration, but the role of calpain in PMC migration has not been investigated. In this study, we found that PMCs migrated into lung parenchyma in patients with IPF. Then using Wt1tm1(EGFP/Cre)Wtp /J knock-in mice, we observed PMC migration into lung parenchyma in bleomycin-induced pleural fibrosis models, and calpain inhibitor attenuated pulmonary fibrosis with prevention of PMC migration. In vitro studies revealed that bleomycin and transforming growth factor-β1 increased calpain activity in PMCs, and activated calpain-mediated focal adhesion (FA) turnover as well as cell migration, cell proliferation, and collagen-I synthesis. Furthermore, we determined that calpain cleaved FA kinase in both C-terminal and N-terminal regions, which mediated FA turnover. Lastly, the data revealed that activated calpain was also involved in phosphorylation of cofilin-1, and p-cofilin-1 induced PMC migration. Taken together, this study provides evidence that calpain mediates PMC migration into lung parenchyma to promote sub-pleural fibrosis in IPF.

Purpose The U.S. Department of Veterans Affairs (VA) health care system monitors time from referral to specialist visit. We compared wait times for carpal tunnel release (CTR) at a VA hospital and its academic affiliate. Methods We selected patients who underwent CTR at a VA hospital and its academic affiliate (AA) (2010–2015). We analyzed time from primary care physician (PCP) referral to CTR, which was subdivided into PCP referral to surgical consultation and surgical consultation to CTR. Electrodiagnostic testing (EDS) was categorized in relation to surgical consultation (prereferral vs postreferral). Multivariable Cox proportional hazard models were used to examine associations between clinical variables and surgical location. Results Between 2010 and 2015, VA patients had a shorter median time from PCP referral to CTR (VA: 168 days; AA: 410 days), shorter time from PCP referral to surgical consultation (VA: 43 days; AA: 191 days), but longer time from surgical consultation to CTR (VA: 98 days; AA: 55 days). Using multivariable models, the VA was associated with a 35% shorter time to CTR (AA hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.52–0.82) and 75% shorter time to surgical consultation (AA HR, 0.25; 95% CI, 0.20–0.03). Receiving both prereferral and postreferral EDS was associated with almost a 2-fold prolonged time to CTR (AA HR, 0.49; 95% CI, 0.36–0.67). Conclusions The VA was associated with shorter overall time to CTR compared with its AA. However, the VA policy of prioritizing time from referral to surgical consultation may not optimally incentivize time to surgery. Repeat EDS was associated with longer wait times in both systems. Clinical Relevance Given differences in where delays occur in each health care system, initiatives to improve efficiency will require targeting the appropriate sources of preoperative delay. Judicious use of EDS may be one avenue to decrease wait times in both systems.

This study aimed to assess health concerns after hysterectomy from different perspectives among Taiwanese women with uterine fibroids. A mixed-methods was used in this study. In a cross-sectional study, 95 patients completed a structured questionnaire (Health Concern Questionnaire-HCQ). Face-to-face interviews with 5 patients were implemented for the qualitative component from OBS-GYN outpatient departments at two hospitals in Northern Taiwan. Participants who met the following criteria, 20 years of age or older, conscious alert without mental disturbances were recruited to this study. Descriptive statistics were calculated for social demographic variables and HCQ. A content analysis was used to analyze the qualitative data. The mean age was 46.28 of 95 patients. Findings of the present study showed that the most health concerns among patients with UFs after hysterectomy are hysterectomy-related complications, follow by impacts on daily life, body image and female identity, and intimacy and sexual relations. The findings of qualitative interviews supported the above findings. In addition, the information needs of post-operative self-care were identify in this qualitative interviews. The results of this research study could help healthcare professionals to address women's health concerns and provide adequate care for Taiwanese women with uterine fibroids after hysterectomy.

We compared chromosomal mosaicism, detected by next-generation sequencing (NGS), during preimplantation genetic testing (PGT) with that detected by single-nucleotide polymorphism (SNP) array-based PGT to assess the pregnancy outcomes associated with both platforms in a retrospective cohort study of patients undergoing in vitro fertilization in a single university-based assisted reproduction center. In total, 6427 blastocysts biopsied from 1513 patients who underwent 2833 oocyte retrievals from January 2017 to February 2019 were identified. The incidence of mosaicism was significantly higher in the NGS-based PGT group than in the SNP array-based PGT group. Furthermore, some aneuploid specimens were affected by mosaicism. The total mosaicism detection rate with NGS-based PGT (23.3%) was significantly higher than that with SNP array-based PGT (7.7%). Mosaicism rates were similar when stratified by maternal age or PGT type. The SNP array cohort showed a significantly higher spontaneous abortion rate than the NGS cohort (10.07% versus 6.33%; P = 0.0403). The ongoing pregnancy/live birth rate was higher in the NGS cohort (44.1%) than in the SNP array cohort (42.28%). Our results confirm that NGS-based PGT can detect mosaicism more frequently than SNP array-based PGT in trophectoderm specimens. Therefore, clinical application of NGS for PGT may improve pregnancy outcomes compared with that of SNP array-based PGT. More detailed blastocyst detection and classification is necessary to prioritize embryo transfers.

The distribution of fibrosis in idiopathic pulmonary fibrosis (IPF) is subpleural with basal predominance. Alveolar epithelial cell was considered as the key cell in the initial phase of IPF. However, the idea of activation and damage of alveolar epithelial cells is very difficult to explain why fibrosis distributes in the subpleural area. In this study, human pleural mesothelial cell (PMC) line and primary rat PMC was used as in vitro model. Intraperitoneal injection of bleomycin was used for making a pulmonary fibrosis model. The integrity of cultured monolayer PMCs was determined by transepithelial electric resistance (TEER). Pleural permeability was estimated by measuring paracellular transport of fluorescein isothiocyanate (FITC)-conjugated dextran. Changes in lung tissue of patients with IPF were analyzed by Masson’s and immunofluorescence staining. We found bleomycin induced PMCs damage and increased PMCs permeability; increased PMCs permeability aggravated bleomycin-induced subpleural inflammation and pulmonary fibrosis. Moreover, bleomycin was found to activate VEGF/Src signaling which increased PMCs permeability. In vivo, inhibition of VEGF/Src signaling prevented bleomycin-induced subpleural pulmonary fibrosis. At last, activation of VEGF/Src signaling was confirmed in subpleural area in patients with IPF. Taken together, our findings indicate that VEGF/Src signaling mediated pleural barrier damage and increased permeability which contributes to subpleural pulmonary fibrosis.

