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Abstract Background Colorectal cancer (CRC) is considered as an age-related disease, and cellular senescence (CS) plays a crucial role in cancer development and progression. Previous studies have shown the role of epigenetic changes in aging and cancer development, but the role of RNA pseudouridine (Ψ) modification in aging and cancer remains to be explored. Results Using bulk RNA sequencing, CRC cells with low Ψ writers expression levels have higher CS levels. We developed the Psi Score for assessing the transcriptomic profile of RNA Ψ modification regulation and found that the Psi Score correlates with CS. Furthermore, Psi-related senescence may be mediated by mTOR, TGF-β, TNF-α, and inflammatory response signaling pathways. Meanwhile, Psi Score could predict the anti-cancer treatment outcomes of anti-aging interventions and could be used to predict the response to immunotherapy. Conclusions Overall, these findings reveal that RNA Ψ modification connected aging and cancer and provided novel insights into biomarker-guided cancer regimens.

Abstract Background Intratumoral heterogeneity emerges from accumulating genetic and epigenetic changes during tumorigenesis, which may contribute to therapeutic failure and drug resistance. However, the lack of a quick and convenient approach to determine the intratumoral epigenetic heterogeneity (eITH) limit the application of eITH in clinical settings. Here, we aimed to develop a tool that can evaluate the eITH using the DNA methylation profiles from bulk tumors. Methods Genomic DNA of three laser micro-dissected tumor regions, including digestive tract surface, central bulk, and invasive front, was extracted from formalin-fixed paraffin-embedded sections of colorectal cancer patients. The genome-wide methylation profiles were generated with methylation array. The most variable methylated probes were selected to construct a DNA methylation-based heterogeneity (MeHEG) estimation tool that can deconvolve the proportion of each reference tumor region with the support vector machine model-based method. A PCR-based assay for quantitative analysis of DNA methylation (QASM) was developed to specifically determine the methylation status of each CpG in MeHEG assay at single-base resolution to realize fast evaluation of epigenetic heterogeneity. Results In the discovery set with 79 patients, the differentially methylated CpGs among the three tumor regions were found. The 7 most representative CpGs were identified and subsequently selected to develop the MeHEG algorithm. We validated its performance of deconvolution of tumor regions in an independent cohort. In addition, we showed the significant association of MeHEG-based epigenetic heterogeneity with the genomic heterogeneity in mutation and copy number variation in our in-house and TCGA cohorts. Besides, we found that the patients with higher MeHEG score had worse disease-free and overall survival outcomes. Finally, we found dynamic change of epigenetic heterogeneity based on MeHEG score in cancer cells under the treatment of therapeutic drugs. Conclusion By developing a 7-loci panel using a machine learning approach combined with the QASM assay for PCR-based application, we present a valuable method for evaluating intratumoral heterogeneity. The MeHEG algorithm offers novel insights into tumor heterogeneity from an epigenetic perspective, potentially enriching current knowledge of tumor complexity and providing a new tool for clinical and research applications in cancer biology.

Abstract Background context Physical activities such as walking and climbing stairs are pervasive in human daily life. Individuals with scoliosis frequently encounter dysfunction in their muscle recruitment. Multiple studies have corroborated the presence of muscle dysfunction in individuals diagnosed with scoliosis. However, there is currently a noteworthy research gap regarding the exploration of changes in muscle characteristics and disparities from those observed in individuals without scoliosis during everyday activities, specifically stair climbing. Purpose This study aims to examine the unique patterns of muscle activity during daily life in individuals with scoliosis and distinguish the specific differences between scoliosis patients and the healthy controls. The findings of this study are significantly important for the future accurate assessment of scoliosis and the development of rehabilitation treatment plans. Study design Case–control study. Sample size Twenty eight idiopathic scoliosis patients and twenty eight controls. Outcome measures Root Mean Square(RMS), Maximum Voluntary Isometric Contraction(MVIC)%, RMS ratio(RMS convex / RMS concave). Methods The surface electromyography (sEMG) device used in this study was the Delsys Trigno, with a sampling frequency of 1500 Hz. It recorded the activation level, peak contraction, and average activation level of the erector spinae (at T6, T10, and L3 levels), gluteus maximus, gluteus medius, external oblique, and rectus abdominis muscles during three different types of locomotion for both the 28 individuals with idiopathic scoliosis and the 28 control participants. Results The movement patterns of the idiopathic scoliosis patients significantly differ from those of the normal population during level walking and ascending or descending stairs. In level walking, there is an asymmetry in the activation levels of the T6 and L3 erector spinae muscles, with lower activation on the convex side compared to the concave side. Similarly, during stair ascent, the activation of the T6 and T10 erector spinae muscles is asymmetric, with higher activation on the convex side than the concave side. Moreover, during stair descent, the activation of the T6 erector spinae muscle is asymmetric, with higher activation on the convex side than the concave side. Conclusions During level walking and stair activities, idiopathic scoliosis patients exhibit pronounced abnormal movement patterns that significantly differ from those of the control group. Under different activity conditions such as level walking, ascending and descending stairs, idiopathic scoliosis patients demonstrate abnormal muscle activation in different segments of the spine. It is crucial for clinicians to prioritize the symmetry of muscle activation in the spinal region of idiopathic scoliosis patients and consider incorporating symmetry training for these muscles.

IntroductionStroke patients with hemiplegia are at an increased risk of falling during sit-to-stand (Si-St) and stand-to-sit (St-Si) tasks, partly due to impaired bilateral lower limb symmetry. Maintaining symmetrical movement between the limbs in these tasks can help reduce fall incidence.MethodThis study aimed to investigate bilateral lower limb symmetry during Si-St and St-Si tasks in stroke patients with hemiplegia to compare their performance with healthy controls. Thirteen stroke patients and 13 healthy controls participated in the study. Participants were instructed to perform the 30-s chair stand test at their self-selected pace. Kinematic and kinetic parameters were calculated using OpenSim's inverse kinematics and inverse dynamics tools. Bilateral symmetry was quantified using the symmetry index (SI), with an asymmetry threshold set at 10%.ResultsThe stroke group exhibited significantly greater lower limb asymmetry in both kinematic and kinetic parameters during Si-St and St-Si tasks compared to the healthy controls, with the kinetic parameters being more pronounced. In the stroke group, notable bilateral asymmetry (SI > 10%) was observed in the ankle joint angle (P < 0.05) during both tasks. Furthermore, severe asymmetry (SI > 30%) was identified joint moments across all lower limb joints, vertical ground reaction forces, and medial-lateral center of pressure.DiscussionThese findings highlight the need for targeted rehabilitation programs focusing on improving strength, coordination, and balance. Close monitoring of SI values, particularly for kinetic parameters, is recommended to guide and evaluate the effectiveness of these interventions.

