Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic ...Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national level.We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program.The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent surgery.Only 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 hours.The total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 hours,which is associated with improved sensorimotor recovery,increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.展开更多
BACKGROUND Traumatic injuries,such as falling,car accidents,and crushing mostly cause spinal fractures in young and middle-aged people,and>50%of them are thoracolumbar fractures.This kind of fracture is easily comb...BACKGROUND Traumatic injuries,such as falling,car accidents,and crushing mostly cause spinal fractures in young and middle-aged people,and>50%of them are thoracolumbar fractures.This kind of fracture is easily combined with serious injuries to peripheral nerves and soft tissues,which causes paralysis of the lower limbs if there is no timely rehabilitation treatment.Young patients with thoracolumbar fractures find it difficult to recover after the operation,and they are prone to depression,low self-esteem,and other negative emotions.AIM To investigate the association between anxiety,depression,and social stress in young patients with thoracolumbar spine fractures and the effect on rehabilitation outcomes.METHODS This study retrospectively analyzed 100 patients admitted to the orthopedic department of Honghui Hospital,Xi’an Jiaotong University who underwent thoracolumbar spine fracture surgery from January 2022 to June 2023.The general data of the patients were assessed with the Hamilton anxiety scale(HAMA),Hamilton depression scale(HAMD),life events scale,and social support rating scale(SSRS)to identify the correlation between anxiety,depression scores,and social stress and social support.The Japanese Orthopedic Association(JOA)was utilized to evaluate the rehabilitation outcomes of the patients and to analyze the effects of anxiety and depression scores on rehabilitation.RESULTS According to the scores of HAMD and HAMA in all patients,the prevalence of depression in patients was 39%(39/100),and the prevalence of anxiety was 49%(49/100).Patients were categorized into non-depression(n=61)and depression(n=39),non-anxiety(n=51),and anxiety(n=49)groups.Statistically significant differences in gender,occupation,Pittsburgh Sleep Quality Index(PSQI)score,and monthly family income were observed between the non-depression and depression groups(P<0.05).A significant difference in occupation and PSQI score was found between the non-anxiety and anxiety groups.Both depression(r=0.207,P=0.038)and anxiety scores(r=0.473,P<0.001)were significantly and positively correlated with negative life events.The difference in negative life event scores as well as SSRS total and item scores was statist-ically significant between patients in the non-depression and depression groups(P<0.05).The difference between the non-anxiety and anxiety groups was statistically significant(P<0.05)in the negative life event scores as well as the total SSRS scores.Additionally,JOA scores were significantly lower in both anxious and depressed patients.CONCLUSION Young patients with thoracolumbar fractures are prone to anxiety and depression.Patients’anxiety and depression are closely associated with social pressure,which reduces the life pressure of young patients with thoracolumbar fractures,enhances social support,and improves the psychology of anxiety and depression.,which affects patients’recovery.展开更多
The incidence of large bone defects caused by traumatic injury is increasing worldwide,and the tissue regeneration process requires a long recovery time due to limited self-healing capability.Endogenous bioelectrical ...The incidence of large bone defects caused by traumatic injury is increasing worldwide,and the tissue regeneration process requires a long recovery time due to limited self-healing capability.Endogenous bioelectrical phenomena have been well recognized as critical biophysical factors in bone remodeling and regeneration.Inspired by bioelectricity,electrical stimulation has been widely considered an external intervention to induce the osteogenic lineage of cells and enhance the synthesis of the extracellular matrix,thereby accelerating bone regeneration.With ongoing advances in biomaterials and energy-harvesting techniques,electroactive biomaterials and self-powered systems have been considered biomimetic approaches to ensure functional recovery by recapitulating the natural electrophysiological microenvironment of healthy bone tissue.In this review,we first introduce the role of bioelectricity and the endogenous electric field in bone tissue and summarize different techniques to electrically stimulate cells and tissue.Next,we highlight the latest progress in exploring electroactive hybrid biomaterials as well as self-powered systems such as triboelectric and piezoelectric-based nanogenerators and photovoltaic cell-based devices and their implementation in bone tissue engineering.Finally,we emphasize the significance of simulating the target tissue’s electrophysiological microenvironment and propose the opportunities and challenges faced by electroactive hybrid biomaterials and self-powered bioelectronics for bone repair strategies.展开更多
Dyslipidemia,a complex disorder characterized by systemic lipid profile abnormalities,affects more than half of adults globally and constitutes a major modifiable risk factor for atherosclerotic cardiovascular disease...Dyslipidemia,a complex disorder characterized by systemic lipid profile abnormalities,affects more than half of adults globally and constitutes a major modifiable risk factor for atherosclerotic cardiovascular disease.Mounting evidence has established the gut microbiota(GM)as a pivotal metabolic modulator that is correlated with atherogenic lipid profiles through dietary biotransformation,immunometabolic regulation,and bioactive metabolite signaling.However,the host-microbe interactions that drive dyslipidemia pathogenesis involve complex gene-environment crosstalk spanning epigenetic modifications to circadian entrainment.Mechanistically,GM perturbations disrupt lipid homeostasis via lipopolysaccharide-triggered hepatic very low-density lipoprotein overproduction,short-chain fatty acid-G protein-coupled receptor 43/41-mediated adipocyte lipolysis,bile acid-farnesoid X receptor/Takeda G proteincoupled receptor 5 axis dysfunction altering cholesterol flux,microbialβ-oxidation intermediates impairing