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BACKGROUND: The efficacy of endoscopic resection in patients with rectal neuroendocrine tumors (NETs) which are less than 20 mm in diameter remains unclear. This study aimed to investigate the efficacy and outcomes of different types of endoscopic resection in patients with NETs. METHODS: We performed a retrospective analysis and follow-up on 98 patients who underwent endoscopic resection for rectal NETs between August 2010 and October 2019 at Guangdong Provincial People’s Hospital, China. The lesions were preoperatively classified according to their endoscopic morphology and measured by endoscopic ultrasound. Patients were divided into modified endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) groups depending on the endoscopic treatment they received. The en bloc resection rate, histopathological complete resection rate, and the complication rate of the 2 groups were evaluated after the operation. The risk factors for incomplete resection were also analyzed. RESULTS: The average diameter of the 98 NETs was 6.29±2.90 mm (range, 2–15 mm). The en bloc resection rate of the modified EMR and ESD treatment groups was 97.2% (35/36) and 100% (62/62), respectively. The histopathological complete resection rate was 86.1% (31/36) and 87.1% (54/62), respectively. No tumor recurrence or tumor-related death occurred. There were no statistically significant differences in the rate of histopathological complete resection, perforation, or delayed hemorrhage between the 2 groups (P>0.05). Multivariate analysis demonstrated that the depth of tumor invasion (P=0.007) and tumor diameter (P

Background For the past two decades, dispute on whether proton pump inhibitor (PPI) leads to digestive tract cancer remains, and emerging studies in recent years still demonstrate inconsistent results, which continues to perpetuate concerns over the safety of PPI use. We performed a systematic review and meta-analysis, with comprehensive evaluation by Bradford Hill criteria of causation, to assess the effect of PPI use on digestive tract cancers. Methods Medline, Embase and Web of Science databases were searched for observational studies published up to 15th January 2021. Pooled relative risks (RRs) were estimated via random effects models. Cumulative defined daily dose- and duration-risk relationships using restricted cubic spline and fractional polynomial models were investigated. Bradford Hill criteria were applied to evaluate causation. PROSPERO Registration: CRD42020211103. Results Thirty-two publications containing 4,355,254 participants were included. PPI use is associated with an increased risk of overall digestive tract cancers (RR = 1.63, 95% confidence interval (CI) 1.33 to 2.00). PPI use is correlated with increased risks of gastric cancer (RR = 1.78, 95% CI 1.38 to 2.31), pancreatic cancer (RR = 1.72, 95% CI 1.05 to 2.82) and liver cancer (RR = 1.62, 95% CI 1.04 to 2.52), but not of esophageal cancer (RR = 2.06, 95% CI 0.65 to 6.57) and colorectal cancer (RR = 1.24, 95% CI 0.93 to 1.66). The association between PPI and digestive tract cancers is stronger in people with minimal exposure. When cumulative defined daily dose or duration increases, the risks decline and become non-significant. Evaluation by Bradford Hill criteria indicates weak evidence of causation. Conclusions A causal relationship between PPI use and digestive tract cancers is not supported by the evidence in the current review. Concerns over carcinogenic side-effects of PPI might be unfounded.

