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Background: Angiogenesis plays an important role in colon cancer (CC) progression., Aim: To investigate the tumor microenvironment (TME) and intratumor microbes of angiogenesis subtypes (AGSs) and explore potential targets for antiangiogenic therapy in CC., Methods: The data were obtained from The Cancer Genome Atlas database and Gene Expression Omnibus database. K-means clustering was used to construct the AGSs. The prognostic model was constructed based on the differential genes between two subtypes. Single-cell analysis was used to analyze the expression level of SLC2A3 on different cells in CC, which was validated by immunofluorescence. Its biological functions were further explored in HUVECs., Results: CC samples were grouped into two AGSs (AGS-A and AGS-B) groups and patients in the AGS-B group had poor prognosis. Further analysis revealed that the AGS-B group had high infiltration of TME immune cells, but also exhibited high immune escape. The intratumor microbes were also different between the two subtypes. A convenient 6-gene angiogenesis-related signature (ARS), was established to identify AGSs and predict the prognosis in CC patients. SLC2A3 was selected as the representative gene of ARS, which was higher expressed in endothelial cells and promoted the migration of HUVECs., Conclusion: Our study identified two AGSs with distinct prognoses, TME, and intratumor microbial compositions, which could provide potential explanations for the impact on the prognosis of CC. The reliable ARS model was further constructed, which could guide the personalized treatment. The SLC2A3 might be a potential target for antiangiogenic therapy., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) is one of the most common types of cancers worldwide, ranking fifth among men and seventh among women, resulting in more than 7 million deaths annually. With the development of medical technology, the 5-year survival rate of HCC patients can be increased to 70%. However, HCC patients are often at increased risk of cardiovascular disease (CVD) death due to exposure to potentially cardiotoxic treatments compared with non-HCC patients. Moreover, CVD and cancer have become major disease burdens worldwide. Thus, further research is needed to lessen the risk of CVD death in HCC patient survivors., Aim: To determine the independent risk factors for CVD death in HCC patients and predict cardiovascular mortality (CVM) in HCC patients., Methods: This study was conducted on the basis of the Surveillance, Epidemiology, and End Results database and included HCC patients with a diagnosis period from 2010 to 2015. The independent risk factors were identified using the Fine-Gray model. A nomograph was constructed to predict the CVM in HCC patients. The nomograph performance was measured using Harrell's concordance index (C-index), calibration curve, receiver operating characteristic (ROC) curve, and area under the ROC curve (AUC) value. Moreover, the net benefit was estimated via decision curve analysis (DCA)., Results: The study included 21545 HCC patients, of whom 619 died of CVD. Age (< 60) [1.981 (1.573-2.496), P < 0.001], marital status (married) [unmarried: 1.370 (1.076-1.745), P = 0.011], alpha fetoprotein (normal) [0.778 (0.640-0.946), P = 0.012], tumor size (≤ 2 cm) [(2, 5] cm: 1.420 (1.060-1.903), P = 0.019; > 5 cm: 2.090 (1.543-2.830), P < 0.001], surgery (no) [0.376 (0.297-0.476), P < 0.001], and chemotherapy(none/unknown) [0.578 (0.472-0.709), P < 0.001] were independent risk factors for CVD death in HCC patients. The discrimination and calibration of the nomograph were better. The C-index values for the training and validation sets were 0.736 and 0.665, respectively. The AUC values of the ROC curves at 2, 4, and 6 years were 0.702, 0.725, 0.740 in the training set and 0.697, 0.710, 0.744 in the validation set, respectively. The calibration curves showed that the predicted probabilities of the CVM prediction model in the training set vs the validation set were largely consistent with the actual probabilities. DCA demonstrated that the prediction model has a high net benefit., Conclusion: Risk factors for CVD death in HCC patients were investigated for the first time. The nomograph served as an important reference tool for relevant clinical management decisions., Competing Interests: Conflict-of-interest statement: We have no financial relationships to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Photoreceptor cell death, primarily through apoptosis, related to retinal disorders like retinitis pigmentosa (RP), would result in vision loss. The pathological processes and crucial mutant conditions preceding photoreceptor cell demise are not well understood. This study aims to conduct an in-depth examination of early-stage changes in the widely utilized Pde6b rd1/rd1 (rd1) mouse model, which has Pde6b gene mutations representing autosomal recessive RP disorder. We investigated the morphology and ultrastructure of retinal cells, including second-order neurons, during the initial phase of disease progression. Our findings revealed that mitochondrial alterations in rod photoreceptors were present as a predeath mutant state as early as postnatal day 3 (P3). The bipolar and horizontal cells from the rd1 mouse retina exhibited significant morphological changes in response to loss of photoreceptor cells, indicating that second-order neurons rely on these cells for their structures. Subsequent oral administration of idebenone, a mitochondria-protective agent, enhanced retinal function and promoted both photoreceptor cell survival and inner retinal second-order synaptogenesis in rd1 mice at P14. Our findings offer a mechanistic framework, suggesting that mitochondrial damage acts as an early driver for photoreceptor cell death in retinal degeneration., (© 2024. The Author(s).)

Introduction: Hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) is the most frequently diagnosed metastatic breast cancer (mBC) subtype. Combinations of endocrine therapy (ET) with cyclin-dependent kinase 4/6 inhibitors (CDK4 & 6is) improve outcomes compared with ET alone. The efficacy and safety of abemaciclib among patients with HR+/HER2- mBC has been demonstrated in the MONARCH clinical trials; however, there is a paucity of real-world evidence, particularly in older patients., Methods and Materials: This retrospective cohort study analyzed the electronic medical record data/charts of adult patients with HR+/HER2- mBC receiving abemaciclib in US-based community oncology settings (1 September 2017 to 30 September 2019). Patients with other primary malignancies, clinical trial enrollment, and incomplete charts were excluded. Patient characteristics, treatment attributes and patterns, and real-world outcomes (clinical benefit rate [CBR] and stable disease among patients with response data available, time to chemotherapy [TTC], time to treatment discontinuation [TTD], and progression-free survival [PFS]) were summarized. Multivariable models evaluated the association between demographic/clinical characteristics and outcomes., Results: Of the 448 final patients, 99% were female, with a median age of 67 years (25% were ≥ 75 years) and median follow-up of 11 months; most (60%) initiated abemaciclib within 2 years of mBC diagnosis. Patients received a median of 1 (P25 = 0, P75 = 3) prior line of therapy for mBC before abemaciclib, including other CDK4 & 6is (48%) and prior chemotherapy (31%); most (57%) had visceral disease. The CBR for the overall population was 53%, with 48% achieving stable disease. The median TTC was not reached; median TTD was 249 days (95% confidence interval [CI]: 202, 304). The median PFS was 329 days (95% CI 266, 386). The discontinuation rate of abemaciclib owing to adverse events (30%) trended higher with age (years) (P = 0.027): 18-49 (n = 42; 19%), 50-64 (n = 155; 25%), 65-74 (n = 138; 32%), 75-84 (n = 82; 37%), ≥ 85 (n = 31; 49%); only 23% of patients overall had a dose hold or reduction prior to discontinuation., Conclusions: These patients were older than those in the MONARCH studies with substantial visceral disease, and prior chemotherapy and CDK4 & 6i use. Discontinuation rates were higher than in previous real-world studies (11.9%), highlighting the need for proactive management to optimize outcomes, particularly in older patients with mBC., (© 2023. The Author(s).)

