Artificial Intelligence-Assisted Colonoscopy for Colorectal Cancer Screening: A Multicenter Randomized Controlled Trial.

BACKGROUND AND AIMS: Artificial intelligence (AI)-assisted colonoscopy improves polyp detection and characterization in colonoscopy. However, data from large-scale multicenter randomized controlled trials (RCT) in an asymptomatic population are lacking. METHODS: This multicenter RCT aimed to compare AI-assisted colonoscopy with conventional colonoscopy for adenoma detection in an asymptomatic population. Asymptomatic subjects 45-75 years of age undergoing colorectal cancer screening by direct colonoscopy or fecal immunochemical test were recruited in 6 referral centers in Hong Kong, Jilin, Inner Mongolia, Xiamen, and Beijing. In the AI-assisted colonoscopy, an AI polyp detection system (Eagle-Eye) with real-time notification on the same monitor of the endoscopy system was used. The primary outcome was overall adenoma detection rate (ADR). Secondary outcomes were mean number of adenomas per colonoscopy, ADR according to endoscopist's experience, and colonoscopy withdrawal time. This study received Institutional Review Board approval (CRE-2019.393). RESULTS: From November 2019 to August 2021, 3059 subjects were randomized to AI-assisted colonoscopy (n = 1519) and conventional colonoscopy (n = 1540). Baseline characteristics and bowel preparation quality between the 2 groups were similar. The overall ADR (39.9% vs 32.4%; P < .001), advanced ADR (6.6% vs 4.9%; P = .041), ADR of expert (42.3% vs 32.8%; P < .001) and nonexpert endoscopists (37.5% vs 32.1%; P = .023), and adenomas per colonoscopy (0.59 ± 0.97 vs 0.45 ± 0.81; P < .001) were all significantly higher in the AI-assisted colonoscopy. The median withdrawal time (8.3 minutes vs 7.8 minutes; P = .004) was slightly longer in the AI-assisted colonoscopy group. CONCLUSIONS: In this multicenter RCT in asymptomatic patients, AI-assisted colonoscopy improved overall ADR, advanced ADR, and ADR of both expert and nonexpert attending endoscopists. (ClinicalTrials.gov, Number: NCT04422548).

Value of serum tumor markers for predicting EGFR mutations in non-small cell lung cancer patients.

OBJECTIVES: We investigated whether serum tumor markers (STMs) represent a valuable noninvasive tool to predict epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) patients. METHODS: A retrospective analysis was performed for 143 NSCLC patients at the Peking University International Hospital from December 2014 to December 2019. EGFR mutations in the tumor tissues were identified by amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) and next generation sequencing (NGS). The relationships between EGFR mutation and several clinicopathological features were analyzed. RESULT: EGFR mutation were found more frequently in female (56.67%, P = 0.01), never-smokers (55.26%, P = 0.004), and those with lung adenocarcinoma (ADC) (52.17%, P < 0.001). The positive mutation rate for the EGFR gene were higher in the squamous cell carcinoma antigen (SCCA)group (≤1.5 ng/ml) and in the gastrin-releasing peptide precursor (preGRP) increased group (≥69.2 pg/ml), and this difference was statistically significant (P < 0.05). Univariate logistic regression analysis demonstrated that females (Odd ratio [OR]: 2.435, 95% confidence interval [CI]: 1.232, 4.813, P = 0.01) and never-smokers (OR = 0.370; CI = 0.186, 0.734; P = 0.004), lung adenocarcinoma patients (OR = 9.091; CI = 2.599, 21.800; P = 0.001), the SCC group (≤1.5 ng/ml) (OR = 0.331, CI = 0.120, 0.914; P = 0.033), and the preGRP group (≥69.2 pg/ml) (OR = 5.478, CI = 1.462, 20.528; P = 0.012) patients were risk factors for EGFR gene mutation. Multivariate logistic regression analysis demonstrated that lung ADC and proGRP elevation were independent risk factors for predicting EGFR gene positivity (P < 0.05). CONCLUSION: STMs are associated with mutant EGFR status and could be integrated with other clinical factors to facilitate the classification of EGFR mutation status among NSCLC patients.

Long non-coding RNA ZFAS1 regulates the malignant progression of gastric cancer via the microRNA-200b-3p/Wnt1 axis.