mitochondrial energetics,and host-microbiota noncoding RNA crosstalk regulating lipogenic genes.This comprehensive review systematically examines three critical dimensions,including bidirectional GMlipid axis interactions,molecular cascades bridging microbial ecology to metabolic dysfunction,and translational applications of GM modulation through precision probiotics,structure-specific prebiotics,and a metabolically optimized fecal microbiota transplantation protocol.Notwithstanding these advances,critical gaps persist in establishing causal microbial taxa-pathway relationships and optimal intervention timing.Future directions require longitudinal multi-omic studies,gnotobiotic models for mechanistic validation,and machine learning-driven personalized microbiota profiling.This synthesis provides a framework for developing microbiotacentric strategies targeting dyslipidemia pathophysiology,with implications for precision dyslipidemia management and next-generation cardiovascular disease prevention.展开更多
Natural killer(NK)cells have emerged as promising therapeutic agents for treating colorectal cancer because of their innate ability to recognize and eliminate tumor cells without prior sensitization.In this review,NK ...Natural killer(NK)cells have emerged as promising therapeutic agents for treating colorectal cancer because of their innate ability to recognize and eliminate tumor cells without prior sensitization.In this review,NK cell-based immunotherapeutic approaches,including cytokine therapy,immune checkpoint inhibition,antibody-dependent cellular cytotoxicity,and adoptive cell transfer,are comprehensively examined,and their respective clinical potential and limitations are highlighted.We discuss critical challenges in NK cell expansion,genetic engineering(particularly chimeric antigen receptor-NK development),and tumor microenvironment-mediated immunosuppression.Furthermore,we explore innovative strategies such as combination therapies,nanotechnology-enhanced delivery,and personalized medicine approaches that aim to overcome the current barriers.The review concludes with future directions emphasizing the need for standardized manufacturing protocols,new strategies to improve NK cell persistence,and clinical validation of emerging technologies,positioning NK cell immunotherapy as a transformative modality for colorectal cancer treatment.展开更多
Owing to their unique biological effects and physicochemical properties,nanomaterials have garnered substantial attention in the field of bone tissue engineering(BTE),targeting the repair and restoration of impaired b...Owing to their unique biological effects and physicochemical properties,nanomaterials have garnered substantial attention in the field of bone tissue engineering(BTE),targeting the repair and restoration of impaired bone tissue.In recent years,strategies for the design and optimization of nanomaterials through thiolation modification have been widely applied in BTE.This review concisely summarizes the categories of nanomaterials commonly used in BTE and focuses on various strategies for the modification of nanomaterials via thiolation.A multifaceted analysis of the mechanisms by which thiolated nanomaterials enhance nanomaterial-cell interactions,promote drug loading and release,and modulate osteogenic differentiation is presented.Furthermore,this review introduces biomedical applications of thiolated nanomaterials in BTE,including as scaffold components for bone regeneration,coatings for bone implants,and drug delivery systems.Finally,the future perspectives and challenges in the development of this field are discussed.Thiolation modification strategies provide a platform for developing new ideas and methods for designing nanomaterials for BTE and are expected to accelerate the development and clinical translation of novel bone repair materials.展开更多
BACKGROUND The occurrence of chronic pain and disability after acute orthopedic trauma is significantly correlated with psychological factors,particularly depression and anxiety.As such,assessment of these factors is ...BACKGROUND The occurrence of chronic pain and disability after acute orthopedic trauma is significantly correlated with psychological factors,particularly depression and anxiety.As such,assessment of these factors is crucial for postoperative rehabilitation.AIM To investigate the correlation between chronic pain,disability,and psychological factors(depression and anxiety)after acute orthopedic trauma surgery.METHODS Data from 120 patients,who underwent surgery for acute orthopedic trauma at Xi’an Traditional Chinese Medicine Hospital(Shaanxi Province,China)between June 2022 and June 2024,were retrospectively analyzed.Basic information and postoperative pain metrics[visual analog scale(VAS)],disability rating index(DRI),Hamilton anxiety rating scale(HAMA)and Hamilton depression rating scale(HAMD)were collected from electronic medical records.Pearson’s correlation analysis was used to examine associations between chronic pain VAS,DRI,HAMD,and HAMA scores.RESULTS Among the 120 patients[79(65.8%)males and 41(34.2%)females],postoperative VAS scores were significantly associated with HAMD and HAMA scores,with correlation coefficients of 0.625(P=0.027)and 0.568(P<0.001),respectively.Postoperative DRI scores were also significantly associated with HAMD and HAMA scores,with correlation coefficients of 0.683 and 0.557,respectively(both P<0.001).CONCLUSION Chronic pain and disability after surgery for acute orthopedic trauma are significantly correlated with psychological factors(depression and anxiety).Multidisciplinary teams should integrate mental health services to improve patient outcomes.展开更多
The occurrence and progression of liver cancer are closely associated with mitochondrial dysfunction.Mitochondria exhibit characteristics,such as decreased oxidative phosphorylation efficiency,abnormal accumulation of...The occurrence and progression of liver cancer are closely associated with mitochondrial dysfunction.Mitochondria exhibit characteristics,such as decreased oxidative phosphorylation efficiency,abnormal accumulation of reactive oxygen species in liver cancer and promoting tumor proliferation and drug resistance through the Warburg effect,as the core of energy metabolism and apoptosis regulation.Mutations in mitochondrial DNA(mtDNA)and dysregulation of mitochondrial autophagy(mitophagy)further enhance the invasive and metastatic capabilities of liver cancer.Current targeted therapeutic strategies focus on modulating the activity of respiratory chain complexes,regulating calcium homeostasis,repairing mtDNA,and activating mitochondrial apoptotic pathways.Although these approaches have shown therapeutic effects,challenges persist,such as tumor heterogeneity,insufficient drug specificity,and drug resistance.Future research needs to integrate the concept of precision medicine by focusing on breakthroughs in the molecular mechanisms underlying mitochondrial dysfunction,development of targeted delivery systems,optimization of combination therapy regimens,and screening of biomarkers to provide new pathways for individualized treatment.With advances in technology,targeting mitochondrial dysfunction is expected to become an important breakthrough for improving the prognosis of liver cancer.展开更多
