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Purpose Hybrid PET/MRI has been increasingly incorporated into the practice of radiation oncologists since it contains both anatomical and biological data and may bring about personalized radiation plans for each patient. The objective of this study was to evaluate the feasibility of GTV delineation from hybrid PET/MRI compared with that from current-practice MRI during radiotherapy planning in patients with colorectal liver metastases. Patients and Methods Twenty-four patients (thirty lesions) with colorectal liver metastases were prospectively enrolled in this study. Three physicians delineated the target volume with the most popular delineating methods—the visual method. First of all, differences among the three observers were assessed. The difference and correlation of GTV values obtained by MRI, PET, and hybrid PET/MRI were subjected to statistical analysis afterwards. Finally, the dice similarity coefficient (DSC) was calculated to assess the spatial overlap. Based on the value of DSC, we also evaluate the correlation between DSC and tumor size. GTV-MRI was set as a reference. Results There was no significant difference among observers in GTV-MRI (F=0.118, p=0.889), GTV-PET (F=0.070, p=0.933) and GTV-PET/MRI (F=0.40, p=0.961). 83.33% of GTV-PET/MRI and 63.33% of GTV-PET were larger than the reference GTV-MRI. Statistical analysis revealed that GTV-PET/MRI (p

Podocyte injury is a characteristic pathological hallmark of diabetic nephropathy (DN). However, the exact mechanism of podocyte injury in DN is incompletely understood. This study was conducted using db/db mice and immortalized mouse podocytes. High-throughput sequencing was used to identify the differentially expressed long noncoding RNAs in kidney of db/db mice. The lentiviral shRNA directed against long noncoding RNA small nucleolar RNA host gene 5 (SNHG5) or microRNA-26a-5p (miR-26a-5p) agomir was used to treat db/db mice to regulate the SNHG5/miR-26a-5p pathway. Here, we found that the expression of transient receptor potential canonical type 6 (TRPC6) was significantly increased in injured podocytes under the condition of DN, which was associated with markedly decreased miR-26a-5p. We determined that miR-26a-5p overexpression ameliorated podocyte injury in DN via binding to 3'-UTR of Trpc6, as evidenced by the markedly reduced activity of luciferase reporters by miR-26a-5p mimic. Then, the upregulated SNHG5 in podocytes and kidney in DN was identified, and it was proved to sponge to miR-26a-5p directly using luciferase activity, RNA immunoprecipitation, and RNA pull-down assay. Knockdown of SNHG5 attenuated podocyte injury in vitro, accompanied by an increased expression of miR-26a-5p and decreased expression of TRPC6, demonstrating that SNHG5 promoted podocyte injury by controlling the miR-26a-5p/TRPC6 pathway. Moreover, knockdown of SNHG5 protects against podocyte injury and progression of DN in vivo. In conclusion, SNHG5 promotes podocyte injury via the miR-26a-5p/TRPC6 pathway in DN. Our findings provide novel insights into the pathophysiology of podocyte injury and a potential new therapeutic strategy for DN.

Chagan Lake is located in the high-fluorine area of western Jilin, with high fluoride content in surface water, soil, and groundwater around it. Due to its unique topography and hydrogeological conditions, Chagan Lake collects surrounding water and is closely connected with groundwater. The complex surrounding water not only affects the groundwater quality through Chagan Lake, but also affects groundwater through the infiltration of vadose zone. In order to further study the characteristics of the migration of F− in the soil around Chagan Lake along with water flow in the vadose zone and its impact on groundwater, soil column experiments were carried out using soil collected in the field, combined with HYDRUS-1D to simulate the migration characteristics of F−. The model was verified by measured data, the sensitivity of each parameter was analyzed by the single-factor disturbance method, and the effect of F− on groundwater was simulated and predicted. The results showed that (1) the soil column experiment was carried out using transport solutions of different pH value. The time required for F− to penetrate the soil column under alkaline conditions was shorter, and the HYDRUS model used has a high degree of fitting. (2) The single-factor disturbance method is used to analyze the sensitivity of the parameters. The parameters that have a greater impact on the migration of fluoride ions in the soil are saturated hydraulic conductivity, adsorption coefficient, and soil bulk density. (3) In the prediction scenario, due to the adsorption and interception of the vadose zone, as the depth increases, the time it takes for F− to accumulate is also longer. The groundwater around Chagan Lake is relatively shallow, and surface F− in alkaline environment reaches the underground aquifer within 2 days. The F− concentration in the groundwater reaches its maximum before the end of the irrigation period. In neutral environment, the F− concentration in groundwater did not reach the maximum before the end of the irrigation period.

