Assessing the responses of ecosystem patterns, structures and functions to drought under climate change in the Yellow River Basin, China.

Understanding how ecosystems respond and adapt to drought has become an urgent issue as drought stress intensifies under climate change, yet this topic is not fully understood. Currently, conclusions on the response of ecosystems in different regions to drought disturbance are inconsistent. Based on long MODIS data and observed data, this study systematically explored the relationships between ecosystem patterns, structures and functions and drought, taking a typical climate change-sensitive area and an ecologically fragile area-the Yellow River Basin-as a case study. Drought assessment results revealed that the Yellow River Basin has experienced meteorological and hydrological drought during most of the last two decades, predominantly characterized by medium and slight droughts. The ecosystem patterns and structures changed dramatically as the grassland decreased and the landscape fragmentation index (F) increased with increasing wetness. The annual gross primary productivity (GPP) increased, the water use efficiency (WUE) declined and ecosystem service value (ESV) exhibited a W-shaped increase at the watershed scale, but there were significant regional differences. There were positive correlations between F, GPP, ESV and drought indices, while there was a negative correlation between WUE and drought indices at the watershed scale. Under drought stress, the ecosystem structure in the basin was disrupted, the GPP and ESV decreased, but the WUE increased. Notably, approximately 106 %, 20 %, and 1 % of the maximum reductions in F, GPP, and ESV, respectively, were caused by drought, while the maximum 4 % of WUE increased. Responses of some functions in the wetland and grassland to drought vary from those in other ecosystems. The mechanisms underlying ecosystem responses to drought were further investigated. This study enhances the understanding of these responses and will help stakeholders formulate drought mitigation policies and protect ecosystem health.

Multicellular ecotypes shape progression of lung adenocarcinoma from ground-glass opacity toward advanced stages.

Lung adenocarcinoma is a type of cancer that exhibits a wide range of clinical radiological manifestations, from ground-glass opacity (GGO) to pure solid nodules, which vary greatly in terms of their biological characteristics. Our current understanding of this heterogeneity is limited. To address this gap, we analyze 58 lung adenocarcinoma patients via machine learning, single-cell RNA sequencing (scRNA-seq), and whole-exome sequencing, and we identify six lung multicellular ecotypes (LMEs) correlating with distinct radiological patterns and cancer cell states. Notably, GGO-associated neoantigens in early-stage cancers are recognized by CD8+ T cells, indicating an immune-active environment, while solid nodules feature an immune-suppressive LME with exhausted CD8+ T cells, driven by specific stromal cells such as CTHCR1+ fibroblasts. This study also highlights EGFR(L858R) neoantigens in GGO samples, suggesting potential CD8+ T cell activation. Our findings offer valuable insights into lung adenocarcinoma heterogeneity, suggesting avenues for targeted therapies in early-stage disease.

The Sanbi Decoction alleviates intervertebral disc degeneration in rats through intestinal flora and serum metabolic homeostasis modulation.