Lifestyle is related to many chronic diseases,such as knee osteoarthritis(KOA).Food intake is important because it can be controlled.However,the causal relationship of food intake and KOA still remain unclear.To ident...Lifestyle is related to many chronic diseases,such as knee osteoarthritis(KOA).Food intake is important because it can be controlled.However,the causal relationship of food intake and KOA still remain unclear.To identify the relationship between food intake and KOA and to screen relevant targets.First,we performed two-sample Mendelian randomization(MR)analysis.A total of 16 kinds of food intake datasets were included,the inverse variance-weighted analysis showed that the KOA was negatively correlated with cereal intake(odds ratio(OR)0.48;95%CI 0.35-0.68;P=1.98×10−5).Second,potential drug targets of KOA in plasma were explored,secreted protein acidic and rich in cysteine(SPARC,or osteonectin),SPARC,Cwcv,and Kazal-like domains proteoglycan 2(SPOCK2)as the causal protein for plasma with KOA,and increased SPOCK2(OR 0.84;95%CI 0.77-0.92;P=5.52×10−5),decreased the risk of KOA.Integrated transcriptomic analysis(P=0.0285)and in vivo(P=0.0395)showed consistent results.Finally,by metabolomics analysis and molecular docking,seven co-expressed small molecules were detected in cereal and were bound to SPOCK2.Our findings indicate the cereal intake was negatively correlated with KOA,and support the SPOCK2 as a novel potential target for cereal intake in KOA.Our study will provide a clinical dietary guidance for KOA patients and a theoretical basis for the development of novel,side-effect-free drugs for KOA.展开更多
Frozen shoulder(FS),also known as adhesive capsulitis,is a condition that causes contraction and stiffness of the shoulder joint capsule.The main symptoms are per-sistent shoulder pain and a limited range of motion in...Frozen shoulder(FS),also known as adhesive capsulitis,is a condition that causes contraction and stiffness of the shoulder joint capsule.The main symptoms are per-sistent shoulder pain and a limited range of motion in all directions.These symp-toms and poor prognosis affect people's physical health and quality of life.Currently,the specific mechanisms of FS remain unclear,and there is variability in treatment methods and their efficacy.Additionally,the early symptoms of FS are difficult to distinguish from those of other shoulder diseases,complicating early diagnosis and treatment.Therefore,it is necessary to develop and utilize animal models to under-stand the pathogenesis of FS and to explore treatment strategies,providing insights into the prevention and treatment of human FS.This paper reviews the rat models available for FS research,including external immobilization models,surgical internal immobilization models,injection modeling models,and endocrine modeling models.It introduces the basic procedures for these models and compares and analyzes the advantages,disadvantages,and applicability of each modeling method.Finally,our paper summarizes the common methods for evaluating FS rat models.展开更多
Wound healing remains a critical challenge in medical treatment,particularly for infected and complex wounds.This study introduces a novel spray able nanocomposite hydrogel dressing(SA/CaCl_(2)/CeO_(2),SCC)that demons...Wound healing remains a critical challenge in medical treatment,particularly for infected and complex wounds.This study introduces a novel spray able nanocomposite hydrogel dressing(SA/CaCl_(2)/CeO_(2),SCC)that demonstrates exceptional potential for accelerated wound healing and bacterial infection control.By integrating cerium oxide nanoparticles(CeO_(2)NPs)with sodium alginate(SA)and calcium chloride(CaCl_(2)),we developed a versatile and portable wound healing solution that possesses the ability to scavenge reactive oxygen species(ROS),remarkable biocompatibility,antibacterial properties,and regenerative capabilities.The synthesized SCC hydrogel was comprehensively characterized through advanced microscopic and spectroscopic techniques,revealing a unique nanostructured composition with intrinsic redox capacity.In vitro assessments demonstrated excellent cytocompatibility,hemocompatibility,and potent antibacterial activity against both gram-positive and gramnegative bacteria.In vivo rat wound model experiments further validated the hydrogel's therapeutic efficacy,showing significantly accelerated wound closure,reduced inflammatory responses,and enhanced tissue regeneration.Key innovations include the hydrothermal synthesis of CeO_(2)nanoparticles,a simple spray-induced crosslinking process,and the strategic incorporation of nanoparticles to modulate wound healing mechanisms.The SCC hydrogel exhibited superior performance in promoting granulation tissue formation,collagen deposition,and bacterial elimination,positioning it as a promising candidate for advanced wound management strategies.展开更多
Epidemiological studies have indicated that branched-chain amino acids(BCAAs)increased and gut microbiota disordered in type 2 diabetes mellitus(T2DM).This study aimed to investigate the mechanism of Lactiplantibacill...Epidemiological studies have indicated that branched-chain amino acids(BCAAs)increased and gut microbiota disordered in type 2 diabetes mellitus(T2DM).This study aimed to investigate the mechanism of Lactiplantibacillus plantarum strain 84-3(Lp84-3)combined with Staphylococcus aureus bacteriophage on ameliorating T2DM.Here we perform a case-control study and identify that Staphylococcus_phage was inversely correlated with fasting blood glucose(FBG).It revealed that Lp84-3 could inhibit the growth of S.aureus,and Lp84-3 contains BCAAs degradation enzymes in its genome.Furthermore,Lp84-3 alone or combined with S.aureus bacteriophage interventions can improve blood glucose,insulin resistance,triglycerides,interleukin-1β,tumor necrosis factor-α(TNF-α),BCAAs,and acetyllactate synthase(ALS)in db/db mice.Lp84-3 and S.aureus bacteriophage decreased S.aureus,Malacoplasma iowae,and Oscillibacter sp.,and increased some beneficial such as L.plantarum and Muribaculaceae bacterium.Transcriptomic analyses revealed that Lp84-3 and S.aureus bacteriophage activated the PI3K/AKT/GLUT4 signaling pathway and upregulated key genes of Il22,Hgf,Col6a1,Gh,Itga10,Fgf23,and Prl involved in glucose metabolism in hypothalamus.Collectively,Lp84-3 and S.aureus bacteriophage alleviate T2DM by modulating gut microbiota and enhancing glucose metabolism in hypothalamus,supporting its potential use as a promising functional compound microecological agent for alleviating T2DM.展开更多