Background: During cirrhosis, the liver is impaired and unable to synthesize and clear thrombopoietin properly. At the same time, the spleen assumes the function of hemofiltration and storage due to liver dysfunction, resulting in hypersplenism and excessive removal of platelets in the spleen, further reducing platelet count. When liver function is decompensated in cirrhotic patients, the decrease of thrombopoietin (TPO) synthesis is the main reason for the decrease of new platelet production. This change of TPO leads to thrombocytopenia and bleeding tendency in cirrhotic patients with hypersplenism., Aim: To investigate the clinical efficacy of recombinant human TPO (rhTPO) in the treatment of perioperative thrombocytopenia during liver transplantation in cirrhotic mice with hypersplenism., Methods: C57BL/6J mice and TPO receptor-deficient mice were used to establish models of cirrhosis with hypersplenism. Subsequently, these mice underwent orthotopic liver transplantation (OLT). The mice in the experimental group were given rhTPO treatment for 3 consecutive days before surgery and 5 consecutive days after surgery, while the mice in the control group received the same dose of saline at the same frequency. Differences in liver function and platelet counts were determined between the experimental and control groups. Enzyme-linked immunosorbent assay was used to assess the expression of TPO and TPO receptor (c-Mpl) in the blood., Results: Preoperative administration of rhTPO significantly improved peri-OLT thrombocytopenia in mice with cirrhosis and hypersplenism. Blocking the expression of TPO receptors exacerbated peri-OLT thrombocytopenia. The concentration of TPO decreased while the concentration of c-Mpl increased in compensation in the mouse model of cirrhosis with hypersplenism. TPO pre-treatment significantly increased the postoperative TPO concentration in mice, which in turn led to a decrease in the c-Mpl concentration. TPO pre-treatment also significantly enhanced the Janus kinase (Jak)/signal transducers and activators of transcription pathway protein expressions in bone marrow stem cells of the C57BL/6J mice. Moreover, the administration of TPO, both before and after surgery, regulated the levels of biochemical indicators, such as alanine aminotransferase, alkaline phosphatase, and aspartate aminotransferase in the C57BL/6J mice., Conclusion: Pre-treatment with TPO not only exhibited therapeutic effects on perioperative thrombocytopenia in the mice with cirrhosis and hypersplenism, who underwent liver transplantation but also significantly enhanced the perioperative liver function., Competing Interests: Conflict-of-interest statement: All authors declare that there are no conflicts of interest., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Fertilizer-based biofortification is a strategy for combating worldwide malnutrition of zinc (Zn), iron (Fe) and selenium (Se). Field experiments were conducted to investigate the effects of foliar treatments on concentrations of Zn, Fe, Se, N and bioavailability of Zn and Fe in grains of three maize cultivars grown at three locations. We compared the efficacy of ZnO nanoparticles (ZnO-NPs), Zn complexed chitosan nanoparticles (Zn-CNPs), conventional ZnSO 4 and a cocktail solution (containing Zn, Fe and Se). All treatments were foliar-applied at rate of 452 mg Zn L -1 , plus urea. Applying ten-fold less Zn (at rate of 45.2 mg Zn L -1 ) plus urea in the form of ZnO-NPs, Zn-CNPs, or ZnSO 4 resulted in no increase, or a negligible increase, in grain Zn concentration compared with deionized water. By contrast, among the different Zn sources plus urea applied by foliar sprays, conventional ZnSO 4 was the most efficient in improving grain Zn concentration. Furthermore, foliar application of a cocktail solution effectively improved grain concentrations of Zn, Fe, Se and N simultaneously, without a grain yield trade-off. For example, the average grain concentrations were simultaneously increased from 13.8 to 22.1 mg kg -1 for Zn, from 17.2 to 22.1 mg kg -1 for Fe, from 21.4 to 413.5 ug kg -1 for Se and from 13.8 to 14.7 g kg -1 for N by foliar application of a cocktail solution. Because grain yield was significantly negatively correlated with grain nutrient concentrations, the magnitude of increase in grain concentrations of Zn and Fe was most pronounced in the maize cultivar with the lowest grain yield (Zhengdan958 grown in Linyi). Foliar application of a cocktail solution also significantly decreased the phytic acid (PA) concentration, ratios of PA/Fe and PA/Zn in grains, indicating an increased bioavailability of Fe and Zn for human health. In conclusion, we found that a foliar application of a cocktail solution including Zn, Fe, Se and N was most effective for biofortification, but that the grains with the lowest yield contained the greatest concentration of these elements. This finding highlights the need to breed maize varieties that are capable of achieving both high grain yield and high grain nutritional quality to address food security and human health challenges., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Xue, Li, Yan, Miao, Zhang, Huang, Sun, Qi, Ding and Cui.)

Purpose: Cyclin Dependent Kinase 4 & 6 inhibitors (CDK4 & 6i) have transformed the management of HR+, HER2- metastatic breast cancer (MBC); however, the optimal sequence of these treatments and other systemic therapies for MBC remains unclear., Methods: This study analyzed electronic medical records from the ConcertAI Oncology Dataset. US patients who received abemaciclib and at least one other systemic line of therapy (LOT) for HR+, HER2- MBC were eligible. Treatment sequences were grouped, and data for two pairs of groups are presented herein (N = 397): Group 1 (1L CDK4 & 6i to 2L CDK4 & 6i) vs. Group 2 (1L CDK4 & 6i to 2L non-CDK4 & 6i), and Group 3 (2L CDK4 & 6i to 3L CDK4 & 6i) vs. Group 4 (2L CDK4 & 6i to 3L non-CDK4 & 6i). Time-to-event outcomes (PFS and PFS-2) were analyzed using Kaplan-Meier method and Cox proportional hazard regression., Results: In the total cohort of 690 patients, the most prevalent sequence was 1L CDK4 & 6i to 2L CDK4 & 6i (n = 165). For the 397 patients across Groups 1-4, sequential CDK4 & 6i demonstrated numerically longer PFS and PFS-2 versus non-sequential CDK4 & 6i. Adjusted results demonstrate that patients in Group 1 demonstrated significantly longer PFS (p = 0.05) versus Group 2., Conclusions: Although retrospective and hypothesis-generating, these data demonstrate numerically longer outcomes in the subsequent LOT associated with sequential CDK4 & 6i treatment., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Aim: To describe real-world treatment sequences of ramucirumab relative to immune checkpoint inhibitors (ICIs) in patients with advanced gastroesophageal cancer. Methods: Retrospective, observational study including adult patients treated with ramucirumab (April 2014-June 2020) from a nationwide health-record database. Results: In 1117 eligible patients, ramucirumab + paclitaxel was the most common ramucirumab-containing regimen (72.0%). A total of 217 patients also received an ICI. For ramucirumab then ICI (n = 148) and ICI then ramucirumab (n = 50), ramucirumab + taxane and ICI monotherapy were the most frequent approaches, most commonly observed as second- and third-line (2L and 3L). Median time on ramucirumab in 2L and 3L was similar regardless of sequence with ICI. Conclusion: Most patients with advanced gastroesophageal cancer received ramucirumab before ICI, with ramucirumab + paclitaxel as the most common ramucirumab-based regimen.

Introduction: Breast cancer in males constitutes approximately 1% of all breast cancer cases globally. Despite extensive treatment experience with abemaciclib in women with metastatic breast cancer (MBC), real-world evidence in male MBC is lacking., Methods: This analysis was a part of a broader, retrospective study that analyzed electronic medical records and charts of 448 men and women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) MBC who initiated an abemaciclib-containing regimen from January 2017 through September 2019. Data were collected from the Florida Cancer Specialists & Research Institute and the Electronic Medical Office Logistics Health Oncology Warehouse Language™ databases and summarized descriptively. Real-world best response was described: complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD)., Results: Data for six male patients with MBC who were treated with abemaciclib in combination with an aromatase inhibitor (AI) or fulvestrant are presented. Four patients were aged ≥ 75 years, and four patients had ≥ 3 metastatic sites, including visceral involvement. Abemaciclib was initiated in/after third-line (≥ 3L) in four patients, and patients had history of treatment with AI (n = 4), chemotherapy (n = 3), and/or prior cyclin-dependent kinase 4 and 6 inhibitors (n = 2) in the metastatic setting. Abemaciclib + fulvestrant was the most common abemaciclib-containing regimen (n = 4). Best response was documented in four patients: 1 each with CR, PR, SD, and PD., Conclusion: Prevalence of male MBC in this dataset was consistent with expected prevalence in the broader population. Most male patients received an abemaciclib-containing regimen in ≥ 3L, with anti-cancer activity observed despite heavy metastatic burden and prior treatments in a metastatic setting., (© 2023. The Author(s).)

Competing Interests: None

Enriched environment (EE) is an important animal experimental paradigm to decipher gene-environment interaction. It is thought to be efficient in aiding recovery from certain metabolism disorders or cognitive impairments. Recently, the effects of EE during adolescence in mice gradually draw much attention. We first established an EE model in adolescent mice, dissected lipid metabolism, and further examined baseline level of anxiety and depression by multiple behavioral tests, including open field test (OFT), elevated zero maze (EZM), tail suspension test (TST), and forced swimming test (FST). EE mice exhibited lower weights, lower cholesterol than standard housing (SH) mice. Behaviorally, EE mice traveled more distance and had higher velocity than SH mice in OFT and EZM. Besides, EE mice showed reduced anxiety levels in OFT and EZM. Furthermore, EE mice also had less immobility time than SH mice in TST and FST. Thus, these results suggest that EE during adolescence has metabolic and behavioral benefits in mice.