The number of older adults is rising rapidly in China. Various concerns such as chronic diseases, financial inadequacy, and a feeling of loneliness have adversely affected the mental health of older adults, and this has become an important public health and social issue. To realize healthy aging, the Nineteenth National People's Congress of China put forth the Healthy China strategy, speeding up the promotion activities of mental health and pension measures, carrying out public welfare pension insurance for the entire population, and contributing to the mental health of older adults. This study used data from China Family Panel Studies. This study mainly uses the random effect estimation method (random effect, RE) and the feasible generalized least squares estimation method (FGLS) to control for heterogeneity to explore the impact of social and commercial pension insurance on the mental health of older adults, the moderating effect of social capital on pension insurance, and the mental health of older adults. The results showed that social pension insurance is proportional to the mental health of older adults, whereas commercial pension insurance is inversely proportional to mental health. Social capital had a significant moderating effect on pension insurance. When a country develops an aging economy, the emphasis on social capital helps make targeted industrial development suggestions. The government's expansion of insurance coverage is crucial for improving the mental health of older adults.

Antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is an autoimmune disease often accompanied by rapidly progressive renal failure, and the genetic background is still unknown. Our study was performed to test whether autophagy-related 16 like 1 (ATG16L1) rs4663402 and rs4663396 single nucleotide polymorphisms (SNPs) were associated with AAV in the Chinese Guangxi population.One hundred seventy seven unrelated AAV patients and 216 healthy controls were included in this case-control study. Multiplex polymerase chain reaction combined with high-throughput sequencing was used for typing, and SNPStats and SHEsis were used for association analysis, pairwise linkage disequilibrium, and haplotype analysis.rs4663402 and rs4663396 were in Hardy-Weinberg equilibrium in AAV and control groups. The frequencies of rs4663402 AA, AT, and TT genotypes were 82.5%, 16.9%, and 0.6%, respectively, in patients with AAV, and 83.5%, 16.2%, and 0.5%, respectively, in controls. The frequencies of rs4663396 CC, CT, and TT genotypes were 63.8%, 33.9%, and 2.3%, respectively, in patients with AAV, and 69.2%, 26.6%, and 4.2%, respectively, in controls. Haplotype analysis revealed two SNPs in a single haplotype block (D' = 1.0). Our logistic regression adjusted for sex and age showed no association between rs4663402 and rs4663396 and the risk for AAV in genetic models (p 0.05). However, ATG16L1 rs4663396 CC and CT + TT genotypes exhibited statistically significant differences in the incidence of arthralgia (p = 0.03).Our results indicated that ATG16L1 rs4663402 and rs4663396 polymorphisms were not associated with AAV in the Chinese Guangxi population. ATG16L1 rs4663396 CT + TT genotype may be associated with arthralgia.

As a widely applied traditional Chinese medicine (TCM), Jian-Pi-Yi-Shen (JPYS) decoction maybe applied in curing premature ovarian failure (POF) besides chronic kidney disease (CKD).

Motor neuron disease (MND), including amyotrophic lateral sclerosis, spinal muscular atrophy and others, involved the upper or lower motor neurons selective loss, is characterized by neurodegeneration and neuroinflammation, in conjunction with microglia. We summarized that pathways and key mediators are associated with microglia, such as fractalkine signaling, purinergic signaling, NF-κB signaling, p38 MAPK signaling, TREM2-APOE signaling, ROCK signaling, C1q signaling, and Ion channel, which are involved in the activation, proliferation, and inflammation of microglia. This review aims to identify the microglia-related molecular target and explore potential treatment strategies for MND based on that target.

The emergence of carbapenem-resistant K. pneumoniae has become a serious problem in medical settings worldwide. The present study demonstrated that carbapenem-resistant K. pneumoniae strains have been spreading in medical settings in Myanmar. In particular, plasmid genes encoding NDMs and 16S rRNA methylases have been spreading in K. pneumoniae high-risk clones.

BackgroundTo evaluate the outcomes in differentiated thyroid cancer (DTC) patients who achieved excellent response to initial treatment and developed distant metastasis during follow-up.MethodsThyroid cancer patients registered in Chang Gung Memorial Hospital thyroid cancer database between January 1979 and December 2019 were assessed.ResultsAmong 1053 DTC patients with excellent response to initial therapy, 14 (1.3%) patients developed metastatic disease during follow-up, including 6 males and 8 females with median age of 50.2 years [interquartile range (IQR), 39.9-53.7]. Nine (64.3%) patients had papillary cancer, four (28.6%) had follicular cancer, and one (7.1%) had Hürthle cell cancer. Most patients (92.9%) had stage I disease at diagnosis. The sites of metastasis were lung (71.4%), bone (7.1%), mediastinum (7.1%) and multiple sites (14.3%). With a median follow-up of 18.3 years (IQR, 14.8-23.8), 2 patients had disease-specific mortality. The 5- and 10-year disease-specific survival after the diagnosis of distant metastasis was 92% and 74%, respectively. Multiple sites of metastasis was associated with increased risk of mortality (P = 0.022).ConclusionsA small proportion of DTC patients with an excellence response to initial therapy developed distant metastasis during follow-up. Multiple organ distant metastases conferred a worse disease-specific survival.