In the past decade, the study of extracellular vesicles (EVs), especially exosomes (50–150 nm) have attracted growing interest in numerous areas of cancer and tissue regeneration due to their unique biological features. A low isolation yield and insufficient targeting abilities limit their therapeutic applicability. Recently, superparamagnetic iron oxide nanoparticles (SPIONs) with magnetic navigation have been exploited to enhance the targeting ability of EVs. To construct targeted EV delivery systems engineered by SPIONs, several groups have pioneered the use of different techniques, such as electroporation, natural incubation, and cell extrusion, to directly internalize SPIONs into EVs. Furthermore, some endogenous ligands, such as transferrins, antibodies, aptamers, and streptavidin, were shown to enable modification of SPIONs, which increases binding with EVs. In this review, we summarized recent advances in targeted EV delivery systems engineered by SPIONs and focused on the key methodological approaches and the current applications of magnetic EVs. This report aims to address the existing challenges and provide comprehensive insights into targeted EV delivery systems. Statement of significance Targeted extracellular vesicle (EV) delivery systems engineered by superparamagnetic iron oxide nanoparticles (SPIONs) have attracted wide attention and research interest in recent years. Such strategies employ external magnet fields to manipulate SPION-functionalized EVs remotely, aiming to enhance their accumulation and penetration in vivo. Although iron oxide nanoparticle laden EVs are interesting, they are controversial at present, hampering the progress in their clinical application. A thorough integration of these studies is needed for an advanced insight and rational design of targeted EV delivery systems. In this review, we summarize the latest advances in the design strategies of targeted EV delivery systems engineered by SPIONs with a focus on their key methodological approaches, current applications, limitation and future perspectives, which may facilitate the development of natural theranostic nanoplatforms.

Emerging evidence suggested that mitophagy may play an important role in the progression of hepatocellular carcinoma (HCC), whereas the association between mitophagy-related genes and HCC patients’ prognosis remains unknown. In this study, we aimed to investigate the potential prognostic values of mitophagy-related genes (MRGs) on HCC patients at the genetic level. According to median immunoscore, we categorized HCC patients from TCGA cohort into two immune score groups, while 39 differential expression MRGs were identified. By using univariate analysis, we screened out 18 survival-associated MRGs, and then, the least absolute shrinkage and selection operator (LASSO) analysis was applied to construct a prognosis model that consisted of 9 MRGs (ATG7, ATG9A, BNIP3L, GABARAPL1, HTRA2, MAP1LC3B2, TFE3, TIGAR, and TOMM70). In our prognostic model, overall survival in the high and low-risk groups was significantly different P < 0.001 , and the respective areas under the curve (AUC) of our prognostic model were 0.686 for 3-year survival in the TCGA cohort and 0.776 for 3-year survival in the ICGC cohort. Moreover, we identified the risk score as the independent factor for predicting the HCC patients’ prognosis by using single and multifactor analyses, and a nomogram was also constructed for future clinical application. Further functional analyses showed that the immune status between two risk groups was significantly different. Our findings may provide a novel mitophagy-related gene signature, and these will be better used for prognostic prediction in HCC, thus improving patient outcome.

Bioactive constituents from Rhodiola rosea L. (RRL) exhibit multiple pharmacological effects on diverse diseases. However, whether they are suitable for the treatment of radiation-induced intestinal injury (RIII) remains unclear. This study aims to investigate their roles and mechanisms in the RIII rat model. The radioprotective effects of the four bioactive constituents of RRL (salidroside, herbacetin, rosavin and arbutin) were evaluated by the cell viability of irradiated IEC-6 cells. Intestinal tissues were collected for histological analysis, localized inflammation and oxidative stress assessments. Our work showed that salidroside, rosavin and arbutin improved the cell viability of the irradiated IEC-6 cells, with the highest improvement in 12.5 μM rosavin group. The rosavin treatment significantly improved survival rate and intestinal damage in irradiated rats by modulating the inflammatory response and oxidative stress. Our work indicated that rosavin may be the optimal constituent of RRL for RIII treatment, providing an attractive candidate for radioprotection.