Mesenchymal stem cells-derived exosomes (MSC-exos) have attracted great interest as a cell-free therapy for acute kidney injury (AKI). However, the in vivo biodistribution of MSC-exos in ischemic AKI has not been established. The potential of MSC-exos in promoting tubular repair and the underlying mechanisms remain largely unknown. Methods: Transmission electron microscopy, nanoparticle tracking analysis, and western blotting were used to characterize the properties of human umbilical cord mesenchymal stem cells (hucMSCs) derived exosomes. The biodistribution of MSC-exos in murine ischemia/reperfusion (I/R) induced AKI was imaged by the IVIS spectrum imaging system. The therapeutic efficacy of MSC-exos was investigated in renal I/R injury. The cell cycle arrest, proliferation and apoptosis of tubular epithelial cells (TECs) were evaluated in vivo and in HK-2 cells. The exosomal miRNAs of MSC-exos were profiled by high-throughput miRNA sequencing. One of the most enriched miRNA in MSC-exos was knockdown by transfecting miRNA inhibitor to hucMSCs. Then we investigated whether this candidate miRNA was involved in MSC-exos-mediated tubular repair. Results: Ex vivo imaging showed that MSC-exos was efficiently homing to the ischemic kidney and predominantly accumulated in proximal tubules by virtue of the VLA-4 and LFA-1 on MSC-exos surface. MSC-exos alleviated murine ischemic AKI and decreased the renal tubules injury in a dose-dependent manner. Furthermore, MSC-exos significantly attenuated the cell cycle arrest and apoptosis of TECs both in vivo and in vitro. Mechanistically, miR-125b-5p, which was highly enriched in MSC-exos, repressed the protein expression of p53 in TECs, leading to not only the up-regulation of CDK1 and Cyclin B1 to rescue G2/M arrest, but also the modulation of Bcl-2 and Bax to inhibit TEC apoptosis. Finally, inhibiting miR-125b-5p could mitigate the protective effects of MSC-exos in I/R mice. Conclusion: MSC-exos exhibit preferential tropism to injured kidney and localize to proximal tubules in ischemic AKI. We demonstrate that MSC-exos ameliorate ischemic AKI and promote tubular repair by targeting the cell cycle arrest and apoptosis of TECs through miR-125b-5p/p53 pathway. This study provides a novel insight into the role of MSC-exos in renal tubule repair and highlights the potential of MSC-exos as a promising therapeutic strategy for AKI.

Background: Chemotherapy combined with radiotherapy is the main treatment strategy for unresectable rectal cancer. However, the prognostic factors of patients with unresectable rectal cancer treated with radiotherapy and chemotherapy have not been systematically studied. Therefore, this study investigated the prognostic factors and prognosis based on surveillance, epidemiology and final results of the SEER medical insurance database. Methods: Primary rectum patients were selected from the SEER database. The independent prognostic factors associated with overall survival (OS), cancer-specific survival (CSS) and noncancer-related death were evaluated using the Kaplan-Meier method and log-rank test, a competing risk model, and the Cox proportional hazards regression model. Two nomograms were established for predicting the 1- and 3-year OS and CSS of patients. Results: A total of 3,998 rectal adenocarcinoma cancer patients who received chemoradiotherapy but had not undergone surgery were included in this study and divided into training (n = 3559) and validation cohorts (n = 439). Patients in the training cohort had a 1-year OS rate of 65.7±0.8%, a 3-year OS rate of 26.6±0.8%, a 5-year OS rate of 1.6±0.8%, and a median survival rate of 20.0 months (range, 19.22-20.8 months). The following factors were significant prognostic factors of OS: age (p< 0.001); tumour grade (p< 0.001); T stage (p< 0.001); M stage (p< 0.001); bone metastasis (p