BACKGROUND Leukaemias comprise a heterogenous group of haematological malignancies. In CONCORD-3, we analysed data for children (aged 0-14 years) and adults (aged 15-99 years) diagnosed with a haematological malignancy during 2000-14 in 61 countries. Here, we aimed to examine worldwide trends in survival from leukaemia, by age and morphology, in young patients (aged 0-24 years). METHODS We analysed data from 258 population-based cancer registries in 61 countries participating in CONCORD-3 that submitted data on patients diagnosed with leukaemia. We grouped patients by age as children (0-14 years), adolescents (15-19 years), and young adults (20-24 years). We categorised leukaemia subtypes according to the International Classification of Childhood Cancer (ICCC-3), updated with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes. We estimated 5-year net survival by age and morphology, with 95% CIs, using the non-parametric Pohar-Perme estimator. To control for background mortality, we used life tables by country or region, single year of age, single calendar year and sex, and, where possible, by race or ethnicity. All-age survival estimates were standardised to the marginal distribution of young people with leukaemia included in the analysis. FINDINGS 164 563 young people were included in this analysis: 121 328 (73·7%) children, 22 963 (14·0%) adolescents, and 20 272 (12·3%) young adults. In 2010-14, the most common subtypes were lymphoid leukaemia (28 205 [68·2%] patients) and acute myeloid leukaemia (7863 [19·0%] patients). Age-standardised 5-year net survival in children, adolescents, and young adults for all leukaemias combined during 2010-14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia. Individuals with lymphoid leukaemia had better age-standardised survival (from 43% in Ecuador to ≥80% in parts of Europe, North America, Oceania, and Asia) than those with acute myeloid leukaemia (from 32% in Peru to ≥70% in most high-income countries in Europe, North America, and Oceania). Throughout 2000-14, survival from all leukaemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries. INTERPRETATION This study offers the first worldwide picture of population-based survival from leukaemia in children, adolescents, and young adults. Adolescents and young adults diagnosed with leukaemia continue to have lower survival than children. Trends in survival from leukaemia for adolescents and young adults are important indicators of the quality of cancer management in this age group. FUNDING Children with Cancer UK, the Institut National du Cancer, La Ligue Contre le Cancer, Centers for Disease Control and Prevention, Swiss Re, Swiss Cancer Research foundation, Swiss Cancer League, Rossy Family Foundation, US National Cancer Institute, and the American Cancer Society.

The expansion of a hexanucleotide repeat GGGGCC (G4C2) in the C9orf72 gene is the most common cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The G4C2 expansion leads to repeat-associated non-AUG (RAN) translation and the production of toxic dipeptide repeat (DPR) proteins, but the mechanisms of RAN translation remain enigmatic. Here, we report that the RNA helicase DHX36 is a robust positive regulator of C9orf72 RAN translation. DHX36 has a high affinity for the G4C2 repeat RNA, preferentially binds to the repeat RNA’s G-quadruplex conformation, and efficiently unwinds the G4C2 G-quadruplex structures. Native DHX36 interacts with the G4C2 repeat RNA and is essential for effective RAN translation in the cell. In induced pluripotent stem cells and differentiated motor neurons derived from C9orf72-linked ALS patients, reducing DHX36 significantly decreased the levels of endogenous DPR proteins. DHX36 is also aberrantly upregulated in tissues of C9orf72-linked ALS patients. These results indicate that DHX36 facilitates C9orf72 RAN translation by resolving repeat RNA G-quadruplex structures and may be a potential target for therapeutic intervention.

Growth arrest‐specific 5 (GAS5) is a kind of long non‐coding RNAs (lncRNAs). Previous studies showed that down‐regulation of LncRNA‐GAS5 was involved in the development of systemic lupus erythematosus (SLE). However, the regulatory mechanism of down‐expressed LncRNA‐GAS5 in SLE remains obscure. In this study, we aimed to investigate the association of LncRNA‐GAS5 polymorphism with SLE risk. And further explore how LncRNA‐GAS5 is involved in the occurrence of SLE. Here, we evaluated the relationship between the risk for the development of SLE and the 5‐base pair (AGGCA/‐) insertion/deletion (I/D) polymorphism (rs145204276) in the LncRNA‐GAS5 promoter region. A custom 36‐Plex SNPscan kit was used for genotyping the LncRNA‐GAS5 polymorphisms. The LncRNA‐GAS5 and miR‐21 target prediction was performed using bioinformatics software. Enzyme‐linked immunosorbent assay (ELISA) and quantitative real‐time PCR (qRT‐PCR) were performed to assess GAS5 and miR‐21 mRNA expression and PTEN protein expression. The results revealed that rs145204276 resulted in a decreased risk of SLE (DD genotypes vs II genotypes: adjusted OR = 0.538, 95% CI, 0.30‐0.97, P = .039; ID genotypes vs II genotypes: adjusted OR = 0.641, 95% CI, 0.46‐0.89, P = .007; ID/DD genotypes vs II genotypes: adjusted OR = 0.621, 95% CI, 0.46‐0.84, P = .002; D alleles vs I alleles: adjusted OR = 0.680, 95% CI, 0.53‐0.87, P = .002). A reduced incidence of renal disorders in SLE was found to be related to ID/DD genotypes and D alleles (ID/DD genotypes vs II genotypes: OR = 0.57, 95% CI, 0.36‐0.92, P = .020; D alleles vs I alleles: OR = 0.63, 95% CI, 0.43‐0.93, P = .019). However, no significant association of rs2235095, rs6790, rs2067079 and rs1951625 polymorphisms with SLE risk was observed (P > .05). Additionally, haplotype analysis showed that a decreased SLE risk resulted from the A‐A‐C‐G‐D haplotype (OR = 0.67, 95% CI, 0.49‐0.91, P = .010). Also, patients in the SLE group showed a down‐regulated expression of LncRNA‐GAS5 and PTEN than the healthy volunteers; however, patients with rs145204276 ID/DD genotypes showed up‐regulated expression of LncRNA‐GAS5 and PTEN compared with patients carrying the II genotype. Furthermore, the miR‐21 levels were considerably up‐regulated in the SLE group than the healthy volunteers, and patients with rs145204276 ID/DD genotype had lower miR‐21 levels than the ones with the II genotype. Thus, we found that the LncRNA‐GAS5/miR‐21/PTEN signalling pathway was involved in the development of SLE, where LncRNA‐GAS5 acted as an miR‐21 target, and miR‐21 regulated the expression of PTEN. These findings indicated that the rs145204276 ID/DD genotypes in the LncRNA‐GAS5 gene promoter region may be protected against SLE by up‐regulating the expression of LncRNA‐GAS5, which consecutively regulated miR‐21 and PTEN levels.

Oncogenic RAS mutations are associated with tumor resistance to radiation therapy. Cell-cell interactions in the tumor microenvironment (TME) profoundly influence therapy outcomes. However, the nature of these interactions and their role in Ras tumor radioresistance remain unclear. Here we use Drosophila oncogenic Ras tissues and human Ras cancer cell radiation models to address these questions. We discover that cellular response to genotoxic stress cooperates with oncogenic Ras to activate JAK/STAT non-cell autonomously in the TME. Specifically, p53 is heterogeneously activated in Ras tumor tissues in response to irradiation. This mosaicism allows high p53-expressing Ras clones to stimulate JAK/STAT cytokines, which activate JAK/STAT in the nearby low p53-expressing surviving Ras clones, leading to robust tumor re-establishment. Blocking any part of this cell-cell communication loop re-sensitizes Ras tumor cells to irradiation. These findings suggest that coupling STAT inhibitors to radiotherapy might improve clinical outcomes for Ras cancer patients., Dong, Vadla et al. find that oncogenic Ras and p53 cooperatively stimulate JAK/STAT cytokines to promote non-autonomous tissue overgrowth in Drosophila. Further, blocking STAT signalling prevents the growth-inducing effect of p53 overexpression and ionising irradiation in human cancer lines in culture and in mouse xenografts, suggesting a therapeutic route.