Abstract Background Immunotherapy is beneficial for some colorectal cancer (CRC) patients, but immunosuppressive networks limit its effectiveness. Cancer‐associatedfibroblasts (CAFs) are significant in immune escape and resistance toimmunotherapy, emphasizing the urgent need for new treatment strategies. Methods Flow cytometric, Western blotting, proteomics analysis, analysis of public database data, genetically modified cell line models, T cell coculture, crystal violetstaining, ELISA, metabonomic and clinical tumour samples were conducted to assess the role of EDEM3 in immune escape and itsmolecular mechanisms. We evaluated theeffects of FMD plus 2‐DG on antitumour immunity using multipleximmunofluorescence, flow cytometry, cytokine profiling, TUNEL assays, xenografttumours, and in vivo studies. Results We show thatCAFs upregulate PD‐L1 glycosylation and contribute to immune evasion byglycosyltransferase EDEM3. Additionally, EDEM3 plays a role in tumour immunityduring tumour progression. However, the EDEM3‐mediated upregulation of PD‐L1 expression underpins PD‐1/PD‐L1 blockade resistance in vivo. This finding contradictsthe previous trend that positive PD‐L1 expression indicates a strong responseto PD‐1/PD‐L1 blockade. Mechanistically, high‐EDEM3 expression facilitates M2‐like This finding contradictsthe previous trend that positive PD‐L1 expression indicates a strong responseto PD‐1/PD‐L1 blockade.Mechanistically, polarizationand chemotactic migration of macrophages, which are enriched in theperipheral region of tumours compared to thecore region, precluding access of CD8+ T cells to tumourfoci. Furthermore, we EDEM3 predominantly activates the recruited M2‐like macrophagesvia a glucose metabolism‐dependent mechanism. Manipulationof glucose utilization by a fasting‐mimicking diet(FMD) plus 2‐DG treatmentsynergistically with PD‐1 antibody elicits potent antitumour activity byeffectively decreasing tumour glycosylated PD‐L1 expression, augmenting the CD8+effector T cell infiltration and activation while concurrently reducing the infiltration.TheCAFs‐EDEM3‐M2‐like macrophage axis plays a critical role in promotingimmunotherapy resistance. infiltration.TheCAFs‐EDEM3‐M2‐like macrophage axis plays a critical role in promotingimmunotherapy resistance. Conclusions Our study suggests that blocking EDEM3‐induced M2‐like macro phage trafficking by FMD plus 2‐DG is a promising and effective strategy to overcomeresistance to checkpoint blockade therapy offeringhope for improved treatment outcomes. Key points Cancer‐associated fibroblasts (CAFs) can enhance PD‐L1 glycosylation through the glycosyltransferase EDEM3, contributing to immune evasion during tumour progression. EDEM3 predominantly activates the recruit M2‐like macrophages via a glucose metabolism‐dependent mechanism. Blocking glucose utilization antagonizes recruiting and polarizing M2‐like macrophages synergistically with PD‐1 antibody to improve anticancer immunity.

Objective: Rituximab (RTX) has been recommended to treat nephrotic syndrome (NS), but its safety has not been quantitatively analyzed. Methods: PubMed, Embase, and the Cochrane Register of Controlled Trials databases were searched from inception to December 31, 2023, for randomized control trials (RCTs) and retrospective studies reporting the adverse events (AEs) related to RTX for treating NS. Data were expressed as odds ratios (OR) and risk difference (RD) with 95 % confidence interval (CI). Heterogeneity was identified using the Cochrane Q test and quantified by the I2 statistic. Results: Ten RCTs and five retrospective studies with 1231 patients were enrolled. RTX significantly reduced the risk of total AEs (OR = 0.32, 95 % CI [0.13, 0.78]) compared to the non-RTX group in retrospective studies but was not in RCTs. The pooled rate of infusion reactions was 32 % (95 % CI = [19 %, 45 %]) in RCTs and 8 % (95 % CI = [3 %, 13 %]) in retrospective studies. Subgroup analyses demonstrated a lower risk of hematological events in adult NS patients (OR = 0.21, 95 % CI [0.09, 0.51]) and the 1000 mg RTX intervention (OR = 0.21, 95 % CI [0.09, 0.51]). There is no significant difference in serious AEs, infection, gastrointestinal, renal, cardiovascular, and cancer events between the two groups. Conclusion: RTX reveals great potential in terms of safety compared to non-RTX treatments due to the relatively few AEs in our results. However, the interaction of other drugs needs to be monitored. The safety of RTX in NS patients needs to be further confirmed in high-quality clinical trials.

Abstract Background The radiogenomic analysis has provided valuable imaging biomarkers with biological insights for gliomas. The radiogenomic markers for molecular profile such as DNA methylation remain to be uncovered to assist the molecular diagnosis and tumor treatment. Methods We apply the machine learning approaches to identify the magnetic resonance imaging (MRI) features that are associated with molecular profiles in 146 patients with gliomas, and the fitting models for each molecular feature (MoRad) are developed and validated. To provide radiological annotations for the molecular profiles, we devise two novel approaches called radiomic oncology (RO) and radiomic set enrichment analysis (RSEA). Results The generated MoRad models perform well for profiling each molecular feature with radiomic features, including mutational, methylation, transcriptional, and protein profiles. Among them, the MoRad models have a remarkable performance in quantitatively mapping global DNA methylation. With RO and RSEA approaches, we find that global DNA methylation could be reflected by the heterogeneity in volumetric and textural features of enhanced regions in T2-weighted MRI. Finally, we demonstrate the associations of global DNA methylation with clinicopathological, molecular, and immunological features, including histological grade, mutations of IDH and ATRX, MGMT methylation, multiple methylation-high subtypes, tumor-infiltrating lymphocytes, and long-term survival outcomes. Conclusions Global DNA methylation is highly associated with radiological profiles in glioma. Radiogenomic global methylation is an imaging-based quantitative molecular biomarker that is associated with specific consensus molecular subtypes and immune features.

Abstract Background Microwave ablation (MWA) is widely used to eliminate colorectal liver metastases (CRLM). However, the risk of tumor recurrence is difficult to predict due to lack of reliable clinical and biological markers. Elevation of gamma-glutamyl transferase (GGT) and aspartate transaminase (AST) provides signals for liver inflammation and cancer progression. The present study evaluated the association between pre-ablation GGT to AST ratio index (GSR) and hepatic recurrence in patients with CRLM after MWA. Methods A retrospectively analyzed 192 CRLM patients who underwent MWA from January 2013 to December 2017. Pre-ablation GSR was classified into high (≤ 2.34) or low (> 2.34) using the upper quartile value. The prognostic value of GSR and other risk factors for liver progression-free survival (LPFS) and cancer-specific survival (CSS) were evaluated by univariate and multivariate analyses. Results High GSR was significantly associated with males (P = 0.041), the presence of cholelithiasis (P = 0.012), but not pre-ablation chemotherapy (P = 0.355), which caused significantly increased levels of GGT (P = 0.015) and AST (P = 0.008). GSR showed a significant association with LPFS and CSS through univariate analysis (P = 0.002 and 0.006) and multivariate analysis (P = 0.043 and 0.037). The subgroup analysis demonstrated no interaction between GSR and all variables except for distribution in the sub-analysis of LPFS. Conclusions Our findings suggest that the pre-ablation GSR can be considered as a promising prognostic indicator for poor prognosis of patients with CRLM underwent MWA. Trial registration Not applicable.

Abstract Traditional total mesorectal excision (TME) for rectal cancer requires partial resection of Denonvilliers’ fascia (DVF), which leads to injury of pelvic autonomic nerve and postoperative urogenital dysfunction. It is still unclear whether entire preservation of DVF has better urogenital function and comparable oncological outcomes. We conducted a randomized clinical trial to investigate the superiority of DVF preservation over resection (NCT02435758). A total of 262 eligible male patients were randomized to Laparoscopic TME with DVF preservation (L-DVF-P group) or resection procedures (L-DVF-R group), 242 of which completed the study, including 122 cases of L-DVF-P and 120 cases of L-DVF-R. The initial analysis of the primary outcomes of urogenital function has previously been reported. Here, the updated analysis and secondary outcomes including 3-year survival (OS), 3-year disease-free survival (DFS), and recurrence rate between the two groups are reported for the modified intention-to-treat analysis, revealing no significant difference. In conclusion, L-DVF-P reveals better postoperative urogenital function and comparable oncological outcomes for male rectal cancer patients.