Aim: This real-world study aims to compare overall survival (OS) associated with biweekly (Q2W) versus weekly (Q1W) cetuximab dosing regimens for metastatic colorectal cancer (mCRC) treatment in the US. Methods: Adult patients with KRAS wild-type mCRC who received cetuximab ± chemotherapy from 2013 to 2019 were selected using Flatiron Health's electronic health records database. Propensity score matching was used to balance Q2W and Q1W cohorts on baseline patient characteristics. The Kaplan-Meier method was used for survival analyses. Several sensitivity analyses were conducted to assess the robustness of findings from the main analysis. Results: Of 1075 patients in the study, 60.7% received cetuximab Q1W and 39.3% Q2W. Median OS (95% confidence interval) in months was 17.2 (15.3, 18.8) for Q2W versus 14.3 (12.8, 16.0) for Q1W; p = 0.246. Similar OS between the dosing cohorts was observed in sensitivity analyses. Conclusion: Weekly and biweekly cetuximab had comparable effectiveness in this real-world study.

Dipeptidyl peptidase III (DPP III) is a zinc-dependent enzyme that specifically hydrolyzes dipeptides from the N-terminal of different-length peptides, and it is involved in a number of physiological processes. Here, DPP III with an atypical pentapeptide zinc binding motif (HELMH) was identified from Corallococcus sp. EGB. It was shown that the activity of recombined Co DPP III was optimal at 50 °C and pH 7.0 with high thermostability up to 60 °C. Unique to Co DPP III, the crystal structure of the ligand-free enzyme was determined as a dimeric and closed form. The relatively small inter-domain cleft creates a narrower entrance to the substrate binding site and the unfavorable binding of the bulky naphthalene ring. The ectopic expression of Co DPP III in M. xanthus DK1622 resulted in a 12 h head start in fruiting body development compared with the wild type. Additionally, the A-signal prepared from the starving DK1622- Co DPP III rescued the developmental defect of the asgA mutant, and the fruiting bodies were more numerous and closely packed. Our data suggested that Co DPP III played a role in the fruiting body development of myxobacteria through the accumulation of peptides and amino acids to act as the A-signal.

Objective: We investigated the effects of COVID-19 fear on negative moods among college students, and assessed the efficacy of physical exercise behavior as a moderator variable., Methods: This was a cross-sectional study. Students from three colleges and universities in Shangqiu City, Henan Province and Yangzhou City, Jiangsu Province were enrolled in this study, which was performed during the COVID-19 pandemic using an online questionnaire. A total of 3,133 college students completed the questionnaire. Measurement tools included the COVID-19 Phobia Scale (C19P-S), Depression-Anxiety-Stress Self-Rating Scale (DASS), and the Physical Activity Behavior Scale (PARS-3)., Results: During the COVID-19 pandemic, the rates of depression, anxiety, and stressful negative moods among college students were 35.5, 65.5, and 10.95%, respectively; there was a positive correlation between COVID-19 fear and negative moods among college students ( r = 0.479, p < 0.001), which was negatively correlated with physical exercise behavior ( r = -0.4, p < 0.001); the regulating effects of physical exercise behavior were significant (ΔR2 = 0.04, p < 0.001)., Conclusion: The rate of negative moods among college students is high, and the fear for COVID-19 is one of the key factors that lead to negative moods. Physical exercise can modulate the impact of COVID-19 fear among college students on negative moods. Studies should elucidate on mental health issues among different populations during the COVID-19 pandemic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Han, Han, Tong, Wang, Ke, Meng, Guo, Cui, Zhang, Ye, Zhang, Li and Li.)

Objective: To explore the effect of problematic mobile phone use on college students' physical activity and their relationships., Methods: A cross-sectional study was conducted among 3980 college students from three universities in Jiangsu province by random cluster sampling. The International Physical Activity Questionnaire Short (IPAQ-SF) measured college students' physical activity. The Mobile Phone Addiction Tendency Scale for College Students (MPATS) measured problematic mobile phone use tendencies. College students' physical activity was measured by the International Physical Activity Questionnaire Short (IPAQ-SF), and the Mobile Phone Addiction Tendency Scale measured their mobile phone addiction tendency for College Students (MPATS)., Results: (1) The proportions of the low-, medium-, and high-intensity physical activity were 83.5%, 10.7%, and 5.8%, respectively, with gender differences; The score of problematic mobile phone use tendency was 38.725 ± 15.139. (2) There were significant differences in problematic mobile phone use tendency among college students with different physical activity intensity (F = 11.839, p < 0.001, η 2 = 0.007). (3) The level of physical activity was significantly correlated with the tendency of problematic mobile phone use ( r = -0.173, p < 0.001). (4) Physical activity of college students could significantly predict the tendency of problematic mobile phone use (F (3,3605) = 11.296, p < 0.001)., Conclusions: The physical activity of college students was mainly moderate to low intensity, while the tendency of problematic mobile phone use was high. College students' physical activity level was one of the important constraints of problematic mobile phone use tendency.

Objective: Negative moods in college students have caused frequent extreme behaviors. This study analyzed the current status and correlation between physical activity and negative moods in college students., Methods: A cross-sectional study design was used in the present research. Data on college students' physical activity and negative moods were collected using the Sports Questionnaire Star software. The questionnaires were administered to college students in five colleges and universities in Henan and Jiangsu Provinces, China, and a total of 3711 correctly completed questionnaires were returned. Data on sociological and demographic information, the International Physical Activity Questionnaire Short Form (IPAQ-SF), and the Depression Anxiety and Stress Scale (DASS) were collected. The research was conducted in December 2021., Results: The low-intensity physical activity rate among college students was 55.56%, while depression, anxiety, and stress symptoms were detected in 35.14%, 65.29%, and 10.99%of the college students, respectively. Depression (K = 35.58, p < 0.001) and anxiety (K = 15.56, p < 0.001) rates were significantly different among the different physical activity intensity groups. The proportion of students who perform high-intensity physical activities was lower than those who perform low- and moderate-intensity physical activities., Conclusion: Low physical activity and high anxiety are evident among college students, and prolonged moderate-to-low-intensity physical activity (including static behavior) induces depression and anxiety. In the future, further studies can be conducted on improving the physical activity intensity of college students, improving the mental health monitoring and intervention systems of college students, and exploring the dose-effect relationship between physical activity and negative moods.

Background: HuR/ELAVL1 (embryonic lethal abnormal vision 1) was a downstream target of miR-29b in some cancer cells. HuR protein exerts important prognostic effects of involving in the pathogenesis and development of acute myeloid leukemia (AML). This study aims to investigate the role of miR-29b-3p in biological behaviors of AML cells by targeting HuR and the involvement of the NF-κB and JAK/STAT signaling pathways., Methods: The expressions of HuR and miR-29b-3p in AML cells were determined using RT-qPCR and Western blot, and the association between them was analyzed using the Spearman method. Next, the target relationship between HuR and miR-29b-3p was predicted by biological information databases and verified by the dual-luciferase reporter gene assay. MTS, methyl cellulose, flow cytometry and transwell assay were employed to detect the cell proliferation, clone formation, cell cycle and apoptosis, invasion and migration respectively, the effect of miR-29b-3p targeted HuR on the biological behaviors of AML cells was explored after over- /down-expression of miR-29b-3p and rescue experiment. Then, immunofluorescence assay and western blot were employed to detect location expression and phosphorylation levels of NF-κB and JAK/STAT signaling pathways related molecules respectively., Results: HuR was negatively correlated with miR-29b-3p, and was the downstream target of miR-29b-3p in AML cells. When miR-29b-3p was overexpressed in AML cells, HuR was down-regulated, accompanied by cell viability decreased, cell cycle arrest, apoptosis increased, invasion and migration weakened. Moreover, the opposite result appeared after miR-29b-3p was down-regulated. The rescue experiment showed that miR-29b-3p inhibitor could reverse the biological effect of HuR down-regulation in AML cells. Molecular pathway results showed that miR-29b-3p could inhibit p65 expression in nucleus and phosphorylation levels of p65, IκBα, STAT1, STAT3 and STAT5., Conclusion: miR-29b-3p can inhibit malignant biological behaviors of AML cells via the inactivation of the NF-κB and JAK/STAT signaling pathways by targeting HuR. miR-29b-3p and its target HuR can be used as a new potential molecular for AML treatment., (© 2022. The Author(s).)

