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Abstract The incidence of Early-Onset Colorectal Cancer (EOCRC) is increasing. However, the prognosis of EOCRC compared to Late-Onset Colorectal Cancer (LOCRC), and the ideal age for initial colorectal cancer (CRC) screening are not clear. In this study, we identified the pathological differences between the groups and determined the optimal screening age for CRC patients. We included 10,172 patients diagnosed with CRC from January 2011 to December 2021 in this study. Survival differences were compared by plotting Kaplan–Meier survival curves and conducting landmark analysis. Additionally, the diagnostic age of CRC patients was analyzed using age cumulative curves. Compared to LOCRC patients, EOCRC patients had a higher proportion of deficient mismatch repair (dMMR) and more advanced TNM staging (P

Abstract Investigating proton transport at the interface in an excited state facilitates the mechanistic investigation and utilization of nanomaterials. However, there is a lack of suitable tools for in-situ and interfacial analysis. Here we addresses this gap by in-situ observing the proton transport of graphene quantum dots (GQDs) in an excited state through reduction of magnetic resonance relaxation time. Experimental results, utilizing 0.1 mT ultra-low-field nuclear magnetic resonance relaxometry compatible with a light source, reveal the light-induced proton dissociation and acidity of GQDs’ microenvironment in the excited state (Hammett acidity function: –13.40). Theoretical calculations demonstrate significant acidity enhancement in –OH functionalized GQDs with light induction ( $${{\mathrm{p}}}{K}_{{\text{a}}}^{*}$$ p K a * = –4.62, stronger than that of H2SO4). Simulations highlight the contributions of edge and phenolic –OH groups to proton dissociation. The light-induced superacidic microenvironment of GQDs benefits functionalization and improves the catalytic performances of GQDs. Importantly, this work advances the understanding of interfacial properties of light-induced sp 2–sp 3 carbon nanostructure and provides a valuable tool for exploring catalyst interfaces in photocatalysis.

BackgroundPrevious epidemiological studies have yielded inconclusive results regarding the causality between blood metabolites and the risk of gastric cancer (GC). To address this shortcoming, we conducted a two-sample Mendelian randomization (MR) study, combined with metabolomics techniques, to elucidate the causality between 486 genetically predicted blood metabolites and GC.MethodsMR analysis and metabolomics techniques such as ultra-high performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) and gas chromatography/tandem mass spectrometry (GC-MS/MS) technologies were employed to assess the causality of 486 genetically predicted blood metabolites on the risk of GC. The genome-wide association study (GWAS) summary data for 486 blood metabolites from 7,824 individuals. The GWAS summary data for GC (ebi-a-GCST90018849) were obtained from the IEU Open GWAS project, including 1,029 GC cases and 474,841 controls. Primary causality estimates were obtained using inverse variance weighting (IVW), supplemented with the weighted median, MR-Egger, weighted mode, and simple mode. In addition, we conducted sensitivity analyses (including Cochran’s Q, MR-Egger intercept, MR-PRESSO, and leave-one-out tests),Steiger’s test, linked disequilibrium score regression, and multivariate MR (MVMR) to improve the assessment of causality between GC and blood metabolite. Finally, we recruited a total of 11 patients diagnosed with gastric cancer from the First Affiliated Hospital of Air Force Military Medical University between September and October 2024. The control group comprised 11 healthy individuals. Serum samples were collected from both groups for the evaluation of blood-related metabolite expression levels using advanced techniques such as ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and gas chromatography-mass spectrometry (GC-MS/MS).ResultsThe MVMR analysis revealed a significant association between genetically predicted elevated levels of tryptophan (odds ratio [OR] = 0.523, 95% confidence interval [CI] = 0.313–0.872, p = 0.013), nonadecanoate (19:0) (odds ratio [OR] = 0.460, 95% confidence interval [CI] = 0.225–0.943, p = 0.034), and erythritol (odds ratio [OR] = 0.672, 95% confidence interval [CI] = 0.468–0.930, p = 0.016) with a decreased risk of gastric cancer. Based on metabolomic techniques such as UPLC-MS/MS and GC-MS/MS analyses, it has been demonstrated that the expression levels of tryptophan, nonadecanoate (19:0), and erythritol are reduced in patients with gastric cancer. This finding aligns with the results obtained from our MR analysis and provides further confirmation regarding the protective role of tryptophan, nonadecanoate (19:0), and erythritol against gastric cancer.ConclusionsThese findings indicate that three blood metabolites are causally related to GC and provide new perspectives for combining genomics and metabolomics to study the mechanisms of metabolite-mediated GC development.

Objective Multiple myeloma (MM) varies in clinical behavior, response to treatment and prognosis due to the heterogeneity of the disease. Data on the association between the immunoparesis status during treatment and prognosis in nontransplant MM patients are limited.Methods In a retrospective analysis of 142 patients with MM, we examined the relationship between immunoparesis status and prognosis during treatment. All patients received novel agent-based therapy and did not undergo autologous stem cell transplantation. One, two, or three uninvolved immunoglobulins (Igs) below the lowest thresholds of normalcy were used to identify immunoparesis.Results Patients with a greater degree of immunoparesis during treatment had shorter progression-free survival (PFS) and overall survival (OS). A total of 46.5% of the patients had severe and continuous immunoparesis (at least two uninvolved Igs suppressed continuously during treatment), representing a worse prognosis than those with complete or partial normalization of Igs during treatment. Among patients who achieved at least complete remission, PFS was poor in patients with severe and continuous immunoparesis. Furthermore, severe and continuous immunoparesis during treatment was a poor prognostic factor for PFS and OS according to multivariate analyses.Conclusion The degree of immunoparesis during treatment is a follow-up indicator for survival in nontransplant myeloma patients, and severe and continuous immunoparesis in nontransplant myeloma patients might be a sign of poor prognosis.

Abstract Background Body weight and its changes have been associated with cancer outcomes. However, the associations of short‐term peridiagnosis weight dynamics in standardized, clinically operational time frames with cancer survival remain largely unknown. This study aimed to screen for and evaluate the optimal indicator of short‐term peridiagnosis weight dynamics to predict overall survival (OS) in patients with cancer. Methods This multicentre cohort study prospectively collected data from 7460 patients pathologically diagnosed with cancer between 2013 and 2019. Body weight data were recorded 1 month before, at the time of and 1 month following diagnosis. By permuting different types (point value in kg, point height‐adjusted value in kg/m2, absolute change in kg or relative change in percentage) and time frames (prediagnosis, postdiagnosis or peridiagnosis), we generated 12 different weight‐related indicators and compared their prognostic performance using Harrell's C‐index, integrated discrimination improvement, continuous net reclassification improvement and time‐dependent C‐index. We analysed associations of peridiagnosis relative weight change (RWC) with OS using restricted cubic spine (RCS), Kaplan–Meier analysis and multivariable‐adjusted Cox regression models. Results The study enrolled 5012 males and 2448 females, with a median age of 59 years. During a median follow‐up of 37 months, 1026 deaths occurred. Peridiagnosis (1 month before diagnosis to 1 month following diagnosis) RWC showed higher prognostic performance (Harrell's C‐index = 0.601, 95% confidence interval [CI] = [0.583, 0.619]) than other types of indicators including body mass index (BMI), absolute weight change, absolute BMI change, prediagnosis RWC and postdiagnosis RWC in the study population (all P 10%, hazard ratio [HR] = 0.530, 95% CI = [0.413, 0.680]) and moderate (gain 5–10%, HR = 0.588, 95% CI = [0.422, 0.819]) weight gain groups were both associated with improved OS. In contrast, the moderate (loss 5–10%, HR = 1.219, 95% CI = [1.029, 1.443]) and significant (loss >10%, HR = 1.280, 95% CI = [1.095, 1.497]) weight loss groups were both associated with poorer OS. Conclusions The prognostic performance of peridiagnosis RWC is superior to other weight‐related indicators in patients with cancer. The findings underscore the importance of expanding the surveillance of body weight from at diagnosis to both past and future, and conducting it within clinically operational time frames, in order to identify and intervene with patients who are at risk of weight change‐related premature deaths.