BACKGROUND: Intervertebral disc degeneration (IVDD) is an essential cause of low back pain (LBP), the incidence of which has risen in recent years and is progressively younger, but treatment options are limited, placing a serious economic burden on society. Sanbi decoction (SBD) is an important classical formula for the treatment of IVDD, which can significantly improve patients' symptoms and is a promising alternative therapy. PURPOSE: The aim of this study is to investigate the safety and efficacy of SBD in the treatment of IVDD and to explore the underlying mechanisms by using an integrated analytical approach of microbiomics and serum metabolomics, as well as by using molecular biology. METHODS: A rat IVDD puncture model was established and treated by gavage with different concentrations of SBD, and clean faeces, serum, liver, kidney, and intervertebral disc (IVD) were collected after 4 weeks. We assessed the safety by liver and kidney weighing, functional tests and tissue staining, the expression of tumor necrosis factor-alpha (TNF-ɑ), interleukin 1ß (IL-1ß) and interleukin 6 (IL-6) inflammatory factors in serum was detected by ELISA kits, and X-ray test, magnetic resonance imaging (MRI) examination, immunohistochemistry (IHC), western blotting (WB), hematoxylin-eosin (HE) staining and safranin O-fast green (SO/FG) staining were used to assess the efficacy. Finally, we performed 16S rRNA sequencing analysis on the faeces of different groups and untargeted metabolomics on serum and analyzed the association between them. RESULTS: SBD can effectively reduce the inflammatory response, regulate the metabolic balance of extracellular matrix (ECM), improve symptoms, and restore IVD function. In addition, SBD can significantly improve the diversity of intestinal flora and maintain the balance. At the phylum level, SBD greatly increased the relative abundance of Patescibacteria and Actinobacteriota and decreased the relative abundance of Bacteroidota. At the genus level, SBD significantly increased the relative abundance of Clostridia_UCG-014, Enterorhabdus, and Adlercreutzia, and decreased the relative abundance of Ruminococcaceae_UCG-005 (p < 0.05). Untargeted metabolomics indicated that SBD significantly improved serum metabolites and altered serum expression of 4alpha-phorbol 12,13-didecanoate (4alphaPDD), euscaphic acid (EA), alpha-muricholic acid (α-MCA), 5-hydroxyindoleacetic acid (5-HIAA), and kynurenine (Kyn) (p < 0.05), and the metabolic pathways were mainly lipid metabolism and amino acid metabolism. CONCLUSIONS: This study demonstrated that SBD can extensively regulate intestinal flora and serum metabolic homeostasis to reduce inflammatory response, inhibit the degradation of ECM, restore IVD height and water content to achieve apparent therapeutic effect for IVDD.

Tet methylcytosine dioxygenase 2 (TET2) deficiency elicits EGFR-TKI (tyrosine kinase inhibitors) resistance in non-small cell lung cancer.

Despite epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) have shown remarkable efficacy in patients with EGFR-mutant non-small cell lung cancer (NSCLC), acquired resistance inevitably develops, limiting clinical efficacy. We found that TET2 was poly-ubiquitinated by E3 ligase CUL7FBXW11 and degraded in EGFR-TKI resistant NSCLC cells. Genetic perturbation of TET2 rendered parental cells more tolerant to TKI treatment. TET2 was stabilized by MEK1 phosphorylation at Ser 1107, while MEK1 inactivation promoted its proteasome degradation by enhancing the recruitment of CUL7FBXW11. Loss of TET2 resulted in the upregulation of TNF/NF-κB signaling that confers the EGFR-TKI resistance. Genetic or pharmacological inhibition of NF-κB attenuate the TKI resistance both in vitro and in vivo. Our findings exemplified how a cell growth controlling kinase MEK1 leveraged the epigenetic homeostasis by regulating TET2, and demonstrated an alternative path of non-mutational acquired EGFR-TKI resistance modulated by TET2 deficiency. Therefore, combined strategy exploiting EGFR-TKI and inhibitors of TET2/NF-κB axis holds therapeutic potential for treating NSCLC patients who suffered from this resistance.

Novel insights into RB1 in prostate cancer lineage plasticity and drug resistance.

Prostate cancer is the second most common malignancy among men in the world, posing a serious threat to men's health and lives. RB1 is the first human tumor suppressor gene to be described, and it is closely associated with the development, progression, and suppression of a variety of tumors. It was found that the loss of RB1 is an early event in prostate cancer development and is closely related to prostate cancer development, progression and treatment resistance. This paper reviews the current status of research on the relationship between RB1 and prostate cancer from three aspects: RB1 and prostate cell lineage plasticity; biological behavior; and therapeutic resistance. Providing a novel perspective for developing new therapeutic strategies for RB1-loss prostate cancer.

Mechanical Factors Regulate Annulus Fibrosus (AF) Injury Repair and Remodeling: A Review.