Gastric cancer is a common malignant tumor. Studies from our laboratory or others have shown that long non-coding RNA (lncRNA) zinc finger antisense (ZFAS)1 often acts as an oncogene. However, the molecular underpinnings of how ZFAS1 regulates gastric cancer remain to be elucidated. Results showed that ZFAS1 expression was upregulated, and microRNA-200b-3p (miR-200b) expression was downregulated in gastric cancer tissues. MiR-200b overexpression suppressed the proliferation, cell cycle process, and Wnt/ß-catenin signaling of gastric cancer cells. Subsequently, we identified miR-200b is a target of ZFAS1 and Wnt1 is a target of miR-200b. Furthermore, promotion of cancer malignant progression and activation of Wnt/ß-catenin signaling induced by ZFAS1 was counteracted by increasing miR-200b expression. In vivo, ZFAS1 knockdown suppressed the tumorigenesis with the upregulated miR-200b and the inactive Wnt/ß-catenin signaling. Summarily, we demonstrated a critical role of miR-200b in gastric cancer, and ZFAS1 can promote malignant progression through regulating miR-200b mediated Wnt/ß-catenin signaling.

Silencing of lncRNA ZFAS1 inhibits malignancies by blocking Wnt/ß-catenin signaling in gastric cancer cells.

Gastric cancer is a common malignancy with high mortality. Long noncoding RNA (lncRNA) zinc finger antisense (ZFAS)1 is upregulated in gastric cancer specimens compared with the para-carcinoma tissues. The silencing of ZFAS1 inhibited the growth, proliferation, cell cycle progress, migration, invasion and epithelial-mesenchymal transition (EMT), and enhanced the sensitivity to cis-platinum or paclitaxel in SGC7901 cells, as evidenced by the expression changes of proliferating cell nuclear antigen, Cyclin D1, Cyclin E, Cyclin B1, E-cadherin, N-cadherin, vimentin, matrix metalloproteinase (MMP)-2 and MMP-14. The ZFAS1 also activated the Wnt/ß-catenin signaling. Subsequently, the ZFAS1 knockdown-induced the inhibition of migration, invasion, EMT and resistance to chemotherapeutic reagens was reversed by the overexpression of ß-catenin. In summary, the silencing of ZFAS1 inhibited the growth, proliferation, cell cycle progress, migration, invasion, EMT and chemotherapeutic tolerance by blocking the Wnt/ß-catenin signaling in gastric cancer cells.

Low-Cost High-Resolution Microendoscopy for the Detection of Esophageal Squamous Cell Neoplasia: An International Trial.

BACKGROUND & AIMS: Esophageal squamous cell neoplasia has a high mortality rate as a result of late detection. In high-risk regions such as China, screening is performed by Lugol's chromoendoscopy (LCE). LCE has low specificity, resulting in unnecessary tissue biopsy with a subsequent increase in procedure cost and risk. The purpose of this study was to evaluate the accuracy of a novel, low-cost, high-resolution microendoscope (HRME) as an adjunct to LCE. METHODS: In this prospective trial, 147 consecutive high-risk patients were enrolled from 2 US and 2 Chinese tertiary centers. Three expert and 4 novice endoscopists performed white-light endoscopy followed by LCE and HRME. All optical images were compared with the gold standard of histopathology. RESULTS: By using a per-biopsy analysis, the sensitivity of LCE vs LCE + HRME was 96% vs 91% (P = .0832), specificity was 48% vs 88% (P < .001), positive predictive value was 22% vs 45% (P < .0001), negative predictive value was 98% vs 98% (P = .3551), and overall accuracy was 57% vs 90% (P < .001), respectively. By using a per-patient analysis, the sensitivity of LCE vs LCE + HRME was 100% vs 95% (P = .16), specificity was 29% vs 79% (P < .001), positive predictive value was 32% vs 60%, 100% vs 98%, and accuracy was 47% vs 83% (P < .001). With the use of HRME, 136 biopsies (60%; 95% confidence interval, 53%-66%) could have been spared, and 55 patients (48%; 95% confidence interval, 38%-57%) could have been spared any biopsy. CONCLUSIONS: In this trial, HRME improved the accuracy of LCE for esophageal squamous cell neoplasia screening and surveillance. HRME may be a cost-effective optical biopsy adjunct to LCE, potentially reducing unnecessary biopsies and facilitating real-time decision making in globally underserved regions. ClinicalTrials.gov, NCT 01384708.

