Despite the adequacy of nodal evaluation was gradually improved for colon cancer (CC), rare attention has been paid for the effect of patient and tumor heterogeneity on nodal evaluation. We identified 109902 CC patients in stage I-III from Surveillance, Epidemiology, and End-Results (SEER) database during 2004-2013. The lymph nodes evaluations were separately assessed in different patient- and tumor-related features, including gender, age, T stage, histology, tumor differentiation, tumor size and tumor location. The 5-year cancer specific survival (CSS) was calculated with Kaplan-Meier method, log-rank tests were used to compare the differences of CSS in patients with ≥12 and <12 lymph nodes examined. Here, we identified features including gender, age, T stage, tumor differentiation, tumor size and location were independently associated with the median number of lymph node, the rate of ≥12 lymph nodes and the rate of node positivity of CC patients. We then divided CC patients into 29 subgroups according to different patient- and tumor-related features. The median number of lymph node presented a large variance from 12 to 24, the rate of ≥12 lymph nodes increased from 53.2% to 91.2% under the combined effect of patient and tumor heterogeneity. Furthermore, the positive association between increased lymph nodes count and improved survival couldn't be observed in 8261 CC patients with the effect of this heterogeneity. In conclusion, the tumor and patient heterogeneity lead to large alterations of nodal evaluation; we should pay more attention to this effect in clinical practice.

The precise role and potential underlying mechanisms of anoctamin 9 (ANO9) remain largely unknown. This study aims to characterize the role and oncogenic mechanisms of ANO9 in stage II and III colorectal cancer (CRC).

Transcription factor 3 (TCF3) implicates Wnt signaling pathway and regulates E-cadherin expression, which is involved in aggressiveness of tumors. This study aims to investigate the role of TCF3 in predicting prognosis of patients with stage II and III colorectal cancer (CRC).

The positive regulatory domain containing 16 (PRDM16) is commonly regarded as a "switch" controlling the transdifferentiation of myoblasts to brown adipocytes. The N-positive regulatory (PR) domain, which is highly homologous to SET domain, is a characteristic structure for the PRDM family. Many SET domain containing proteins and several PRDM members have been found to possess histone methyltransferase activity, yet the role of PRDM16 and its PR domain in the epigenetic regulation of myogenic and adipogenic genes during myoblasts/adipocytes transdifferentiation remains unexplored. In this study, we transfected C2C12 myoblasts to stably express PRDM16 and observed the repression of myogenic genes and activation of adipogenic genes at both proliferation and differentiation stages. Ectopic PRDM16-induced reprogramming of myogenic and adipogenic genes was associated with the hypermethylation on some CpG sites in the enhancer or promoter of MyoD and myogenin, but the methylation status of PPARγ promoter was not affected. C2C12 cells expressing truncated PRDM16 lacking PR domain (ΔPR-PRDM16) demonstrated attenuation of both adipogenic and myogenic potentials, indicated by PPARγ inactivation and decreased triglyceride deposition, as well as a downregulation of MyoD, MyHC and MCK genes, as compared with C2C12 cells expressing intact PRDM16. Furthermore, C2C12 cells expressing ΔPR-PRDM16 exhibited significant differences in histone modifications on the promoters of MyoD and PPARγ genes. Taken together, PRDM16-induced C2C12 transdifferentiation is associated with alterations in CpG methylation of myogenic factors, and PR domain affects both myogenesis and adipogenesis with modified histone methylation marks on MyoD and PPARγ promoters.