To compare clinical outcomes between the use of robotic-assisted laparoscopic radical prostatectomy (RP) and radiotherapy (RT) with long-term androgen deprivation therapy (ADT) in locally advanced prostate cancer (PC), 315 patients with locally advanced PC (clinical T-stage 3/4) were considered for analysis retrospectively. Propensity score-matching at a 1:1 ratio was performed. The median follow-up period was 59.2 months (IQR 39.8–87.4). There were 117 (37.1%) patients in the RP group and 198 (62.9%) patients in the RT group. RT patients were older and had higher PSA at diagnosis, higher Gleason score grade group and more advanced T-stage (all p p p = 0.470, p = 0.268 and p = 0.509, respectively). This information supported a clinical benefit in BCR control for patients undergoing RT plus long-term ADT compared to RP.

Reduced nitric oxide synthase (NOS) activity and decreased reparative potentials in stem cells may be involved in the pathogenesis of osteonecrosis of the femoral head (ONFH), but the underlying mechanism is not clear. Ankyrin, a cytoskeletal protein, can promote NOS expression and many cellular functions when it interacts with the CD44 receptors on the stem cells. This study investigated whether ankyrin is involved in the pathogenesis of ONFH.Bone marrow stem cells (BMSCs) from ONFH patients were compared with cells from patients with proximal femoral fracture and BMSC cell lines (PT-2501, Lonza, NC, USA). Differences in the expression levels and downstream signal pathway of ankyrin-Akt-eNOS in BMSCs were studied between ONFH and control. The involvement of ankyrin in the signal cascade, cell proliferation, and differentiation were further investigated by silencing ankyrin using small interfering (si)RNA.We found the basal mRNA levels of ankyrin and CD44 in BMSCs from the ONFH group were significantly lower as compared with those from the control group. The signal transduction of CD44-ankyrin-Akt-eNOS was significantly repressed in the ONFH group as compared with the control group after hyaluronic acid treatment. Knockdown of ankyrin by siRNA could attenuate the eNOS signaling as well as the BMSCs proliferation and osteogenic differentiation. The proliferation ability and osteogenic differentiation potential of the BMSCs from the ONFH group were significantly reduced as compared with the control group, but they can be enhanced to the baseline levels of the control group by hyaluronic acid treatment.The aberrant eNOS signaling, reduced cell proliferation, and osteogenic differentiation potential in BMSCs from ONFH patients are associated with the decreased ankyrin expression.Altered signal transduction, proliferation, and osteogenic differentiation ability in BMSCs may be involved in the pathogenesis of ONFH. These need further studies especially in BMSC-based cell therapy.

Older adults living alone is becoming the main family structure in rural China. This study aimed to explore the mediating effect of coping style on the relationship between perceived stress and mental health in rural older adults living alone in China.356 rural older adults living alone were recruited in Huzhou, China. Subjects were investigated using the Chinese Perceived Stress Scale (CPSS), Chinese Coping Style Questionnaire (CCSQ), and Mental Health Questionnaire (MHQ). Data were analysed using a structural equation. Bootstrapping was used to validate the mediation effects.Mental health showed significant correlations with a sense of nervousness, of uncontrollability, and with positive and negative coping styles (P 0.05). The results of structural equation modeling showed a good fit for the total sample (χCoping style partially mediated the relationship between perceived stress and mental health of rural older adults living alone in China. Consequently, to improve the mental health of rural older adults living alone, perceived stress and coping styles should be the focus. Geriatr Gerontol Int 2022; 22: 523-528.

BackgroundFollicular thyroid cancer (FTC) is the second most common malignancy of thyroid. About 7%–23% of patients with FTC have distant metastasis. The aim of this study was to investigate the risk factors associated with distant metastasis and the impact of distant metastasis on survival in FTC patients.MethodsPatients with FTC were analyzed using a prospectively maintained dataset of thyroid cancer registered at a tertiary hospital in Taiwan between December 1976 and May 2020.ResultsA total of 190 patients with a mean follow-up of 7.7 years were included in this study, including 29 with distant metastasis at diagnosis, 14 who developed metastasis during follow-up, and 147 without metastasis. Multivariate analysis adjusted for age, gender, tumor stage, and extrathyroidal invasion revealed old age (≥ 55 years) (adjusted odds ratio, 27.6; 95% confidence interval [CI], 8.75–86.8; P < 0.001) and extrathyroidal invasion (odds ratio, 24.1; 95% CI, 3.50–166.5; P = 0.001) were significantly associated with an increased risk of distant metastasis. Metastasis was correlated with higher cancer-specific mortality (adjusted hazard ratio, 35.5; 95% CI, 6.1–206.1; P < 0.001). In addition, patients with metastatic FTC diagnosed on initial presentation had the lowest 10-year cancer-specific survival rate (26.0%), followed by those who developed metastatic disease after initial treatment (76.6%), while patients without metastasis were all alive (100%) (P ≤ 0.002 for all comparisons).ConclusionsAge and extrathyroidal invasion are significant risk factors for distant metastasis of FTC. Patients with metastatic FTC, especially when diagnosed on initial presentation, have dismal survival outcomes.

A series of fluorescent ligands, which were systematically constructed from thiazole orange scaffold, was investigated for their interactions with G-quadruplex structures and antitumor activity. Among the ligands, compound 3 was identified to exhibit excellent specificity toward telomere G4-DNA over other nucleic acids. The affinity of 3-Htg24 was almost 5 times higher than that of double-stranded DNA and promoter G4-DNA. Interaction studies showed that 3 may bind to both G-tetrad and the lateral loop near the 5'-end. The intracellular colocalization with BG4 and competition studies with BRACO19 reveal that 3 may interact with G4-structures. Moreover, 3 reduces the telomere length and downregulates hTERC and hTERT mRNA expression in HeLa cells. The cytotoxicity of 3 against cancer cells (IC50 = 12.7-16.2 μM) was found to be generally higher than noncancer cells (IC50 = 52.3 μM). The findings may support that the ligand is telomere G4-DNA specific and may provide meaningful insights for anticancer drug design.