Immune-inflammatory markers and clinical characteristics as predictors of the depth of response and prognosis of patients with PD-L1 ≥50% metastatic non-small cell lung cancer receiving first-line immunotherapy.

BACKGROUND: Patients with programmed cell death-ligand 1 (PD-L1) ≥50% metastatic non-small cell lung cancer (NSCLC) treated with first-line immunotherapy showed heterogeneous tumor responses. In this study, we investigated the clinical and immune-inflammatory markers distinguishing patients with metastatic NSCLC achieving high depth of tumor response (HDPR) from those with non-high depth of response (NHDPR). The impact of clinical features on the prognosis of patients with PD-L1 ≥50% were further clarified. METHODS: The clinical characteristics and immune-inflammatory markers of 17 patients with PD-L1 ≥50% metastatic NSCLC at Beijing Tiantan Hospital between July 2020 and December 2023 were retrospectively analyzed. RESULTS: Among the 17 patients, seven (41.2%) patients achieved HDPR (range: -50%, -72%) and 10 (58.8%) patients achieved NHDPR (range: -13%, -45%). Below normal CD4 + T lymphocytes/CD8 + T lymphocytes (CD4/CD8) ratio (p = 0.01) and oncogenes and/or tumor suppressor gene mutations (TP53/KRAS/EGFR) (p = 0.001) were found enriched for NHDPR compared with HDPR. With a median follow-up of 26.0 months (range: 17.2-34.8 months), the median progression-free survival (PFS) following first-line immunotherapy and overall survival (OS) were 9.0 months (95% CI: 5.0-13.0) and not reached (NR), respectively. The neutrophil-to-lymphocyte ratio (NLR) was identified as an independent prognostic factor on first-line PFS. Patients with an NLR ≥4 exhibited a shorter median PFS (7.0 months vs. NR; p = 0.033; 95% CI: 1.2-80.2) than those with an NLR <4 following first-line immunotherapy. CONCLUSIONS: Among patients with PD-L1 ≥50% metastatic NSCLC who received first-line immunotherapy, a lower CD4/CD8 ratio and the presence of genes mutations showed a diminished tumor response and a higher NLR ratio exhibited a worse median PFS.

In vitro CRISPR screening uncovers CRTC3 as a regulator of IFN-γ-induced ferroptosis of hepatocellular carcinoma.

Interferon-gamma (IFN-γ) exerts anti-tumor effects by inducing ferroptosis. Based on CRISPR/Cas9 knockout screening targeting genome-wide protein encoding genes in HepG2 and SK-Hep-1 cell lines, we found that cAMP response element-binding protein (CREB) regulated transcription coactivator 3 (CRTC3) protects tumor cells from drug-induced ferroptosis and significantly inhibits the efficacy of IFN-γ treatment in hepatocellular carcinoma (HCC). Mechanistically, CRTC3 knockout altered tumor cell lipid patterns and increased the abundance of polyunsaturated fatty acids (PUFAs), which enables lipid peroxidation and enhances the susceptibility of HCC cells to ferroptosis inducers. To scavenge for accumulated lipid peroxides (LPO) and maintain redox equilibrium, HCC cells up-regulate SLC7A11 and glutathione peroxidase 4 (GPx4) expressions to enhance the activities of glutamate-cystine antiporter (system xc-) and LPO clearance. As IFN-γ inhibiting system xc-, simultaneous treatment with IFN-γ disrupts the compensatory mechanism, and generates a synergistic effect with CRTC3 knockout to facilitate ferroptosis. Sensitizing effects of CRTC3 depletion were confirmed using typical ferroptosis inducers, including RSL3 and erastin. Sorafeinib, a commonly used target drug in HCC, was repeatedly reported as a ferroptosis inducer. We then conducted both in vitro and vivo experiments and demonstrated that CRTC3 depletion sensitized HCC cells to sorafenib treatment. In conclusion, CRTC3 is involved in the regulation of PUFAs metabolism and ferroptosis. Targeting CRTC3 signaling in combination with ferroptosis inducers present a viable approach for HCC treatment and overcoming drug resistance.