GADD45B acts as a member of the growth arrest DNA damage-inducible gene family, which has demonstrated to play critical roles in DNA damage repair, cell growth, and apoptosis. This study aimed to explore the potential relationship between GADD45B expression and tumor progression and evaluate the clinical value of GADD45B in stage II colorectal cancer (CRC). The expression patterns and prognostic value of GADD45B in CRC were analyzed based on The Cancer Genomic Atlas (TCGA). GADD45B expression features of 306 patients with stage II CRC and 201 patients with liver metastasis of CRC were investigated using immunochemical staining on tissue microarrays. Afterward, survival analysis and stratification analysis were performed in stage II to explore the prognostic and predictive significance of GADD45B. Overexpressed GADD45B is associated with poorer prognosis for CRC patients both in overall survival (OS) (p < 0.001) and disease-free survival (DFS) (p = 0.001) based on the TCGA database. Analysis results according to the stage II CRC cohort and the liver metastatic CRC cohort revealed that GADD45B was gradually upregulated in normal mucosa including primary colorectal cancer (PCC). Colorectal liver metastases (CLM) tissues were arranged in order (normal tissue vs. PCC p = 0.005 and PCC vs. CLM p = 0.001). The low GADD45B group had a significantly longer five-year OS (p = 0.001) and progression-free survival (PFS) (p < 0.001) than the high GADD45B group for the stage II patients. The multivariate Cox regression analysis results proved that the expression level of GADD45B was an independent prognostic factor for stage II after radical surgery (OS: Hazard Ratio (HR) 0.479, [95% confidence interval (CI) 0.305⁻0.753] and PFS:HR 0.490, [95% CI 0.336⁻0.714]). In high GADD45B expression subgroup of stage II cohort, the patients who underwent adjuvant chemotherapy had longer PFS than those who did not (p = 0.008). High expression levels of GADD45B is an independent prognostic factor of decreased OS and PFS in stage II CRC patients. The stage II CRC patients with high GADD45B expression might benefit from adjuvant chemotherapy.

Direction-selective responses to motion can be to the onset (On) or cessation (Off) of illumination. Here, we show that the transmembrane protein semaphorin 6A and its receptor plexin A2 are critical for achieving radially symmetric arborization of On starburst amacrine cell (SAC) dendrites and normal SAC stratification in the mouse retina. Plexin A2 is expressed in both On and Off SACs; however, semaphorin 6A is expressed in On SACs. Specific On-Off bistratified direction-selective ganglion cells in semaphorin 6A(-/-) mutants exhibit decreased tuning of On directional motion responses. These results correlate the elaboration of symmetric SAC dendritic morphology and asymmetric responses to motion, shedding light on the development of visual pathways that use the same cell types for divergent outputs.

Increasing evidence suggest that low-dose alcohol consumption (LAC) reduces the incidence and improves the functional outcome of ischemic stroke. We determined the influence of LAC on post-ischemic inflammation. Male Sprague-Dawley rats were divided into 3 groups, an ethanol (13.5% alcohol) group, a red wine (Castle Rock Pinot Noir, 13.5% alcohol) group, and a control group. The amount of alcohol given to red wine and ethanol groups was 1.4 g/kg/day. After 8 weeks, the animals were subjected to a 2-hour middle cerebral artery occlusion (MCAO) and sacrificed at 24 hours of reperfusion. Cerebral ischemia/reperfusion (I/R) injury, expression of adhesion molecules and pro- and anti-inflammatory cytokines/chemokines, microglial activation and neutrophil infiltration were evaluated. The total infarct volume and neurological deficits were significantly reduced in red wine- and ethanol-fed rats compared to control rats. Both red wine and ethanol suppressed post-ischemic expression of adhesion molecules and microglial activation. In addition, both red wine and ethanol upregulated expression of tissue inhibitor of metalloproteinases 1 (TIMP-1), downregulated expression of proinflammatory cytokines/chemokines, and significantly alleviated post-ischemic expression of inflammatory mediators. Furthermore, red wine significantly reduced post-ischemic neutrophil infiltration. Our findings suggest that LAC may protect the brain against its I/R injury by suppressing post-ischemic inflammation.

The embryological stages of palatal shelf elongation and elevation, mainly induced by the proliferation and extracellular matrix secretion of embryonic palatal mesenchymal (MEPM) cells, are essential for normal palatal development. Wingless-related MMTV integration site gene family (Wnt) signaling pathways serve key roles in craniofacial development and palate formation. Recent studies have indicated that Wnt6 participates in embryonic development of the palate, though its exact role in palate development remains unclear. In the present study, to investigate the role of Wnt6 during the stages of palatal shelves elongation and elevation, mouse MEPM cells were cultured from dissected palatal shelves at embryonic day 13.5. Results of an MTT assay and flow cytometric analysis demonstrated that treatment with recombinant Wnt6 increased the viability of MEPM cells (P<0.01) and the proportion of cells in the S and G2/M phases (P<0.01). Meanwhile, Wnt6 activated the β-catenin signaling pathway as indicated by the dual luciferase assay result, and blockade of the WNT/β-catenin pathway reduced the cytoactivity of Wnt6 in MEPM cells (P<0.01). Collectively, these findings indicate that Wnt6 promotes the vitality of MEPM cells by increasing the S + G2/M-phase cell population, potentially through activation of the β-catenin pathway during palatal shelf elongation and elevation.