Low back pain is a common chronic disease that can severely affect the patient's work and daily life. The breakdown of spinal mechanical homeostasis caused by intervertebral disc (IVD) degeneration is a leading cause of low back pain. Annulus fibrosus (AF), as the outer layer structure of the IVD, is often the first affected part. AF injury caused by consistent stress overload will further accelerate IVD degeneration. Therefore, regulating AF injury repair and remodeling should be the primary goal of the IVD repair strategy. Mechanical stimulation has been shown to promote AF regeneration and repair, but most studies only focus on the effect of single stress on AF, and lack realistic models and methods that can mimic the actual mechanical environment of AF. In this article, we review the effects of different types of stress stimulation on AF injury repair and remodeling, suggest possible beneficial load combinations, and explore the underlying molecular mechanisms. It will provide the theoretical basis for designing better tissue engineering therapy using mechanical factors to regulate AF injury repair and remodeling in the future.

Intervertebral disc degeneration and inflammatory microenvironment: expression, pathology, and therapeutic strategies.

BACKGROUND: Intervertebral disc degeneration (IDD) is a leading cause of low back pain (LBP), posing a significant socioeconomic burden. Recent studies highlight the crucial role of inflammatory microenvironment in IDD progression. METHOD: A keyword-based search was performed using the PubMed database for published articles. RESULTS AND CONCLUSIONS: Dysregulated expression of inflammatory cytokines disrupts intervertebral disc (IVD) homeostasis, causing atrophy, fibrosis, and phenotypic changes in nucleus pulposus cells. Modulating the inflammatory microenvironment and restoring cytokine balance hold promise for IVD repair and regeneration. This comprehensive review systematically examines the expression regulation, pathological effects, therapeutic strategies, and future challenges associated with the inflammatory microenvironment and relevant cytokines in IDD. Key inflammatory cytokines, including interleukins (IL), tumor necrosis factor-alpha (TNF-α), and chemokines, exhibit significant pathological effects in IDD. Furthermore, major therapeutic modalities such as chemical antagonists, biologics, plant extracts, and gene transcription therapies are introduced to control and ameliorate the inflammatory microenvironment. These approaches provide valuable insights for identifying potential targets in future anti-inflammatory treatments for IDD.

Stress stimulation maintaining by genipin crosslinked hydrogel promotes annulus fibrosus healing.