Background: Emerging data have suggested colorectal cancer (CRC) often coexists with cardiovascular diseases, but whether cardiovascular risk factors play a role in CRC remains unclear. We performed a systematic review and meta-analysis of prospective cohort studies to better illustrate the associations between cardiovascular risk factors and CRC. Methods: We searched EMBASE, MEDLINE and Web of Science databases from inception up to June 14, 2020. Studies were included if they evaluated the association between at least one of cardiovascular risk factors and CRC incidence, contained sufficient data to obtain relative risk (RR) and 95% confidence interval (CI). We performed separate meta-analyses for each cardiovascular risk factor using random-effect model. Findings: Data from 84 prospective cohort studies, reporting 52, 348, 827 individuals and 384, 973 incident cases were included in the analysis. Overall, the risk of CRC was 1.31(95% CI, 1.21-1.42) for obesity, 1.14 (95% CI, 1.08-1.20) for per 5 kg/m 2 increase in BMI, 1.18 (95% CI, 1.14-1.23) for former smoker, 1.20 (95% CI, 1.11-1.30) for current smoker, 1.25 (95% CI, 1.16-1.35) for diabetes, 1.07 (95% CI, 1.02-1.12) for hypertension. The summary RRs of CRC for the highest versus lowest quartiles of total cholesterol, triglyceride, low-density lipoprotein were 1.12 (95% CI, 1.03-1.22), 1.18 (95% CI, 1.04-1.35), 0.85 (95% CI, 0.62-1.17) respectively and the pooled RR for the lowest versus highest quartile of high-density lipoprotein was 1.14 (95% CI, 1.02-1.28). Interpretation: Unfavorable cardiovascular risk factors are associated with increased risk of CRC. Although the potential mechanisms are still under investigation, these findings may provide novel insight into the primary and secondary prevention of CRC. Registration: PROSPERO CRD42020175537. Funding Statement: This work was supported by National Natural Science Foundation of China (Grant No. 81300279, 81741067 and 81600260), Guangdong Natural Science Foundation (Grant No. 2016A030313815, 2016A030313210, 2017A030313464 and 2018A030310655), Science and Technology Planning Project of Guangdong Province (Grant No. 2015A020212029 and 2017A020215174), Science and Technology Program of Guangzhou (Grant No. 201707010419 and 201804010050), Medical Scientific Research Foundation of Guangdong Province (Grant No. A2018343 and A2019063), Guangdong Basic and Applied Basic Research Foundation (Grant No. 2020A1515011161), High-level Hospital Construction Project (Grant No. DFJH201803, KJ012019099 and DFJH201923), the Fundamental Research Funds for the Central Universities (Grant No. D2180600), the project of Kelin new star of the First Affiliated Hospital of Sun Yat-Sen University (Grant No. Y50186), and the Fundamental Research Funds for the Central Universities in Sun Yat-Sen University (Grant No.18ykpy08). Declaration of Interests: The authors declare that they have no potential conflicts of interest.

Background Emerging data have suggested colorectal cancer (CRC) often coexists with cardiovascular diseases, but whether cardiovascular risk factors play a role in CRC remains unclear. We performed a systematic review and meta-analysis to better illustrate the associations between cardiovascular risk factors and CRC. Methods We searched EMBASE, MEDLINE and Web of Science databases from inception up to June 14, 2020. Prospective cohort studies were included if they evaluated the association between at least one of cardiovascular risk factors and CRC incidence, containing sufficient data to obtain relative risk (RR) and 95% confidence interval (CI). We performed separate meta-analyses for each cardiovascular risk factor using random-effect model. PROSPERO registration number: CRD42020175537. Findings Data from 84 studies, reporting 52, 348, 827 individuals and 384, 973 incident cases were included in the analysis. Overall, the risk of CRC was 1.31(95% CI, 1.21–1.42) for obesity, 1.14 (95% CI, 1.09–1.20) for per 5 kg/m2 increase in body mass index, 1.18 (95% CI, 1.14–1.23) for former smoker, 1.20 (95% CI, 1.11–1.30) for current smoker, 1.25 (95% CI, 1.16–1.35) for diabetes, 1.07 (95% CI, 1.02–1.12) for hypertension. The summary RRs of CRC for the highest versus lowest quartiles of total cholesterol, triglyceride, low-density lipoprotein were 1.12 (95% CI, 1.03–1.22), 1.18 (95% CI, 1.04–1.35), 0.85 (95% CI, 0.62–1.17) respectively and the pooled RR for the lowest versus highest quartile of high-density lipoprotein was 1.14 (95% CI, 1.02–1.28). Interpretation Unfavorable cardiovascular risk factors are associated with increased risk of CRC, which may provide novel insight into the screening strategies of CRC in patient with these risk factors.