Golgi Membrane Protein 1 (GOLM1), a protein involved in the trafficking of proteins through the Golgi apparatus, has been shown to be oncogenic in a variety of human cancers. Here, we examined the role of GOLM1 in the development of human glioma.

In situ tuning of the electronic structure of active sites is a long-standing challenge. Herein, we propose a strategy by controlling the hydrogen spillover distance to in situ tune the electronic structure. The strategy is demonstrated to be feasible with the assistance of CoOx/Al2O3/Pt catalysts prepared by atomic layer deposition in which CoOx and Pt nanoparticles are separated by hollow Al2O3 nanotubes. The strength of hydrogen spillover from Pt to CoOx can be precisely tailored by varying the Al2O3 thickness. Using CoOx/Al2O3 catalyzed styrene epoxidation as an example, the CoOx/Al2O3/Pt with 7 nm Al2O3 layer exhibits greatly enhanced selectivity (from 74.3% to 94.8%) when H2 is added. The enhanced selectivity is attributed to the introduction of controllable hydrogen spillover, resulting in the reduction of CoOx during the reaction. Our method is also effective for the epoxidation of styrene derivatives. We anticipate this method is a general strategy for other reactions.

Background: The causal relationship between serum lipid levels and the risk of Parkinson's disease (PD) remains largely uncertain. We summarized the existing controversial evidence on this topic. Methods: We searched the electronic databases for observational studies from January 1988 to March 2020. We applied random-effects models to calculate pooled relative risk (RR) with their 95% confidence intervals (CI). Random-effects dose-response meta-analyses were further conducted to explore the dose-risk relationship. Results: Twelve cohort studies and three case-control studies were included in this meta-analysis. Higher levels of serum low-density lipoprotein cholesterol (LDL-C) were inversely associated with the subsequent risk of PD (RR 0.73, 95% CI 0.57-0.93), whereas, there were no associations between serum levels of total cholesterol (TC) (RR 0.91, 95% CI 0.73-1.13), high-density lipoprotein cholesterol (HDL-C) (RR 0.97, 95% CI 0.73-1.27), or triglycerides (TG) (RR 0.85, 95% CI 0.55-1.29) and the risk of PD. Further dose-response meta-analysis revealed that every 38.6 mg/dL (1mmol/L) increase in serum LDL-C correlates with a 7% decreased risk of PD. Conclusions: Our paper supports the protective effect of higher serum LDL-C on the subsequent risk of PD. More prospective cohort studies are warranted to confirm the conclusion, and further fundamental researches are needed to elucidate the underlying biological mechanisms.

Background: The prognosis of synchronous bone metastasis (BM) in colorectal cancer (CRC) is poor and rarely concerned. A clinical tool to evaluate the prognosis and clinical outcomes for BM would be attractive in current clinical practice. Methods: A total of 342 CRC patients with synchronous BM were identified from Surveillance, Epidemiology, and End Results (SEER) database. The cancer specific survival (CSS) was estimated with the Kaplan-Meier method. Prognostic factors were identified from multivariate Cox model, and the final clinical nomogram was developed to predict the CSS. The concordance index (C-index) was used to assess the discriminative ability. Calibration curves were provided to internally validate the performance of the nomogram. Results: The nomogram finally consisted of 6 prognostic factors including age, tumor grade, AJCC N stage, carcinoembryonic antigen (CEA) levels, primary tumor resection and chemotherapy, which translated the effects of prognostic factors into certain scores to predict the 1-, 2- and 3-year CSS for the synchronous BM in CRC patients. The nomogram presented a good accuracy for predicting the CSS with the C-index of 0.742. The calibration of the nomogram predictions was also accurate. Conclusions: This nomogram was accurate enough to predict the CSS of CRC patients with synchronous BM using readily available clinicopathologic factors and could provide individualized clinical decisions for both physicians and patients.