Thyroid transcription factor 1 (TTF-1) negativity as a predictor of unfavorable response to EGFR-TKI therapy in advanced lung adenocarcinoma patients with EGFR mutations.

BACKGROUND: The absence of thyroid transcription factor 1 (TTF-1) is associated with a lower frequency of epidermal growth factor receptor (EGFR) mutations in lung adenocarcinoma (LUAD). The aim of this study was to assess the impact of TTF-1 expression on the clinical response to EGFR-tyrosine kinase inhibitor (TKI) treatment in patients with advanced LUAD. METHODS: The data of patients with advanced LUAD who were admitted to the Beijing Tiantan Hospital and Peking University Cancer Hospital (China) between April 2009 and May 2023 was retrospectively analyzed. RESULTS: A total of 227 patients diagnosed with advanced LUAD were included, of which 28.2% (64/227) had TTF-1-negative adenocarcinoma, while 54.6% (124/227) harbored EGFR mutations. Negative TTF-1 expression significantly correlated with male sex (68.8% vs. 42.3%, p < 0.001), history of heavy smoking (57.8% vs. 36.2%, p = 0.003), poorly differentiated tumors (86.5% vs. 43.2%, p < 0.001), and lower frequency of EGFR mutations (26.6% vs. 65.6%, p < 0.001) compared with TTF-1 positivity. Multivariable logistic regression showed that low prevalence of EGFR mutations (p < 0.001) and male sex (p = 0.006) were independent predictive factors for the negative expression of TTF-1. Patients lacking TTF-1 also exhibited worse overall response rate (ORR; 23.5% vs. 54.2%, p = 0.019), disease control rate (DCR; 58.8% vs. 89.7%, p = 0.003), and median progression-free survival (PFS; 2.9 vs. 11.6 months, p < 0.001) following treatment with EGFR-TKIs compared to the TTF-1-positive patients with EGFR mutations. CONCLUSIONS: Patients with TTF-1-negative and EGFR-mutant LUAD show a diminished response to EGFR-TKIs.

The prognostic value of cancer stage-associated genes in clear cell renal cell carcinoma.

OBJECTIVES: Clear cell renal cell carcinoma (ccRCC) is a highly prevalent subtype of malignant renal tumor, but unfortunately, the survival rate remains unsatisfactory. The aim of the present study is to explore genomic features that are correlated with cancer stage, allowing for the identification of subgroups of ccRCC patients with high risk of unfavorable outcomes and enabling prompt intervention and treatment. METHODS: We compared the gene expression levels across ccRCC patients with diverse cancer stages from The Cancer Genome Atlas (TCGA) database, which revealed characteristic genes associated with tumor stage. We then extracted prognostic genes and used least absolute shrinkage selection operator (LASSO) regression to select four genes for feature extraction and the construction of a prognostic risk model. RESULTS: We have identified a total of 171 differentially expressed genes (DEGs) that are closely linked to the tumor stage of ccRCC through difference analysis. A prognostic risk model constructed based on the expression levels of ZIC2, TFAP2A-AS1, ITPKA, and SLC16A12 holds significant prognostic value in ccRCC. The results of the functional enrichment analysis imply that the DEGs are mainly involved in the regulation of immune-related signaling pathways, and therefore may have a significant function in immune system regulation of ccRCC. CONCLUSIONS: Our study has successfully identified significant DEGs between high- and low-staging groups of ccRCC using bioinformatics methods. The construction of a prognostic risk model based on the expression levels of ZIC2, TFAP2A-AS1, ITPKA, and SLC16A12 has displayed promising prognostic significance, indicating its valuable potential for clinical application.

Apatinib combined with camrelizumab in advanced acral melanoma patients: An open-label, single-arm phase 2 trial.