Introduction: Diabetic nephropathy (DN) remains a major cause of end-stage renal disease. The development of novel biomarkers and early diagnosis of DN are of great clinical importance. The goal of this study was to identify hub genes with diagnostic potential for DN by weighted gene co-expression network analysis (WGCNA). Methods: Gene Expression Omnibus database was searched for microarray data including distinct types of CKD. Gene co-expression network was constructed, and modules specific for DN were identified by WGCNA. Gene ontology (GO) analysis was performed, and the hub genes were screened out within the selected gene modules. In addition, cross-validation was performed in an independent dataset and in samples of renal biopsies with DN and other types of glomerular diseases. Results: Dataset GSE99339 was selected, and a total of 179 microdissected glomeruli samples were analyzed, including DN, normal control, and 7 groups of other glomerular diseases. Twenty-three modules of the total 10,947 genes were grouped by WGCNA, and a module was specifically correlated with DN (r = 0.54, p = 9e−15). GO analysis showed that module genes were mainly enriched in the accumulation of extracellular matrix (ECM). LUM, ELN, FBLN1, MMP2, FBLN5, and FMOD were identified as hub genes. Cross verification showed LUM and FMOD were higher in the DN group and were negatively correlated with estimated glomerular filtration rate (eGFR). In renal biopsies, expression levels of LUM and FMOD were higher in DN than IgA nephropathy, membranous nephropathy, and normal controls. Conclusion: By using WGCNA approach, we identified LUM and FMOD related to ECM accumulation and were specific for DN. These 2 genes may represent potential candidate diagnostic biomarkers of DN.

Purpose: We aimed to probe the clinical value of 18F-PSMA-1007 and 68Ga-PSMA-11 PET/MRI in the GTV delineation of radiotherapy for prostate cancer (PCa). Methods: 69 patients were retrospectively enrolled (57 in 18F subgroup and 12 in 68Ga subgroup). First, three physicians delineated the GTVs by visual method and threshold method with thresholds of 30%, 40%, 50%, and 60% SUVmax. The volume correlation and differences in GTVs were assessed. Second, the DSC was applied to estimate the spatial overlap between GTVs. Then we also evaluated the association between DSCs and clinical parameters (including age, the reference GTV-MRI, PSA, Gleason score, risk classification, and SUVmax). Last, the interobserver variability was evaluated. GTV-MRI was set as a reference. Results: In 18F subgroup: (1) GTV-PET/MRI and GTV-PET60% had significant correlation and difference with the reference GTV-MRI (p0.7. (3) The GTV-MRI (R2=0.462, p68Ga subgroup: (1) GTV-PET/MRI, GTV-PET30% had significant correlation and difference with the reference GTV-MRI (p0.7. (3) There was a significant correlation between GTV-MRI (r=0.580, pConclusion: It is feasible to visually delineate GTV on PSMA PET/MRI in PCa radiotherapy, we emphasize the GTV delineation on the PET/MRI fusion image. In addition, the overlap degree was the highest between GTV-MRI and GTV-PET/MRI, and it increased with increasing volume.