Objective: To explore the repair effect of tissue engineering for annulus fibrosus (AF) injury in stress-stimulation environment. Methods: Non-adhesive fibrinogen (Fib) representing the repair with non-stress stimulation and adhesive hydrogel of fibrinogen, thrombin and genipin mixture (Fib-T-G) representing the repair with stress stimulation were prepared to repair the AF lesion. The relationship between adhesion and stress stimulation was studied in rheological measurements, tension tests and atomic force microscopy (AFM) experiments. The repair effect of stress stimulation was studied in designed acellular AF scaffold models with fissures and defects. The models were repaired by the two different hydrogels, then implanted subcutaneously and cultured for 21 â€‹d in rats. Histology and qPCR of COL1A1, COL2A1, aggrecan, RhoA, and ROCK of the tissue engineering of the interface were evaluated afterward. Moreover, the repair effect was also studied in an AF fissure model in caudal disc of rats by the two different hydrogels. Discs were harvested after 21 â€‹d, and the disc degeneration score and AF healing quality were evaluated by histology. Result: In interfacial stress experiment, Fib-T-G hydrogel showed greater viscosity than Fib hydrogel (24.67 â€‹± â€‹1.007 vs 459333 â€‹± â€‹169205 â€‹mPa â€‹s). Representative force-displacement and sample modulus for each group demonstrate that Fib-T-G group significantly increased the interfacial stress level and enhanced the modulus of samples, compared with Fib group (P â€‹< â€‹0.01). The Fib-T-G group could better bond the interface to resist the loading strain force with the broken point at 1.11 â€‹± â€‹0.10 â€‹N compared to the Fib group at 0.12 â€‹± â€‹0.08 â€‹N â€‹(P â€‹< â€‹0.01). Focusing on the interfacial healing in acellular AF scaffold model, compared with Fib â€‹+ â€‹MSCs group, the fissure and defect were connected closely in Fib-T-G â€‹+ â€‹MSCs group (P â€‹< â€‹0.01). Relative higher gene expression of COL2A1 and RhoA in Fib-T-G â€‹+ â€‹MSCs group than Fib â€‹+ â€‹MSCs group in AF fissure and AF defect model (P â€‹< â€‹0.05). The immunohistochemistry staining showed more positive staining of COL2A1 and RhoA in Fib-T-G â€‹+ â€‹MSCs group than in Fib â€‹+ â€‹MSCs group in both AF fissure and AF defect models. The degree of disc degeneration was more severe in Fib â€‹+ â€‹MSCs group than Fib-T-G â€‹+ â€‹MSCs group in vivo experiment (11.80 â€‹± â€‹1.11 vs 7.00 â€‹± â€‹1.76, P â€‹< â€‹0.01). The dorsal AF defect in Fib-T-G â€‹+ â€‹MSCs group (0.02 â€‹± â€‹0.01 â€‹mm2) was significantly smaller than that (0.13 â€‹± â€‹0.05 â€‹mm2) in Fib â€‹+ â€‹MSCs group (P â€‹< â€‹0.05). Immunohistochemical staining showed more positive staining of COL2A1 and Aggrecan in Fib-T-G â€‹+ â€‹MSCs group than in Fib â€‹+ â€‹MSCs group. Conclusion: Genipin crosslinked hydrogel can bond the interface of AF lesions and transfer strain force. Stress stimulation maintained by adhesive hydrogel promotes AF healing. The translational potential of this article: We believe the effect of stress stimulation could be concluded through this study and provides more ideals in mechanical effects for further research, which is a key technique for repairing intervertebral disc in clinic. The adhesive hydrogel of Fib-T-G+MSCs has low toxicity and helps bond the interface of AF lesion and transfer strain force, having great potential in the repair of AF lesion.

The epigenetic regulatory mechanism of PIWI/piRNAs in human cancers.

PIWI proteins have a strong correlation with PIWI-interacting RNAs (piRNAs), which are significant in development and reproduction of organisms. Recently, emerging evidences have indicated that apart from the reproductive function, PIWI/piRNAs with abnormal expression, also involve greatly in varieties of human cancers. Moreover, human PIWI proteins are usually expressed only in germ cells and hardly in somatic cells, so the abnormal expression of PIWI proteins in different types of cancer offer a promising opportunity for precision medicine. In this review, we discussed current researches about the biogenesis of piRNA, its epigenetic regulatory mechanisms in human cancers, such as N6-methyladenosine (m6A) methylation, histone modifications, DNA methylation and RNA interference, providing novel insights into the markers for clinical diagnosis, treatment and prognosis in human cancers.

Mechanical stimulation promotes MSCs healing the lesion of intervertebral disc annulus fibrosus.

Mesenchymal stem cells (MSCs) and scaffolds offer promising perspectives for annulus fibrosus (AF) repair. The repair effect was linked to features of the local mechanical environment related to the differentiation of MSCs. In this study, we established a Fibrinogen-Thrombin-Genipin (Fib-T-G) gel which is sticky and could transfer strain force from AF tissue to the human mesenchymal stem cells (hMSCs) embedded in the gel. After the Fib-T-G biological gel was injected into the AF fissures, the histology scores of intervertebral disc (IVD) and AF tissue showed that Fib-T-G gel could better repair the AF fissure in caudal IVD of rats, and increase the expression of AF-related proteins including Collagen 1 (COL1), Collagen 2 (COL2) as well as mechanotransduction-related proteins including RhoA and ROCK1. To clarify the mechanism that sticky Fib-T-G gel induces the healing of AF fissures and the differentiation of hMSCs, we further investigated the differentiation of hMSCs under mechanical strain in vitro. It was demonstrated that both AF-specific genes, including Mohawk and SOX-9, and ECM markers (COL1, COL2, aggrecan) of hMSCs were up-regulated in the environment of strain force. Moreover, RhoA/ROCK1 proteins were also found to be significantly up-regulated. In addition, we further -demonstrated that the fibrochondroinductive effect of the mechanical microenvironment process could be significantly blocked or up-regulated by inhibiting the RhoA/ROCK1 pathway or overexpressing RhoA in MSCs, respectively. Summarily, this study will provide a therapeutic alternative to repair AF tears and provide evidence that RhoA/ROCK1 is vital for hMSCs response to mechanical strain and AF-like differentiation.