Objective: Many studies have shown that long non-coding RNAs (lncRNAs) are closely related to various cancers. This study aims to explore the roles of lncRNA HOXA11-AS in the development and progression of osteosarcoma (OS). Methods: The expression levels of HOXA11-AS and miR-125a-5p in tumor tissues and the adjacent tissues were detected by RT-PCR method. The proliferation, migration and invasion of MG-63 and KHOS cells were determined. Results: It was found that HOXA11-AS expression levels in OS tissues and OS cell lines were higher than those in OS adjacent tissues and normal human osteoblast cell lines. The higher expression level of HOXA11-AS was positively correlated with more severe clinical stage, distant metastasis and poor prognosis of OS. Inhibition of HOXA11-AS expression could reduce metastasis and invasion of OS cell lines. In addition, HOXA11-AS was found to be an endogenous inhibitor of miR-125a-5p, it down regulated the expression level of miR-125a-5p, and this process could promote the expression of Rab3D, the target gene of miR-125a-5p. Conclusion: Our study elucidated the role of a new HOXA11-AS/miR-125a-5p/Rab3D regulatory pathway in promoting OS metastasis.

Pursuing and developing effective methodologies to construct highly active catalytic sites to maximize the atomic and energy efficiency by material engineering are attractive. Relative to the tremendous researches of carbon-based single atom systems, the construction of bio-applicable single atom materials is still in its infancy. Herein, we propose a facile and general interfacial-confined coordination strategy to construct high-quality single-atom nanotherapeutic agent with Fe single atoms being anchored on defective carbon dots confined in a biocompatible mesoporous silica nanoreactor. Furthermore, the efficient energy conversion capability of silica-based Fe single atoms system has been demonstrated on the basis of the exogenous physical photo irradiation and endogenous biochemical reactive oxygen species stimulus in the confined mesoporous network. More importantly, the highest photothermal conversion efficiency with the mechanism of increased electron density and narrow bandgap of this single atom structure in defective carbon was proposed by the theoretical DFT calculations. The present methodology provides a scientific paradigm to design and develop versatile single atom nanotherapeutics with adjustable metal components and tune the corresponding reactions for safe and efficient tumor therapeutic strategy.

Background This study aimed to investigate the association between radiotherapy for cancer and cardiovascular disease (CVD) deaths and evaluate the relative risk for CVD deaths in the general population and among patients with cancer treated with radiotherapy. Methods and Results The statistics of cancers from 16 sites were extracted from the Surveillance, Epidemiology, and End Results database and evaluated. Multivariable Cox proportional hazards regression analysis was used to analyze the association between radiotherapy and cardiovascular-specific survival. The standardized mortality ratio for CVD deaths was estimated by comparing the observed deaths of patients with cancer treated with radiotherapy to the expected deaths of the general population. Of the 2 214 944 patients identified from the database, 292 102 (13.19%) died from CVD. Multivariable Cox proportional hazards regression analyses demonstrated that radiotherapy was an independent risk factor for cardiovascular-specific survival among patients with lung and bronchus, cervix uteri, corpus uteri, and urinary bladder cancers. The long-term cardiovascular-specific survival of patients with cancer who underwent radiotherapy was significantly lower than that of patients who did not undergo radiotherapy. The incidence of CVD deaths among patients with lung and bronchus, cervix uteri, corpus uteri, and urinary bladder cancers who underwent radiotherapy was higher than that among the general population. Standardized mortality ratio significantly decreased with increasing age at cancer diagnosis, gradually decreased within 10 years of diagnosis and increased after 10 years of diagnosis. Conclusions Radiotherapy is associated with worse cardiovascular-specific survival in patients with lung and bronchus, cervix uteri, corpus uteri, and urinary bladder cancers. Long-term surveillance of cardiovascular conditions should be performed after radiotherapy.