Osteoarthritis(OA)is one of the most common degenerative joint diseases in the elderly,increasing in prevalence and posing a substantial socioeconomic challenge,while no disease-modifying treatments available.Better u...Osteoarthritis(OA)is one of the most common degenerative joint diseases in the elderly,increasing in prevalence and posing a substantial socioeconomic challenge,while no disease-modifying treatments available.Better understanding of the early molecular events will benefit the early-stage diagnosis and clinical therapy.Here,we observed the nucleus accumulation of ZBTB20,a member of ZBTB-protein family,in the chondrocytes of early-stage OA.Chondrocytes-specific depletion of Zbtb20 in adult mice attenuated DMM-induced OA progress,restored the balance of extracellular matrix anabolism and catabolism.The NF-κB signaling mediated disturbance of ECM maintenance by ZBTB20 requires its suppression of Pten and consequent PI3K-Akt signaling activation.Furthermore,the subcellular localization of ZBTB20 was modulated by the kinase LATS1.Independent approaches to modulating ZBTB20 via utilizing TRULI and DAPA can restore ECM homeostasis,improving the abnormal behavior and moderating cartilage degeneration.The compounds TRULI and DAPA modulating ZBTB20 may serve as anti-OA drugs.展开更多
Wearable healthcare sensors can convert various physical signals, physiological signals, and electrophysiological activities of the human body into quantifiable resistive or capacitive changes for real-time health mon...Wearable healthcare sensors can convert various physical signals, physiological signals, and electrophysiological activities of the human body into quantifiable resistive or capacitive changes for real-time health monitoring. Gallium(Ga)-based liquid metal(LM) has become an ideal candidate for wearable healthcare sensors due to its excellent physical and chemical properties, such as high stretchability, high electrical conductivity, self-healing and thermal conductivity, and good biocompatibility. However,the high surface tension of LM makes it difficult to be processed. After LM is modified, the LM surface tension is reduced to be able to form LM composites by tightly bonding with the elastomer matrix, and the LM composites exhibit enhanced electromechanical, thermal, and magnetic properties, among others. Here, we review the fabrication methods of LM composites;we describe in detail the composite forms of LM composites and recent advances in tensile, thermal and electrical conductivity, high dielectric constant and biocompatibility. Sensor devices(e.g.,piezoelectric sensors, friction electric sensors, strain sensors, and magnetic sensors) of LM composites for wearable healthcare monitoring are summarized. Finally, challenges and opportunities of LM composites in the neighborhood of wearable healthcare sensors are also discussed.展开更多
BACKGROUND Despite the promising prospects of utilizing artificial intelligence and machine learning(ML)for comprehensive disease analysis,few models constructed have been applied in clinical practice due to their com...BACKGROUND Despite the promising prospects of utilizing artificial intelligence and machine learning(ML)for comprehensive disease analysis,few models constructed have been applied in clinical practice due to their complexity and the lack of reasonable explanations.In contrast to previous studies with small sample sizes and limited model interpretability,we developed a transparent eXtreme Gradient Boosting(XGBoost)-based model supported by multi-center data,using patients'basic information and clinical indicators to forecast the occurrence of anastomotic leakage(AL)after rectal cancer resection surgery.The model demonstrated robust predictive performance and identified clinically relevant thresholds,which may assist physicians in optimizing perioperative management.AIM To develop an interpretable ML model for accurately predicting the occurrence probability of AL after rectal cancer resection and define our clinical alert values for serum calcium ions.METHODS Patients who underwent anterior resection of the rectum for rectal carcinoma at the Department of Digestive Surgery,Xijing Hospital of Digestive Diseases,Air Force Medical University,and Shaanxi Provincial People's Hospital,were retrospectively collected from January 2011 to December 2021.Ten ML models were integrated to analyze the data and develop the predictive models.Receiver operating characteristic(ROC)curves,calibration curve,decision curve analysis,accuracy,sensitivity,specificity,positive predictive value,negative predictive value,and F1 score were used to evaluate model performance.We employed the SHapley Additive exPlanations(SHAP)algorithm to explain the feature importance of the optimal model.RESULTS A total of ten features were integrated to construct the predictive model and identify the optimal model.XGBoost was considered the best-performing model with an area under the ROC curve(AUC)of 0.984(95%confidence interval:0.972-0.996)in the test set(accuracy:0.925;sensitivity:0.92;specificity:0.927).Furthermore,the model achieved an AUC of 0.703 in external validation.The interpretable SHAP algorithm revealed that the serum calcium ion level was the crucial factor influencing the predictions of the model.CONCLUSION A superior predictive model,leveraging clinical data,has been crafted by employing the most effective XGBoost from a selection of ten algorithms.This model,by predicting the occurrence of AL in patients after rectal cancer resection,has identified the significant role of serum calcium ion levels,providing guidance for clinical practice.The integration of SHAP provides a clear interpretation of the model's predictions.展开更多