Mechanical Loading Promotes the Migration of Endogenous Stem Cells and Chondrogenic Differentiation in a Mouse Model of Osteoarthritis.

Osteoarthritis (OA) is a major health problem, characterized by progressive cartilage degeneration. Previous works have shown that mechanical loading can alleviate OA symptoms by suppressing catabolic activities. This study evaluated whether mechanical loading can enhance anabolic activities by facilitating the recruitment of stem cells for chondrogenesis. We evaluated cartilage degradation in a mouse model of OA through histology with H&E and safranin O staining. We also evaluated the migration and chondrogenic ability of stem cells using in vitro assays, including immunohistochemistry, immunofluorescence, and Western blot analysis. The result showed that the OA mice that received mechanical loading exhibited resilience to cartilage damage. Compared to the OA group, mechanical loading promoted the expression of Piezo1 and the migration of stem cells was promoted via the SDF-1/CXCR4 axis. Also, the chondrogenic differentiation was enhanced by the upregulation of SOX9, a transcription factor important for chondrogenesis. Collectively, the results revealed that mechanical loading facilitated cartilage repair by promoting the migration and chondrogenic differentiation of endogenous stem cells. This study provided new insights into the loading-driven engagement of endogenous stem cells and the enhancement of anabolic responses for the treatment of OA.

A bibliometric and visualization study of global research trends in sacral Tarlov cyst from 2000 to 2022.

Background: Symptomatic sacral Tarlov cyst (STC) exerts a significant negative impact on the patient's quality of life, highlighting the significance of the increasing number of studies on STC. However, bibliometric analyses in this research field are scarce. Thus, this study aims to provide a comprehensive knowledge structure and identify the research trends of STC through bibliometrics. Methods: Articles related to STC from 2000 to 2022 were sourced from the Web of Science Core Collection database. VOSviewer 1.6.16, CiteSpace 6.1.6, GraphPad Prism 8.2.1 and R-package "bibliometrix" were used to analyse the data and generate knowledge maps. Results: A total of 930 studies on STC from 2000 to 2022 were included. The findings revealed a consistent yet upward trend in the number of annual publications in this field. The United States, China and Turkey were the most prolific and influential countries contributing to this field, with the University of Illinois, the University of Maryland and the National Institute of Standards & Technology being the most notable research institutions. Key journals include World Neurosurgery [Impact Factor (IF) = 2.210], Journal of Vascular Surgery (IF = 4.860) and Journal of Neurosurgery-Spine (IF = 3.467). Additionally, Tarlov Mj, Tarlov E and Zachariah Mr exhibit the highest number of publications, making them the leading authors in this field. A twenty-year retrospection of research trends using keyword analysis reveals four principal directions, namely "definition", "pathogenesis", "diagnosis" and "treatment". Currently, therapeutic surgical intervention is the key treatment for this disease, with future treatments primarily hinging on minimally invasive methodologies rooted in microendoscopic and endoscopic techniques. Conclusion: This pioneering, comprehensive scientific bibliometric study provides a holistic summary of STC research trends and hot spots spanning the past 22 years. The results identify existing research frontiers and chart maps for future studies, serving as a valuable reference for scholars vested in this field.

Therapeutic application of hydrogels for bone-related diseases.