The mudstone within the Upper Triassic Adula Formation constitutes a crucial hydrocarbon source rock reservoir in the Qiangtang Basin, yet there is considerable debate regarding its paleo-depositional environment. Through systematic studies, including petrology, organic geochemistry, and elemental geochemistry analyses of the Adula Formation at the Eertuolongba section in the Quemocuo area of the eastern Qiangtang Basin, this study investigated the paleo-depositional environment of the Adula Formation source rocks and its impact on hydrocarbonsource rock development. The total organic carbon (TOC) content of the Adula Formation mudstone ranges from 0.27% to 3.46%, with an average of 1.60%, indicating overall favorable source rocks with locally deve-loped high-quality source rocks. The shelf facies mudstone in the lower section of the Adula Formation was formed during a phase of sea-level rise, characterized by deeper, oxygen-poor water, a semi-arid to semi-humid paleoclimate, moderate chemical weathering, minimal terrigenous input, and higher salinity. The deposition of the upper section occurred during a phase of basin contraction and demise, suggesting a transition from shelf facies to delta facies. This period was marked by relatively shallower, oxygen-rich water and a shift from arid to semi-arid to semi-humid paleoclimate, with increased terrigenous input and a saline to semi-saline water environment influenced by freshwater input. The source rocks of the Adula Formation are felsic volcanic rocks, primarily from a continental island arc tectonic setting, likely sourced from the island arc source domain in the Jinsha River suture zone during the Early to Middle Triassic. In the lower section of the Adula Formation, the TOC content of shelf facies mudstone shows a robust positive correlation with redox condition indicators, suggesting that source rock development was mainly controlled by oxygen-poor water conditions during sea-level rise period. In contrast, no significant correlation was observed between TOC content and paleo-environmental parameters in the upper shelf delta facies mudstones. Mudstones with TOC content greater than 2% were likely deposited during periods of high terrigenous input and relatively humid paleoclimate, indicating that source rock development was influenced by multiple factors such as paleoclimate and terrigenous input.

Abstract Radar‐based human activity recognition is considered as a competitive solution for the elderly care health monitoring problem, compared to alternative techniques such as cameras and wearable devices. However, raw radar signals are often contaminated with noise, clutter, and other artifacts that significantly impact recognition performance, which highlights the importance of prepossessing techniques that enhance radar data quality and improve classification model accuracy. In this study, two different human activity classification models incorporated with pre‐processing techniques have been proposed. The authors introduce wavelet denoising methods into a cyclostationarity‐based classification model, resulting in a substantial improvement in classification accuracy. To address the limitations of conventional pre‐processing techniques, a deep neural network model called Double Phase Cascaded Denoising and Classification Network (DPDCNet) is proposed, which performs end‐to‐end signal‐level classification and achieves state‐of‐the‐art accuracy. The proposed models significantly reduce false detections and would enable robust activity monitoring for older individuals with radar signals, thereby bringing the system closer to a practical implementation for deployment.

Abstract Background Epigenetic alterations play an important role in hepatocellular carcinoma (HCC) development. Enhancer of zeste homolog 2 (EZH2) is a well-known epigenetic modifier that functions as an oncogene in tumors by promoting the H3K27me3-mediated transcriptional repression of tumor suppressor genes. “Senescent cells” has been proposed as a possible core component of the hallmarks of cancer conceptualization. Induction of cell senescence and targeted elimination of these senescent tumor cells are new strategies for tumor therapy. However, the role of EZH2 in regulating cellular senescence remains poorly understood. Methods Bioinformatics analyses suggested that EZH2 and DNA topoisomerase II alpha (TOP2A) are coexpressed in tumors, including HCC. Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analyses and gene set enrichment analyses (GSEA) suggests a correlation of EZH2 and TOP2A expression with cellular senescence in HCC. MicroRNA (miRNA) inhibitor and mimics, siRNA, PLKO-shRNA, and plenti6.3-miR-139 were used to upregulate or downregulate the expression of target genes. CCK8, EdU, clone formation, and senescence-associated β-galactosidase (SA-β-gal) staining assays were performed to assess cell proliferation and cellular senescence phenotypes. Dual-luciferase reporter and chromatin immunoprecipitation assays were performed to investigate the targeted binding and inhibition of TOP2A 3′ untranslated region (UTR) by miR-139-5p and the DNA enrichment of miR139-5p by EZH2 and H3K27me3. BALB/c nude mice were used to establish a xenograft tumor model and verify the phenotypes upon EZH2 and TOP2A silencing and miR-139 overexpression in vivo. In addition, tissue microarrays were used to analyze the expression patterns and correlations among EZH2, TOP2A, and miR-139-5p expression in HCC. Results Bioinformatics analysis revealed that EZH2 and TOP2A are coexpressed in HCC. In vitro gain- and loss-of-function experiments showed that inhibition of EZH2 and TOP2A induces cellular senescence and inhibits proliferation of HCC cells. In vivo tumorigenesis assays indicated that EZH2 and TOP2A knockdown inhibits tumorigenesis by inducing cellular senescence. Mechanistically, EZH2 promotes TOP2A expression by regulating the H3K27me3-mediated epigenetic silencing of miR-139-5p. TOP2A is a direct target of miR-139-5p, and inhibition of miR-139-5p can reverse the promotion by EZH2 of TOP2A expression. The overexpression of miR-139-5p induces cellular senescence and inhibits proliferation of HCC cells both in vitro and in vivo. Clinically, expression of EZH2 and TOP2A are higher in HCC tissues than in normal tissues, and this high coexpression indicates a worse outcome of patients with HCC. Moreover, expression of EZH2 and TOP2A is significantly correlated with tumor differentiation grade, tumor invasion, and TNM stage in HCC. miR-139-5p expression is lower in HCC tumors than in normal tissues and is correlated with better prognosis of HCC patients. Conclusions Our study revealed the role of the EZH2/miR-139-5p/TOP2A axis in regulating cellular senescence and cell proliferation in HCC, enriching the molecular mechanisms of EZH2-mediated epigenetic regulation in HCC. Therefore, our results provide insight into the therapeutic potential of targeting EZH2 to induce cellular senescence and then destroy senescent cells for HCC. Graphic Abstract

BackgroundBaseline serological biomarkers have the potential to predict the benefits of adjuvant chemotherapy in patients with gastric cancer. However, the fluctuating nature of postoperative recurrence risk makes precise treatment challenging. We aimed to develop a risk score in real-time predicting outcomes for postoperative GC patients using blood chemistry tests.Materials and methodsThis was a retrospective, multicentre, longitudinal cohort study from three cancer centres in China, with a total of 2737 GC patients in the pTNM stage Ib to III. Among them, 1651 patients with at least two serological records were assigned to the training cohort. Model validation was carried out using separate testing data with area under curve (AUC). The least absolute shrinkage and selection operator (LASSO) and random forest-recursive feature elimination (RF-RFE) algorithm were used to select the parameters.ResultsThe Cox regression model derived six risk factors to construct a composite score (low-risk: 0-2 score; high risk: 3-6 score), including CEA, CA125, CA199, haemoglobin, albumin, and neutrophil to lymphocyte ratio. The risk score accurately predicted mortality in 1000-time bootstrap (AUROCs:0.658; 95% CI: 0.645, 0.670), with the highest AUROC (0.767; 95% CI: 0.743, 0.791) after 1 year since the gastrectomy. In validation dataset, the risk score had an AUROC of 0.586 (95% CI 0.544, 0.628). Furthermore, patients with high risk at 1 month derived significant clinical benefits from adjuvant chemotherapy (P for interaction

According to the unstable and nonlinear performances of the servo valve-controlled hydraulic motor, classical control methods based on linear theory are gradually unable to meet the high-performance requirements of the system. Using the servo valve-controlled hydraulic motor based on the third-order active disturbance rejection control (ADRC) to improve the dynamic performance of the system is feasible. The mathematical model and the simulation model of the third-order ADRC for the servo valve-controlled hydraulic motor system are established respectively. For the phase lag caused by the third-order ADRC controller, the control performance of the ADRC controller is significantly improved using the advance forecast. The simulation experiment results show that the designed ADRC controller has good tracking performance and stronger robustness of the system than the traditional PID controller.