Abstract Background Patients with DNA mismatch repair‐proficient/microsatellite stable (pMMR/MSS) colorectal cancer (CRC), which accounts for 85% of all CRC cases, display a poor respond to immune checkpoint inhibitors (i.e., anti‐PD‐1 antibodies). pMMR/MSS CRC patients with locally advanced cancers need effective combined therapies. Methods In this pilot study, we administered six preoperative doses of each 2‐week cycle of the anti‐PD‐1 antibody sintilimab (at a fixed dose of 200 mg), oxaliplatin, and 5‐FU/CF (mFOLFOX6) combined with five doses of bevacizumab (the number of doses was reduced to prevent surgical delays) to patients with cT4NxM0 colon or upper rectal cancers. And radical surgery was performed approximately 2 weeks after the last dose of neoadjuvant therapy. The primary endpoint was a pathologic complete response (pCR). We also evaluated major pathologic response (MPR, ≤10% residual viable tumor), radiological and pathological regression, safety, and tumor mutation burden (TMB), and tumor microenvironment (TME) characteristics. Results By the cutoff date (September 2023), 22 patients with cT4NxM0 pMMR/MSS colon or upper rectal cancers were enrolled and the median follow‐up was 24.7 months (IQR: 21.1–26.1). All patients underwent R0 surgical resection without treatment‐related surgical delays. pCR occurred in 12 of 22 resected tumors (54.5%) and MPR occurred in 18 of 22 (81.8%) patients. At the cutoff date, all patients were alive, and 21/22 were recurrence‐free. Treatment‐related adverse events of grade 3 or higher occurred in of 2/22 (9.1%) patients. Among the pCR tumors, two were found to harbor POLE mutations. The degree of pathological regression was significantly greater than that of radiological regression (p = 1.35 × 10−8). The number of CD3+/CD4+ cells in the tumor and stroma in pretreated biopsied tissues was markedly lower in pCR tumors than in non‐pCR tumors (p = 0.038 and p = 0.015, respectively). Conclusions Neoadjuvant sintilimab combined with bevacizumab and mFOLFOX6 was associated with few side effects, did not delay surgery, and led to pCR and non‐pCR in 54.5% and 81.8% of the cases, respectively. Downregulation of CD3/CD4 expression in the tumor and stroma is related to pCR. However, the molecular mechanisms underlying PD‐1 blockade‐enhanced targeted chemotherapy require further investigation.

Abstract Background Inter-joint coordination is an important factor affecting postural stability, and its variability increases after fatigue. This study aimed to investigate the coordination pattern of lower limb joints during the sit-to-stand (Si-St) and stand-to-sit (St-Si) tasks in stroke patients and explore the influence of duration on inter-joint coordination. Methods Thirteen stroke hemiplegia patients (five with left paretic and eight right paretic) and thirteen age-matched healthy subjects were recruited. The Si-St and St-Si tasks were performed while each subject’s joint kinematics were recorded using a three-dimensional motion capture system. Sagittal joint angles of the bilateral hip, knee and ankle joints as well as the movement duration were extracted. The angle-angle diagrams for the hip-knee, hip-ankle and knee-ankle joint were plotted to assess the inter-joint coordination. The inter-joint coordination was quantified using geometric characteristics of the angle-angle diagrams, including perimeter, area and dimensionless ratio. The coefficient of variation (CV) was performed to compare variability of the coordination parameters. Results There were no significant differences in the perimeter, area and dimensionless ratio values of the bilateral hip-knee, hip-ankle and knee-ankle inter-joints during Si-St and St-Si tasks in the stroke group. The perimeter values of bilateral hip-knee and knee-ankle inter-joints in the stroke group were lower (P

Helicobacter pylori (H. pylori) infection may alter the host’s resistance to tsutsugamushi disease pathogens through the Th1 immune response, leading to potential synergistic pathogenic effects. A total of 117 scrub typhus cases at Beihai People’s Hospital and affiliated hospitals of Youjiang University for Nationalities and Medical Sciences were studied from January to December 2022, alongside 130 healthy individuals forming the control group. All participants underwent serum H. pylori antibody testing. The prevalence of H. pylori infection was significantly higher among scrub typhus patients (89.7%) compared to healthy individuals (54.6%) (p

Purpose: This study aims to explore the dynamic balance of human beings and investigate the relationship between functional structure as well as functional connectivity. Through a comprehensive bibliometric and visual analysis of the research literature from 1995 to 2022, we quantitatively display the development of the dynamic balance and brain structure as well as functional connection. Our objective is to present new trends and frontiers in the study of dynamic balance and brain function through bibliometrics software, providing valuable insights for future research in this domain. Methods: The literature on dynamic balance, brain structure and functional connectivity between 1995 and 2022 was retrieved from the Web of Science database. We employed CiteSpace software to analyze various aspects, including the year of publication, journal, authors, keywords, institutions, countries, and references. Based on the analysis results, a co-reference map was generated to visually observe research hotspots and knowledge structures. Results: A total of 1533 records were retrieved during the survey period (1995–2022), with a gradually increase in the number of annual publications. Notably, the data suggests a notable increase in publications between 2020 and 2021. The number of publications increased by 20 % from 2020 to 2021. The journal “Proceedings of the National Academy of Sciences (PNAS)” emerged as the most prolific journal. Among the cited authors, Deco and Gustavo ranked at the top. Key research terms in this field include ''neural network'', ''functional connectivity'', ''dynamic'', ''model'' and ''brain''. Particularly, the keyword ''neural network'' exhibited the strongest growth. The analysis of keywords cluster revealed the top 10 clusters of research themes. Oxford University stood out as the most productive institution, while the United States held the greatest influence with the highest number of publications and centrality. The reference cluster analysis further demonstrated the top 10 clusters in the literature. Conclusion: Through the use of CiteSpace software, this study performed a comprehensive bibliometric and visual analysis of the Web of Science research literature on human dynamic balance and brain structural as well as functional connectivity over the past few decades. This may help researchers identify new perspectives on potential collaborators as well as collaborating institutions, hot topics, and research frontiers in the research field. The results provided an intuitive displayed overview of research trends, hotspots and frontiers in this field, facilitating a general understanding of its progression. Through unremitting efforts, it provides valuable guidance and reference for future research work.

Abstract Background The relationship between the radiological lymph node (rLN) size and survival outcome in node‐negative rectal cancer is still uncertain. In this study, we aimed to explore the role of enlarged rLN in predicting the survival of node‐negative rectal cancers. Methods We retrospectively reviewed the records of 722 node‐negative rectal cancer who underwent curative resection. Factors associated with DFS (disease‐free survival) and CSS (cancer‐specific survival) were assessed with univariate and multivariate analysis. Survival analysis was performed according to presence with or without enlarged rLN. Combining rLN with NLR as a new index‐inflammation immune score (IIS) for predicting survival. Comparing different models to assess the predictive powers. Results A total of 119 patients had tumor recurrence and 73 patients died due to cancer. Patients with enlarged rLN (≥5 mm) was significantly associated with better DFS (HR:0.517, 95%CI:0.339–0.787, p = 0.002) and CSS (HR:0.43, 95%CI:0.242–0.763, p = 0.004). The risk factors of recurrence were rLN, neutrophil‐lymphocyte ratio (NLR), CEA level, and distance from the anal verge. The risk of recurrence increased by 1.88‐ and 2.83‐fold for the high score in IIS compared with the low and intermediate score group (All p

Abstract Background DNA methylation is one of the most promising biomarkers in predicting the prognosis of colorectal cancer (CRC). We aimed to develop a DNA methylation biomarker that could evaluate the prognosis of CRC. Methods A promising DNA methylation biomarker was developed by hypermethylated genes in cancer tissue that were identified from Illumina EPIC methylation arrays. A cohort comprising 30 pairs of snap-frozen tumor tissue and adjacent normal tissue was used for correlation analysis between the methylation and expression status of the marker. The other cohort comprising 254 formalin-fixed paraffin-embedded (FFPE) tumor tissue from 254 CRC patients was used for prognosis analysis. Results Regulating synaptic membrane exocytosis 2 (RIMS2) was hypermethylated and lowly expressed in CRC comparing to adjacent normal tissue. Hypermethylation of RIMS2 in CRC was correlated with less frequent KRAS mutant and high differentiation. RIMS2 promoter methylation showed independent predictive value for survival outcome (P = 0.015, HR 1.992, 95% CI [(1.140–3.48)]), and a combination of RIMS2 methylation with KRAS status could predict prognosis better. Conclusions RIMS2 is frequently hypermethylated in CRC, which can silence the expression of RIMS2. RIMS2 methylation is a novel biomarker for predicting the prognosis of CRC.