Bone-related diseases caused by trauma, infection, and aging affect people's health and quality of life. The prevalence of bone-related diseases has been increasing yearly in recent years. Mild bone diseases can still be treated with conservative drugs and can be cured confidently. However, serious bone injuries caused by large-scale trauma, fractures, bone tumors, and other diseases are challenging to heal on their own. Open surgery must be used for intervention. The treatment method also faces the problems of a long cycle, high cost, and serious side effects. Studies have found that hydrogels have attracted much attention due to their good biocompatibility and biodegradability and show great potential in treating bone-related diseases. This paper mainly introduces the properties and preparation methods of hydrogels, reviews the application of hydrogels in bone-related diseases (including bone defects, bone fracture, cartilage injuries, and osteosarcoma) in recent years. We also put forward suggestions according to the current development status, pointing out a new direction for developing high-performance hydrogels more suitable for bone-related diseases.

Hope for bone regeneration: The versatility of iron oxide nanoparticles.

Although bone tissue has the ability to heal itself, beyond a certain point, bone defects cannot rebuild themselves, and the challenge is how to promote bone tissue regeneration. Iron oxide nanoparticles (IONPs) are a magnetic material because of their excellent properties, which enable them to play an active role in bone regeneration. This paper reviews the application of IONPs in bone tissue regeneration in recent years, and outlines the mechanisms of IONPs in bone tissue regeneration in detail based on the physicochemical properties, structural characteristics and safety of IONPs. In addition, a bibliometric approach has been used to analyze the hot spots and trends in the field in order to identify future directions. The results demonstrate that IONPs are increasingly being investigated in bone regeneration, from the initial use as magnetic resonance imaging (MRI) contrast agents to later drug delivery vehicles, cell labeling, and now in combination with stem cells (SCs) composite scaffolds. In conclusion, based on the current research and development trends, it is more inclined to be used in bone tissue engineering, scaffolds, and composite scaffolds.

BMSC-derived exosomal lncRNA PTENP1 suppresses the malignant phenotypes of bladder cancer by upregulating SCARA5 expression.

LncRNAs can be transported to tumor cells where they exert regulatory effects by bone marrow mesenchymal stem cells (BMSC)-derived exosomes. Here, we aimed to investigate the functional mechanism of BMSC-derived exosomal lncRNA PTENP1 in the progression of bladder cancer (BC). Methods of BMSC were identified by detecting surface markers through flow cytometry. Exosomes from BMSC were identified by transmission electron microscopy, nanoparticle tracking analysis (NTA), and western blot analysis of exosome markers. Cellular internalization of BMSC-derived exosomes (BMSC-Exo) into BC cells was detected by confocal microscopy. CCK-8, colony formation, flow cytometry, wound healing, and transwell assays were adopted to estimate cell proliferation, apoptosis, migration, and invasion abilities, respectively. Interplay between miR-17 and lncRNA PTENP1 or SCARA5 was verified by dual-luciferase reporter, RNA pull down, and/or RNA immunoprecipitation (RIP) assays. Tumor xenograft assay was conducted in nude mice to study the role of exosomal lncRNA PTENP1 in BC progression in vivo. We showed exosomal lncRNA PTENP1 can be delivered into and suppress the malignant phenotypes of BC cells. LncRNA PTENP1 was identified as a sponge of miR-17, and SCARA5 was identified as a target gene of miR-17. The exosomes derived from PTENP1-overexpressing BMSC (BMSCOE-PTENP1-Exo) abolished the promotive effects of miR-17 overexpression or SCARA5 knockdown on the malignant phenotypes of BC cells. Moreover, exosomal lncRNA PTENP1 was demonstrated to inhibit BC tumor growth in nude mice by miR-17/SCARA5 axis. In conclusion, BMSC-derived exosomal PTENP1 suppressed the BC progression by upregulating the expression of SCARA5 via sponging miR-17, offering a potential novel therapeutic target for BC therapy.

Vascular Repair by Grafting Based on Magnetic Nanoparticles.