BACKGROUND: At present, immune monotherapy and combination therapy has not shown satisfactory effects on acral melanoma, and still no standard treatment is available for advanced acral melanoma. Here, a phase II trial was performed to explore the safety and efficacy of apatinib combined with camrelizumab in advanced acral melanoma patients as first-line therapy (NCT03955354). METHODS: Patients with pathologically confirmed, locally unresectable or metastatic treatment native acral melanoma received 250 mg apatinib once daily and camrelizumab 200 mg once every two weeks intravenously every 28-day cycle. The primary end-point was objective response rate and the secondary end-points were disease control rate, overall survival, progression-free survival and safety. RESULTS: Thirty patients were recruited between January 2015 and January 2022. Among them, 21 (70.0%) had stage IV, and a median tumour burden was 50 mm (range: 11-187). Objective response rate was 24.1%, and 7 of 29 patients had an anti-tumour response, including partial response (n = 5) and complete response (n = 2). Disease control rate was 82.8%, median progression-free survival was 7.39 months (confidence interval: 3.65-9.92), and median overall survival was 13.4 months (confidence interval: 1.9-25.0). Grade 3-4 treatment-related toxicity (grade 3 50.5%; grade 4 3.3%) included transaminase elevations, proteinuria, leukocytopenia, vomiting, diarrhea and drug-induced liver injury. No treatment-related mortality occurred. The mutations of TTN, MUC16, VPS13D, ALPK2 and SCUBE1 showed significant alterations with survival outcome. CONCLUSIONS: Apatinib combined with camrelizumab showed manageable safety profile and reasonable anti-tumour activity in advanced acral melanoma patients as first-line therapy.

Bevacizumab reduces peritumoral brain edema in lung cancer brain metastases after radiotherapy.

BACKGROUND: The aim of this study was to investigate the efficacy of bevacizumab (Bev) in reducing peritumoral brain edema (PTBE) after stereotactic radiotherapy (SRT) for lung cancer brain metastases. METHODS: A retrospective analysis was conducted on 44 patients with lung cancer brain metastases (70 lesions) who were admitted to our oncology and Gamma Knife center from January 2020 to May 2022. All patients received intracranial SRT and had PTBE. Based on treatment with Bev, patients were categorized as SRT + Bev and SRT groups. Follow-up head magnetic resonance imaging was performed to calculate PTBE and tumor volume changes. The edema index (EI) was used to assess the severity of PTBE. Additionally, the extent of tumor reduction and intracranial progression-free survival (PFS) were compared between the two groups. RESULTS: The SRT + Bev group showed a statistically significant difference in EI values before and after radiotherapy (p = 0.0115), with lower values observed after treatment, but there was no difference in the SRT group (p = 0.4008). There was a difference in the distribution of EI grades in the SRT + Bev group (p = 0.0186), with an increased proportion of patients at grades 1-2 after radiotherapy, while there was no difference in the SRT group (p > 0.9999). Both groups demonstrated a significant reduction in tumor volume after radiotherapy (p < 0.05), but there was no difference in tumor volume changes between the two groups (p = 0.4089). There was no difference in intracranial PFS between the two groups (p = 0.1541). CONCLUSION: Bevacizumab significantly reduces the severity of PTBE after radiotherapy for lung cancer. However, its impact on tumor volume reduction and intracranial PFS does not reach statistical significance.

A supervised topic embedding model and its application.

We propose rTopicVec, a supervised topic embedding model that predicts response variables associated with documents by analyzing the text data. Topic modeling leverages document-level word co-occurrence patterns to learn latent topics of each document. While word embedding is a promising text analysis technique in which words are mapped into a low-dimensional continuous semantic space by exploiting the local word co-occurrence patterns within a small context window. Recently developed topic embedding benefits from combining those two approaches by modeling latent topics in a word embedding space. Our proposed rTopicVec and its regularized variant incorporate regression into the topic embedding model to model each document and a numerical label paired with the document jointly. In addition, our models yield topics predictive of the response variables as well as predict response variables for unlabeled documents. We evaluated the effectiveness of our models through experiments on two regression tasks: predicting stock return rates using news articles provided by Thomson Reuters and predicting movie ratings using movie reviews. Results showed that the prediction performance of our models was more accurate in comparison to three baselines with a statistically significant difference.

Octagonal Quasicrystal Defect Mode Laser-Based PVK: Ir(ppy)3 Polymer Driven by Optical Pumping.