Syllable-final nasals /n/ and /ŋ/ in Taiwan Mandarin have been reported to be undergoing merging. Perceptual studies have reported that the alleged merging is context-sensitive and the merging directions are vowel-dependent. These findings have been mostly attributed to dialectal and social factors. The current study uses ultrasonography to capture postures of the entire tongue during the production of syllable-final nasals. The results, though confirming previous findings that the merging directions of syllable-final nasals are vowel-dependent, are best accounted for by the biomechanics of the tongue, as supported by computational 3D model simulations. Furthermore, for some speakers, although nasals were merged in terms of tongue posture, the degrees of nasalization of the preceding vowel were contrastive, suggesting that the merging process may be incomplete.

Significance Protein homeostasis is fundamental to the functioning of all living cells. Perturbation of the homeostasis, or proteotoxicity, plays an important role in the pathogenesis of amyotrophic lateral sclerosis and related neurodegenerative diseases. To guard against proteotoxicity, cells have evolved sophisticated quality-control mechanisms that make adaptations including enhanced turnover of misfolded proteins. However, how the quality-control systems are coordinated through higher-order regulatory pathways is not fully understood. We have discovered a unique suppressor of proteotoxicity, the ubiquitin-specific protease USP7, whose action is conserved from invertebrate to mammalian systems and mediated by a substrate cascade involving NEDD4L and SMAD2. These findings reveal a previously unknown regulatory pathway for protein quality control and provide new strategies for developing interventions for neurodegenerative diseases., An imbalance in cellular homeostasis occurring as a result of protein misfolding and aggregation contributes to the pathogeneses of neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Here, we report the identification of a ubiquitin-specific protease, USP7, as a regulatory switch in a protein quality-control system that defends against proteotoxicity. A genome-wide screen in a Caenorhabditis elegans model of SOD1-linked ALS identified the USP7 ortholog as a suppressor of proteotoxicity in the nervous system. The actions of USP7 orthologs on misfolded proteins were found to be conserved in Drosophila and mammalian cells. USP7 acts on protein quality control through the SMAD2 transcription modulator of the transforming growth factor β pathway, which activates autophagy and enhances the clearance of misfolded proteins. USP7 deubiquitinates the E3 ubiquitin ligase NEDD4L, which mediates the degradation of SMAD2. Inhibition of USP7 protected against proteotoxicity in mammalian neurons, and SMAD2 was found to be dysregulated in the nervous systems of ALS patients. These findings reveal a regulatory pathway of protein quality control that is implicated in the proteotoxicity-associated neurodegenerative diseases.

Selenium (Se) is an essential micronutrient with antioxidative properties, but previous studies have shown that extremely high circulating Se concentrations are associated with a higher prevalence of cardiovascular diseases (CVDs). To date, it remains unknown whether this association has connections with arterial calcification. A total of 982 participants with both serum Se concentration and abdominal aortic calcification (AAC) score data were enrolled from the 2013-2014 National Health and Nutrition Examination Survey (NHANES), a cross-sectional study of a noninstitutionalized population in the USA. Serum Se levels were determined by inductively coupled plasma-dynamic reaction cell-mass spectrometry. AAC was obtained from dual-energy X-ray absorptiometry and quantified by the Kauppila score system. Severe AAC was defined as Kauppila score ≥ 5. Among all participants, the mean serum Se level was 132.89 μg/L. The average AAC score was 1.51, and 11.7% had severe AAC. Compared with those in the lowest quartile of Se ( 121.1 μg/L), the highest quartile subgroup ( 143.1 μg/L) was associated with a higher mean AAC score (β-coefficient 0.88; 95% CI 0.28, 1.47; p = 0.004) and greater odds of having severe AAC (odds ratio 2.19; 95% CI 1.10, 4.36; p = 0.026) after adjusting for demographic, biochemical, and clinical characteristics. The concentrations of other circulating trace elements showed no statistically significant association with the AAC score. High serum Se levels were independently associated with an increased mean AAC score and aggravated AAC severity among noninstitutionalized US adults. Serum Se might adversely affect the cardiovascular system when the serum Se concentration exceeds 143 μg/L.

Registered nurses have to adequately prepare to respond to disasters, as they have become increasingly frequent worldwide. The aim of this study was to identify the factors influencing registered nurses' disaster preparedness in Bengkulu, Indonesia.This study used a descriptive correlational study design. A total of 130 registered nurses working in 2 governmental hospitals in Bengkulu, Indonesia, were recruited by using a convenience sampling technique. A self-administered questionnaire, the Disaster Preparedness Evaluation Tool, was used to determine their current levels of registered nurses' disaster preparedness.The registered nurses reported a moderate level of disaster knowledge, skills and preparedness. Their knowledge and skills were significantly correlated with disaster preparedness (r = 0.39-0.71, P0.01). Three significant factors associated with disaster preparedness were identified in this study: educational level, disaster knowledge, and disaster skills (RContinuing disaster drills training and implementing a formal disaster educational program into nursing curriculum and professional development are recommended to achieve effective disaster preparedness in the hospital setting.

The treatment of relapse or refractory multiple myeloma (RRMM) is still a big challenge in clinic. Recently, several clinical trials indicated that the XPO1 inhibitor, selinexor could significantly improve the remission rate in MM patients. However, the heterogeneous genetic background greatly influenced the efficiency of selinexor among MM. Here, we tried to characterized the biomarkers associated with selinexor sensitivity by analyzing gene expression data in MM patients. We found the cytogenetic background of selinexor sensitive MM patients was not limited to specific cytogenetic subtypes. In addition, by weighted gene co-expression network analysis (WGCNA), we obtained 10 key genes which showed a strong correlation with the selinexor sensitivity in MM patients. Notably, ABCC4 (MRP4) was the only gene which was both differentially expressed and proved to be clinical prognostic valuable (both for event-free survival and overall survival) in MM patients. We further validated the heterogenous expression of ABCC4 in MM cell lines and its value as a novel indicator for selinexor sensitivity. Moreover, immune infiltration analysis showed that ABCC4 expression had a significantly positive correlation with NK infiltration as well as immunotherapy target TIM-3 (HAVCR2) expression. Collectively, our findings indicated that ABCC4 might be a predictive biomarker of selinexor sensitivity in MM patients, which could be enhanced if combined with immunotherapy drugs such as TIM-3 inhibitor.