Background: In the period of the COVID-19 pandemic, the level of college students' physical exercise, the detection rate of negative emotions, and their correlation should attract extensive attention. Therefore, this study aimed to explore the correlation between college students' physical exercise and negative emotions., Methods: Data were collected via a web-based cross-sectional survey. A questionnaire survey was conducted among 3118 college students from five universities in Shanghai in March 2022. In addition to sociodemographic information, measures included Physical Activity Rating Scale (PARS-3) and Depression Anxiety Stress Scale (DASS). The chi-squared test and logistic regression were used to analyze the differences and test the relative risk of negative emotions caused by different amounts of physical exercise., Results: Most students (66.1%) performed a small amount of physical exercise. Male students' physical-exercise level was higher than female students', and the detection rate of negative emotions was lower than that of female students. Moderate and low physical-exercise levels were associated with a higher risk of depression (beta of 0.289 and 0.345, respectively) and anxiety (beta of 0.301 and 0.418) symptoms than high physical-exercise level., Conclusions: The anxiety symptoms of college students were significant during the COVID-19 pandemic period. The physical-exercise behavior of college students was closely related to negative emotions, and the weakening of physical-exercise behavior was one of the factors that induced negative emotions in college students.

Background: Self-efficacy is an important component of the mental well-being of college students. This study aimed to evaluate the development and the correlation between physical fitness (PF), exercise behavior, and self-efficacy in college students. To examine whether PF in individual college students can predict self-efficacy, and whether exercise behavior mediates this relationship., Methods: This was an observational study of 1923 randomly selected college students (50.5% girl). Measures included the Physical Activity Rating Scale, the Self-Efficacy Scale, and PF testing., Results: Self-efficacy was weakly correlated to both PF ( r = 0.240) and exercise behavior ( r = 0.248). In regression analysis, PF explained 24.7% of the variance in self-efficacy, increasing to 29.4% when exercise behavior was considered. Therefore, the predictive effect of PF on self-efficacy is partially realized through healthy exercise behavior., Conclusion: Physical fitness can predict self-efficacy among college students, with exercise behavior being an important mediation of this relationship. Strategies to improve positive exercise behaviors and PF could improve students' self-efficacy and overall mental health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Han, Li, Wang, Ke, Meng, Li, Cui and Tong.)

Aim: To assess invasive disease-free survival (IDFS) and distant relapse-free survival (DRFS) in hormone receptor-positive, HER2-negative early breast cancer with combined clinicopathological criteria from monarchE, a phase III study of abemaciclib. Methods: US electronic health records were used to compare outcomes between high-risk (≥4 lymph nodes, or 1-3 lymph nodes and grade 3, tumor ≥5 cm or Ki-67 ≥20%) versus nonhigh-risk groups using Kaplan-Meier methods and Cox regression models. Results: The high-risk group (n = 557) was at higher risk for IDFS and DRFS events than the nonhigh-risk group (n = 3471). IDFS events (hazard ratio: 3.07; 95% CI: 2.45-3.83) and DRFS events (hazard ratio: 3.15; 95% CI: 2.49-3.97) were significantly higher for the high-risk group. Conclusion: Risk of recurrence was three-times greater in the high-risk group, highlighting the need for better therapies.

Background: Gastric or gastroesophageal junction (GEJ) adenocarcinoma is the most common form of gastric cancer diagnosed in the United States (US) each year. Diagnosis typically is in later stages of disease when it has advanced. Patients have been treated with a variety of regimens., Methods: The goal of this retrospective study was to understand if treatment patterns were becoming more homogeneous or remaining heterogeneous using the Herfindahl-Hirschman index (HHI) and if treatments were becoming more concordant to treatment guidelines published by the National Comprehensive Cancer Network (NCCN). HHI scores were calculated for each site by 2-year increments. Trend analyses were conducted for HHI scores over time using a linear regression model. Concordance to Category 1 and any category NCCN guidelines was determined based on the date treatment was initiated with the version of the NCCN guidelines at that time. Time trend analyses were conducted using linear regression models. This study utilized data from the Flatiron Advanced Gastric/Esophageal cohort. This study also examined overall survival (OS) rates estimated by the Kaplan-Meier method by line of therapy., Results: There were no statistically significant differences in HHI scores in the first-line setting over time, suggesting heterogeneity has not improved. Concordance to NCCN treatment guidelines for any category significantly increased over time, however Category 1 regimen concordance remained low in the first-line setting. Concordance over time improved in second-line treatment. Median OS from the start of first-line therapy was 13.57 months. There was no relationship between OS time from initiation of first-line therapy and HHI score, concordance with NCCN guidelines, or concordance with NCCN Category 1 guidelines in the first-line setting., Conclusions: Treatment heterogeneity persists in gastric cancer care, though there is a significant association between heterogeneity and concordance with both Category 1 and any category in the NCCN treatment guidelines, and that concordance has increased over time., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-21-890/coif). All authors are employees of Eli Lilly and Company. JAD, ZLC, XL, CW are also shareholders of Eli Lilly and Company., (2022 Journal of Gastrointestinal Oncology. All rights reserved.)

Background: Regorafenib is a standard 2nd-line treatment for patients with advanced hepatocellular carcinoma (HCC), but the efficacy and safety of sequential therapy with sorafenib and regorafenib among advanced HCC patients in China is not clear., Methods: This was a retrospective, two-center, cohort study of advanced HCC patients who received sequential therapy of sorafenib and regorafenib from October 2018 to April 2020 at 2 Chinese institutions. The patients were converted directly to regorafenib after failing to respond to sorafenib monotherapy. The patients underwent evaluations every 4-6 weeks to determine the efficacy and safety of the treatment according to physiological, laboratory, and radiological results. A radiological evaluation using computed tomography or magnetic resonance imaging scans was conducted. The outcomes included overall survival (OS) and progression-free survival (PFS)., Results: A total of 43 patients received regorafenib as a 2nd-line treatment after sorafenib progression. Of these patients, 26 (60.5%) and 17 (39.5%) were diagnosed with Barcelona Clinic Liver Cancer (BCLC) stages B and C, respectively. The median PFS was 11.0 [95% confidence interval (CI): 5.8-16.2] months, and the median OS was 17.0 (95% CI: 12.8-21.2) months. Conversely, the most common toxicities were hand-foot skin reaction (48.8%), diarrhea (32.6%), and hypertension (14%). The most common grade 3-4 toxicities were hypoalbuminemia (4.7%), anemia (4.7%), and thrombocytopenia (4.7%). Alpha-fetoprotein (AFP) ≥400, alanine transaminase (ALT) ≥60 IU/L, and aspartate aminotransferase (AST) ≥60 IU/L before 2nd-line treatment were associated with PFS in the univariable analyses. The Cox proportional-hazards regression analysis showed that AFP [hazard ratio (HR) =0.225; 95% CI: 0.073-0.688; P=0.009], ALT (HR =0.195; 95% CI: 0.051-0.741; P=0.016), AST (HR =0.209; 95% CI: 0.063-0.697; P=0.011), and presence of extrahepatic metastasis (HR =0.074; 95% CI: 0.009-0.608; P=0.015) before 2nd-line treatment were independently associated with PFS., Conclusions: The sequential therapy of sorafenib and regorafenib is well-tolerated and effective in advanced HCC patients after sorafenib progression based on our two-center real-world data. Patients with good liver function reserve and a high level of AFP before 2nd-line treatment may benefit from sequential treatment. These results still need further validation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-22-397/coif). The authors have no conflicts of interest to declare., (2022 Journal of Gastrointestinal Oncology. All rights reserved.)

Aim: This retrospective study estimated efficacy and safety of sintilimab + pemetrexed + platinum (SPP) versus placebo + pemetrexed + platinum (PPP) in untreated locally advanced/metastatic, nonsquamous non-small-cell lung cancer (NSCLC), after adjusting each ORIENT-11 trial patient's contribution to ORIENT-11 data based on characteristics of a target US population. Materials & methods: The target US population (n = 557) was selected from a real-world deidentified advanced NSCLC database based on key ORIENT-11 eligibility criteria. Inverse probability weights for ORIENT-11 patients (n = 397) relative to US patients were calculated. Efficacy and safety of SPP versus PPP were adjusted by inverse probability weights. Results: After adjustment, progression-free survival remained superior for SPP. Other efficacy and safety outcomes were consistent. Conclusion: These results provide evidence on how the effects observed with SPP in ORIENT-11 could translate to a US population with untreated locally advanced/metastatic nonsquamous NSCLC.