Based on the conjugated complex PVK: Ir(ppy)3, a green-emitting organic quasicrystal microcavity laser is demonstrated driven by optical pumping. The organic laser adopts a sandwich structure of DBR/organic gain membrane/output Ag-layer for the vertical oscillation and an octagonal quasi-crystal for in-plane light localization. The experimental results show that the single-mode lasing action is observed at 521 nm with an FWHM of 0.8 nm. The threshold of lasing is lowered to 0.181 µJ/cm2.

Case Report: Complete Remission With Anti-PD-1 and Anti-VEGF Combined Therapy of a Patient With Metastatic Primary Splenic Angiosarcoma.

Primary splenic angiosarcoma (PSA) is a rare malignancy with poor prognosis. At present, little study is available on immunotherapy in PSA. Here, we report a case of a patient with metastatic PSA who was treated with programmed death-1 (PD-1) inhibitors and vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors combined therapy and achieved complete response (CR). The patient was a 57-year-old woman with three liver metastases. She was treated with seven cycles of toripalimab plus anlotinib. Programmed death-ligand 1 (PD-L1) immunohistochemistry and next-generation sequencing was performed, and the PD-L1 tumor proportion score was 75%. Finally, she achieved CR after six cycles of the combined therapy regimen. No serious adverse events were detected. To the best of our knowledge, this is the first clinical evidence that anti-PD-1 plus anti-VEGF therapy might be a promising option for patients with metastatic PSA. However, more clinical trials are needed to verify this conclusion.

The combination therapy with the cytotoxic T lymphocyte-associated antigen-4 and programmed death 1 antibody-induced asthma in a patient with advanced melanoma.

The combination of programmed death 1 (PD-1) inhibitors and cytotoxic T lymphocyte-associated antigen-(CTLA-4) inhibitors have markedly improved the survival of melanoma patients. We report the case of a patient with advanced melanoma who developed asthma during anti-PD-1 and anti-CTLA-4 combination therapy. The patient was a 57-year-old woman enrolled in a clinical trial regarding novel CTLA-4 antibody and sintilimab treatment. The patient was diagnosed with asthma after three cycles of therapy. Subsequently, she was treated with corticosteroids, shortcostero ß2 agonists, and antihistamines. The symptoms were relieved after 7 days. This is the first report of asthma in a patient treated with combination immunotherapy to the best of our knowledge. The mechanism remains to be further explored.

Prognostic nomograms for predicting overall survival and cause-specific survival of signet ring cell carcinoma in colorectal cancer patients.

BACKGROUND: Signet ring cell carcinoma (SRCC) is an uncommon subtype in colorectal cancer (CRC), with a short survival time. Therefore, it is imperative to establish a useful prognostic model. As a simple visual predictive tool, nomograms combining a quantification of all proven prognostic factors have been widely used for predicting the outcomes of patients with different cancers in recent years. Until now, there has been no nomogram to predict the outcome of CRC patients with SRCC. AIM: To build effective nomograms for predicting overall survival (OS) and cause-specific survival (CSS) of CRC patients with SRCC. METHODS: Data were extracted from the Surveillance, Epidemiology, and End Results database between 2004 and 2015. Multivariate Cox regression analyses were used to identify independent variables for both OS and CSS to construct the nomograms. Performance of the nomograms was assessed by concordance index, calibration curves, and receiver operating characteristic (ROC) curves. ROC curves were also utilized to compare benefits between the nomograms and the tumor-node-metastasis (TNM) staging system. Patients were classified as high-risk, moderate-risk, and low-risk groups using the novel nomograms. Kaplan-Meier curves were plotted to compare survival differences. RESULTS: In total, 1230 patients were included. The concordance index of the nomograms for OS and CSS were 0.737 (95% confidence interval: 0.728-0.747) and 0.758 (95% confidence interval: 0.738-0.778), respectively. The calibration curves and ROC curves demonstrated good predictive accuracy. The 1-, 3-, and 5-year area under the curve values of the nomogram for predicting OS were 0.796, 0.825 and 0.819, in comparison to 0.743, 0.798, and 0.803 for the TNM staging system. In addition, the 1-, 3-, and 5-year area under the curve values of the nomogram for predicting CSS were 0.805, 0.847 and 0.863, in comparison to 0.740, 0.794, and 0.800 for the TNM staging system. Based on the novel nomograms, stratified analysis showed that the 5-year probability of survival in the high-risk, moderate-risk, and low-risk groups was 6.8%, 37.7%, and 67.0% for OS (P < 0.001), as well as 9.6%, 38.5%, and 67.6% for CSS (P < 0.001), respectively. CONCLUSION: Convenient and visual nomograms were built and validated to accurately predict the OS and CSS rates for CRC patients with SRCC, which are superior to the conventional TNM staging system.