Background/purpose: Dental implantation has become an efficient and important method of replacing lost teeth. However, the success rate of dental-implant treatment in diabetics is higher than patients without diabetes. The aim of this study was to prospectively evaluate long-term marginal bone loss (MBL) and the stability of a self-assembling nano-modified implant in patients with type 2 diabetes mellitus compared with a conventional implant. Materials and methods: Twenty-five patients with type 2 diabetes were recruited for this study. Through a random selection process, one site in each patient received a conventional implant and the other site received a nano-modified implant. The implant stability quotient was measured using resonance frequency analysis (RFA), and MBL was measured using panoramic radiography from uncovering to four-year follow-up. Results: No significant difference in implant stability quotient was found between the two groups (P > 0.05), except for the time at implant insertion (P 0.05). Conclusion: There was potentially increased implant stability and diminished MBL around the self-assembling nano-modified implant in the uncovering-loading stage of early osseointegration in patients with type 2 diabetes.

Background Major depressive disorder (MDD) is a serious and common mood disorder with unknown etiology. Emerging evidence has demonstrated the critical roles of SIRT1 and microRNAs (miRNAs) in the progression of MDD. However, the underlying molecular mechanisms remain to be fully understood. Methods In the present study, the expression level of miR-138 and SIRT1 were analyzed by RT-PCR or Western blotting in a chronic unpredictable mild stress (CUMS) model. The depressive-like behaviors were analyzed by forced swimming test (FST) and sucrose preference test (SPT) in mice injected with miR-138 and SIRT1 overexpression lentivirus. The luciferase reporter assay was used to assess the direct regulation of miR-138 on SIRT1 expression. Results The upregulation of miR-138 was found in the hippocampus of the CUMS mice and correlated with decreased SIRT1 expression. C57BL/6J mice treated with SIRT1- and miR-138-expressing (miR-138) lentivirus showed increased depressive-like behaviors. In contrast, SIRT1 or si-miR-138 lentivirus treated C57BL/6J mice showed decreased depressive-like behaviors. Moreover, the Sirt1/PGC-1α/FNDC5/BDNF pathway was downregulated following miR-138 overexpression and increased upon miR-138 knockdown in hippocampus in CUMS mice and cultured primary neuronal cells. Mechanistically, luciferase reporter assay demonstrated that SIRT1 gene was a downstream transcriptional target of miR-138. Conclusion Our data demonstrated the regulation role of miR-138 on SIRT1 gene expression, miR-138 increased depressive-like behaviors by regulating SIRT1 expression in hippocampus.

Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) are orally active first-in-class new generation drugs for renal anemia. This extensive meta-analysis of randomized controlled trials (RCTs) was designed to provide clear information on the efficacy and safety of HIF-PHIs on anemia in chronic kidney disease (CKD) patients. Searches included PubMed, Web of Science, Ovid MEDLINE, and Cochrane Library database up to October 2019. RCTs of patients with CKD comparing HIF-PHIs with erythropoiesis-stimulating agents (ESAs) or placebo in the treatment of anemia. The primary outcome was hemoglobin change from baseline (Hb CFB); the secondary outcomes included iron-related parameters and the occurrence of each adverse event. 26 trials in 17 articles were included, with a total of 2804 dialysis or patients with CKD. HIF-PHIs treatment produced a significant beneficial effect on Hb CFB compared with the placebo group (MD, 0.69; 95% CI, 0.36 to 1.02). However, this favored effect of HIF-PHIs treatment was not observed in subgroup analysis among trials compared with ESAs (MD, 0.06; 95% CI, −0.20 to 0.31). The significant reduction in hepcidin by HIF-PHIs was observed in all subgroups when compared with the placebo group, whereas this effect was observed only in NDD-CKD patients when compared with ESAs. HIF-PHIs increased the risk of nausea (RR, 2.20; 95% CI, 1.06 to 4.53) and diarrhea (RR, 1.75; 95% CI, 1.06 to 2.92). We conclude that orally given HIF-PHIs are at least as efficacious as ESAs treatment to correct anemia short term in patients with CKD. In addition, HIF-PHIs improved iron metabolism and utilization in patients with CKD.