Hypochlorous acid(HClO)is a critical biomolecule in living organisms,playing an essential role in numerous physiological or pathological processes.Abnormal levels of HClO in the body may lead to a series of diseases,f...Hypochlorous acid(HClO)is a critical biomolecule in living organisms,playing an essential role in numerous physiological or pathological processes.Abnormal levels of HClO in the body may lead to a series of diseases,for instance,inflammation and cancer.Thus,accurate measurement of HClO levels should be more beneficial for understanding its role in diseases and gaining a deeper insight into the pathogenesis of diseases.In this work,we designed a near-infrared two-photon fluorescent probe(HDM-Cl-HClO)for detecting fluctuations in HClO levels in inflammatory and tumor-bearing mice.Notably,the probe can respond to HClO within 5 s and trigger a brilliant red fluorescence at 660 nm.It exhibits high specificity and sensitivity for HClO.The superior spectral capability of the probe has enabled the detection of HClO levels in cells and zebrafish,as well as achieved the detection of HClO in inflammatory and tumor mice.This work not only provides a novel strategy and tool for HClO imaging in living systems,but also holds great potential for the diagnosis of inflammation and cancer.展开更多
Crucial for mediating inflammation and the perception of pain,the ion channel known as transient receptor potential ankyrin 1(TRPA1)holds significant importance.It contributes to the increased production of cytokines ...Crucial for mediating inflammation and the perception of pain,the ion channel known as transient receptor potential ankyrin 1(TRPA1)holds significant importance.It contributes to the increased production of cytokines in the inflammatory cells of cartilage affected by osteoarthritis and represents a promising target for the treatment of this condition.By leveraging the unique advantages of liposomes,a composite microsphere drug delivery system with stable structural properties and high adaptability can be developed,providing a new strategy for osteoarthritis(OA)drug therapy.The liposomes as drug reservoirs for TRPA1 inhibitors were loaded into hyaluronic acid methacrylate(HAMA)hydrogels to make hydrogel microspheres via microfluidic technology.An in vitro inflammatory chondrocyte model was established with interleukin-1β(IL-1β)to demonstrate HAMA@Lipo@HC’s capabilities.A destabilization of the medial meniscus(DMM)mouse model was also created to evaluate the efficacy of intra-articular injections for treating OA.HAMA@Lipo@HC has a uniform particle-size distribution and is injectable.The drug encapsulation rate was 64.29%±2.58%,with a sustained release period of 28 days.Inhibition of TRPA1 via HC-030031 effectively alleviated IL-1β-induced chondrocyte inflammation and matrix degradation.In DMM model OA mice,microspheres showed good long-term sustained drug release properties,improved joint inflammation microenvironment,reduced articular cartilage damage and decreased mechanical nociceptive threshold.This research pioneers the creation of a drug delivery system tailored for delivery into the joint cavity,focusing on TRPA1 as a therapeutic target for osteoarthritis.Additionally,it offers a cutting-edge drug delivery platform aimed at addressing diseases linked to inflammation.展开更多
As a highly invasive carcinoma,esophageal cancer(EC)was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020.Esophageal squamous cell carcinoma(ESCC)is the major h...As a highly invasive carcinoma,esophageal cancer(EC)was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020.Esophageal squamous cell carcinoma(ESCC)is the major histological subtype of EC,and its incidence and mortality rates are decreasing globally.Due to the lack of specific early symptoms,ESCC patients are usually diagnosed with advanced-stage disease with a poor prognosis,and the incidence and mortality rates are still high in many countries,especially in China.Therefore,enormous challenges still exist in the management of ESCC,and novel strategies are urgently needed to further decrease the incidence and mortality rates of ESCC.Although the key molecular mechanisms underlying ESCC pathogenesis have not been fully elucidated,certain promising biomarkers are being investigated to facilitate clinical decision-making.With the advent and advancement of highthroughput technologies,such as genomics,proteomics and metabolomics,valuable biomarkers with high sensitivity,specificity and stability could be identified for ESCC.Herein,we aimed to determine the epidemiological features of ESCC in different regions of the world,especially in China,and focused on novel molecular biomarkers associated with ESCC screening,early diagnosis and prognosis prediction.展开更多
BACKGROUND Acute non-variceal upper gastrointestinal bleeding(ANVUGIB)constitutes a prevalent emergency within Gastroenterology,encompassing 80%-90%of all gastrointestinal hemorrhage incidents.This condition is distin...BACKGROUND Acute non-variceal upper gastrointestinal bleeding(ANVUGIB)constitutes a prevalent emergency within Gastroenterology,encompassing 80%-90%of all gastrointestinal hemorrhage incidents.This condition is distinguished by its abrupt onset,swift progression,and notably elevated mortality rate.AIM To gather clinical data from patients with ANVUGIB at our hospital in order to elucidate the clinical characteristics specific to our institution and analyze the therapeutic effectiveness of endoscopic hemostasis.METHODS We retrospectively retrieved the records of 532 patients diagnosed with ANVUGIB by endoscopy at our hospital between March 2021 and March 2023,utilizing our medical record system.Data pertaining to general patient information,etiological factors,disease outcomes,and other relevant variables were meticulously collected and analyzed.RESULTS Among the 532 patients diagnosed with ANVUGIB,the male-to-female ratio was 2.91:1,with a higher prevalence among males.Notably,43.6%of patients presented with black stool as their primary complaint,while 27.4%had hematemesis as their initial symptom.Upon admission,17%of patients exhibited both hematemesis and black stool,while most ANVUGIB patients primarily complained of overt gastrointestinal bleeding.Urgent routine blood examinations at admission revealed that 75.8%of patients had anemia,with 63.4%experiencing moderate to severe anemia,and 1.5%having extremely severe anemia(hemoglobin<30 g/L).With regard to etiology,53.2%of patients experienced bleeding without a definitive trigger,24.2%had a history of using gastric mucosa-irritating medications,24.2%developed bleeding after alcohol consumption,2.8%attributed it to improper diet,1.7%to emotional excitement,and 2.3%to fatigue preceding the bleeding episode.Drug-induced ANVUGIB was more prevalent in the elderly than middle-aged and young individuals,while bleeding due to alcohol consumption showed the opposite trend.Additionally,diet-related bleeding was more common among the young age group compared to the middle-aged group.Gastrointestinal endoscopy identified peptic ulcers as the most frequent cause of ANVUGIB(73.3%),followed by gastrointestinal malignancies(10.9%),acute gastric mucous lesions(9.8%),and androgenic upper gastrointestinal bleeding(1.5%)among inpatients with ANVUGIB.Of the 532 patients with gastrointestinal bleeding,68 underwent endoscopic hemostasis,resulting in an endoscopic treatment rate of 12.8%,with a high immediate hemostasis success rate of 94.1%.展开更多