Cognitive Impairment and Related Factors Among Middle-Aged and Elderly Patients with Type 2 Diabetes from a Bio-Psycho-Social Perspective.

OBJECTIVE: This study investigated the biomedical, psychological, and social behavior risk factors for cognitive impairment in middle-aged and elderly patients with type 2 diabetes mellitus (T2DM). METHODS: This cross-sectional study included 240 patients with T2DM. A questionnaire was used to collect demographic and disease-related data on patients, and the Self-rating Depression Scale (SDS), Diabetes Self-care Scale (DSCS), and Social Support Rating Scale (SSRS) were used to assess patients' depression status, self-management behavior, and social support, respectively. The Chinese version of the Montreal Cognitive Assessment (MoCA) was used to evaluate cognitive function, with a score <26 set as the threshold for cognitive impairment. RESULTS: The prevalence of cognitive dysfunction in middle-aged and elderly patients with T2DM was 52.5%. Multivariate logistic regression analysis showed that older age, a history of hypoglycemia within 1 month, and depression were independent risk factors for cognitive impairment. Education for >12 years, urban living, and a higher total score on the DSCS were independent protective factors against cognitive impairment. CONCLUSION: T2DM patients with high risk of cognitive impairment can be identified early from the bio-psycho-social perspective. Patients with T2DM who are older, less educated, living in rural areas, have hypoglycemia history, and have poor self-management of diabetes are at increased risk of cognitive impairment. Closer monitoring of patients with hypoglycemia, early detection of depression, and improving patients' self-management capacity can prevent cognitive impairment in middle-aged and elderly patients with T2DM.

Prognostic nomograms for patients undergoing radical operation for stage I-III appendiceal adenocarcinoma: A surveillance, epidemiology, and end results database analysis.

Objective: To develop nomograms for effective prediction of cause-specific survival (CSS) and overall survival (OS) of patients who underwent radical operation for stage I-III appendiceal adenocarcinoma. Methods: Clinical information from the surveillance, epidemiology, and end results database was retrieved from 2004 to 2015 and subjected to multivariate analysis to explore variables that affect the OS and CSS. Results were used to construct nomograms to assess the 1-, 3-, and 5-year OS and CSS rates, then their calibration accuracy and discriminative power were examined using Kaplan-Meier curves, calibration plots, and C statistics. Results: Overall, 1,241 patients were included in the analysis. We found 7 and 5 factors that could independently alter the prognosis, then used for creating nomograms for evaluating the OS and CSS, respectively, with respective C-index values of 0.741 (95% confidence interval [CI]: 0.729-0.754) and 0.747 (95% CI: 0.733-0.762). Calibration and receiver operating characteristic curves further revealed excellent predictive performance. Conclusions: We successfully built highly accurate nomograms for evaluating the 1-, 3-, and 5-year CSS and OS rates in subjects who underwent radical operation for stage I-III appendiceal adenocarcinoma. Further studies, involving prospective validations, are required to validate these nomograms.

Decreased expression of ARID1A invasively downregulates the expression of ribosomal proteins in hepatocellular carcinoma.

Background: There was increasing evidence showing that ARID1A alterations correlated with higher tumor mutational burden, but there were limited studies focusing on the adaptive mechanisms for tumor cells to survive under excessive genomic alterations. Materials & methods: To further explore the adaptive mechanisms under ARID1A alterations, we performed RNA sequencing in ARID1A knockdown hepatocellular carcinoma cell lines, and demonstrated that decreased expression of ARID1A controlled global ribosomal proteins synthesis. The results were further confirmed by quantitative reverse transcription-PCR and bioinformatic analysis in The Cancer Genome Atlas Liver Hepatocellular Carcinoma database. Conclusion: The present study was the first to demonstrate that ARID1A might be involved in the translation pathway and served as an adaptive mechanism for tumor cells to survive under stress.