Abstract Background The role of anticoagulation or antiplatelet on post-vitrectomy vitreous hemorrhage (POVH) in patients with proliferative diabetic retinopathy (PDR) is rarely investigated in the small-gauge vitrectomy era. We investigate the relationship between the long-term use of those medications and POVH in a group of PDR patients. Methods A retrospective cohort study was carried out in a group of PDR patients who underwent small-gauge vitrectomy in our center. The baseline data on diabetes, diabetic complications, long-term use of anticoagulants and antiplatelet agents, ocular findings, and vitrectomy details were collected. The occurrence of POVH was recorded during at least three-month follow-up. Factors related to POVH were analyzed using logistic analysis. Results During a median follow-up of 16 weeks, 5% (11/220) of patients had POVH, and 75 had received antiplatelet or anticoagulation agents before the operation. Factors related to persistent POVH were the use of antiplatelet or anticoagulation agents (5.98, 1.75–20.45, p = 0.004), the presence of myocardial revascularization (130.65, 3.53-4834.50, p = 0.008), the presence of coronary artery disease (CAD) treated with medicine (56.52, 1.99–1604.06, p = 0.018), and younger age (0.86, 0.77–0.96, p = 0.012). For those receiving preoperative antiplatelet or anticoagulation agents, the probability of developing POVH was higher in the patients whose previous therapy was adjusted compared to those with continued therapy (p = 0.02 by Log-rank test). Conclusions We identified long-term use of anticoagulation or antiplatelet medication, the presence of CAD, and younger age as three independent factors related to POVH. In PDR patients on long-term antiplatelet or anticoagulation medications, particular attention should be given to controlling intraoperative bleeding, and follow-up for POVH should be scheduled.

AimTo investigate reasons for delayed presentation in patients with proliferative diabetic retinopathy (PDR).MethodsA questionnaire was designed to investigate consecutive PDR patients with delayed presentation who visited our center between January 2021 and December 2021. The questionnaire was divided into four sections: knowledge regarding diabetic retinopathy (DR), attitude toward DR treatment, difficulties adhering to follow-up plans, and medical care. The systemic disease status and severity of DR were recorded. Logistic analysis was undertaken to investigate DR treatment refusal and delay factors.ResultsA total of 157 patients were included in this study, with an average age of 50.0 ± 11.6 years. The median glycated hemoglobin level (HbA1c) was 7.8% (IQR 2.5%). Among the 157 eyes, most required vitrectomy intervention (144, 91.7%); 17 developed neovascular glaucoma (NVG), while only 13 required additional photocoagulation. Among the 36 patients with undiagnosed DM, the reason for delayed DR presentation was a lack of awareness of DM status among these patients (36 cases, 100.0%). Most of the patients with a known history of DM exhibited inadequate DR knowledge (29, 24.0%), believed their good visual acuity did not require DR screening (98, 81.0%), and had poorly controlled diabetes (113, 93.3%). Factors related to refusing DR treatment were patients with an inability to receive regular diabetes treatment in internal medicine clinics (OR 6.78, 95% CI 1.73-26.59, p = 0.006), patients who could not tolerate discomfort during ophthalmic examination and treatment (OR 15.15, 95% CI 2.70-83.33, pConclusionsThis study investigated the factors contributing to delayed presentation among patients with PDR. Many individuals in the delayed population were found to have undiagnosed DM. Among patients already aware of their DM status, reasons for delay included insufficient knowledge about DR, negative attitudes toward screening and treatment, and difficulties seeking medical care in real-life situations. Furthermore, there needed to be more improvements in the detection, treatment, and follow-up of DR by internal medicine practitioners and ophthalmologists.

Abstract Colorectal cancer (CRC) is the most common and fatal tumor in the gastrointestinal system. Its incidence and mortality rate have increased in recent years. Hypoxia, a persistent physiological tumor feature, plays a vital role in CRC tumorigenesis, metastasis, and tumor microenvironment (TME). Therefore, we constructed a hypoxia-related gene (HRG) nomogram to predict overall survival (OS) and explored the role of HRGs in the CRC TME. The Cancer Genome Atlas (TCGA) dataset was used as the training set, and two Gene Expression Omnibus datasets (GSE39582 and GSE103479) were used as the testing sets. HRGs were identified using the Gene Set Enrichment Analysis (GSEA) database. An HRG prognostic model was constructed in the training set using the least absolute shrinkage and selection operator regression algorithm and validated in the testing sets. Then, we analyzed tumor-infiltrating cells (TICs) using the cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm. Furthermore, single-cell next-generation RNA sequencing (RNA-seq) was used to investigate HRG expression in different TICs in the GSE139555 dataset. Finally, reverse transcription polymerase chain reactions (RT-PCR) were used to validate HRG mRNA expression in ten pairs of CRC normal and cancer tissue samples. A six HRG prognostic signature was constructed, with a superior OS prediction ability in CRC patients (area under the receiver operating characteristic curve (AUC) at one year: 0.693, AUC at three years: 0.712, and AUC at five years: 0.780). GSEA enrichment analysis identified six pathways enriched in the high-risk group. The TIC analysis indicated that the high-risk group had lower T-cell expression and higher neutrophil expression than the low-risk group. Furthermore, immune-related genes had an inseparable relationship with the HRG prognostic signature. Based on single-cell RNA-seq data, we found elevated hexokinase 1 (HK1) and glucose-6-phosphate isomerase (GPI) gene expression in natural killer (NK) and CD8+ T cells. RT-PCR in ten CRC normal-tumor tissue pairs showed that expression of the signature’s six HRGs varied differently in cancerous and paracancerous tissues. The constructed HRG signature successfully predicted the OS of whole-stage CRC patients. In addition, we showed that the signature’s six HRGs were closely associated with the TME in CRC, where hypoxia inhibits the antitumor function of T cells.

The molecular differences between the two major gastric cancer subtypes diffuse-type gastric cancer (DGC) and intestinaltype gastric cancer (IGC) remain to be investigated. Here, integrated analysis of proteome, phospho-proteome and transcription factor activity for DGC and IGC reveals potential subtypes.

High-precision tracking of an electro-hydraulic servo material testing machine’s force control system was achieved using a proposed integral sliding mode control method based on feedback linearization to improve the machine’s force control performance and anti-interference ability. First, the electro-hydraulic servo system’s nonlinear mathematical model was established, and its input–output linearization was realized using differential geometry theory. Second, integral sliding mode control was introduced into the controller and the feedback-linearized integral sliding mode controller was designed. The controller’s stability was proven based on the Lyapunov stability principle. Finally, a simulation model of the electro-hydraulic servo material testing machine’s force control system was established using AMESim/Simulink software. The designed controller was simulated and verified, and the control effects of the system’s different amplitudes and frequency signals were analyzed. The results showed that the feedback-linearized integral sliding mode control algorithm could effectively improve the system’s force tracking accuracy and parameter adaptability, yielding better robustness and a better control effect.

Abstract Notch ligands are expression changes in a great many malignancies including gastric cancer (GC) frequently. The prognostic value of each Notch ligands in GC patients remains lack of large sample data results. In present research, we researched the prognostic value of Notch ligands in GC patients in order to fill the shortage areas. We used an online database ( http://kmplot.com/analysis/index.php?p=service&cancer=gastric ) to identify the relationship between mRNA expression of each Notch ligand and overall survival (OS) in GC. We analyze the relevance of overall survival and clinical data which includes gender, Lauren's classification, differentiation, clinical stage and treatment. The study found that high DLL1, DLL3, DLL4 and JAG2 mRNA expression were tied to worse OS in all GC patients followed up for 10 years. There is no significant relevance to the expression of JAG1 mRNA and OS in patients with GC. We also did a survey of each Notch ligands in different clinical and pathological features present different prognosis. The information will help to better understand the biology of gastric cancer heterogeneity, provide more accurate prognostic evaluation tools and provide new targets for targeted drug development besides.