Acute myeloid leukemia (AML) is a malignant proliferative disease of myeloid hematopoietic origin and cannot be treated appropriately at present. This is due to the fact that leukemia cells are not sensitive to some of the traditional chemotherapy drugs. Or some chemotherapeutic drugs are too toxic to normal cells, affecting their wide clinical application. In this study, we identified BAM15 as a novel mitochondrial uncoupling agent by screening a library of small molecule compounds that inhibit AML cell activity. BAM15 significantly inhibited proliferation and promoted apoptosis in AML cells while at the same time being less cytotoxic to normal cells. The mechanism may be related to the disturbance of the ROS production balance. In vivo investigations revealed that BAM15 effectively suppressed AML progression and prolonged the survival time of mice. In addition, we found that BAM15 can be used in combination with cytarabine to enhance its anti-cancer activity and inhibit the activity of primary cells in AML. Therefore, we identified BAM15 as a potential drug candidate for the treatment of AML., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To investigate the correlation between thyroid nodules and microalbuminuria in type 2 diabetic mellitus., Methods: A total of 270 patients with type 2 diabetes at Tongzhou Branch of Dongzhimen Hospital were enrolled in this retrospective study. Data were collected from the inpatient electronic files between January 2018 and January 2020. The laboratory indexes of the two groups (thyroid nodule group with 172 cases and control group including 98 cases without thyroid nodules) were statistically analyzed by binomial logistic regression analysis and Spearman correlation analysis., Results: The proportion of microalbuminuria (MAU) in the thyroid nodule group was larger than that in the control group. Age, serum TT4, and FT4 in the thyroid nodule group were significantly higher compared with the control group. The binary logistic regression analysis indicated that age, sex, FT4, and MAU were the risk factors for thyroid nodule in T2DM patients. Spearman correlation analysis showed that the thyroid nodule was significantly positively correlated with MAU, age, FT4, and TT4., Conclusions: MAU might be an independent risk factor for thyroid nodule in type 2 diabetic mellitus., Competing Interests: The authors declare that there are no conflicts of interest., (Copyright © 2022 Can Cao et al.)

Objective: To analyze the efficacy and safety of toripalimab combined with axitinib in the treatment of advanced renal cell carcinoma. Methods: Clinical data of 50 patients with advanced renal cell carcinoma who received axitinib combined with toripalimab were retrospectively collected from the database of Peking University Cancer Hospital. ORR, DCR, PFS, and OS were analyzed. Results: Among the 50 patients, 37 were males; median age was 56 (22-73) years; 38 were pathologically diagnosed as clear cell renal cell carcinoma and 12 were non-clear cell carcinoma. Common metastatic sites included lung, bone, lymph node, liver, and so on. 90% of the patients had received at least one-line of systemic therapy. With a median follow-up time of 11.9 months (0.8-24), 27 of the 50 patients are still on treatment, ORR was 34%, DCR was 86%, median PFS was 13.1 months (95% CI 5.8-20.4), and median OS has not yet reached. One-year OS rate was 84.6%. Common adverse reactions were proteinuria, diarrhea, hypertension, abnormal thyroid function, elevated transaminase, and hand-foot syndrome. Most adverse events were grade 1-2. Conclusion: Toripalimab combined with axitinib was efficient in the treatment of advanced renal cell carcinoma, and had manageable adverse reactions.

Objective: This retrospective, observational study examined patient characteristics, treatment patterns, testing patterns, and outcomes of US patients receiving first-/second- or third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs)., Methods: This study used an electronic health record-derived de-identified database. Eligible patients had advanced EGFR m + non-small cell lung cancer. Descriptive statistics were used to describe demographic, clinical, and treatment characteristics. Logistic regression models were used to identify patient characteristics that were associated with the use of osimertinib vs. a first-/second-generation EGFR TKI. Kaplan-Meier methods were used for survival analysis., Results: Of the 782 patients who received first-line (1L) therapy with first-/second-generation EGFR TKIs in cohort A, erlotinib was the most common (58%), and osimertinib was the most widely prescribed second-line (2L) therapy (52%). Of the patients who received 1L therapy with osimertinib, a greater range of treatments were prescribed in 2L. A third of patients treated with first-/second-generation EGFR TKIs underwent EGFR testing near the end of 1L, and 44% of these patients had T790M positive disease. The median time on targeted therapy (TTT) of the cohort was 11.1 months (95% confidence interval [CI] 9.7, 12.3), and the median overall survival from the start of 1L therapy was 23.5 months (95% CI 20.7, 24.8)., Conclusions: The majority of patients treated with first-/second-generation EGFR TKIs went on to receive osimertinib in the 2L setting, but overall, only a third of patients had received molecular testing at progression. Improved testing frequency is vital to inform treatment decisions.

This study aimed to measure the expression of SAA2 in plasma and to assess its diagnostic efficacy as a biomarker for non-small cell lung cancer (NSCLC). The gene expression of SAA2 in NSCLC was analyzed based on a database. Then, SAA2 expression was detected by immunohistochemistry in lung tissue and by enzyme-linked immunosorbent assay in 90 patients with NSCLC and 61 normal controls. Finally, the diagnostic performance was assessed in terms of accuracy, sensitivity, and specificity. At the gene and protein levels, the SAA2 expression was significantly higher in the NSCLC group than in the control group (p<0.01). It was higher in lung squamous carcinoma than in lung adenocarcinoma and in males than in females, and this trend was also observed in the lung squamous carcinoma group. Of note, the expression of SAA2 increased with increasing disease stage. Receiver operating characteristic (ROC) curve analysis revealed that the sensitivity of SAA2 was 83.61%, the specificity was 91.11%, and the area under the curve (AUC) was 0.9252. Its accuracy was 68.89%, which was higher than that of other conventional diagnostic biomarkers, and the combined application can effectively improve the diagnostic efficiency. Based on the results, SAA2 expression was positively correlated with the disease stage of NSCLC. Notably, SAA2 is more concerning in male patients with lung squamous carcinoma, and it can help in the screening and diagnosis of NSCLC. SAA2 may represent a novel diagnostic biomarker in NSCLC.

Aim: To predict optimal treatments maximizing overall survival (OS) and time to treatment discontinuation (TTD) for patients with metastatic breast cancer (MBC) using machine learning methods on electronic health records. Patients/methods: Adult females with HR+/HER2- MBC on first- or second-line systemic therapy were eligible. Random survival forest (RSF) models were used to predict optimal regimen classes for individual patients and each line of therapy based on baseline characteristics. Results: RSF models suggested greater use of CDK4 & 6 inhibitor-based therapies may maximize OS and TTD. RSF-predicted optimal treatments demonstrated longer OS and TTD compared with nonoptimal treatments across line of therapy (hazard ratios = 0.44∼0.79). Conclusion: RSF may help inform optimal treatment choices and improve outcomes for patients with HR+/HER2- MBC.

Retrospective observational research relies on databases that do not routinely record lines of therapy or reasons for treatment change. Standardized approaches to estimate lines of therapy were developed and evaluated in this study. A number of rules were developed, assumptions varied and macros developed to apply to large datasets. Results were investigated in an iterative process to refine line of therapy algorithms in three different cancers (lung, colorectal and gastric). Three primary factors were evaluated and included in the estimation of lines of therapy in oncology: defining a treatment regimen, addition/removal of drugs and gap periods. Algorithms and associated Statistical Analysis Software (SAS ® ) macros for line of therapy identification are provided to facilitate and standardize the use of real-world databases for oncology research.

Background: The integration of data from disparate sources could help alleviate data insufficiency in real-world studies and compensate for the inadequacies of single data sources and short-duration, small sample size studies while improving the utility of data for research., Objective: This study aims to describe and evaluate a process of integrating data from several complementary sources to conduct health outcomes research in patients with non-small cell lung cancer (NSCLC). The integrated data set is also used to describe patient demographics, clinical characteristics, treatment patterns, and mortality rates., Methods: This retrospective cohort study integrated data from 4 sources: administrative claims from the HealthCore Integrated Research Database, clinical data from a Cancer Care Quality Program (CCQP), clinical data from abstracted medical records (MRs), and mortality data from the US Social Security Administration. Patients with lung cancer who initiated second-line (2L) therapy between November 01, 2015, and April 13, 2018, were identified in the claims and CCQP data. Eligible patients were 18 years or older and received atezolizumab, docetaxel, erlotinib, nivolumab, pembrolizumab, pemetrexed, or ramucirumab in the 2L setting. The main analysis cohort included patients with claims data and data from at least one additional data source (CCQP or MR). Patients without integrated data (claims only) were reported separately. Descriptive and univariate statistics were reported., Results: Data integration resulted in a main analysis cohort of 2195 patients with NSCLC; 2106 patients had CCQP and 407 patients had MR data. The claims-only cohort included 931 eligible patients. For the main analysis cohort, the mean age was 62.1 (SD 9.27) years, 48.56% (1066/2195) were female, the median length of follow-up was 6.8 months, and for 37.77% (829/2195), death was observed. For the claims-only cohort, the mean age was 66.6 (SD 12.69) years, 52.1% (485/931) were female, the median length of follow-up was 8.6 months, and for 29.3% (273/931), death was observed. The most frequent 2L treatment was immunotherapy (1094/2195, 49.84%), followed by platinum-based regimens (472/2195, 21.50%) and single-agent chemotherapy (441/2195, 20.09%); mean duration of 2L therapy was 5.6 (SD 4.9, median 4) months. We describe challenges and learnings from the data integration process, and the benefits of the integrated data set, which includes a richer set of clinical and outcome data to supplement the utilization metrics available in administrative claims., Conclusions: The management of patients with NSCLC requires care from a multidisciplinary team, leading to a lack of a single aggregated data source in real-world settings. The availability of integrated clinical data from MRs, health plan claims, and other sources of clinical care may improve the ability to assess emerging treatments., (©Michael Grabner, Cliff Molife, Liya Wang, Katherine B Winfree, Zhanglin Lin Cui, Gebra Cuyun Carter, Lisa M Hess. Originally published in JMIR Cancer (http://cancer.jmir.org), 12.04.2021.)