Abstract Background The incidence of colorectal cancer is increasing among young adults and more rectal cancers are reported. This study aimed to identify the clinical features specific for early‐onset rectal cancer and provide insights on cancer management. Methods Early‐onset (

Spasticity is a complex neurological disorder, causing significant physical disabilities and affecting patients' independence and quality of daily lives. Current spasticity assessment methods are questioned for their non-standardized measurement protocols, limited reliabilities, and capabilities in distinguishing neuron or non-neuron factors in upper motor neuron lesion. A series of new approaches are developed for improving the effectiveness of current clinical used spasticity assessment methods with the developing technology in biosensors, robotics, medical imaging, biomechanics, telemedicine, and artificial intelligence. We investigated the reliabilities and effectiveness of current spasticity measures employed in clinical environments and the newly developed approaches, published from 2016 to date, which have the potential to be used in clinical environments. The new spasticity scales, taking advantage of quantified information such as torque, or echo intensity, the velocity-dependent feature and patients' self-reported information, grade spasticity semi-quantitatively, have competitive or better reliability than previous spasticity scales. Medical imaging technologies, including near-infrared spectroscopy, magnetic resonance imaging, ultrasound and thermography, can measure muscle hemodynamics and metabolism, muscle tissue properties, or temperature of tissue. Medical imaging-based methods are feasible to provide quantitative information in assessing and monitoring muscle spasticity. Portable devices, robotic based equipment or myotonometry, using information from angular, inertial, torque or surface EMG sensors, can quantify spasticity with the help of machine learning algorithms. However, spasticity measures using those devices are normally not physiological sound. Repetitive peripheral magnetic stimulation can assess patients with severe spasticity, which lost voluntary contractions. Neuromusculoskeletal modeling evaluates the neural and non-neural properties and may gain insights into the underlying pathology of spasticity muscles. Telemedicine technology enables outpatient spasticity assessment. The newly developed spasticity methods aim to standardize experimental protocols and outcome measures and enable quantified, accurate, and intelligent assessment. However, more work is needed to investigate and improve the effectiveness and accuracy of spasticity assessment.

Introduction: With the global prevalence of coronavirus disease 2019 (COVID-19), an increasing number of people are experiencing respiratory discomfort. Respiratory biomechanics can monitor breathing patterns and respiratory movements and it is easier to prevent, diagnose, treat or rehabilitate. However, there is still a lack of global knowledge structure in the field of respiratory biomechanics. With the help of CiteSpace software, we aim to help researchers identify potential collaborators and collaborating institutions, hotspots and research frontiers in respiratory biomechanics.Methods: Articles on respiratory biomechanics from 2003 to 2022 were retrieved from the Web of Science Core Collection by using a specific strategy, resulting a total of 2,850 publications. We used CiteSpace 6.1.R6 to analyze the year of publication, journal/journals cited, country, institution, author/authors cited, references, keywords and research trends. Co-citation maps were created to visually observe research hot spots and knowledge structures.Results and discussion: The number of annual publications gradually increased over the past 20 years. Medical Physics published the most articles and had the most citations in this study. The United States was the most influential country, with the highest number and centrality of publications. The most productive and influential institution was Harvard University in the United States. Keall PJ was the most productive author and MCCLELLAND JR was the most cited authors The article by Keall PJ (2006) article (cocitation counts: 55) and the article by McClelland JR (2013) were the most representative and symbolic references, with the highest cocitation number and centrality, respectively. The top keywords were “radiotherapy”, “volume”, and “ventilation”. The top Frontier keywords were “organ motion,” “deep inspiration,” and “deep learning”. The keywords were clustered to form seven labels. Currently, the main area of research in respiratory biomechanics is respiratory motion related to imaging techniques. Future research may focus on respiratory assistance techniques and respiratory detection techniques. At the same time, in the future, we will pay attention to personalized medicine and precision medicine, so that people can monitor their health status anytime and anywhere.

Abstract Background N6‐methyladenosine (m6A) modification is an emerging epigenetic regulatory mechanism in tumourigenesis. Considering that AlkB homolog 5 (ALKBH5) is a well‐described m6A demethylase in previous enzyme assays, we aimed to investigate the role of m6A methylation alteration conferred by disturbed ALKBH5 in colorectal cancer (CRC) development. Methods Expression of ALKBH5 and its correlation with clinicopathological characteristics of CRC were evaluated using the prospectively maintained institutional database. The molecular role and underlying mechanism of ALKBH5 in CRC were explored using in vitro and in vivo experiments with methylated RNA immunoprecipitation sequencing (MeRIP‐seq), RNA‐seq, MeRIP‐qPCR, RIP‐qPCR and luciferase reporter assays. Results ALKBH5 expression was significantly upregulated in CRC tissues compared to the paired adjacent normal tissues, and higher expression of ALKBH5 was independently associated with worse overall survival in CRC patients. Functionally, ALKBH5 promoted the proliferative, migrative and invasive abilities of CRC cells in vitro and enhanced subcutaneous tumour growth in vivo. Mechanistically, RAB5A was identified as the downstream target of ALKBH5 in CRC development, and ALKBH5 posttranscriptionally activated RAB5A by m6A demethylation, which impeded the YTHDF2‐mediated degradation of RAB5A mRNA. In addition, we demonstrated that dysregulation of the ALKBH5‐RAB5A axis could affect the tumourigenicity of CRC. Conclusions ALKBH5 facilitates the progression of CRC by augmenting the expression of RAB5A via an m6A‐YTHDF2‐dependent manner. Our findings suggested that ALKBH5‐RAB5A axis might serve as valuable biomarkers and effective therapeutic targets for CRC.