Visual Abstract, Highlights • miR-155 was synthesized and loaded into exosomes in increased infiltration of macrophages in a uremic heart. • The released exosomal fusion with the plasma membrane leads to the release of miR-155 into the cytosol and translational repression of forkhead transcription factors of the O class in cardiomyocytes. • Macrophage-derived miR-155–containing exosomes promoted cardiomyocyte pyroptosis and uremic cardiomyopathy changes (cardiac hypertrophy and fibrosis) by directly targeting FoxO3a in uremic mice. Inhibiting secretion from macrophage-derived miR-155–containing exosomes represents a novel therapeutic strategy for the management of uremic cardiomyopathy., Summary miR-155 was synthesized and loaded into exosomes in increased infiltration of macrophages in a uremic heart. The released exosomal fusion with the plasma membrane leads to the release of miR-155 into the cytosol and translational repression of forkhead transcription factors of the O class (FoxO3a) in cardiomyocytes. Finally, macrophage-derived miR-155–containing exosomes promoted cardiomyocyte pyroptosis and uremic cardiomyopathy changes (cardiac hypertrophy and fibrosis) by directly targeting FoxO3a in uremic mice.

Supplemental material, sj-docx-1-tag-10.1177_17562848221137758 for Adjuvant chemotherapy improves survival in high-risk stage II colon cancer: a retrospective cohort study by Lin-Lin Liu and Zuo-Lin Xiang in Therapeutic Advances in Gastroenterology

Additional file 3: Supplemental Table 3. Clinical and pathological characteristics, treatment modalities, and outcomes.

Additional file 2: Supplemental Table 2. Univariate and multivariate analysis for the presence of lung metastasis in CRC patients.

Additional file 1: Supplemental Table 1. Clinical and demographic characteristics of the external cohort.

Acute kidney injury (AKI) is a common adverse reaction of the anticancer drug. Among these chemotherapeutic agents, cisplatin, an effective chemotherapeutic drug, is extensively applied to the treatment of solid tumours, yet various adverse reactions, especially AKI, often limit their use. However, the pathogenesis of AKI caused by cisplatin remains poorly clarified. Therefore, we tested whether microRNAs, which have been certified as key regulators of disease are involved in this process. AKI mouse and HK2 cells were treated with cisplatin. Annexin V/PI staining and cleaved caspase-3 were used to assess apoptosis. Western blot analyses and qRT-PCR were used to evaluate the protein and mRNA level of TRPC6 and DRP1. miR-26a was remarkably decreased in cisplatin-induced AKI and in cisplatin co-cultured HK2 cells. Furthermore, we used a miR-26a mimics in vitro and found that apoptosis was alleviated than that in the control cells. We further verified that miR-26a protected against cisplatin-induced cell apoptosis by acting on transient receptor potential channel 6 (TRPC6) which can regulate the expression of dynamin-related protein 1 (DRP1), thus inhibited the mitochondrial apoptosis pathway. Therefore, the study unveiled that miR-26a/TRPC6/DRP1 is a novel protective pathway in cisplatin-induced AKI and may be targeted for the prevention and treatment of drug-related renal injury. SIGNIFICANCE OF THE STUDY: Our study found that miR-26a was significantly downregulated during cisplatin-induced AKI and during cisplatin co-cultured HK2 cells. Further, in vitro we used miR-26a mimic to intervene cells and found that apoptosis alleviated compared with control group. We further verified that miR-26a protected cisplatin-induced apoptosis by target transient receptor potential channel 6 (TRPC6) which can regulate the expression of dynamic-related protein 1 (DRP1) and inhibit the mitochondrial apoptosis pathway. Thus, miR-26a/TRPC6/DRP1 is a new protective pathway in cisplatin-induced AKI and may be targeted for the prevention and treatment of drug-related acute kidney injury.

Recent music tourism researches are notable owing to growing socioeconomic significance of music. But the question about how music affects tourists’ behaviors in travel practice remains there. This...