Objectives: Therapeutic advances for the treatment of patients with advanced/metastatic non-small cell lung cancer (NSCLC) have led to additional options for care. This observational study was designed to describe emerging treatment patterns and survival outcomes., Materials and Methods: Flatiron Health's oncology electronic health records database was to identify eligible patients who were age 18+ who initiated second-line therapy for NSCLC Survival analyses were conducted using Kaplan Meier methods and Cox proportional hazard model using SAS 9.4. both unadjusted and adjusted, using generalized propensity score, to account for imbalances between groups., Results: The 10,060 eligible patients from Dec 2014 to Feb 2019 were 52.6% male; mean age 67.1 years; 70.3% white; 26.0% squamous/70.0% non-squamous (4.1% not specified); and 92.7% were treated at community practices. Immune checkpoint inhibitors (ICIs) were used by 79.9% of the cohort during any line of therapy; 12.1% and 53.7% used ICIs during first- and second-line therapy, respectively. There was heterogeneity in treatment sequencing, as the three most common first→second line sequences accounted for 7.7% (carboplatin + paclitaxel→nivolumab), 5.0% (carboplatin + pemetrexed→nivolumab), and 3.8% (carboplatin + nab-paclitaxel→nivolumab) of the total population, respectively. Unadjusted median overall survival was 21.1 months (95% confidence interval, CI: 20.5-21.6) from metastatic diagnosis. Median survival was 23.0 months (95% CI, 22.3-23.6) for non-squamous and 18.1 months (95% CI, 17.3-18.8) for squamous disease., Conclusion: There is heterogeneity in sequencing strategies that limit the ability to conduct robust comparative effectiveness research of treatment sequences. Since few patients follow a similar treatment trajectory, comparative effectiveness research will be challenged to identify treatment sequences with sufficient sample size.

Purpose: In REVEL, patients with advanced non-small-cell lung cancer (aNSCLC) and patients with increased tumor aggressiveness (rapid disease progression (RDP), platinum-refractory disease (PRD), and high symptom burden (HSB)) benefited from second-line treatment with ramucirumab plus docetaxel over placebo plus docetaxel. This post hoc analysis describes healthcare resource utilization (HCRU) associated with the treatment., Methods: aNSCLC patients who had progressed during or after first-line platinum-based chemotherapy were randomized to receive docetaxel and either ramucirumab or placebo until disease progression, unacceptable toxicity, withdrawal, or death. HCRU included hospitalizations, transfusions, and concomitant medications. Categorical variables (counts and percentages) were compared using Fisher's exact test. Continuous variables (mean, standard deviation (SD), median, minimum, and maximum) were compared using the Wilcoxon rank sum test., Results: Patient characteristics were largely similar between treatment arms. Within the intent-to-treat (ITT) population (n = 1253), the mean treatment duration was 19.7 and 16.9 weeks in the ramucirumab and control arms, respectively; 51.0% versus 54.9% of patients received subsequent anticancer therapy, respectively. Hospitalization rates were 41.9% versus 42.6% (p = 0.863), mean length of hospital stay was 14.5 days versus 11.3 days (p = 0.066), transfusion rates were 9.9% versus 12.3% (p = 0.206), and use of granulocyte colony-stimulating factors was 41.8% versus 36.6% (p = 0.063), respectively. No significant difference was observed in HCRU between treatment arms in both ITT population and in aggressive disease subgroups including RDP (n = 209), PRD (n = 360), and HSB (n = 497)., Conclusion: In REVEL, the addition of ramucirumab to docetaxel did not increase HCRU among patients with aggressive aNSCLC disease. These results may help inform economic evaluation of treatment for patients with aNSCLC.

Aims: The ability of a patient to receive anti-cancer treatment depends on a variety of factors, including performance status (PS), which is typically measured using the Eastern Cooperative Oncology Group (ECOG) scale. This study hypothesized that there would be a strong and positive correlation between ECOG PS values and healthcare resource utilization (HCRU) and a strong and negative correlation with the use of anti-cancer therapy., Materials and Methods: Patients with colorectal, lung or gastric cancer were included in this retrospective analysis of administrative claims data linked to electronic medical records (EMR). All-cause HCRU (hospitalization/inpatient care, emergency room visits, systemic anti-cancer therapy, radiation therapy, outpatient physician visits, hospice, home health care and key supportive care treatments such as anti-emetics, hematopoietic treatments, transfusions, and durable medical equipment) was evaluated by baseline ECOG PS value and PS over time. Adjusted multivariable regression analysis was used to assess the relationship between baseline ECOG PS and HCRU. Regression analyses were conducted to explore the relationship between other baseline variables and HCRU., Results: There were 1311 patients included in this study. There was low correlation between PS and any HCRU variable or receipt of anti-cancer therapy (correlation coefficients all <0.10). In regression analyses, the proportion of patients with poor PS (PS = 2+) who were hospitalized was not significantly different from those with good PS (PS = 0/1) (28.9% versus 19.3%, p  = .07)., Limitations: The low rate of reporting of PS and the small sample size of patient groups in this study., Conclusions: There is very little evidence of a relationship between ECOG PS and HCRU, ECOG PS, or anti-cancer therapy in this study, in part due to low rates of and lack of variability in reported PS. There is some evidence that baseline comorbidities were significantly associated with HCRU and should be accounted for in future research evaluating HCRU., (© 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Background: Chemotherapy is the major choice for advanced non-small-cell lung cancer (NSCLC) patients with epidermal growth factor receptor exon 20 insertion (EGFR ex20ins). The efficacy of pemetrexed-based with other chemotherapy regimens and EGFR ex20ins subtypes in this population has not been well studied., Methods: We screened patients with EGFR ex20ins by next-generation sequencing (NGS) from a large cohort. The clinicopathologic and medical information were collected in advanced NSCLC patients with EGFR ex20ins. We also compared the clinical outcomes among patients with different subtypes of EGFR ex20ins., Results: We retrospectively collected 119 stage IIIB/IV NSCLC patients with EGFR ex20ins from 9142 NSCLC patients across China from June 2013 to December 2018. The subtypes of EGFR ex20ins included A767&#95;V769dupASV (33/119, 27.73%), S768&#95;D770dupSVD (19/119, 15.97%), N771&#95;H773dupNPH (11/119, 9.24%), A763&#95;Y764insFQEA (2/119, 1.68%) and others (54/119, 45.38%). A total of 64.7% (77/119) of patients received pemetrexed-based first-line chemotherapy and 13.45% (16/119) of patients received pemetrexed-based second-line chemotherapy. Pemetrexed-based chemo-treated patients had longer median progression-free survival (PFS) than patients without pemetrexed-based chemo-treated (5.5 vs. 3.0 months, P=0.0026). Survival data was available for 66 patients and the median overall survival (OS) was 24.7 months. Pemetrexed-based chemo-treated patients had longer OS tendency than patients without pemetrexed-based chemo-treated (25.0 vs. 19.6 months, P=0.0769). Patients harboring A767&#95;V769dupASV had better OS than other subtypes of EGFR ex20ins but without statistical significance (P=0.0676). Multivariate analysis revealed that histological type of NSCLC and bone-metastasis before treatment were independent prognostic factors for OS in all patients after adjusting all characteristic and treatment factors (P<0.05)., Conclusions: To the best of our knowledge, it is the largest cohort study of advanced NSCLC patients with EGFR ex20ins across China. Pemetrexed-based treatment could have better control of disease than non-pemetrexed-based chemotherapies in this population. Furthermore, more effective agents are expected for patients harboring EGFR ex20ins., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tlcr-20-382). The authors have no conflicts of interest to declare., (2020 Translational Lung Cancer Research. All rights reserved.)

Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest.

Objective: To explore the clinical effect of X-N advancement flap in repairing pressure ulcer on the buttock or back. Methods: From June 2018 to June 2019, 20 patients with grade Ⅳ pressure ulcers on the buttock or back were hospitalized and treated in the Department of Traumatology, Burns and Plastic Surgery of Fourth Affiliated Hospital of Guangxi Medical University, including 15 males and 5 females, aged 48-89 years. The area of the patient's wound was 8 cm×5 cm-15 cm×12 cm after debridement, and all were repaired with the X-N advancement flap designed by the author. The flap was designed according to the direction of skin relaxation on both sides of the wound, and the skin was incised in X-shape and sutured in N-shape. The width and advancement distance of the flap were recorded, and the ratio of the advancement distance to the width of the flap was calculated. The flap survival, complication, and follow-up were observed and recorded. Results: The width of the flap was (5.9±1.2) cm, the advancement distance of the flap was (10.3±2.5) cm, and the ratio of the advancement distance to the width of the flap was 1.8±0.4. All the flaps survived, and none of the flaps had blood flow disorder. Local dehiscence occurred in the flap of one patient 1 week after surgery, which was healed after laying on the floating bed, strengthened care, and wound dressing change. The flap of one patient developed infection 5 days after surgery, which was healed after partial suture removal, smooth drainage, and replacement with sensitive antibiotics. The wounds of the remaining 18 patients were all cured. After 3 months of follow-up, the flaps survived well with good elasticity and texture. Conclusions: The X-N advancement flap can make the skin and soft tissue move forward effectively. It is simple and effective to repair pressure ulcers on the back or buttock of patients with this flap, which is worthy of clinical promotion and application.

Background: As real-world data resources expand and improve, there will increasingly be opportunities to study the effectiveness of interventions. There is a need to ensure that study designs explore potential sources of bias and either acknowledge or mitigate them, in order to improve the accuracy of findings. The objective of this study was to understand newly approved drug utilization patterns in real-world clinical settings over time., Methods: This retrospective study included three sources of real-world data (claims, electronic health records, and recoded data from a quality care program) collected from patients diagnosed with gastric cancer who initiated therapy with either trastuzumab or ramucirumab. Linear regression was used to investigate trends in the use of these drugs for the care of patients with gastric cancer over time from Food and Drug Administration (FDA) approval., Results: Eligible patients (n=1700) had consistent demographic and clinical characteristics over time. After regulatory approval, trastuzumab was used in later lines of therapy and then shifted to earlier lines (p=0.002), while ramucirumab utilization remained consistent over time after FDA approval (p=0.49). Ramucirumab augmentation, defined as the addition of the drug after initiation of a line of therapy, decreased over time (p=0.03), and trastuzumab augmentation remained consistent over time (p=0.58)., Conclusion: Since treatment effectiveness may change across lines of treatment, bias may arise if there are changes in the use of the drug (such as line migration) during the time period of analysis using real-world data., Competing Interests: LMH, AML, XIL, ZLC, LB and WS are employees of Eli Lilly and Company. MG is an employee of HealthCore, Inc., an independent research organization that received funding from Eli Lilly and Company for the conduct of the study. LW was an employee of HealthCore, Inc. when the study was conducted. The authors report no other conflicts of interest in this work., (© 2020 Hess et al.)

Aims: The objective of this feasibility study was to determine the extent to which data from randomized controlled trials (RCTs) may serve as a useful source for collecting health care resource use (HCRU) for the purposes of estimating costs of managing adverse events (AEs), specifically, grade 3-4 nausea and thrombocytopenia, which may be experienced during chemotherapy treatment. Materials and Methods: The feasibility study was conducted in four steps: (1) HCRU data were extracted from patient narratives in four phase 3 RCTs in non-small cell lung cancer; (2) missing HCRU data were imputed; (3) unit costs were applied to the resulting HCRU data set and costs of managing AEs were estimated; and (4) the overall utility of using RCT data as a source for estimating costs of AEs was evaluated. Results: 33 nausea and 68 thrombocytopenia AEs met eligibility criteria and were evaluated in this study. Medication usage was recorded as a treatment in 76% of nausea AEs, although only 14% of the instances of medication usage included the minimum data elements required for costing. Platelet transfusions were provided in 24% of thrombocytopenia AEs; however, in only one instance were the minimum data elements recorded. Of nausea and thrombocytopenia AEs, 18% and 72%, respectively, required no missing data assumptions or imputation. Limitations: Only two AEs were considered, and they may not be representative of all AEs in terms of suitability for use in estimating HCRU and costs of managing AEs. Not all grade 3-4 AEs met the criteria for requiring a patient narrative. HCRU data in the narratives were incomplete. Conclusions: The usefulness of RCTs for estimating the costs of AEs may be improved by using a standardized form to collect HCRU data for key AEs, including an appropriate level of detail required to estimate costs of managing the AEs.

Aim: To describe treatment patterns and outcomes for advanced/metastatic non-small-cell lung cancer (aNSCLC) treated with single-agent or combination ramucirumab (ramucirumab-based) and/or immune checkpoint inhibitor (ICI-based) therapy. Materials & methods: Retrospective study of aNSCLC patients (n = 4054) identified in the Flatiron Health database, who received at least two treatment lines including ramucirumab- and/or ICI-based regimens between December 2014 and May 2017. Results: Median overall survival (95% CI) from aNSCLC diagnosis was 29.3 (25.5-33.0) months for patients receiving sequential ramucirumab- and ICI-based therapy (n = 245), 15.1 (12.6-18.2) months for patients receiving sequences including ramucirumab- without ICI-based therapy (n = 112), and 23.1 (21.9-24.2) months for patients receiving ICI-based therapy without ramucirumab-based therapy in sequence (n = 3697). Conclusion: Results provide real-world survival estimates for aNSCLC treated with sequences including ramucirumab- and/or ICI-based therapies.

Background: Colorectal cancer is the third most common cause of cancer death in the USA. It is important to identify patients who may experience poor outcomes from available treatments., Methods: In this retrospective observational study, treatment patterns and survival outcomes were described among adult patients from the Flatiron Health electronic medical records database who were treated with at least two lines of therapy for metastatic colorectal cancer in the USA between January 2013 and May 2018. Patients with rapid progression were defined as those whose time from start of first- to second-line therapy was ≤ 183 days., Results: A total of 14,315 patients formed the study cohort. The most common first-line treatments were FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) plus bevacizumab, received by 34.7% (n = 4962) of patients, followed by FOLFOX alone (17.1%, n = 2445). Of all patients, 6991 (48.9%) also received second-line anti-cancer therapy and of those, 3338 (47.7%) had rapid progression and 3653 (52.3%) did not. Median overall survival from the start of first- and second-line therapy was 20.8 months (95% CI 20.2-21.3) and 14.5 months (95% CI 13.9-15.0) for the entire study population, respectively. Median overall survival from the start of second-line therapy was 14.1 (95% CI 13.2-14.8) for patients with rapid progression and 14.6 months (95% CI 13.8-15.4) for patients without rapid progression., Conclusions: Patients diagnosed with metastatic colorectal cancer lived less than 2 years in this real-world database. While the time to initiation of second-line therapy was by definition longer among patients without rapidly progressing disease, survival outcomes were comparable from initiation of second-line therapy.