Background: Aging confers an increased risk of developing cancer, and the global burden of cancer is cumulating as human longevity increases. Providing adequate care for old patients with rectal cancer is challenging and complex. Method: A total of 428 and 44,788 patients diagnosed with non-metastatic rectal cancer from a referral tertiary care center (SYSU cohort) and the Surveillance Epidemiology and End Results database (SEER cohort) were included. Patients were categorized into old (over 65 years) and young (aged 50–65 years) groups. An age-specific clinical atlas of rectal cancer was generated, including the demographic and clinicopathological features, molecular profiles, treatment strategies, and clinical outcomes. Results: Old and young patients were similar in clinicopathological risk factors and molecular features, including TNM stage, tumor location, tumor differentiation, tumor morphology, lymphovascular invasion, and perineural invasion. However, old patients had significantly worse nutritional status and more comorbidities than young patients. In addition, old age was independently associated with less systemic cancer treatment (adjusted odds ratio 0.294 [95% CI 0.184–0.463, P

Summary: Background: More than ten randomized clinical trials are being tested to evaluate the efficacy, effectiveness and safety of a fasting-mimicking diet (FMD) combined with different antitumor agents. Methods: UMI-mRNA sequencing, Cell-cycle analysis, Label retention, metabolomics, Multilabeling et al. were used to explore mechanisms. A tandem mRFP-GFP-tagged LC3B, Annexin-V-FITC Apoptosis, TUNEL, H&E, Ki-67 and animal model was used to search for synergistic drugs. Findings: Here we showed that fasting or FMD retards tumor growth more effectively but does not increase 5-fluorouracil/oxaliplatin (5-FU/OXA) sensitivity to apoptosis in vitro and in vivo. Mechanistically, we demonstrated that CRC cells would switch from an active proliferative to a slow-cycling state during fasting. Furthermore, metabolomics shows cell proliferation was decreased to survive nutrient stress in vivo, as evidenced by a low level of adenosine and deoxyadenosine monophosphate. CRC cells would decrease proliferation to achieve increased survival and relapse after chemotherapy. In addition, these fasting-induced quiescent cells were more prone to develop drug-tolerant persister (DTP) tumor cells postulated to be responsible for cancer relapse and metastasis. Then, UMI-mRNA sequencing uncovered the ferroptosis pathway as the pathway most influenced by fasting. Combining fasting with ferroptosis inducer treatment leads to tumor inhibition and eradication of quiescent cells by boosting autophagy. Interpretation: Our results suggest that ferroptosis could improve the antitumor activity of FMD + chemotherapy and highlight a potential therapeutic opportunity to avoid DTP cells-driven tumor relapse and therapy failure. Funding: A full list of funding bodies can be found in the Acknowledgements section.

BackgroundGlioma is the most malignant cancer in the brain. As a major vitamin-K-dependent protein in the central nervous system, PROS1 not only plays a vital role in blood coagulation, and some studies have found that it was associated with tumor immune infiltration. However, the prognostic significance of PROS1 in glioma and the underlying mechanism of PROS1 in shaping the tumor immune microenvironment (TIME) remains unclear.MethodsThe raw data (including RNA-seq, sgRNA-seq, clinicopathological variables and prognosis, and survival data) were acquired from public databases, including TCGA, GEPIA, CGGA, TIMER, GEO, UALCAN, and CancerSEA. GO enrichment and KEGG pathway analyses were performed using “cluster profiler” package and visualized by the “ggplot2” package. GSEA was conducted using R package “cluster profiler”. Tumor immune estimation resource (TIMER) and spearman correlation analysis were applied to evaluate the associations between infiltration levels of immune cells and the expression of PROS1. qRT-PCR and WB were used to assay the expression of PROS1. Wound-healing assay, transwell chambers assays, and CCK-8 assays, were performed to assess migration and proliferation. ROC and KM curves were constructed to determine prognostic significance of PROS1 in glioma.ResultsThe level of PROS1 expression was significantly increased in glioma in comparison to normal tissue, which was further certificated by qRT-PCR and WB in LN-229 and U-87MG glioma cells. High expression of PROS1 positively correlated with inflammation, EMT, and invasion identified by CancerSEA, which was also proved by downregulation of PROS1 could suppress cells migration, and proliferation in LN-229 and U-87MG glioma cells. GO and KEGG analysis suggested that PROS1 was involved in disease of immune system and T cell antigen receptor pathway. Immune cell infiltration analysis showed that expression of PROS1 was negatively associated with pDC and NK CD56 bright cells while positively correlated with Macrophages, Neutrophils in glioma. Immune and stromal scores analysis indicated that PROS1 was positively associated with immune score. The high level of PROS1 resulted in an immune suppressive TIME via the recruitment of immunosuppressive molecules. In addition, Increased expression of PROS1 was correlated with T-cell exhaustion, M2 polarization, poor Overall-Survival (OS) in glioma. And it was significantly related to tumor histological level, age, primary therapy outcome. The results of our experiment and various bioinformatics approaches validated that PROS1 was a valuable poor prognostic marker.ConclusionIncreased expression of PROS1 was correlated with malignant phenotype and associated with poor prognosis in glioma. Besides, PROS1 could be a possible biomarker and potential immunotherapeutic target through promoting the glioma immunosuppressive microenvironment and inducing tumor-associated macrophages M2 polarization.

Objective: Individuals with knee osteoarthritis are at higher risk for falls during transitions between floor and stair walking due to their reduced lower extremity function. However, the adjust gait characteristics of knee osteoarthritis subjects for dealing with stair transitions have not been explored. We aimed to investigate gait strategies in individuals with knee osteoarthritis compared to age-matched individuals without knee OA during the transition between walking on floor and stairs.Method: Gait of 30 individuals with knee osteoarthritis and 30 individuals without knee osteoarthritis during floor-to-stair and stair-to-floor walking transitions were accessed using a 3D motion capture system. Foot-tread clearance, and angles of lower extremity joints and trunk at Foot-tread clearance timepoint were analyzed by using biomechanical software (Visual 3D).Results: Compared with asymptomatic control group, the knee osteoarthritis group demonstrated no difference in vertical Foot-tread clearance and horizontal Foot-tread clearance during stair transitions. However, ankle dorsiflexion (p = 0.01) decreased, hip flexion (p = 0.02) and trunk lateral tilt (p = 0.02) increased in knee osteoarthritis group during the stair ascent transition. Moreover, trunk lateral tilt to the support side (p = 0.003) and pelvic rotation (p = 0.03) increased, while hip abduction of the swing leg (p = 0.03) decreased during the stair descent transition in individuals with knee osteoarthritis.Conclusion: Increased trunk lateral tilt and altered angle of hip may be a strategy utilized by individuals with knee OA to increase the foot clearance ability and compensate for the disease-related loss of lower extremity strength, range of motion, and balance. However, compensatory manifestations, such as the increased lateral tilt of the trunk and movement of the gravity center may enhance the risk of falls and result in more abnormal knee joint loading.

Abstract Objective We conducted this multicenter cohort study to evaluate the current tumor‐node‐metastasis staging system and treatment modality by analyzing the survival outcomes of patient groups with stage III and IV colon cancer. Patients and Methods Stage III and IV colon cancer patients from the Surveillance, Epidemiology, and End Results (SEER) database (SEER cohort) and prospectively maintained Sun Yat‐sen University (SYSU) cohort were included in this study. Kaplan‐Meier method was used to estimate the cumulative rate of overall survival (OS) between patient groups, and the inverse probability weighting method was used to calculated age and sex‐adjusted survival curves. The Cox regression model was used to identify the risk factors for OS. Results A total of 17,911 and 1135 stage III–IV cases were included in the SEER and SYSU cohorts, respectively. Among them, 1448 and 124 resectable stage IV cases underwent curative‐intent treatment in the SEER and SYSU cohorts, respectively. The T4N2b group showed a significantly worse survival outcome compared with the M1a subset receiving curative‐intent treatment (HR, 1.46; p