Background Spinal dural arteriovenous fistula (SDAVF) usually occurs during the 4th to 6th decades of life, and adolescent SDAVF is rarely reported. SDAVF arising around a tumor is also rare, and reported tumors are mostly schwannoma and lipoma. Case presentation We reported a 16-year-old male presented with progressive weakness and numbness of lower limbs for 3 months. A SDAVF was found, which was fed by right radicular arteries from segmental artery at L2 level and drained retrogradely into perimedullary veins. A concomitant spinal extradural nodular fasciitis at right L1/L2 intervertebral foramen was also noted. The SDAVF was completely obliterated by endovascular treatment and the tumor was debulked. The patient recovered well after the procedures. Conclusions Our case report suggests SDAVF can occur in adolescent. The concomitant presence with a nodular fasciitis indicates that although it usually arises in subcutaneous tissue but can rarely form on the dura of spine.

Background. Epithelial-mesenchymal transition (EMT) plays a vital role in tumor metastasis and drug resistance. It has been reported that EMT is regulated by several long noncoding RNAs (lncRNAs). We aimed to identify EMT-related lncRNAs and develop an EMT-related lncRNA prognostic signature in kidney renal clear cell carcinoma (KIRC). Materials and Methods. In total, 530 ccRCC patients with 611 transcriptome profiles were included in this study. We first identified differentially expressed EMT-related lncRNAs. Then, all the samples with transcriptional data and clinical survival information were randomly split into training/test sets at a ratio of 1 : 1. Accordingly, we further developed a twelve differentially expressed EMT-related lncRNA prognostic signature in the training set. Following this, risk analysis, survival analysis, subgroup analysis, and the construction of the ROC curves were applied to verify the efficacy of the signature in the training set, test set, and all patients. Besides, we further investigated the differential immune infiltration, immune checkpoint expression, and immune-related functions between high-risk patients. Finally, we explored the different drug responses to targeted therapy (sunitinib and sorafenib) and immunotherapy (anti-PD1 and anti-CTLA4). Results. A twelve differentially expressed EMT-related lncRNA prognostic signature performed superior in predicting the overall survival of KIRC patients. High-risk patients were observed with a significantly higher immune checkpoint expression and showed better responses to the targeted therapy and immunotherapy. Conclusions. Our study demonstrates that the twelve differentially expressed EMT-related lncRNA prognostic signature could act as an efficient prognostic indicator for KIRC, which also contributes to the decision-making of the further treatment.

To investigate the correlation of the single nucleotide polymorphisms (SNP) rs1126772, rs117291487, rs11730582, rs142608941 and rs6813526 of the osteopontin (OPN) gene with the risk of asthenozoospermia (AZS).We included 135 AZS patients in the AZS group and another 239 fertile men as normal controls. Using the SNaPshot technique, we genotyped the rs1126772, rs117291487, rs11730582, rs142608941 and rs6813526 polymorphisms of the OPN gene in all the subjects and analyzed the correlation of the five SNPs with AZS.The GA genotype and A allele of the OPN gene rs1126772 were found to be correlated with the risk of AZS (GA vs AA: OR = 0.55, 95% CI: 0.35－0.86, P = 0.009; A vs G: OR = 0.64, 95% CI: 0.46－0.89, P = 0.007), and so was the CT genotype and T allele at the RS11730582 locus (CT vs TT: OR = 0.526, 95% CI: 0.34－0.82, P = 0.009; T vs C: OR = 0.60, 95% CI: 0.44－0.83, P = 0.002). Haplotype analysis showed that the AATCT haplotype decreased the risk of AZS (AATCT: OR = 0.61, 95% CI: 0.42－0.88, P = 0.008) .The polymorphisms of the OPN gene RS1126772 and RS11730582 may reduce the risk of AZS.

This study explored the association between social support, resilience and coping strategies among patients with liver cancer and evaluated the extent to which patients' use of various coping strategies can be explained by social support and resilience.This cross-sectional study comprised 119 patients who experienced transarterial chemoembolization related to liver cancer and who completed the Social Support Scale, the Resilience Scale and the Ways of Coping Checklist-Revised.Results indicated a significant positive correlation between social support and use of problem-focused coping strategies and overall coping strategies. In addition, results showed a significant positive correlation between resilience and use of problem-focused strategies, emotion-focused strategies and overall coping strategies. Social support accounted for 14% of variance in use of problem-focused strategies and 7.6% of the variance in overall coping strategies. Resilience accounted for 30.5% of the variance in use of problem-focused strategies, 8.5% in use of emotion-focused strategies and 21.6% of overall coping strategies.Results of this study highlight the importance of social support and resilience in patients' coping strategies related to liver cancer treatment.

In this article, the TiN sensitive film as a sensing membrane was deposited onto n

Exercise and sport practitioners frequently utilize rating of perceived exertion (RPE) to evaluate the players’ psychophysiological strains during training sessions. The subjective rating of physical exertion level during sports training has been shown to have a reciprocal relationship with wellness status during periodic training or competitive seasons. However, the relationship between subjective physical exertions and wellness status during short-term overseas training camps (OTCs) has not been extensively investigated. This study aimed to examine the perceived responses of physical exertions [session-RPE (sRPE), training monotony, and training strain] and wellness status (fatigue, sleep, delayed onset muscle soreness, stress, and mood) measures in elite young adult futsal players from four separate OTCs with different training tasks. Twenty-seven U-20 male national team futsal players voluntarily participated in this study. The players recruited for OTCs were based on their performance during domestic training camps and the tactical demand of the team. The task of each OTCs was defined as: 1) 1st OTC = game-based camp (n = 14); 2) 2nd and 3rd OTC = training-based camp (n = 20 and n = 17, respectively); and 3) 4th OTC = pre-tournament camp (n = 14). The OTCs consisted of 11 training sessions (18.9 hours) and 16 friendly matches (23.8 hours). During daily training sessions and friendly matches, sRPE was used to quantify training load (TL). Additionally, a five-elements general wellness questionnaire was used to evaluate daily wellness status in the morning. The results demonstrated that the mean and sum sRPE in the game-based OTCs were significantly lower compared to the mean sRPE [p < 0.01, effect size (ES) = -4.8; p < 0.01, ES = -2.9] and sum sRPE in the training-based OTCs (p < 0.01, ES = -3.6; p < 0.01, ES = -3.1). The mean (p = 0.01; ES = -2.0) and sum sRPE (p < 0.01; ES = -3.4) in the game-based OTC were also lower than that in the pre-tournament OTC. Conversely, the wellness scores in the game-based OTC were higher compared to the training-based (p = 0.01; ES = 1.8) and the pre-tournament OTCs (p < 0.01; ES = 1.6). There was a negative relationship between mean and sum sRPE and all wellness scores (mean sRPE = r = -0.441 ~ -0.575, p < 0.001; sum sRPE = r = -0.41 ~ -0.559, p < 0.001). Our findings suggested that responses to training sessions, derived from mean and sum sRPE and wellness scores, are dependent upon the task-specific nature of OTCs among elite futsal players. Utilization of mean and sum sRPE and wellness measures to monitor the psychophysiological health during short-term OTCs is recommended.