As a highly invasive malignancy,esophageal cancer(EC)is a global health issue,and was the eighth most prevalent cancer and the sixth leading cause of cancerrelated death worldwide in 2020.Due to its highly immunogenic...As a highly invasive malignancy,esophageal cancer(EC)is a global health issue,and was the eighth most prevalent cancer and the sixth leading cause of cancerrelated death worldwide in 2020.Due to its highly immunogenic nature,emerging immunotherapy approaches,such as immune checkpoint blockade,have demonstrated promising efficacy in treating EC;however,certain limitations and challenges still exist.In addition,tumors may exhibit primary or acquired resistance to immunotherapy in the tumor immune microenvironment(TIME);thus,understanding the TIME is urgent and crucial,especially given the importance of an immunosuppressive microenvironment in tumor progression.The aim of this review was to better elucidate the mechanisms of the suppressive TIME,including cell infiltration,immune cell subsets,cytokines and signaling pathways in the tumor microenvironment of EC patients,as well as the downregulated expression of major histocompatibility complex molecules in tumor cells,to obtain a better understanding of the differences in EC patient responses to immunotherapeutic strategies and accurately predict the efficacy of immunotherapies.Therefore,personalized treatments could be developed to maximize the advantages of immunotherapy.展开更多
基金supported by the National Key Research and Development Project,No.2019YFA0112100(to SF).
文摘Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death.China has the largest population of patients with traumatic spinal cord injury.Previous studies of traumatic spinal cord injury in China have mostly been regional in scope;national-level studies have been rare.To the best of our knowledge,no national-level study of treatment status and economic burden has been performed.This retrospective study aimed to examine the epidemiological and clinical features,treatment status,and economic burden of traumatic spinal cord injury in China at the national level.We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China.Patient epidemiological and clinical features,treatment status,and total and daily costs were recorded.Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program.The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall(annual percentage change,-0.5%and 2.1%,respectively).A total of 10,053(74.7%)patients underwent surgery.Only 2.8%of patients who underwent surgery did so within 24 hours of injury.A total of 2005(14.9%)patients were treated with high-dose(≥500 mg)methylprednisolone sodium succinate/methylprednisolone(MPSS/MP);615(4.6%)received it within 8 hours.The total cost for acute traumatic spinal cord injury decreased over the study period(-4.7%),while daily cost did not significantly change(1.0%increase).Our findings indicate that public health initiatives should aim at improving hospitals’ability to complete early surgery within 24 hours,which is associated with improved sensorimotor recovery,increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.
文摘BACKGROUND Traumatic injuries,such as falling,car accidents,and crushing mostly cause spinal fractures in young and middle-aged people,and>50%of them are thoracolumbar fractures.This kind of fracture is easily combined with serious injuries to peripheral nerves and soft tissues,which causes paralysis of the lower limbs if there is no timely rehabilitation treatment.Young patients with thoracolumbar fractures find it difficult to recover after the operation,and they are prone to depression,low self-esteem,and other negative emotions.AIM To investigate the association between anxiety,depression,and social stress in young patients with thoracolumbar spine fractures and the effect on rehabilitation outcomes.METHODS This study retrospectively analyzed 100 patients admitted to the orthopedic department of Honghui Hospital,Xi’an Jiaotong University who underwent thoracolumbar spine fracture surgery from January 2022 to June 2023.The general data of the patients were assessed with the Hamilton anxiety scale(HAMA),Hamilton depression scale(HAMD),life events scale,and social support rating scale(SSRS)to identify the correlation between anxiety,depression scores,and social stress and social support.The Japanese Orthopedic Association(JOA)was utilized to evaluate the rehabilitation outcomes of the patients and to analyze the effects of anxiety and depression scores on rehabilitation.RESULTS According to the scores of HAMD and HAMA in all patients,the prevalence of depression in patients was 39%(39/100),and the prevalence of anxiety was 49%(49/100).Patients were categorized into non-depression(n=61)and depression(n=39),non-anxiety(n=51),and anxiety(n=49)groups.Statistically significant differences in gender,occupation,Pittsburgh Sleep Quality Index(PSQI)score,and monthly family income were observed between the non-depression and depression groups(P<0.05).A significant difference in occupation and PSQI score was found between the non-anxiety and anxiety groups.Both depression(r=0.207,P=0.038)and anxiety scores(r=0.473,P<0.001)were significantly and positively correlated with negative life events.The difference in negative life event scores as well as SSRS total and item scores was statist-ically significant between patients in the non-depression and depression groups(P<0.05).The difference between the non-anxiety and anxiety groups was statistically significant(P<0.05)in the negative life event scores as well as the total SSRS scores.Additionally,JOA scores were significantly lower in both anxious and depressed patients.CONCLUSION Young patients with thoracolumbar fractures are prone to anxiety and depression.Patients’anxiety and depression are closely associated with social pressure,which reduces the life pressure of young patients with thoracolumbar fractures,enhances social support,and improves the psychology of anxiety and depression.,which affects patients’recovery.