Background Colony-stimulating factor 1 receptor (CSF1R), a classic tyrosine kinase receptor, has been identified as a proto-oncogene in multiple cancers. The CSF1/CSF1R axis is essential for the survival and differentiation of M2-phenotype tumor-associated macrophages (M2 TAMs). However, we found here that the CSF1R expression was abnormally down-regulated in colorectal cancer (CRC), and its biological functions and underlying mechanisms have become elusive in CRC progression.Methods The expression of class III receptor tyrosine kinases in CRC and normal intestinal mucosa was accessed using The Cancer Genome Atlas and Gene Expression Omnibus datasets and was further validated by our tested cohort. CSF1R was reconstructed in CRC cells to identify its biological functions in vitro and in vivo. We compared CSF1R expression and methylation differences between CRC cells and macrophages. Furthermore, a co-culture system was used to mimic a competitive mechanism between CSF1R-overexpressed CRC cells and M2-like macrophages. We utilized a CSF1R inhibitor PLX3397 to ablate M2 TAMs and evaluated its efficacy on CRC treatment in animal models.Results We found here that the CSF1R is silenced in CRC, and the reintroduced expression of the receptor in CRC cells can be cleaved by caspases and constrain tumor growth in vitro and in vivo, functioning as a tumor suppressor gene. We further identified CSF1R as a novel dependence receptor, which has the potential to act as either a tumor suppressor gene or an oncogene, depending on its activated state. In CRC tumors, CSF1R expression is enriched in TAMs, and its expression is associated with poor prognosis in patients ith CRC. In a co-culture system, CRC cells expressing CSF1R compete with M2-like macrophages for CSF1R ligands, resulting in a decrease in CSF1R activation and cell proliferation in macrophages. Blocking CSF1R by PLX3397 could deplete M2 TAMs and augments CD8+ T cell infiltration, effectively inhibiting tumor growth and metastasis and improving responses to chemotherapy and immunotherapy.Conclusion Our findings revealed that CSF1R is a novel identified dependence receptor silenced in CRC. The silence abalienates its ligands to stimulate CSF1R expressed on M2 TAMs, which is an appealing therapeutic target for M2 TAM depletion and CRC treatment.

Abstract Background We aimed to develop a radiomic model based on pre-treatment computed tomography (CT) to predict the pathological complete response (pCR) in patients with rectal cancer after neoadjuvant treatment and tried to integrate our model with magnetic resonance imaging (MRI)-based radiomic signature. Methods This was a secondary analysis of the FOWARC randomized controlled trial. Radiomic features were extracted from pre-treatment portal venous-phase contrast-enhanced CT images of 177 patients with rectal cancer. Patients were randomly allocated to the primary and validation cohort. The least absolute shrinkage and selection operator regression was applied to select predictive features to build a radiomic signature for pCR prediction (rad-score). This CT-based rad-score was integrated with clinicopathological variables using gradient boosting machine (GBM) or MRI-based rad-score to construct comprehensive models for pCR prediction. The performance of CT-based model was evaluated and compared by receiver operator characteristic (ROC) curve analysis. The LR (likelihood ratio) test and AIC (Akaike information criterion) were applied to compare CT-based rad-score, MRI-based rad-score and the combined rad-score. Results We developed a CT-based rad-score for pCR prediction and a gradient boosting machine (GBM) model was built after clinicopathological variables were incorporated, with improved AUCs of 0.997 [95% CI 0.990–1.000] and 0.822 [95% CI 0.649–0.995] in the primary and validation cohort, respectively. Moreover, we constructed a combined model of CT- and MRI-based radiomic signatures that achieve better AIC (75.49 vs. 81.34 vs.82.39) than CT-based rad-score (P = 0.005) and MRI-based rad-score (P = 0.003) alone did. Conclusions The CT-based radiomic models we constructed may provide a useful and reliable tool to predict pCR after neoadjuvant treatment, identify patients that are appropriate for a 'watch and wait' approach, and thus avoid overtreatment. Moreover, the CT-based radiomic signature may add predictive value to the MRI-based models for clinical decision making.

Abstract Background Neurotrophic tropomyosin receptor kinases (NTRKs) are a gene family function as oncogene or tumor suppressor gene in distinct cancers. We aimed to investigate the methylation and expression profiles and prognostic value of NTRKs gene in colorectal cancer (CRC). Methods An analysis of DNA methylation and expression profiles in CRC patients was performed to explore the critical methylations within NTRKs genes. The methylation marker was validated in a retrospectively collected cohort of 229 CRC patients and tested in other tumor types from TCGA. DNA methylation status was determined by quantitative methylation-specific PCR (QMSP). Results The profiles in six CRC cohorts showed that NTRKs gene promoter was more frequently methylated in CRC compared to normal mucosa, which was associated with suppressed gene expression. We identified a specific methylated region within NTRK3 promoter targeted by cg27034819 and cg11525479 that best predicted survival outcome in CRC. NTRK3 promoter methylation showed independently predictive value for survival outcome in the validation cohort (P = 0.004, HR 2.688, 95% CI [1.355, 5.333]). Based on this, a nomogram predicting survival outcome was developed with a C-index of 0.705. Furthermore, the addition of NTRK3 promoter methylation improved the performance of currently-used prognostic model (AIC: 516.49 vs 513.91; LR: 39.06 vs 43.64, P = 0.032). Finally, NTRK3 promoter methylation also predicted survival in other tumors, including pancreatic cancer, glioblastoma and stomach adenocarcinoma. Conclusions This study highlights the essential value of NTRK3 methylation in prognostic evaluation and the potential to improve current prognostic models in CRC and other tumors.

Abstract Background The incidence of anal squamous cell carcinoma (SCC) has been steadily growing globally in the past decade. Clinical data on anal SCC from China are rare. We conducted this study to describe the clinical and epidemiological characteristics of anal SCC in China and explore prognostic factors of outcomes among patients with anal SCC. Methods We audited demographic characteristics, relevant symptoms, risk factors, treatment modalities and outcomes for patients diagnosed with anal SCC at 11 medical institutions in China between January 2007 and July 2018. Results A total of 144 patients (109 females) were diagnosed with SCC during this period. Median age at initial diagnosis was 52.0 (interquartile range: 46.0–61.8) years. The most common symptoms were bleeding (n = 93, 64.6%), noticing a lump (n = 49, 34.0%), and pain (n = 47, 32.6%). The proportion of patients at the American Joint Committee on Cancer (AJCC) stages I-IV were 10 (6.9%), 22 (15.3%), 61 (42.4%) and 8 (5.6%), respectively, and AJCC stages in 43 (29.9%) patients were unknown. Thirty-six patients (25.0%) underwent abdominoperineal resection initially. Univariable analysis showed that T stage predicted recurrence-free survival (RFS) (Hazard ratio [HR] = 3.03, 95% Confidence interval [CI]: 1.10–8.37, p = 0.032), and age group (HR = 2.90, 95% CI: 1.12–7.49, p = 0.028), AJCC stage (HR = 4.56, 95% CI: 1.02–20.35, p = 0.046), and N stage (HR = 3.05, 95% CI: 1.07–8.74, p = 0.038) predicted overall survival (OS). Conclusions T stage was identified as prognostic factor of RFS, and age, AJCC stage, and N stage were identified as prognostic factors of OS. Improving symptom awareness and earlier presentation among patients potentially at risk for anal SCC should be encouraged. Familiarity with the standard treatment among health care providers in China should be further improved.

PurposeTelerehabilitation, as an effective means of treatment, is not inferior to traditional rehabilitation, and solves the problem of many patients who do not have access to hospital-based training due to costs and distance. So far, the knowledge structure of the global use of telerehabilitation has not been formed. This study aimed to demonstrate the state of emerging trends and frontiers concerning the studies of telerehabilitation through bibliometric software.MethodsLiterature about telerehabilitation from 2000 to 2021 was retrieved from the Web of Science Core Collection. We used CiteSpace 5.8.R3 to analyze the publication years, journals/cited journals, countries, institutions, authors/cited authors, references, and keywords. Based on the analysis results, we plotted the co-citation map to more intuitively observe the research hotspots and knowledge structure.ResultsA total of 1,986 records were obtained. The number of annual publications gradually increased over the investigated period. The largest increase occurred between 2019 and 2020. J TELEMED TELECARE was the most prolific and the most cited journal. The United States was the most influential country, with the highest number of publications and centrality. The University of Queensland was the most productive institution. The author Tousignant M ranked the highest in the number of publications and Russell TG ranked the first in the cited authors. Respectively, the articles published by Cottrell MA and Russell TG ranked the first in the frequency and centrality of cited references. The four hot topics in telerehabilitation were “care”,“stroke”, “telemedicine” and “exercise”. The keyword “stroke” showed the strongest citation burst. The two frontier keywords were “physical therapy” and “participation”. The keywords were clustered to form 21 labels.ConclusionThis study uses visualization software CiteSpace to provide the current status and trends in clinical research of telerehabilitation over the past 20 years, which may help researchers identify new perspectives concerning potential collaborators and cooperative institutions, hot topics, and research frontiers in the research field. Bibliometric analysis of telerehabilitation supplements and improves the knowledge field of telemedicine from the concept of rehabilitation medicine and provides new insights into therapists during the COVID-19 pandemic.