As an important transcription factor, zinc-finger and BTB domain-containing 7B (ZBTB7C) plays an important role in a variety of tumors. However, its relationship with human immunity is unclear. This article aims to study its differential expression and survival across cancers and explore the relationships between its differential expression and the tumor microenvironment and immune cell infiltration. In this study, we used R software to process The Cancer Genome Atlas (TCGA) data and explored the expression pattern and prognostic value of ZBTB7C across cancers. Next, we comprehensively explained the important role of ZBTB7C in several tumor types in terms of tumor mutational burden (TMB), microsatellite instability (MSI) and immune cell infiltration. In general, the expression level of ZBTB7C in tumor tissues was lower than that in normal tissues. Highly expressed ZBTB7C was beneficial to the survival of patients with colon adenocarcinoma (COAD), lymphoid neoplasm diffuses large B cell lymphoma (DLBC), esophageal carcinoma (ESCA) and mesothelioma (MESO). Multivariate analysis showed that the expression of ZBTB7C was an independent prognostic factor in COAD and MESO. In COAD, the expression of ZBTB7C was positively correlated with both TMB and MSI. In colorectal cancer (CRC), there was a significant positive correlation between ZBTB7C expression and immune cell infiltration, especially the infiltration of mast cells and B cells. In conclusion, ZBTB7C can be used as a potential therapeutic target across cancers and is related to immune cell infiltration.

Natural orifice specimen extraction surgery (NOSES) is an intra-abdominal procedure that does not require an auxiliary incision to take a surgical sample from the abdominal wall through the natural orifice, but there are few systematic clinical studies on it. The aim of this study was to demonstrate the safety and feasibility of NOSES. We retrospectively analyzed the clinical data and follow-up of 165 patients with low rectal cancer who underwent NOSES or conventional laparoscopic surgery at our center from January 2013 to June 2015. From the perioperative data and postoperative follow-up results of both groups, patients in the NOSES group had less intraoperative bleeding (49.3 ± 55.8 ml vs. 75.1 ± 57.3 ml, p = 0.02), shorter postoperative gastrointestinal recovery (42.3 ± 15.5 h vs. 50.1 ± 17.0 h, p = 0.01), less postoperative analgesic use (35.6% vs. 57.6%, p = 0.02), lower postoperative pain scores, lower rate of postoperative complications (6.8% vs. 25.4%, p = 0.01), better satisfaction of the image and cosmesis of the abdominal wall postoperatively, and higher quality of life. Moreover, there was no significant difference in overall survival (OS) and disease-free survival (DFS) between two groups. Overall, NOSES is a safe and reliable minimally invasive surgical technique for patients with low rectal cancer.

To evaluate whether the control status of type 2 diabetes mellitus (DM) influences the progression of Parkinson's disease (PD).

Background: Parkinson's disease (PD) and sarcopenia are two common diseases in aging people. To date, the prevalence of sarcopenia in PD patients and the relationship between clinical features and sarcopenia in PD patients are not clear. The aim of the study was to (1) assess the prevalence of sarcopenia in PD patients and (2) reveal the clinical features between PD patients with and without sarcopenia. Method: A systematic review was carried out through screening PubMed, EMBASE, and Cochrane database in May 2020. All study designs (case-control, cohort, and cross-sectional studies) were eligible for meta-analysis. Data of patients' characteristics, sarcopenia criteria, sarcopenia prevalence, and sarcopenia measures were retrieved. The primary outcome was estimated prevalence of sarcopenia by a pooled prevalence (%) and its 95% confidence interval (CI), using a random-effects model. The secondary outcome was the differences in clinical features between PD patients with and without sarcopenia by meta-analysis. Included articles were assessed for risk of bias. Potential sources of variation were investigated by using subgroup analyses and meta-regression. Result: Ten studies were included in the review. Among them, nine were cross-sectional studies, and one was a prospective cohort study. Age of participants with PD in the studies ranged from 51.1 to 80.7 years. The estimated prevalence of sarcopenia ranged from 6 to 55.5%. The random-effects pooled prevalence was 29% (95% CIs: 0.18-0.40). When only studies at low risk of bias were considered, pooled prevalence decreased to 17% (95% CIs: 0.02-0.33), with still high heterogeneity. The incidence of falls in PD patients with sarcopenia was higher than that in PD patients without sarcopenia. There was no difference in sex ratio between PD patients with and without sarcopenia. Conclusion: Sarcopenia seems to be common in patients with PD. Early assessment of sarcopenia should be implemented in PD to avoid fall and disability.

Brain metastasis (BM) from colorectal cancer (CRC) is rarely encountered clinically, and its prognosis has not been fully evaluated.