To investigate the changes of blood pressure (BP) on patients with obstructive sleep apnea/hypopnea syndrome (OSA) before and after upper airway surgery.Case series with chart review.Tertiary academic medical center.Patients with OSA who underwent upper airway surgery were enrolled. We retrospectively investigated the nighttime and daytime BP before and at least 3 months after OSA surgery. PairedIn total, 176 patients with OSA (149 men, 27 women; mean age, 42.9 years; mean apnea/hypopnea index, 43.1/h) were enrolled in this study. The overall nighttime and daytime BP decreased significantly before and after OSA surgery (daytime systolic BP was reduced from 137.3 ± 14.0 mm Hg to 132.7 ± 17.0 mm Hg,Surgical modifications of the upper airways for patients with OSA could benefit blood pressure.

Background This report presents the third case of trochlear schwannoma arising from the pineal region and the first case to be resected using a paramedian infratentorial supracerebellar approach. Schwannomas of cranial nerves have traditionally been thought to arise from the transitional point where the axonal envelopment switches from glial cells to Schwann cells; however, recent temporal bone histopathologic evidence from vestibular schwannomas challenges this view. Of the 38 cases of pathology-confirmed trochlear schwannoma in the literature, there are only 2 cases arising from the pineal region, where the nerve sheath transition zone is located. Here, we discuss an unusual case of trochlear schwannoma arising from this transition zone. Case Description A 65-year-old man was admitted to our institute after a traffic accident. He complained of headache and dizziness, and a computed tomography scan revealed an isodense mass in the pineal region with obstructive hydrocephalus. Magnetic resonance imaging with contrast showed an enhancing mass in the pineal region. The tumor was subtotally resected using a paramedian infratentorial supracerebellar approach, and pathology confirmed the diagnosis of trochlear schwannoma. Conclusions Trochlear schwannoma should be considered when a mass is identified in the pineal region. This diagnosis should still be entertained for mass lesions along the free tentorial edge because the tumor may arise distant from the glial-Schwann transition zone located by the dorsal midbrain. We propose a treatment algorithm for this rare tumor that seeks to maximize functional outcome.

Urothelial carcinomas (UCs) are highly prevalent in patients with end-stage renal disease. Chronic kidney disease (CKD) is the predecessor of end-stage renal disease, and it is also associated with UC. However, the interplay between CKD and UC lacks solid evidence. Acrolein is produced by polyamines and has been suggested to be the uremic "toxin." The level of acrolein correlates well with chronic renal failure. We recently found that acrolein-induced DNA damage and inhibited DNA repair in urothelial cells, which contribute to bladder cancer. Therefore, we hypothesize that acrolein is involved in the formation of UC in patients with CKD.A total of 62 UC patients and 43 healthy control subjects were recruited. Acrolein-DNA (Acr-dG) adducts and p53 gene mutations in UC tissues, plasma acrolein-protein conjugates (Acr-PC) and S-(3-hydroxypropyl)-N-acetylcysteine levels, and urinary Acr metabolites were analyzed in these patients.Acr-dG levels were statistically correlated with CKD stages in UC patients (P0.01). Most p53 mutations were G to A and G to T mutations in these patients, and 50% of mutations at G:C pairs occurred in CpG sites, which is similar to the mutational spectra induced by Acr-dG adducts. Acr-PC levels in the plasma of UC patients with CKD were significantly higher than those of control subjects (P0.001). Altered urinary S-(3-hydroxypropyl)-N-acetylcysteine was also found in UC patients with CKD compared to control subjects (P0.005).These results indicate that acrolein acts as an endogenous uremic toxin and contributes to UC formation in patients with CKD.

Conventional treatment for treating primary central nervous system lymphoma (PCNSL) has consisted of either whole-brain radiotherapy (WBRT) or methotrexate (MTX)-based combined modality therapy. However, delayed cognitive sequelae have emerged as a significant debilitating complication in PCNSL patients. A prospective observational case-series study with prospective assessments of neurocognitive functions (NCFs), neuroimaging, and activities of daily living in newly-diagnosed PCNSL patients was undertaken. A battery of neuropsychological measures, used to evaluate NCFs, is composed of ten standardized NCF tests, representing four domains sensitive to disease and treatment effects (executive function, attention, verbal memory, psychomotor speed), and activities of daily living. A total of 15 patients with newly-diagnosed PCNSL were consecutively enrolled in this study. Comparing the NCF scores between the baseline (before WBRT) and post-treatment (after combined chemoradiation therapy) intervals (Mean = 122.33 days, SD = 34.49, range = 77-196), neurobehavioral outcomes consistently remained improving or stable in almost each domain of NCF. Specifically, the scores on Paced Auditory Serial Addition Test-Revised (PASAT-R) were significantly improved between the baseline and post-chemoradiation assessment. Under the multidisciplinary treatment guidelines for treating patients with newly-diagnosed PCNSL, multi-domain NCF become stabilized and even improved after the course of conformal WBRT combined with or without MTX-based chemotherapy.