BackgroundLymphatic metastasis is an important mechanism of renal cell carcinoma (RCC) dissemination and is an indicator of poor prognosis. Therefore, we aimed to identify predictors of lymphatic metastases (LMs) in RCC patients and to develop a new nomogram to assess the risk of LMs.MethodsThis study included patients with RCC from 2010 to 2018 in the Surveillance, Epidemiology, and Final Results (SEER) database into the training cohort and included the RCC patients diagnosed during the same period in the Second Affiliated Hospital of Dalian Medical University into the validation cohort. Univariate and multivariate logistic regression analysis were performed to identify risk factors for LM, constructing a nomogram. The receiver operating characteristic (ROC) curves were generated to assess the nomogram’s performance, and the concordance index (C-index), area under curve value (AUC), and calibration plots were used to evaluate the discrimination and calibration of the nomogram. The nomogram’s clinical performance was evaluated by decision curve analysis (DCA), probability density function (PDF) and clinical utility curve (CUC). Furthermore, Kaplan-Meier curves were performed in the training and the validation cohort to evaluate the survival risk of the patients with lymphatic metastasis or not. Additionally, on the basis of the constructed nomogram, we obtained a convenient and intuitive network calculator.ResultsA total of 41837 patients were included for analysis, including 41,018 in the training group and 819 in the validation group. Eleven risk factors were considered as predictor variables in the nomogram. The nomogram displayed excellent discrimination power, with AUC both reached 0.916 in the training group (95% confidence interval (CI) 0.913 to 0.918) and the validation group (95% CI 0.895 to 0.934). The calibration curves presented that the nomogram-based prediction had good consistency with practical application. Moreover, Kaplan-Meier curves analysis showed that RCC patients with LMs had worse survival outcomes compared with patients without LMs.ConclusionsThe nomogram and web calculator (https://liwenle0910.shinyapps.io/DynNomapp/) may be a useful tool to quantify the risk of LMs in patients with RCC, which may provide guidance for clinicians, such as identifying high-risk patients, performing surgery, and establishing personalized treatment as soon as possible.

Objective: Stand-to-sit task is an important daily function, but there is a lack of research evidence on whether knee osteoarthritis (knee OA) affects the postural balance during the task. This study aimed to compare individuals with knee OA and asymptomatic controls in postural balance and identify kinematic and lower extremity muscle activity characteristics in individuals with knee OA during the stand-to-sit task.Methods: In total, 30 individuals with knee OA and 30 age-matched asymptomatic controls performed the 30-s Chair Stand Test (30sCST) at self-selected speeds. Motion analysis data and surface electromyography (sEMG) were collected while participants performed the 30sCST. To quantify postural balance, the displacement of the center of mass (CoM) and the peak instantaneous velocity of the CoM were calculated. The kinematic data included forward lean angles of the trunk and pelvic, range of motion (RoM) of the hip, knee, and ankle joints in the sagittal plane. The averaged activation levels of gluteus maximus, vastus lateralis, vastus medialis, rectus femoris, biceps femoris (BF), tibialis anterior (TA), and medial head of gastrocnemius muscles were indicated by the normalized root mean square amplitudes.Results: Compared with the asymptomatic control group, the knee OA group prolonged the duration of the stand-to-sit task, demonstrated significantly larger CoM displacement and peak instantaneous CoM velocity in the anterior-posterior direction, reduced ankle dorsiflexion RoM, greater anterior pelvic tilt RoM, and lower quadriceps femoris and muscles activation level coupled with higher BF muscle activation level during the stand-to-sit task.Conclusion: This study indicates that individuals with knee OA adopt greater pelvic forward lean RoM and higher BF muscle activation level during the stand-to-sit task. However, these individuals exist greater CoM excursion in the anterior-posterior direction and take more time to complete the task. This daily functional activity should be added to the rehabilitation goals for individuals with knee OA. The knee OA group performs reduced ankle dorsiflexion RoM, quadriceps femoris, and TA activation deficit. In the future, the rehabilitation programs targeting these impairments could be beneficial for restoring the functional transfer in individuals with knee OA.

Purpose: To investigate the clinical effectiveness and safety of ultrasound (US)-guided percutaneous microwave ablation (MWA) for colorectal liver metastasis (CRLM) and evaluate the influencing factors of local efficacy. Methods: From January 2013 to January 2017, 137 CRLM patients accepting US-guided percutaneous MWA were included. The 2450-MHz microwave ablation system and a cooled-shaft antenna were used. All patients were regularly followed up for at least 6 months. Technical success, complete ablation, local tumor progression (LTP), complications and side effects were assessed. Logistic regression analysis was used to identify the independent prognostic factors for LTP. Results: In total, 411 lesions (mean diameter 15.4 ± 7.2 mm, range 5–67 mm) were treated. Complete ablation was achieved in 99.27% (408/411) of lesions and 97.81% (134/137) of patients. LTP occurred in 5.35% (22/411) of lesions and 16.06% (22/137) of patients. LTP was more likely to occur in lesions larger than 3 cm in diameter (OR: 14.71; p

Abstract Background The clinical factors that accurately predict the response to preoperative treatment in rectal cancer were yet unknown. The carcinoembryonic antigen (CEA) clearance pattern during neoadjuvant treatment has been developed and the predictive value explored in rectal cancer patients with elevated CEA levels (> 5 ng/mL). Methods The training cohort was derived from the FOWARC prospective phase III trial, and 71/483 eligible patients were included. The validation cohort consisted of 75/587 consecutive rectal cancer patients from Xiangya Hospital between 2014 and 2015. The kinetic changes in serum CEA were measured at different time points during the neoadjuvant treatment. An exponential trend line was drawn using the CEA values. The patients were categorized into two groups based on the R2 value of the trend line, which indicates the correlation coefficient between the exponential graph and measured CEA values: exponential decrease group (0.9

Objective:To systematically review the therapeutic effect of Tai Chi on low back pain.Methods:We searched NCBI, CNKI, WanFang Data and VIP databases to collect randomized controlled trials (RCTs) about Tai Chi exercise on low back pain, and the search period was from January 2000 to December 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Meta-analysis was performed by using RevMan 5.3 software.Results:A total of 327 related articles were retrieved and six articles were included. Pain numerical rating scale (NRS) score of the Tai Chi exercise group was significantly lower than that of control group [MD=-3.11, 95%CI (-3.40, -2.82), PCI (-1.05, -0.63), P