Purpose: This study aimed to explore the effect of biomaterials with different stiffness on Adipose Derived Mesenchymal Stem Cells (ADSC)–macrophage crosstalk in bone tissue engineering and its role in bone repair.Methods: Biomaterials with Young’s modulus of 64 and 0.2 kPa were selected, and the crosstalk between ADSCs and macrophages was investigated by means of conditioned medium treatment and cell co-culture, respectively. Polymerase chain reaction (PCR) and flow cytometry were used to evaluate the polarization of macrophages. Alkaline phosphatase (ALP) and alizarin red staining (ARS) solutions were used to evaluate the osteogenic differentiation of ADSCs. Transwell assay was used to evaluate the chemotaxis of ADSCs and macrophages. Moreover, mass spectrometry proteomics was used to analyze the secreted protein profile of ADSCs of different substrates and macrophages in different polarization states.Results: On exploring the influence of biomaterials on macrophages from ADSCs on different substrates, we found that CD163 and CD206 expression levels in macrophages were significantly higher in the 64-kPa group than in the 0.2-kPa group in conditioned medium treatment and cell co-culture. Flow cytometry showed that more cells became CD163+ or CD206+ cells in the 64-kPa group under conditioned medium treatment or cell co-culture. The Transwell assay showed that more macrophages migrated to the lower chamber in the 64-kPa group. The proteomic analysis found that ADSCs in the 64-kPa group secreted more immunomodulatory proteins, such as LBP and RBP4, to improve the repair microenvironment. On exploring the influence of biomaterials on ADSCs from macrophages in different polarization states, we found that ALP and ARS levels in ADSCs were significantly higher in the M2 group than in the other three groups (NC, M0, and M1 groups) in both conditioned medium treatment and cell co-culture. The Transwell assay showed that more ADSCs migrated to the lower chamber in the M2 group. The proteomic analysis found that M2 macrophages secreted more extracellular remodeling proteins, such as LRP1, to promote bone repair.Conclusion: In bone tissue engineering, the stiffness of repair biomaterials can affect the crosstalk between ADSCs and macrophages, thereby regulating local repair immunity and affecting bone repair.

This paper proposes a sliding mode synchronous control approach to enhance the position synchronization performance and anti-interference capability of a double lifting point hydraulic hoist. Building upon the cross-coupling synchronous control method, a coupling sliding mode surface is formulated, incorporating the single-cylinder following error and double-cylinder synchronization error. Additionally, a sliding mode synchronous controller is devised to ensure the convergence of both the single-cylinder following and synchronization error. The hyperbolic tangent function is introduced to reduce the single-cylinder following error and the buffeting of the double-cylinder synchronization error curve under sliding mode synchronous control. The simulation results show that the synchronization accuracy of the sliding mode cross-coupling synchronization control in the initial stage of the system is 53.1% higher than that of the Proportional-Derivative (PD) cross-coupling synchronization, and the synchronization accuracy in the steady state of the system is improved by 90%. The designed synchronous controller has better performance under external disturbances.

In this study, an on-line Gas Chromatography-Pyrolysis-Gas Chromatography-Isotope Ratio Mass Spectrometer (GC-Py-GC-IRMS) was established to conduct position-specific isotope analysis (PSIA) by enrichment of compound interested, chromatographic separation, instantaneous pyrolysis and isotope ratio measurement. Propane, as its instantaneous pyrolysis can be kinetically controlled, was selected for tests. The molar conversion (mol%) of propane during pyrolysis and the carbon isotopic compositions of pyrolysis products upon temperature sequence show that the optimal pyrolysis temperature of propane is 780-820 ℃ for its position-specific carbon isotope analysis. Integrated with carbon isotopic fractionation during the propane pyrolysis, the carbon isotopes of central and terminal carbon were successfully calculated. Two natural gas samples from the Daniudi Gas Field, Ordos Basin were collected for central and terminal carbon isotope measurements in propane. Similar δ13C values of central carbon of propane in natural gas from the Ordovician and Carboniferous-Permian reservoirs could be indicative of the same source strata. While 13C-enrichment in the terminal C-atom of propane in natural gas from the Carboniferous-Permian reservoirs probably indicates that natural gas accumulated in the Carboniferous-Permian reservoir maybe have experienced a higher thermal maturation compared to that from the Ordovician reservoirs. The results suggest that the PSIA in propane can be a potentially powerful tool to probe the mechanisms on natural gas generation.

Molecular design of redox-active materials with higher solubility and greater redox potential windows is instrumental in enhancing the performance of redox flow batteries Here we propose a computational procedure for a systematic evaluation of organic redox-active species by combining machine learning, quantum-mechanical, and classical density functional theory calculations. 1,517 small quinone molecules were generated from the building blocks of benzoquinone, naphthoquinone, and anthraquinone with different substituent groups. The physics-based methods were used to predict HOMO-LUMO gaps and solvation free energies that account for the redox potential differences and aqueous solubility, respectively. The high-throughput calculations were augmented with the quantitative structure-property relationship analyses and machine learning/graph network modeling to evaluate the materials’ overall behavior. The computational procedure was able to reproduce high-performance cathode electrolyte materials consistent with experimental observations and identify new electrolytes for RFBs by screening 100,000 di-substituted quinone molecules, the largest library of redox-active quinone molecules ever investigated. The efficient computational platform may facilitate a better understanding of the structure-function relationship of quinone molecules and advance the design and application of all-organic active materials for RFBs.

Simple summaryDetecting deficient mismatch repair (dMMR) in patients with colorectal cancer is essential for clinical decision-making, including evaluation of prognosis, guidance of adjuvant chemotherapy and immunotherapy, and primary screening for Lynch syndrome. However, outside of tertiary care centers, existing detection methods are not widely disseminated and highly depend on the experienced pathologist. Therefore, it is of great clinical significance to develop a broadly accessible and low-cost tool for dMMR prediction, particularly prior to surgery. In this study, we developed a convenient and reliable model for predicting dMMR status in CRC patients on routine preoperative characterization utilizing multiple machine learning algorithms. This model will work as an automated screening tool for identifying patients suitable for mismatch repair testing and consequently for improving the detection rate of dMMR, while reducing unnecessary labor and cost in patients with proficient mismatch repair.BackgroundDeficient mismatch repair (dMMR) indicates a sustained anti-tumor immune response and has a favorable prognosis in patients with colorectal cancer (CRC). Although all CRC patients are recommended to undergo dMMR testing after surgery, current diagnostic approaches are not available for all country hospitals and patients. Therefore, efficient and low-cost predictive models for dMMR, especially for preoperative evaluations, are warranted.MethodsA large scale of 5596 CRC patients who underwent surgical resection and mismatch repair testing were enrolled and randomly divided into training and validation cohorts. The clinical features exploited for predicting dMMR comprised the demographic characteristics, preoperative laboratory data, and tumor burden information. Machine learning (ML) methods involving eight basic algorithms, ensemble learning methods, and fusion algorithms were adopted with 10-fold cross-validation, and their performance was evaluated based on the area under the receiver operating characteristic curve (AUC) and calibration curves. The clinical net benefits were assessed using a decision curve analysis (DCA), and a nomogram was developed to facilitate model clinical practicality.ResultsAll models achieved an AUC of nearly 0.80 in the validation cohort, with the stacking model exhibiting the best performance (AUC = 0.832). Logistical DCA revealed that the stacking model yielded more clinical net benefits than the conventional regression models. In the subgroup analysis, the stacking model also predicted dMMR regardless of the clinical stage. The nomogram showed a favorable consistence with the actual outcome in the calibration curve.ConclusionWith the aid of ML algorithms, we developed a novel and robust model for predicting dMMR in CRC patients with satisfactory discriminative performance and designed a user-friendly and convenient nomogram.

Abstract Backgrounds To describe changes in rhegmatogenous retinal detachment (RRD) surgical procedures in Beijing during the COVID-19 Pandemic. Methods A retrospective cohort of RRD patients was analyzed. Patients were divided into the COVID-19 pandemic group and pre-COVID-19 group according to their presentation. The presurgery characteristics, surgical procedures, and surgery outcomes were collected. The potential factors related to the choice of pars plana vitrectomy (PPV) or scleral buckling (SB) were analyzed using logistic regression. The differences in the procedure choice under specific conditions were compared. Surgery outcomes were compared between the two groups. Results In the COVID-19 pandemic group, less patients received SB (27.8, 41.3%, p = 0.02) while more patients received PPV (72.2, 58.6%, p = 0.02); in patients who received SB, fewer patients received subretinal fluid drainage (45.4,75.7%, p = 0.01); in patients who received PPV, fewer patients received phacovitrectomy (7.0, 21.0%, p = 0.02). The choice of PPV was related to older age (1.03, p = 0.005), the presence of RRD with choroidal detachment (RRD-CD) (2.92, p = 0.03), pseudophakia (5.0, p = 0.002), retinal breaks located posterior to the equator (4.87, p