Magnetic nanoparticles (MNPs) have attracted much attention in the past few decades because of their unique magnetic responsiveness. Especially in the diagnosis and treatment of diseases, they are mostly involved in non-invasive ways and have achieved good results. The magnetic responsiveness of MNPs is strictly controlled by the size, crystallinity, uniformity, and surface properties of the synthesized particles. In this review, we summarized the classification of MNPs and their application in vascular repair. MNPs mainly use their unique magnetic properties to participate in vascular repair, including magnetic stimulation, magnetic drive, magnetic resonance imaging, magnetic hyperthermia, magnetic assembly scaffolds, and magnetic targeted drug delivery, which can significantly affect scaffold performance, cell behavior, factor secretion, drug release, etc. Although there are still challenges in the large-scale clinical application of MNPs, its good non-invasive way to participate in vascular repair and the establishment of a continuous detection process is still the future development direction.

Application of Microfluidics in Detection of Circulating Tumor Cells.

Tumor metastasis is one of the main causes of cancer incidence and death worldwide. In the process of tumor metastasis, the isolation and analysis of circulating tumor cells (CTCs) plays a crucial role in the early diagnosis and prognosis of cancer patients. Due to the rarity and inherent heterogeneity of CTCs, there is an urgent need for reliable CTCs separation and detection methods in order to obtain valuable information on tumor metastasis and progression from CTCs. Microfluidic technology is increasingly used in various studies of CTCs separation, identification and characterization because of its unique advantages, such as low cost, simple operation, less reagent consumption, miniaturization of the system, rapid detection and accurate control. This paper reviews the research progress of microfluidic technology in CTCs separation and detection in recent years, as well as the potential clinical application of CTCs, looks forward to the application prospect of microfluidic technology in the treatment of tumor metastasis, and briefly discusses the development prospect of microfluidic biosensor.

The effectiveness of telephone and internet-based supportive care for patients with esophageal cancer on enhanced recovery after surgery in China: A randomized controlled trial.

Objective: The aim of this study was to establish a nurse-led supportive care program based on telephone and Internet support and evaluate its efficacy in comparison with conventional care on enhanced recovery after surgery. Methods: The study was designed as an open-label, randomized controlled trial to value the efficacy of a nurse-led supportive care program in comparison with conventional care. A convenience sampling method was employed to recruit patients with esophageal cancer in a tertiary Grade A cancer center in Beijing from November 2018 to January 2019. Patients were assigned randomly (1:1) to one of the two groups (intervention group vs control group) via a web randomization system. The control group received conventional care. Patients from the intervention group received conventional care and one-on-one phone calls from nurses following their discharge assessments and education about nutrition and symptoms. Nurses also set up a WeChat group, which they invited patients to join in before discharge for better communication during follow-up. Statistical testing, including nutritional status, quality of life, the helpfulness of the follow-up service, and the patients' satisfaction with their care, was conducted 6 months after discharge to assess for differences between the two groups. The independent sample t, chi-squared, and Mann-Whitney tests were used to compare between the experiences of the intervention and control groups. The Spearman correlation analysis was used for the analysis of correlation of the nutritional index and quality of life. Results: Finally, 168 patients were included in the study, with 86 patients in the intervention group and 82 in the control group. Significant differences between the intervention and control groups were found in the nutrition risk screening 2002 and simple diet self-assessment tool scores. The changes in blood albumin, prealbumin, and transferrin were also statistically significant. All (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire) QLQ-C30 results of the intervention group were better than those of the control group. A significant positive correlation of the simple diet self-assessment tool (the higher, the better) and the scores for total health/quality of life were detected (r â€‹= â€‹0.214, P â€‹= â€‹0.005). A significant negative correlation of the nutrition risk screening 2002 (the lower, the better) and the scores of total health/quality of life was detected (r â€‹= â€‹-0.446, P â€‹= â€‹0.000). The patients' scores on the helpfulness of the follow-up service and their satisfaction with it were both significantly higher in the intervention group than in the control group. Conclusions: This study highlighted the important role of nurse-led supportive care based on telephone and Internet-based support for patients after enhanced recovery after surgery. The supportive care improved patients' nutritional status, elevated their quality of life, and improved their satisfaction with the care provided to them.