Introduction Stair ascent and descent require complex integration between sensory and motor systems; individuals with knee osteoarthritis (KOA) have an elevated risk for falls and fall injuries, which may be in part due to poor dynamic postural control during locomotion. Tai chi exercise has been shown to reduce fall risks in the ageing population and is recommended as one of the non-pharmocological therapies for people with KOA. However, neuromuscular mechanisms underlying the benefits of tai chi for persons with KOA are not clearly understood. Postural control deficits in performing a primary motor task may be more pronounced when required to simultaneously attend to a cognitive task. This single-blind, parallel design randomised controlled trial (RCT) aims to evaluate the effects of a 12-week tai chi programme versus balance and postural control training on neuromechanical characteristics during dual-task stair negotiation.Methods and analysis Sixty-six participants with KOA will be randomised into either tai chi or balance and postural control training, each at 60 min per session, twice weekly for 12 weeks. Assessed at baseline and 12 weeks (ie, postintervention), the primary outcomes are attention cost and dynamic postural stability during dual-task stair negotiation. Secondary outcomes include balance and proprioception, foot clearances, self-reported symptoms and function. A telephone follow-up to assess symptoms and function will be conducted at 20 weeks. The findings will help determine whether tai chi is beneficial on dynamic stability and in reducing fall risks in older adults with KOA patients in community.Ethics and dissemination Ethics approval was obtained from the Ethics Committee of the Affiliated Rehabilitation Hospital of Fujian University of Traditional Chinese Medicine (#2018KY-006–1). Study findings will be disseminated through presentations at scientific conferences or publications in peer-reviewed journals.Trial registration number ChiCTR1800018028.

Background. The interventions for hemorrhoid increase access to rectal cancer screening and thus might reduce cancer death. We aimed to examine the impact of hemorrhoid on survival outcomes in rectal cancer. Methods. We identified 510 patients with stage I to III rectal cancer from a prospectively collected database. Patients were divided into hemorrhoid and non-hemorrhoid group. The primary endpoints were disease-free survival (DFS) and overall survival (OS). Results. Hemorrhoid group had significantly more stage I-II diseases in comparison to nonhemorrhoid group (71.1% vs. 55.9%, P=0.049). The hemorrhoid group had significantly better DFS and OS compared to nonhemorrhoid group, the hazard ratios (HRs) of which were 0.39 (95% CI 0.17-0.88, P=0.018) and 0.33 (95% CI 0.12-0.92, P=0.034), respectively. Multivariate analysis revealed that hemorrhoid was independently associated with DFS [adjusted HR 0.43 (95% CI 0.17-0.95, P=0.045)]. A nomogram for predicting DFS outcome was generated based on hemorrhoid history, with a concordance index of 0.71 (95% CI 0.66-0.75, P

In gait analysis, the accuracy of knee joint angles and moments is critical for clinical decision-making. The purpose of this study was to determine the efficacy of two existing algorithms for knee joint axis correction under pathological conditions. Gait data from 20 healthy participants and 20 patients with knee osteoarthritis (OA) were collected using a motion capture system. An algorithm based on Principal Component Analysis (PCA) and a functional joint-based algorithm (FJA) were used to define the knee joint flexion axis. The results show that PCA decreased crosstalk for both groups, and FJA reduced crosstalk in patients with knee OA only. PCA decreased the range of motions of patients with knee OA in the direction of abduction/adduction significantly. There was a significant increase in the maximum knee flexion moment of patients with knee OA by FJA. The results indicate that both algorithms can efficiently reduce crosstalk for gait from patients with knee OA, which can further influence the results of knee joint angles and moments. We recommend that the correction algorithms be applied in clinical gait analysis with patients with knee OA.

Osteosarcoma is an aggressive bone tumor with high resistance to radiotherapy. Pleckstrin homology-like domain family A member 2 (PHLDA2) displays low expression in human osteosarcoma as a proapoptosis factor. miRNAs have been shown to be important in modulating translation and therapeutic responsiveness in solid tumors. Herein, we used luciferase assay to show that miR-214 downregulates the PHLDA2 expression by targeting its 3′-untranslated region (UTR). A high level of miR-214 was identified in tumor tissues from 30 osteosarcoma patients via qPCR analysis, associated positively with lung metastasis. Ectopic expression miR-214 enhanced radioresistance in osteosarcoma cells, with decreased IR-induced apoptosis. Moreover, the depletion of miR-214 enhanced radiosensitivity in both osteosarcoma cells and mouse xenograft models. Importantly, we showed that miR-214 regulated the activation of phosphatidylinositol-3-kinase/Akt signaling pathway by inhibiting PHLDA2. Finally, the introduction of PHLDA2 cDNA lacking the 3′-UTR or treatment with Akt inhibitor LY294002 partially abrogated miR-214-induced radioresistance. In summary, our results reveal that the upregulation of miR-214 as a frequent event in osteosarcoma contributes to radioresistance by regulating the PHLDA2/Akt pathway. The miR-214/PHLDA2/Akt axis provides a new avenue toward understanding the mechanism of radiosensitivity and may be a potential target for osteosarcoma intervention.

Objective:Combined with a static finite element model of knee joint and the gait data, a dynamic finite element (FE) model was established to simulate the stress change within the knee joint during level walking, aiming to provide an objective outcome measurement from biomechanical perspectives.Methods:Knee MRI images of a male and a female volunteers were scanned, four FE models were built by using Mimics, Geomagic, Ansys software. Gait data was imported to static finite element model to establish the dynamic FE model of knee joint during level walking. Models were verified before the volumes and stress on medial and lateral menisci were calculated in it.Results:The rigid structure of femur and tibia was set with grid size of 2 mm. The elements were 6, 349 and 4, 020, and the nodes were 18, 945 and 11, 966 respectively. Elastic material of menisci was set with grid size of 1 mm, elastic modulus of 120 MPa and poisson's ratio of 0.45. The elements of medial and lateral meniscus were 25, 801 and 23, 241, and nodes were 36, 903 and 33, 488. The volumes of medial and lateral menisci in the male volunteer were bigger than those in female one. But volume ratio between medial and lateral menisci on both knees was close in two volunteers. Ratios of medial and lateral menisci on left and right knee in male volunteer were 0.99 and 0.97, while in female volunteer were 0.93 and 0.96. Larger stress was shown on medial meniscus than on lateral part which ratio was between 1.11-1.43. Stress on medial meniscus was more concentrate and stress distribution on two menisci was less symmetrical in female than in male (1.22-1.27 vs 1.11-1.14).Conclusion:Knee dynamic finite element model by integrated gait data could well reflect stress change in menisci at different events during level walking.

Purpose: To analyze whether HBV infection can reduce the risk of colorectal liver metastasis (CRLM) in stage 2 colorectal cancer (CRC)., Methods: The data of postoperative pathological stage 2 CRC patients treated at the Sixth Affiliated Hospital of Sun Yat-sen University between 2013 and 2015 were analyzed. The patients were divided into an infection group (group A) and a non-infection group (group B). The correlations between HBV infection and CRLM, 5-year liver disease-free survival, and 5-year overall survival were compared., Results: A total of 884 patients who met the inclusion criteria were included in the study. Group A included 297 patients (33.60%), and 5 patients (1.68%) had CRLM. Group B included 587 patients (66.40%), and 31 patients (5.28%) had CRLM. The results of correlation analysis and logistic regression analysis showed that HBV infection (P = 0.013, HR = 0.29, 95% CI 0.11-0.77) was a protective factor for CRLM, while CEA > 5 ng/ml (P = 0.002, HR = 3.12, 95% CI 1.51-6.47) and hypertension (P = 0.010, HR = 3.50, 95% CI 1.34-9.09) were risk factors for CRLM. Group A had a significantly better 5-year liver disease-free survival than group B (P = 0.011, HR = 0.31, 95% CI 0.16-0.63), but there was no significant difference in the 5-year overall survival (P = 0.433)., Conclusion: HBV infection may reduce the risk of metachronous liver metastasis in stage 2 colorectal cancer.