基金support of the National Natural Science Foundation of China(Grant No.52205593)Shaanxi Natural Science Foundation Project(2024JC-YBMS-711).
文摘The incidence of large bone defects caused by traumatic injury is increasing worldwide,and the tissue regeneration process requires a long recovery time due to limited self-healing capability.Endogenous bioelectrical phenomena have been well recognized as critical biophysical factors in bone remodeling and regeneration.Inspired by bioelectricity,electrical stimulation has been widely considered an external intervention to induce the osteogenic lineage of cells and enhance the synthesis of the extracellular matrix,thereby accelerating bone regeneration.With ongoing advances in biomaterials and energy-harvesting techniques,electroactive biomaterials and self-powered systems have been considered biomimetic approaches to ensure functional recovery by recapitulating the natural electrophysiological microenvironment of healthy bone tissue.In this review,we first introduce the role of bioelectricity and the endogenous electric field in bone tissue and summarize different techniques to electrically stimulate cells and tissue.Next,we highlight the latest progress in exploring electroactive hybrid biomaterials as well as self-powered systems such as triboelectric and piezoelectric-based nanogenerators and photovoltaic cell-based devices and their implementation in bone tissue engineering.Finally,we emphasize the significance of simulating the target tissue’s electrophysiological microenvironment and propose the opportunities and challenges faced by electroactive hybrid biomaterials and self-powered bioelectronics for bone repair strategies.
基金Supported by Shaanxi Natural Science Foundation of China,No.2025JC-YBMS-916and Xi’an Municipal Health Commission of China,No.2023ms11.
文摘Natural killer(NK)cells have emerged as promising therapeutic agents for treating colorectal cancer because of their innate ability to recognize and eliminate tumor cells without prior sensitization.In this review,NK cell-based immunotherapeutic approaches,including cytokine therapy,immune checkpoint inhibition,antibody-dependent cellular cytotoxicity,and adoptive cell transfer,are comprehensively examined,and their respective clinical potential and limitations are highlighted.We discuss critical challenges in NK cell expansion,genetic engineering(particularly chimeric antigen receptor-NK development),and tumor microenvironment-mediated immunosuppression.Furthermore,we explore innovative strategies such as combination therapies,nanotechnology-enhanced delivery,and personalized medicine approaches that aim to overcome the current barriers.The review concludes with future directions emphasizing the need for standardized manufacturing protocols,new strategies to improve NK cell persistence,and clinical validation of emerging technologies,positioning NK cell immunotherapy as a transformative modality for colorectal cancer treatment.
基金financially supported by the National Natural Science Foundation of China(Nos.52103184 and 8226030956)the National Key Research and Development Program of China(No.2022YFC2407503)+3 种基金Key Project of the Natural Science Basic Research Plan of Shaanxi Province(No.2022JZ43)Natural Science Basic Research Program of Shaanxi Province(No.2024JCYBQN-0874)Medical Research Key Project of Xi'an Science and Technology Bureau(No.2024JH-YXZD-0055)Medical Research Project of Xi'an Science and Technology Bureau(No.22YXYJ0083)
文摘Owing to their unique biological effects and physicochemical properties,nanomaterials have garnered substantial attention in the field of bone tissue engineering(BTE),targeting the repair and restoration of impaired bone tissue.In recent years,strategies for the design and optimization of nanomaterials through thiolation modification have been widely applied in BTE.This review concisely summarizes the categories of nanomaterials commonly used in BTE and focuses on various strategies for the modification of nanomaterials via thiolation.A multifaceted analysis of the mechanisms by which thiolated nanomaterials enhance nanomaterial-cell interactions,promote drug loading and release,and modulate osteogenic differentiation is presented.Furthermore,this review introduces biomedical applications of thiolated nanomaterials in BTE,including as scaffold components for bone regeneration,coatings for bone implants,and drug delivery systems.Finally,the future perspectives and challenges in the development of this field are discussed.Thiolation modification strategies provide a platform for developing new ideas and methods for designing nanomaterials for BTE and are expected to accelerate the development and clinical translation of novel bone repair materials.
文摘BACKGROUND The occurrence of chronic pain and disability after acute orthopedic trauma is significantly correlated with psychological factors,particularly depression and anxiety.As such,assessment of these factors is crucial for postoperative rehabilitation.AIM To investigate the correlation between chronic pain,disability,and psychological factors(depression and anxiety)after acute orthopedic trauma surgery.METHODS Data from 120 patients,who underwent surgery for acute orthopedic trauma at Xi’an Traditional Chinese Medicine Hospital(Shaanxi Province,China)between June 2022 and June 2024,were retrospectively analyzed.Basic information and postoperative pain metrics[visual analog scale(VAS)],disability rating index(DRI),Hamilton anxiety rating scale(HAMA)and Hamilton depression rating scale(HAMD)were collected from electronic medical records.Pearson’s correlation analysis was used to examine associations between chronic pain VAS,DRI,HAMD,and HAMA scores.RESULTS Among the 120 patients[79(65.8%)males and 41(34.2%)females],postoperative VAS scores were significantly associated with HAMD and HAMA scores,with correlation coefficients of 0.625(P=0.027)and 0.568(P<0.001),respectively.Postoperative DRI scores were also significantly associated with HAMD and HAMA scores,with correlation coefficients of 0.683 and 0.557,respectively(both P<0.001).CONCLUSION Chronic pain and disability after surgery for acute orthopedic trauma are significantly correlated with psychological factors(depression and anxiety).Multidisciplinary teams should integrate mental health services to improve patient outcomes.