Liver resection for hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT) offers a chance of cure, although survival is often limited. The actual 3-year survival and its associated prognostic factors have not been reported. A nationwide database of HCC patients with PVTT who underwent liver resection with ‘curative’ intent was analyzed. The clinicopathologic characteristics, the perioperative, and survival outcomes for the actual long-term survivors were compared with the non-long-term survivors (patients who died within 3 years of surgery). Univariable and multivariable regression analyses were performed to identify predictive factors associated with long-term survival outcomes. The study included 1590 patients with an actuarial 3-year survival of 16.6%, while the actual 3-year survival rate was 11.7%. There were 171 patients who survived for at least 3 years after surgery and 1290 who died within 3 years of surgery. Multivariable regression analysis revealed that total bilirubin > 17.1 μmol/l, AFP > 400 ng/ml, types of hepatectomy, extent of PVTT, intraoperative blood loss > 400 ml, tumor diameter > 5 cm, tumor encapsulation, R0 resection, liver cirrhosis, adjuvant TACE, postoperative early recurrence (

Aim: To establish and validate a nomogram for the estimation of overall survival of patients with uterine leiomyosarcoma (uLMS). Methods: Information on patients diagnosed as uLMS was retrospectively retrieved from the Surveillance, Epidemiology, and End Results database. The patients were randomly assigned into the training and the validation cohorts. Univariate and multivariate analyses were used to determine the independent prognostic factors for building a nomogram for predicting overall survival. The predictive accuracy was evaluated based on the concordance indices and the calibration plots. Results: A nomogram that combined age, marital status, tumor size, Surveillance, Epidemiology, and End Result stage, surgery and radiation was established. The internal and external concordance indices were 0.748 and 0.745, respectively. The calibration plots approached 45 degrees. Conclusion: The nomogram might be an effective tool for predicting the survival of patients with uLMS.

Aims and objectives The primary aim of this study is to explore the influence of obesity, healthy lifestyle and sleep quality of endometrial cancer survivors on their fatigue level. Background As many as 30% of endometrial cancer survivors still suffer from fatigue 5 years after completing therapy. Fatigue may hinder cancer survivors from participating in daily activities or returning to their original roles and functions, thus affecting their health-related quality of life. Design This study adopted a cross-sectional correlational research design. The STROBE checklist for cross-sectional studies was used as a reference for reporting the study. Methods A consecutive sample of 134 endometrial cancer survivors was recruited from the outpatient clinics of a medical centre in Taipei, Taiwan. Data were collected using structured questionnaires. Results Study subjects scored 44 points (SD = 7.09) on average for the fatigue levels. Results of linear regression showed that sleep quality (s = -0.38), comorbidity index (s = -0.024) and age (s = 0.20) were important predictors of fatigue. However, differences in obesity, vegetable and fruit intake, physical activity did not lead to significant differences in fatigue level. Conclusions Survivors who had poorer sleep quality, higher comorbidity index and younger age reported higher fatigue. Relevance to clinical practice The study findings are relevant for assessing and preventing fatigue in endometrial cancer survivors. Those with poorer sleep quality, higher comorbidity index and younger age are at a greater risk for fatigue and deserve further attention. Although the study results failed to support the link between obesity, vegetable and fruit intake, physical activity and fatigue, the ratio of survivors who comply with recommended healthy lifestyles was low. Hence, it is of urgent necessity that this population receives the help to maintain a healthy lifestyle.

Purpose: The purpose of this study was to assess the amount of variance in the coping strategies of patients with brain tumors that could be accounted for by resilience. Methods: This cross-sectional survey involved 95 patients who had experienced surgical, chemotherapy, or radiotherapy therapies for their brain tumors at least 1 month before data collection. The investigator collected data using the scales of the Ways of Coping Checklist-Revised and Resilience Scale. Data were analyzed using descriptive statistics, t tests, analysis of variance, Pearson product–moment correlation, and hierarchical multiple regression. Results: The results revealed that resilience was significantly positively associated with patients' problem-focused coping (r = .65, p

To evaluate the predictive accuracy of the %p2PSA and prostate health index (PHI) in predicting aggressive pathological outcomes in patients with prostate cancer (PCa) undergoing radical prostatectomy (RP), we enrolled 91 patients with organ-confined PCa who were treated with robot-assisted RP. p2PSA levels and the PHI were investigated for their ability to predict pathological results. The %p2PSA and PHI were both significantly higher in patients with ≥pT3 disease, high-risk disease, positive surgical margin, or seminal vesical invasion (SVI). In univariable analysis, p2PSA derivatives were significant predictors of the presence of ≥pT3 disease, high-risk disease, positive surgical margin, and SVI. To predict adverse pathological outcomes at a sensitivity of 90%, p2PSA derivatives had higher specificity than standard PSA derivatives. In multivariable analysis, additional increases in the area under the receiver operating characteristic curve (AUC) were observed with the %p2PSA and PHI for ≥pT3 disease, high-risk disease, and positive surgical margin (8.2% and 2.7%, 6.2% and 4.1%, and 8.6% and 5.4%, respectively). A PHI ≥61.26 enhanced the predictive accuracy of the model for SVI by increasing the AUC from 0.624 to 0.819 (p = 0.009). The preoperative %p2PSA and PHI accurately predict adverse pathological results and are useful for decision-making.

Microsatellite instability (MSI) has been approved as a pan-cancer biomarker for immune checkpoint blockade (ICB) therapy. However, current MSI identification methods are not available for all patients. We proposed an ensemble multiple instance deep learning model to predict microsatellite status based on histopathology images, and interpreted the pathomics-based model with multi-omics correlation. Methods: Two cohorts of patients were collected, including 429 from The Cancer Genome Atlas (TCGA-COAD) and 785 from an Asian colorectal cancer (CRC) cohort (Asian-CRC). We established the pathomics model, named Ensembled Patch Likelihood Aggregation (EPLA), based on two consecutive stages: patch-level prediction and WSI-level prediction. The initial model was developed and validated in TCGA-COAD, and then generalized in Asian-CRC through transfer learning. The pathological signatures extracted from the model were analyzed with genomic and transcriptomic profiles for model interpretation. Results: The EPLA model achieved an area-under-the-curve (AUC) of 0.8848 (95% CI: 0.8185-0.9512) in the TCGA-COAD test set and an AUC of 0.8504 (95% CI: 0.7591-0.9323) in the external validation set Asian-CRC after transfer learning. Notably, EPLA captured the relationship between pathological phenotype of poor differentiation and MSI (P < 0.001). Furthermore, the five pathological imaging signatures identified from the EPLA model were associated with mutation burden and DNA damage repair related genotype in the genomic profiles, and antitumor immunity activated pathway in the transcriptomic profiles. Conclusions: Our pathomics-based deep learning model can effectively predict MSI from histopathology images and is transferable to a new patient cohort. The interpretability of our model by association with pathological, genomic and transcriptomic phenotypes lays the foundation for prospective clinical trials of the application of this artificial intelligence (AI) platform in ICB therapy.