Perioperative ctDNA-Based Molecular Residual Disease Detection for Non-Small Cell Lung Cancer: A Prospective Multicenter Cohort Study (LUNGCA-1).

PURPOSE: We assessed whether perioperative circulating tumor DNA (ctDNA) could be a biomarker for early detection of molecular residual disease (MRD) and prediction of postoperative relapse in resected non-small cell lung cancer (NSCLC). EXPERIMENTAL DESIGN: Based on our prospective, multicenter cohort on dynamic monitoring of ctDNA in lung cancer surgery patients (LUNGCA), we enrolled 950 plasma samples obtained at three perioperative time points (before surgery, 3 days and 1 month after surgery) of 330 stage I-III NSCLC patients (LUNGCA-1), as a part of the LUNGCA cohort. Using a customized 769-gene panel, somatic mutations in tumor tissues and plasma samples were identified with next-generation sequencing and utilized for ctDNA-based MRD analysis. RESULTS: Preoperative ctDNA positivity was associated with lower recurrence-free survival (RFS; HR = 4.2; P < 0.001). The presence of MRD (ctDNA positivity at postoperative 3 days and/or 1 month) was a strong predictor for disease relapse (HR = 11.1; P < 0.001). ctDNA-based MRD had a higher relative contribution to RFS prediction than all clinicopathologic variables such as the TNM stage. Furthermore, MRD-positive patients who received adjuvant therapies had improved RFS over those not receiving adjuvant therapy (HR = 0.3; P = 0.008), whereas MRD-negative patients receiving adjuvant therapies had lower RFS than their counterparts without adjuvant therapy (HR = 3.1; P < 0.001). After adjusting for clinicopathologic variables, whether receiving adjuvant therapies remained an independent factor for RFS in the MRD-positive population (P = 0.002) but not in the MRD-negative population (P = 0.283). CONCLUSIONS: Perioperative ctDNA analysis is effective in early detection of MRD and relapse risk stratification of NSCLC, and hence could benefit NSCLC patient management.

The Clinical Efficacy of Suture-Button Fixation and Trans-Syndesmotic Screw Fixation in the Treatment of Ankle Fracture Combined With Distal Tibiofibular Syndesmosis Injury: A Retrospective Study.

Twenty percent of ankle fractures present with concomitant syndesmosis injury which results in poor clinical outcomes. Surgical stabilization of the syndesmosis can be achieved with either trans-syndesmotic screws or a suture button device. The aim of this study is to investigate the clinical efficacy of suture button fixation and trans-syndesmotic screw fixation in the treatment of ankle fracture combined with distal tibiofibular syndesmosis injury. A retrospective analysis was conducted by enrolling 76 patients with ankle fractures combined with distal tibiofibular syndesmosis injury who were admitted in our trauma center from January 2018 to January 2019, including 34 cases of suture button group and 42 cases of the syndesmotic screw group with a mean follow-up period of 16 ± 7 (range 12-21) months. The demographic data included gender, age, injury mechanism, AO classification and the operation duration were recorded, the radiographic and clinical outcomes were determined by tibiofibular clear space, tibiofibular overlap distance, complications, and the Olerud-Molander Ankle Score at the last follow-up. All the indexes were compared between the 2 groups to discover the related statistical differences. With the numbers available, no significant difference could be detected in the surgical duration, tibiofibular clear space, tibiofibular overlap distance, total complication rate, and middle-term Olerud-Molander Ankle scores between the 2 groups. However, the suture button fixation group showed higher early stage Olerud-Molander Ankle scores (p = .027) and shorter full weightbearing time (p = .018) than that of syndesmotic screw fixation group. Considering the outcomes, we conclude that the suture button fixation not only shows equivalent efficacy to the traditional syndesmotic screw, but also has advantages of allowing early weightbearing, low requirements for routine removal.