Abstract Background Gastric cancer (GC) is a globally prevalent cancer, ranking fifth for incidence and fourth for mortality worldwide. The N6-methyladenosine (m6A) related long noncoding RNAs (lncRNAs) were widely investigated in recent studies. Nevertheless, the underlying prognostic implication and tumor immune mechanism of m6A-related lncRNA in GC remain unknown. Methods We systematically assessed the m6A modification expression of 407 GC clinical samples based on 23 m6A regulators and comprehensively associated these genes with lncRNAs. Then, we constructed a m6A-related lncRNA prognostic signature (m6A-LPS) to evaluate both status and prognosis of the disease. Immune-related mechanisms were explored via dissecting tumor-infiltrating cells as well as applying tumor immune dysfunction and the exclusion algorithm. Furthermore, we validated the latent regulative mechanism of m6A-related lncRNA in GC cell lines. Results The m6A-LPS containing nine hub lncRNAs was built, which possessed a superior capability to predict the outcomes of GC patients. Meanwhile, we found an intimate correlation between the m6A-LPS and tumor infiltrating cells, and that the low-risk group had a higher expression of immune checkpoints and responsed more to immunotherapy than the high-risk group. Clinically, these crucial lncRNAs expression levels were verified in ten pairs of GC samples. In in vitro experiments, the abilities of migration and proliferation were significantly enhanced via downregulating the lncRNA AC026691.1. Both migrative and proliferative capabilities of tumor cells were significantly enhanced via downregulating the lncRNA AC026691.1. in vitro. Conclusions Collectively, the m6A-LPS could provide a novel prediction insight into the prognosis of GC patients and serve as an independent clinical factor for GC. These m6A-related lncRNAs might remodel the tumor microenvironment and affect the anti-cancer ability of immune checkpoint blockers. Importantly, lncRNA AC026691.1 could inhibit both migration and proliferation of GC by means of FTO regulation.

The tumor development and metastasis are closely related to the structure and function of the tumor microenvironment (TME). Recently, TME modulation strategies have attracted much attention in cancer immunotherapy. Despite the preliminary success of immunotherapeutic agents, their therapeutic effects have been restricted by the limited retention time of drugs in TME. Compared with traditional delivery systems, nanoparticles with unique physical properties and elaborate design can efficiently penetrate TME and specifically deliver to the major components in TME. In this review, we briefly introduce the substitutes of TME including dendritic cells, macrophages, fibroblasts, tumor vasculature, tumor-draining lymph nodes and hypoxic state, then review various nanoparticles targeting these components and their applications in tumor therapy. In addition, nanoparticles could be combined with other therapies, including chemotherapy, radiotherapy, and photodynamic therapy, however, the nanoplatform delivery system may not be effective in all types of tumors due to the heterogeneity of different tumors and individuals. The changes of TME at various stages during tumor development are required to be further elucidated so that more individualized nanoplatforms could be designed.

Abstract Backgrounds The COVID-19 Pandemic has a great impact on hospitals and patients. The 14-day quarantine caused surgery of rhegmatogenous retinal detachment (RRD) postponed. We aimed to explore the risk factors of RRD progression in a group of patients whose surgery was postponed during the top-level emergency response of COVID-19. Methods A retrospective case series. Medical records of all consecutive patients with a diagnosis of RRD who underwent a surgical treatment at Beijing Tongren Hospital’s retina service from February 16, 2020, to April 30, 2020 have been reviewed retrospectively. Medical history, symptoms, and clinical signs of progression of RRD were recorded. RRD progression was defined as the presence of either choroidal detachment or proliferative vitreoretinopathy (PVR) progression during the quarantine period. Risk factors were analyzed using the Cox proportional hazards model, survival analysis, and logistic regression. Results Seventy-nine eyes of 79 patients met the inclusion criteria and were included in the study. The median time from the patients’ presentation at the clinic to admission for surgery was 14 days (3–61 days). There were 70 cases (88.6%) who did not present to the hospital within 1 week of the onset of visual symptoms. There were 69 (87.3%) macular-off cases at the presentation and 27 (34.2%) cases combined with choroidal detachment. There were 49 (62.0%) cases with PVR B, 22 (27.8%) cases with PVR C, 4 (5.1%) cases with PVR D, and 4 (5.1%) cases with anterior PVR. After the 14-day quarantine, 21 (26.6%) cases showed RRD progression, and 9 cases showed RRD regression at the time of surgery. Neither the time of onset of the visual symptom (p = 0.46) nor the time between presentation and admission (p = 0.31) was significantly different between the patients with RRD progression and patients without RRD progression. The combination of choroidal detachment (3.07, 1.68-5.60, p

Abstract Fork-head box protein M1 (FoxM1) is a transcriptional factor which plays critical roles in cancer development and progression. However, the general regulatory mechanism of FoxM1 is still limited. STMN1 is a microtubule-binding protein which can inhibit the assembly of microtubule dimer or promote depolymerization of microtubules. It was reported as a major responsive factor of paclitaxel resistance for clinical chemotherapy of tumor patients. But the function of abnormally high level of STMN1 and its regulation mechanism in cancer cells remain unclear. In this study, we used public database and tissue microarrays to analyze the expression pattern of FoxM1 and STMN1 and found a strong positive correlation between FoxM1 and STMN1 in multiple types of cancer. Lentivirus-mediated FoxM1/STMN1-knockdown cell lines were established to study the function of FoxM1/STMN1 by performing cell viability assay, plate clone formation assay, soft agar assay in vitro and xenograft mouse model in vivo. Our results showed that FoxM1 promotes cell proliferation by upregulating STMN1. Further ChIP assay showed that FoxM1 upregulates STMN1 in a transcriptional level. Prognostic analysis showed that a high level of FoxM1 and STMN1 is related to poor prognosis in solid tumors. Moreover, a high co-expression of FoxM1 and STMN1 has a more significant correlation with poor prognosis. Our findings suggest that a general FoxM1-STMN1 axis contributes to cell proliferation and tumorigenesis in hepatocellular carcinoma, gastric cancer and colorectal cancer. The combination of FoxM1 and STMN1 can be a more precise biomarker for prognostic prediction.

Objective: The systemic inflammation index and body mass index (BMI) are easily accessible markers that can predict mortality. However, the prognostic value of the combined use of these two markers remains unclear. The goal of this study was therefore to evaluate the association of these markers with outcomes based on a large cohort of patients with gastric cancer. Methods A total of 2,542 consecutive patients undergoing radical surgery for gastric or gastroesophageal junction adenocarcinoma between 2009 and 2014 were included. Systemic inflammation was quantified by the preoperative neutrophil-to-lymphocyte ratio (NLR). High systemic inflammation was defined as NLR ≥ 3, and underweight was defined as BMI < 18.5 kg/m2. Results Among 2,542 patients, NLR ≥ 3 and underweight were common [627 (25%) and 349 (14%), respectively]. In the entire cohort, NLR ≥ 3 or underweight independently predicted overall survival (OS) [hazard ratio (HR): 1.236, 95% confidence interval (95% CI): 1.069–1.430; and HR: 1.600, 95% CI: 1.350–1.897, respectively] and recurrence-free survival (RFS) (HR: 1.230, 95% CI: 1.054–1.434; and HR: 1.658, 95% CI: 1.389–1.979, respectively). Patients with both NLR ≥ 3 and underweight (vs. neither) had much worse OS (HR: 2.445, 95% CI: 1.853–3.225) and RFS (HR: 2.405, 95% CI: 1.802–3.209). Furthermore, we observed similar results in subgroup analyses according to pathological stage, age, and postoperative chemotherapy. Conclusions Our results showed that preoperative elevated NLR and decreased BMI had a significant negative effect on survival. Underweight combined with severe inflammation could enhance prognostication. Taking active therapeutic measures to reduce inflammation and increase nutrition may help improve outcomes.

Abstract Endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are well-established therapeutics for gastrointestinal neoplasias, but complications after EMR/ESD, including bleeding and perforation, result in additional treatment morbidity and even threaten the lives of patients. Thus, designing biomaterials to treat gastric bleeding and wound healing after endoscopic treatment is highly desired and remains a challenge. Herein, a series of injectable pH-responsive self-healing adhesive hydrogels based on acryloyl-6-aminocaproic acid (AA) and AA-g-N-hydroxysuccinimide (AA-NHS) were developed, and their great potential as endoscopic sprayable bioadhesive materials to efficiently stop hemorrhage and promote the wound healing process was further demonstrated in a swine gastric hemorrhage/wound model. The hydrogels showed a suitable gelation time, an autonomous and efficient self-healing capacity, hemostatic properties, and good biocompatibility. With the introduction of AA-NHS as a micro-cross-linker, the hydrogels exhibited enhanced adhesive strength. A swine gastric hemorrhage in vivo model demonstrated that the hydrogels showed good hemostatic performance by stopping acute arterial bleeding and preventing delayed bleeding. A gastric wound model indicated that the hydrogels showed excellent treatment effects with significantly enhanced wound healing with type I collagen deposition, α-SMA expression, and blood vessel formation. These injectable self-healing adhesive hydrogels exhibited great potential to treat gastric wounds after endoscopic treatment.