Aim: The study is aimed to investigate the protective effects and possible mechanism of tacrolimus (FK506) pre-treatment in hepatic ischemia-reperfusion injury in rats., Methods: The rats were randomly assigned into four groups, which were S, IR, L and H group, and then all groups were subjected to 60min of 70% partial warm liver ischemia, except S group. Rats in the L and H group were pre-treated with two different doses FK506 at 60min before ischemia. The rats of the IR group received an identical volume of normal saline. All animals were sacrificed after 6h of reperfusion. Transaminases were measured by biochemistry analyzer. Elisa kit was used to detect TNF-α, IL-6 and IL-1β levels in serum. Liver specimens were stained with hematoxylin and eosin (HE) to assess the pathologic changes. The expressions of heme oxygenase-1 (HO-1), hypoxia-inducible factor-1α (HIF-1α), nuclear factor of activated T cells (NFAT3) were measured by real-time quantitative PCR and western blotting and the Bcl-2 and the Bax protein were tested by western blotting., Results: In rats pre-treated with FK506, the levels of transaminases, TNF-α and IL-1β were reduced significantly and also liver damage was dramatically mitigated compared to those without FK506 pre-treatment. Moreover, the expression of HO-1 at the level of both transcription and translation increased clearly and the activation of the HIF-1α was found in FK506 pre-treated livers. Moreover, NFAT3 protein transportation to the nucleus was reduced and Bax protein expression was decreased, but the expression of Bcl-2 protein was markedly increased after FK506 pre-treatment., Conclusion: FK506 pre-treatment could lessen hepatic ischemia-reperfusion injury through up-regulating the expression of HIF-1α and HO-1, and inhibiting nuclear translocation of NFAT3 in liver tissues., (Copyright © 2017. Published by Elsevier Masson SAS.)

An unstudied β- N -acetylhexosaminidase (SnHex) from the soil bacterium Stackebrandtia nassauensis was successfully cloned and subsequently expressed as a soluble protein in Escherichia coli . Activity tests and the biochemical characterization of the purified protein revealed an optimum pH of 6.0 and a robust thermal stability at 50 °C within 24 h. The addition of urea (1 M) or sodium dodecyl sulfate (1% w / v ) reduced the activity of the enzyme by 44% and 58%, respectively, whereas the addition of divalent metal ions had no effect on the enzymatic activity. PUGNAc ( O -(2-acetamido-2-deoxy-D-glucopyranosylidene)amino- N -phenylcarbamate) strongly inhibited the enzyme in sub-micromolar concentrations. The β- N -acetylhexosaminidase was able to hydrolyze β1,2-linked, β1,3-linked, β1,4-linked, and β1,6-linked GlcNAc residues from the non-reducing end of various tested glycan standards, including bisecting GlcNAc from one of the tested hybrid-type N-glycan substrates. A mutational study revealed that the amino acids D306 and E307 bear the catalytically relevant side acid/base side chains. When coupled with a chitinase, the β- N -acetylhexosaminidase was able to generate GlcNAc directly from colloidal chitin, which showed the potential of this enzyme for biotechnological applications.

Background: Inadequate understanding of interpretation of quality of life (QoL) instruments leads to unsatisfactory data reporting and clinical decision-making, including in gastric cancer care., Materials and Methods: Pooled QoL data from two phase III studies of ramucirumab with or without paclitaxel in previously treated patients with gastric or gastroesophageal junction cancer were used to explore associations with clinical attributes, including tumour response, disease measurability and performance status (PS). The European Organisation for Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire (QLQ)-C30 was used in both studies. Changes in QLQ-C30 scores from baseline to week 6 as a predictor of clinical outcomes and impacts of changes in clinical status on QoL were estimated by multivariate logistic regression and analyses of variance, respectively., Results: Baseline QoL data were available for 989 patients. Fatigue, pain and appetite loss were prominent baseline symptoms. Disease progression resulted in worse QoL in all functional scales (p < 0.0001 to p = 0.0306), global QoL (p = 0.0011) and symptom scales (fatigue, p < 0.0001; nausea/vomiting, p = 0.0007; pain, p = 0.0052; appetite loss, p = 0.0061). Similar trends were seen with deterioration of PS on QoL. A 15- to 20-point change in global QoL and functional scale scores predicted change in tumour status as did change in fatigue, pain and appetite loss scores. Smaller QoL changes (5-15 points) predicted PS change. Results were similar in patients regardless of baseline disease measurability., Conclusions: Our study underscores the importance of disease control for maintaining or improving QoL. These data could improve future trial design and routine clinical care for patients receiving therapy for previously treated gastric cancer. NCT00917384, NCT01170663., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To investigate the expression of Apelin and Snail proteins in breast cancer and their relationship with the clinicopathological features and prognosis. Methods: The expression of Apelin and Snail proteins was detected by immunohistochemistry in 89 cases of breast cancer and 50 cases of mammary adenosis collected from January to June in 2008 at Fujian Cancer Hospital; the expression was correlated with the clinicopathological features and outcome of the patients. Results: Apelin and Snail were expressed in 42 cases(47.2%)and 36 cases(40.4%)of breast cancers, respectively, and the expression was higher than that of control group ( P <0.01). The expression of Apelin was positively correlated with Snail ( r =0.230, P <0.05). Apelin expression was associated with lymph node metastasis and TNM staging( P <0.05). Snail expression was associated with lymph node metastasis( P <0.05). Kaplan-Meier survival curve showed that the prognosis of Apelin positive group was worse than that of Apelin negative group ( P <0.01). There was no significant difference in prognosis between Snail negative and positive groups ( P >0.05). The prognosis of Apelin and Snail in both positive groups was worse than that of Apelin and Snail both negative groups ( P <0.01). Multivariate COX regression analysis showed that Apelin and TNM staging could be used as independent prognostic factors for breast cancer ( P <0.05). Conclusions: Apelin and Snail are highly expressed in breast cancer, and associated with lymph node metastasis and TNM stage. There is a positive correlation between Apelin and Snail expression, which may suggest a role in breast carcinogenesis. The prognosis of breast cancer with expression of Apelin and co-expression of Apelin and Snail is poor. Therefore, Apelin may be used as an effective indicator to evaluate the prognosis of breast cancer patients.

Objective: This study aims to investigate whether microRNA-373-3p could inhibit the progression of prostate cancer (PCa) by targeting and degrading AKT1., Patients and Methods: Expression levels of microRNA-373-3p and AKT1 in PCa tissues and benign prostate hyperplasia (BPN) tissues were detected by quantitative Real-Time-Polymerase Chain Reaction (qRT-PCR). According to the follow-up data, survival curves and receiver operating characteristic (ROC) curves were drawn to investigate whether microRNA-373-3p could be served as a biomarker for early diagnosis and prognosis of PCa. The effect of microRNA-373-3p on cell proliferation was examined by cell counting kit-8 (CCK-8) assay. Subsequently, we explored the direct binding condition of AKT1 and microRNA-373-3p by dual-luciferase reporter gene assay and Western blot., Results: QRT-PCR results showed that microRNA-373-3p level was significantly lower in PCa tissues compared with that of BPN tissues, whereas AKT1 expression was significantly increased. By analyzing the survival curve and ROC curve, we found that the overall survival (OS) of PCa patients with higher microRNA-373-3p expression was markedly longer than those with lower expression. Besides, microRNA-373-3p could be used as an early diagnostic marker to distinguish PCa from BPH. Overexpression of microRNA-373-3p in PCa cells (LNCaP and PC3 cells) remarkably inhibited cell proliferation. Dual-luciferase reporter gene assay and Western blot showed that microRNA-373-3p targeted the 3'UTR of AKT1 and inhibited its expression., Conclusions: Downregulated microRNA-373-3p promoted the proliferation of prostate cancer cells via targeting AKT1.

Background: Limited real-world research has investigated ramucirumab for the treatment of patients with gastric or gastroesophageal junction (GEJ) cancer. This study was designed to describe ramucirumab monotherapy or combination therapy use in a community oncology practice setting., Methods: This was a retrospective observational cohort study to describe the treatment of adult patients with gastric or GEJ cancer who initiated ramucirumab treatment between 4/21/14 and 6/30/16 within the US Oncology Network. Kaplan-Meier method and Cox proportional hazards regression analyses were used to assess clinical outcomes. Multivariable logistic regression models were used to assess patient-level predictors of ramucirumab monotherapy or combination therapy., Results: A total of 505 patients (mean age 64.4 years; 75.1% male) were included in the analysis; subgroups included: monotherapy (22.8%; n = 115), combination therapy (77.2%; n = 390). Monotherapy patients were significantly older (67.7 vs. 63.4 years; P = 0.0006), received ramucirumab approximately 3 months later after diagnosis (16.9 vs. 14.1 months; P = 0.0318) and more frequently initiated ramucirumab in the third or later lines of treatment (38.3 vs. 8.2%; P<0.0001) than patients receiving combination therapy. Median overall survival (OS) for monotherapy and combination therapy from the start of second-line therapy was 5.5 months (confidence interval [CI] 4.3, 7.8) and 7.4 months (CI 6.6, 8.8), respectively., Conclusions: The results showed that patients who received ramucirumab monotherapy started ramucirumab therapy later after diagnosis and were older than those who received ramucirumab in combination. Additionally, survival data suggest that outcomes observed in community oncology practices are similar to data from phase 3 clinical trials.