In order to study the influence of assembly parallelism error caused by the axis tilt on the tooth root bending deformation， a set of gearbox test platform with adjustable gear axis and a complete strain acquisition and analysis system are designed and test verification is carried out. Based on the allowable deflection of the inner and outer rings of the spherical roller bearing， a finite element model of gear contact with different degrees of axis offset is established， and dynamic simulation analysis is performed to obtain the tooth root strain and stress distribution curve during the meshing process. Through the design of different adjustment methods of different axes， the actual and theoretical values of the angular deviation of the two axes before and after adjustment are compared to verify the feasibility of the adjustment device. Finally， the tooth root strain of different axis parallel error are tested through a strain acquisition system composed of a strain gauge acquisition card， the corresponding strain and stress distribution curve is obtained， and compared with the simulation strain and stress curve， the influence of the axis parallel error on the bending deformation at the dangerous root cross section is obtained.

PurposeWe investigated the influence of impaired renal function on fundus characteristics, pars-plana vitrectomy (PPV) details, and outcomes in patients with proliferative diabetic retinopathy (PDR).DesignA retrospective cohort study.MethodsWe investigated a consecutive series of PDR patients who underwent PPV. The diabetic complications, previous photocoagulation, intravitreal injections before PPV, ocular findings during PPV, surgical details, short-term visual outcome and post-PPV complications were recorded and compared between patients with and without impaired renal function.Results149 patients had normal renal function (67.7%), and 71 (32.3%) patients had impaired renal function; 85.4% of patients were identified with chronic kidney disease (CKD) during the preoperative assessment. Impaired renal function was related to hypertension (3.40[1.58-7.29], p = 0.002), incomplete pan-retinal photocoagulation (PRP) (3.18[1.50-6.72], p = 0.002), severe fibrovascular membrane (8.19[3.43-19.54], pConclusionsIn PDR patients, screening for CKD was required before PPV. PDR patients with impaired renal function tended to have more severe ischemic retinal conditions. Comparable PPV outcomes could be obtained in patients with and without impaired renal damage.

Background: Epilepsy is a complex chronic disease of the nervous system which influences the health of approximately 70 million patients worldwide. In the past few decades, despite the development of novel antiepileptic drugs, around one-third of patients with epilepsy have developed drug-resistant epilepsy. We performed a bioinformatic analysis to explore the underlying diagnostic markers and mechanisms of drug-resistant epilepsy.Methods: Weighted correlation network analysis (WGCNA) was applied to genes in epilepsy samples downloaded from the Gene Expression Omnibus database to determine key modules. The least absolute shrinkage and selection operator (LASSO) regression and support vector machine-recursive feature elimination (SVM-RFE) algorithms were used to screen the genes resistant to carbamazepine, phenytoin, and valproate, and sensitivity of the three-class classification SVM model was verified through the receiver operator characteristic (ROC) curve. A protein–protein interaction (PPI) network was utilized to analyze the protein interaction relationship. Finally, ingenuity pathway analysis (IPA) was adopted to conduct disease and function pathway and network analysis.Results: Through WGCNA, 72 genes stood out from the key modules related to drug resistance and were identified as candidate resistance genes. Intersection analysis of the results of the LASSO and SVM-RFE algorithms selected 11, 4, and 5 drug-resistant genes for carbamazepine, phenytoin, and valproate, respectively. Subsequent union analysis obtained 17 hub resistance genes to construct a three-class classification SVM model. ROC showed that the model could accurately predict patient resistance. Expression of 17 hub resistance genes in healthy subjects and patients was significantly different. The PPI showed that there are six resistance genes (CD247, CTSW, IL2RB, MATK, NKG7, and PRF1) that may play a central role in the resistance of epilepsy patients. Finally, IPA revealed that resistance genes (PRKCH and S1PR5) were involved in “CREB signaling in Neurons.”Conclusion: We obtained a three-class SVM model that can accurately predict the drug resistance of patients with epilepsy, which provides a new theoretical basis for research and treatment in the field of drug-resistant epilepsy. Moreover, resistance genes PRKCH and S1PR5 may cooperate with other resistance genes to exhibit resistance effects by regulation of the cAMP-response element-binding protein (CREB) signaling pathway.

Background: Immune checkpoint blockers (ICBs) are increasingly being used to treat patients with advanced hepatocellular carcinoma (HCC), but only a third of these patients are sensitive to ICBs. Emerging evidence suggests that ferroptosis could be a novel target for antitumor treatment, and combined treatment with ferroptosis inducers might enhance sensitivity to immunotherapy. However, there is a lack of information on the crosstalk between ferroptosis-related lncRNAs and anti-tumor immunity. Therefore, we aim to explore prognostic value of ferroptosis-related lncRNAs and clarify potential role in ICBs of HCC.Methods: We obtained mRNA and lncRNA expression data from two independent cohorts (TCGA and GEO database). Univariate Cox, the least absolute shrinkage and selection operator (Lasso) algorithm and multivariate Cox analysis were used to construct a lncRNA signature, which was evaluated using the area under the receiver operating characteristic curve (AUC) and Kaplan–Meier curves. Tumor-infiltrating cell (TIC) profiling and the tumor immune dysfunction and exclusion (TIDE) algorithm were used to validate the signature model and immunotherapy. Finally, we adopted RT-PCR assay to evaluate the differential expression of lncRNAs in HCC tissues in our hospital.Results: The ferroptosis-related lncRNA signature included five lncRNAs, most of which were positively correlated with clinical stage and grade. The signature could stratify patients into two risk groups, with the high-risk group associated with a shorter overall survival (OS, p < 0.05) in TCGA-LIHC and GSE76427. Besides, the AUCs of the 1-, 3-, and 5-years OS were 0.772, 0.707, and 0.666, respectively. Gene set enrichment analysis (GESA) of lncRNAs revealed enrichment of oncogenic and immune-related pathways. The TIC profiling indicated a close correlation between the signature and immune cells. Furthermore, the high-risk group had a better response to immunotherapy than low-risk group. RT-PCR demonstrated these five lncRNAs were upregulated in cancerous tissue than normal tissues.Conclusions: The ferroptosis-related lncRNA signature could accurately predict the OS of HCC patients and may serve as an independent clinical factor for patients’ outcomes. Ferroptosis-related lncRNAs may remodel the tumor microenvironment (TME) and affect the anti-cancer ability of ICBs, and therefore, could potentially act as an indicator for the response to immunotherapy in HCC.

At present, there are many challenges in the field of pedestrian attribute recognition, such as small targets of some attributes, imbalanced samples, and low recognition accuracy of complex samples. In view of the above problems, we improved the model in two perspectives: 1) We proposed Feature Pyramid Attention Model (FPAM). In order to solve the problem that attributes are distributed in different locations in the pedestrian image, FPAM adopted the attention mechanism on the basis of ResNet-50, by which the model’s attention could be focused on key areas of the image. As for the difficulty in small targets attributes, we adopted feature pyramid integration strategy; 2) We proposed Multi Label Focal Loss (MLFL). Referring to Binary Cross Entropy Loss Function (CE) and Weight Binary Cross Entropy Loss Function (WCE), we added the weight parameters of samples which are difficult to classify to improve the recognition accuracy, and the rate of convergence was increased. Results show that our proposed method achieves 84.83% mA, 79.37% Accuracy, 87.47% Precision, 86.09% Recall, and 86.77% F1 on PETA dataset.

Abstract Background Many observational studies have reported correlations between postoperative complications and prognosis after radical gastrectomy but the results are controversial. This meta-analysis was performed to investigate whether there is a correlation between postoperative complications and prognosis after radical gastrectomy. Methods Literature searches were performed in PubMed, EMBASE, and the Cochrane Library. Studies that investigated the correlations between any postoperative complications and prognosis after radical gastrectomy were included. The pooled hazard ratio (HR) with 95% confidence interval (CI) for postoperative complications regarding overall survival (OS) or recurrence-free survival (RFS) was calculated by using RevMan 5.3.5. Subgroup analyses were performed within pathological stages I, II, and III. Results Sixteen retrospective studies comprising 12,065 patients were included. The pooled HR (95% CI) for complications regarding OS was 1.79 (1.39, 2.30) and was 1.40 (1.06, 1.84) after excluding in-hospital mortality; the pooled HR (95% CI) for complications regarding RFS was 1.28 (1.10, 1.49). The pooled HR (95% CI) for infectious complications and leakage regarding OS was 1.86 (1.22, 2.83) and 2.02 (1.02, 4.00), respectively. The pooled HR (95% CI) for any reported postoperative complications regarding OS for stage I, II, and III diseases was 2.39 (0.77, 7.46), 4.35 (2.58, 7.35), and 2.84 (1.77, 4.56), respectively. Conclusions Postoperative complications correlate with poor prognosis after radical gastrectomy. Such correlations are found in stage II and III gastric cancer patients but remain to be determined in stage I gastric cancer patients.

BackgroundEmerging evidence shows that serum tumor biomarkers (TBs) and log odds of positive lymph node scheme (LODDS) are closely associated with the prognosis of colorectal cancer (CRC) patients. The aim of our study is to validate the predictive value of TBs and LODDS clinically and to develop a robust prognostic model to predict the overall survival (OS) of patients with CRC.MethodsCRC patients who underwent radical resection and with no preoperative chemotherapy were enrolled in the study. The eligible population were randomized into training (70%) and test (30%) cohorts for the comprehensive evaluation of the prognostic model. Clinical implications of serum biomarkers and LODDS were identified by univariate and multivariate Cox proportion regression analysis. The predictive ability and discriminative performance were evaluated by Kaplan–Meier (K–M) curves and receiver operating characteristic (ROC) curves. Clinical applicability of the prognostic model was assessed by decision curve analysis (DCA), and the corresponding nomogram was constructed based on the above factors.ResultsA total of 1,202 eligible CRC patients were incorporated into our study. Multivariable COX analysis demonstrated that CA199 (HR = 1.304), CA125 (HR = 1.429), CEA (HR = 1.307), and LODDS (HR = 1.488) were independent risk factors for OS (all P < 0.0001). K–M curves showed that the high-risk group possessed a shorter OS than the low-risk counterparts. The area under curves (AUCs) of the model for 1-, 3- and 5-year OS were 86.04, 78.70, and 76.66% respectively for the train cohort (80.35, 77.59, and 74.26% for test cohort). Logistic DCA and survival DCA confirmed that the prognostic model displayed more clinical benefits than the conventional AJCC 8th TNM stage and CEA model. The nomograms were built accordingly, and the calibration plot for the probability of survival at 3- or 5-years after surgery showed an optimal agreement between prediction and actual observation.ConclusionsPreoperative serum TBs and LODDS have significant clinical implications for CRC patients. A novel prognostic model incorporating common TBs (CA199, CA125, and CEA) and LODDS displayed better predictive performance than both single factor and the TNM classification. A novel nomogram incorporating TBs and LODDS could individually predict OS in patients with CRC.

Metabolic changes, especially in glucose metabolism, are widely established during the occurrence and development of tumors and regarded as biological markers of pan-cancer. The well-known ‘Warburg effect’ demonstrates that cancer cells prefer aerobic glycolysis even if there is sufficient ambient oxygen. Accumulating evidence suggests that aerobic glycolysis plays a pivotal role in colorectal cancer (CRC) development. However, few studies have examined the relationship of glycolytic gene clusters with prognosis of CRC patients. Here, our aim is to build a glycolysis-associated gene signature as a biomarker for colorectal cancer. The mRNA sequencing and corresponding clinical data were downloaded from TCGA and GEO databases. Gene set enrichment analysis (GSEA) was performed, indicating that four gene clusters were significantly enriched, which revealed the inextricable relationship of CRC with glycolysis. By comparing gene expression of cancer and adjacent samples, 236 genes were identified. Univariate, multivariate, and LASSO Cox regression analyses screened out five prognostic-related genes (ENO3, GPC1, P4HA1, SPAG4, and STC2). Kaplan–Meier curves and receiver operating characteristic curves (ROC, AUC = 0.766) showed that the risk model could become an effective prognostic indicator (P < 0.001). Multivariate Cox analysis also revealed that this risk model is independent of age and TNM stages. We further validated this risk model in external cohorts (GES38832 and GSE39582), showing these five glycolytic genes could emerge as reliable predictors for CRC patients’ outcomes. Lastly, based on five genes and risk score, we construct a nomogram model assessed by C-index (0.7905) and calibration plot. In conclusion, we highlighted the clinical significance of glycolysis in CRC and constructed a glycolysis-related prognostic model, providing a promising target for glycolysis regulation in CRC.

For the problem of the system state variable taking a long time to reach the sliding mode surface and the chattering frequency being high in the sliding mode surface, a sliding mode control method based on the adaptive reaching law is proposed, the system state variable is introduced based on the subreaching law, and an improved variable-speed reaching law is added with reference to the characteristics of the hyperbolic tangent function. The sliding mode control method is divided into two stages, namely, the initial state to the critical value s = ±1 and the system state variable reaching the equilibrium point of the sliding mode surface, and the total time obtained is less than the sum of these two stages. Secondly, this method is adopted in the electro-hydraulic position servo system, and a sliding mode controller is established. Through an AMESim/Simulink co-simulation, it is compared with the sliding mode controller based on the traditional exponential reaching law. The results show that this method can effectively reduce the jitter of the system, reduce the time for the system to reach the sliding surface, and improve the robustness of the system.

PurposeTo investigate the impact on services for rhegmatogenous retinal detachment (RRD) patients during the COVID-19 (2019coronal virus disease) pandemic in one tertiary center in Beijing.MethodsA retrospective cohort study. Two reviewed consecutive RRD patients cohorts of the same length were treated during two different periods: the COVID-19 pandemic and the pre-COVID-19 group. The characteristics of patients, surgery, anesthesia methods, length of hospital stay, and the latest follow-up were recorded and analyzed.ResultsThere were 79 patients in the COVID-19 pandemic group with a 55.9% reduction (179). Compared to patients in the pre-COVID-19, patients in the COVID-19 pandemic had a longer presurgical waiting times (28days, 3days, pConclusionThe COVID-19 pandemic lockdown caused prolonged presurgical waiting times, shorter hospital stays, less general anesthesia, and a significant reduction of RRD surgeries. The RD were more complicated, the surgeons were more conservative on procedures and patients selection, while the surgery outcomes were comparable.

Background: Paracellular barriers play an important role in the pathogenesis of Inflammatory bowel disease (IBD) and maintain gut homeostasis. N-myc downstream-regulated gene 2 (NDRG2) has been reported to be a tumour suppressor gene and to inhibit colorectal cancer metastasis. However, whether NDRG2 affects colitis initiation and colitis-associated colorectal cancer is unclear. Methods: Intestine-specific Ndrg2 deficiency mice (Ndrg2ΔIEC) were subjected to DSS- or TNBS-induced colitis, and AOM-DSS-induced colitis-associated tumour. HT29 cells, Caco2 cells, primary intestinal epithelial cells (IECs) from Ndrg2ΔIEC mice, mouse embryo fibroblasts (MEFs) from systemic Ndrg2 knockout mice, HEK293 cells and human UC and DC specimens were used to investigate NDRG2 function in colitis and colitis-associated tumour. Findings: Ndrg2 loss led to adherens junction (AJ) structure destruction via E-cadherin expression attenuation, resulting in diminished epithelial barrier function and increased intestinal epithelial permeability. Mechanistically, NDRG2 enhanced the interaction of E3 ligase FBXO11 with Snail, the repressor of E-cadherin, to promote Snail degradation by ubiquitination and maintained E-cadherin expression. In human ulcerative colitis patients, reduced NDRG2 expression is positively correlated with severe inflammation. Interpretation: These findings demonstrate that NDRG2 is an essential colonic epithelial barrier regulator and plays an important role in gut homeostasis maintenance and colitis-associated tumour development. Funding: National Natural Science Foundation of China (No. 81770523, 31571437, 81672751), Creative Research Groups of China (No. 81421003), State Key Laboratory of Cancer Biology Project (CBSKL2019ZZ11, CBSKL201406, CBSKL2017Z08 and CBSKL2017Z11), Fund for Distinguished Young Scholars of ShaanXi province (2019JC-22).

Application of sand can ameliorate rice paddy fields converted from saline–sodic land. However, the requirement of huge amount of sand has been limiting its practical application. In this study, flushing during saline sodic-sensitive stages of rice plant growth was incorporated into the ameliorating system to reduce the sand usage. A split-plot design was adopted with sand application (SA) with two levels as main plots and flushing during the sensitive stages (FL) with two levels as subplots in a hard saline–sodic soil, Northeast China. Four treatments included CK (no-sand, no-flush flooding), NF (non-sand, flush flooding), SN (sand, no-flush flooding), and SF (sand, flush flooding). The results showed that both SA and FL significantly affected all the investigated yield parameters. The combined effect of SA and FL on the grain yield was additive in the first year in respect of the effect on panicle density and seed weight per panicle; while it showed synergistic effect on the seed weight per panicle and grain yield in the second year. The rice yield in different treatments was in the order of SF > SN > NF > CK in both years, with the highest yield (4.37 t ha−1) obtained by SF treatment in the second year. Our results demonstrate that half the traditional amount of sand in combination with water-flushing during the saline–sodic-sensitive growth stages of rice is sufficiently effective in ameliorating saline–sodic soil and thereby enhancing rice grain yield in saline–sodic paddy fields.

Long non-coding RNAs have been implicated in human cancer but their mechanisms of action are mainly undocumented. In this study, we found that HOXA11-AS expression was upregulated in non–small cell lung cancer tissues and cell lines. High levels of HOXA11-AS expression were correlated with larger tumor size and lymph node metastasis. Functional analysis revealed that HOXA11-AS promotes non–small cell lung cancer cell proliferation and invasion. In particular, HOXA11-AS functions as a competing endogenous RNA to regulate transcriptional factor Sp1 expression via sponging miR-124. Collectively, our findings reveal an oncogenic role for HOXA11-AS in non–small cell lung cancer tumorigenesis.

The capacity of silencing genes makes small interfering RNA (siRNA) appealing for curing fatal diseases. However, the naked siRNA is vulnerable to and degraded by endogenous enzymes and is too large and too negatively charged to cross cellular membranes. An effective siRNA carrier, PMAL (poly(maleic anhydride-alt-1-decene) substituted with 3-(dimethylamino) propylamine), has been demonstrated to be able to assist siRNA transmembrane by both experiments and molecular simulation. In the present work, the mechanism of siRNA transmembrane assisted by PMAL was studied using steered molecular dynamics simulations based on the martini coarse-grained model. Here two pulling rates, i.e., 10−6 and 10−5 nm·ps−1, were chosen to imitate the passive and active transport of siRNA, respectively. Potential of mean force (PMF) and interactions among siRNA, PMAL, and lipid bilayer membrane were calculated to describe the energy change during siRNA transmembrane processes at various conditions. It is shown that PMAL-assisted siRNA delivery is in the mode of passive transport. The PMAL can help siRNA insert into lipid bilayer membrane by lowering the energy barrier caused by siRNA and lipid bilayer membrane. PMAL prefers to remain in the lipid bilayer membrane and release siRNA. The above simulations establish a molecular insight of the interaction between siRNA and PMAL and are helpful for the design and applications of new carriers for siRNA delivery.

CD147 is correlated with tumor aggressiveness in various human malignancies. Here, we investigated CD147 protein expression in 223 patients with gastric cancer by immunohistochemistry and analyzed its association with disease-free and overall survival. CD147 was increased in gastric cancer compared to normal tissues. Additionally, CD147 expression was associated with gastric cancer invasion, metastasis and TNM stage, whereas it was not related to age, sex, differentiation status, tumor site or Lauren classification. Kaplan-Meier analysis confirmed that CD147 was associated with disease-free and overall survival in patients with gastric cancer; i.e., patients with positive CD147 staining tend to have worse disease-free and overall survival. Moreover, Cox's proportional hazards analysis demonstrated that CD147 was an independent marker of disease-free and overall survival for patients with gastric cancer. These results confirm the association of CD147 with gastric cancer invasion and metastasis and prove that CD147 might be an indicator of tumor recurrence and prognosis in gastric cancer.

MicroRNAs are noncoding RNAs that regulate multiple cellular processes during cancer progression. Among various microRNAs, MiR-630 has recently been identified to be implicated in many critical processes in human malignancies. We aimed to investigate the significance and prognostic value of miR-630 in human gastric cancer. Gastric cancer and adjacent normal specimens from 236 patients from who had not received neoadjuvant chemotherapy were collected. The expression of miR-630 was investigated by quantitative real-time PCR assay and its association with overall survival of patients was analyzed by statistical analysis. MiR-630 expression level was significantly elevated in gastric cancer in comparison to adjacent normal specimens. It is also proved that miR-630 expression was to be associated with gastric cancer invasion, lymph node metastasis, distant metastasis and TNM stage. In addition, survival analysis proved that elevated miR-630 expression was associated with poor overall survival of patients. Multivariate survival analysis also proved that miR-630 was an independent prognostic marker after adjusted for known prognostic factors. The present study proved the over-expression of miR-630 and its association with tumor progression in human gastric cancer. It also provided the first evidence that miR-630 expression was an independent prognostic factor for patients with gastric cancer, which might be a potential valuable biomarker for gastric cancer.

We report a facile approach to preparing laponite (LAP) bioceramics via sintering LAP powder compacts for bone tissue engineering applications. The sintering behavior and mechanical properties of LAP compacts under different temperatures, heating rates, and soaking times were investigated. We show that LAP bioceramic with a smooth and porous surface can be formed at 800°C with a heating rate of 5°C/h for 6 h under air. The formed LAP bioceramic was systematically characterized via different methods. Our results reveal that the LAP bioceramic possesses an excellent surface hydrophilicity and serum absorption capacity, and good cytocompatibility and hemocompatibility as demonstrated by resazurin reduction assay of rat mesenchymal stem cells (rMSCs) and hemolytic assay of pig red blood cells, respectively. The potential bone tissue engineering applicability of LAP bioceramic was explored by studying the surface mineralization behavior via soaking in simulated body fluid (SBF), as well as the surface cellular response of rMSCs. Our results suggest that LAP bioceramic is able to induce hydroxyapatite deposition on its surface when soaked in SBF and rMSCs can proliferate well on the LAP bioceramic surface. Most strikingly, alkaline phosphatase activity together with alizarin red staining results reveal that the produced LAP bioceramic is able to induce osteoblast differentiation of rMSCs in growth medium without any inducing factors. Finally, in vivo animal implantation, acute systemic toxicity test and hematoxylin and eosin (H&E)-staining data demonstrate that the prepared LAP bioceramic displays an excellent biosafety and is able to heal the bone defect. Findings from this study suggest that the developed LAP bioceramic holds a great promise for treating bone defects in bone tissue engineering.

PURPOSE:This study investigates the neck/shoulder pain (NSP) and low back pain (LBP) among current high school students in Shanghai and explores the relationship between these pains and their possible influences, including digital products, physical activity, and psychological status. METHODS:An anonymous self-assessment was administered to 3,600 students across 30 high schools in Shanghai. This questionnaire examined the prevalence of NSP and LBP and the level of physical activity as well as the use of mobile phones, personal computers (PC) and tablet computers (Tablet). The CES-D (Center for Epidemiological Studies Depression) scale was also included in the survey. The survey data were analyzed using the chi-square test, univariate logistic analyses and a multivariate logistic regression model. RESULTS:Three thousand sixteen valid questionnaires were received including 1,460 (48.41%) from male respondents and 1,556 (51.59%) from female respondents. The high school students in this study showed NSP and LBP rates of 40.8% and 33.1%, respectively, and the prevalence of both influenced by the student's grade, use of digital products, and mental status; these factors affected the rates of NSP and LBP to varying degrees. The multivariate logistic regression analysis revealed that Gender, grade, soreness after exercise, PC using habits, tablet use, sitting time after school and academic stress entered the final model of NSP, while the final model of LBP consisted of gender, grade, soreness after exercise, PC using habits, mobile phone use, sitting time after school, academic stress and CES-D score. CONCLUSIONS:High school students in Shanghai showed high prevalence of NSP and LBP that were closely related to multiple factors. Appropriate interventions should be implemented to reduce the occurrences of NSP and LBP.