基金supported by the National Natural Science Foundation of China(Grant No.81860653)Qiankehe Foundation[Grant No.QN(2025)383].
文摘The occurrence and progression of liver cancer are closely associated with mitochondrial dysfunction.Mitochondria exhibit characteristics,such as decreased oxidative phosphorylation efficiency,abnormal accumulation of reactive oxygen species in liver cancer and promoting tumor proliferation and drug resistance through the Warburg effect,as the core of energy metabolism and apoptosis regulation.Mutations in mitochondrial DNA(mtDNA)and dysregulation of mitochondrial autophagy(mitophagy)further enhance the invasive and metastatic capabilities of liver cancer.Current targeted therapeutic strategies focus on modulating the activity of respiratory chain complexes,regulating calcium homeostasis,repairing mtDNA,and activating mitochondrial apoptotic pathways.Although these approaches have shown therapeutic effects,challenges persist,such as tumor heterogeneity,insufficient drug specificity,and drug resistance.Future research needs to integrate the concept of precision medicine by focusing on breakthroughs in the molecular mechanisms underlying mitochondrial dysfunction,development of targeted delivery systems,optimization of combination therapy regimens,and screening of biomarkers to provide new pathways for individualized treatment.With advances in technology,targeting mitochondrial dysfunction is expected to become an important breakthrough for improving the prognosis of liver cancer.
基金supported by the National Natural Science Foundation of China(82072432)Scientific Research and Innovation Platform for Intelligent and Precise Treatment of Bone and Joint Diseases in Shaanxi Province(2024PT-13)Key Project of Shaanxi Provincial Natural Science Foundation(2024JC-ZDXM-55).
文摘Lifestyle is related to many chronic diseases,such as knee osteoarthritis(KOA).Food intake is important because it can be controlled.However,the causal relationship of food intake and KOA still remain unclear.To identify the relationship between food intake and KOA and to screen relevant targets.First,we performed two-sample Mendelian randomization(MR)analysis.A total of 16 kinds of food intake datasets were included,the inverse variance-weighted analysis showed that the KOA was negatively correlated with cereal intake(odds ratio(OR)0.48;95%CI 0.35-0.68;P=1.98×10−5).Second,potential drug targets of KOA in plasma were explored,secreted protein acidic and rich in cysteine(SPARC,or osteonectin),SPARC,Cwcv,and Kazal-like domains proteoglycan 2(SPOCK2)as the causal protein for plasma with KOA,and increased SPOCK2(OR 0.84;95%CI 0.77-0.92;P=5.52×10−5),decreased the risk of KOA.Integrated transcriptomic analysis(P=0.0285)and in vivo(P=0.0395)showed consistent results.Finally,by metabolomics analysis and molecular docking,seven co-expressed small molecules were detected in cereal and were bound to SPOCK2.Our findings indicate the cereal intake was negatively correlated with KOA,and support the SPOCK2 as a novel potential target for cereal intake in KOA.Our study will provide a clinical dietary guidance for KOA patients and a theoretical basis for the development of novel,side-effect-free drugs for KOA.
基金National Key R&D Program of China,Grant/Award Number:2021YFC2502100,2023YFC3603404 and 2019YFA0111900The National Natural Science Foundation of China,Grant/Award Number:82072506,82272611 and 92268115+7 种基金The Hunan Provincial Science Fund for Distinguished Young Scholars,Grant/Award Number:2024JJ2089The Hunan Young Talents of Science and Technology,Grant/Award Number:2021RC3025The Provincial Clinical Medical Technology Innovation Project of Hunan,Grant/Award Number:2023SK2024 and 2020SK53709The Provincial Natural Science Foundation of Hunan,Grant/Award Number:2020JJ3060The National Natural Science Foundation of Hunan Province,Grant/Award Number:2023JJ30949The National Clinical Research Center for Geriatric Disorders,Xiangya Hospital,Grant/Award Number:2021KFJJ02 and 2021LNJJ05The Hunan Provincial Innovation Foundation for Postgraduate,Grant/Award Number:CX20230308 and CX20230312The Independent Exploration and Innovation Project for Postgraduate Students of Central South University,Grant/Award Number:2024ZZTS0163。
文摘Frozen shoulder(FS),also known as adhesive capsulitis,is a condition that causes contraction and stiffness of the shoulder joint capsule.The main symptoms are per-sistent shoulder pain and a limited range of motion in all directions.These symp-toms and poor prognosis affect people's physical health and quality of life.Currently,the specific mechanisms of FS remain unclear,and there is variability in treatment methods and their efficacy.Additionally,the early symptoms of FS are difficult to distinguish from those of other shoulder diseases,complicating early diagnosis and treatment.Therefore,it is necessary to develop and utilize animal models to under-stand the pathogenesis of FS and to explore treatment strategies,providing insights into the prevention and treatment of human FS.This paper reviews the rat models available for FS research,including external immobilization models,surgical internal immobilization models,injection modeling models,and endocrine modeling models.It introduces the basic procedures for these models and compares and analyzes the advantages,disadvantages,and applicability of each modeling method.Finally,our paper summarizes the common methods for evaluating FS rat models.
基金financially supported by the National Natural Science Foundation of China(No.81802690)the Natural Science Foundation of Shaanxi Province(No.S2024-JCYB-1354)
文摘Wound healing remains a critical challenge in medical treatment,particularly for infected and complex wounds.This study introduces a novel spray able nanocomposite hydrogel dressing(SA/CaCl_(2)/CeO_(2),SCC)that demonstrates exceptional potential for accelerated wound healing and bacterial infection control.By integrating cerium oxide nanoparticles(CeO_(2)NPs)with sodium alginate(SA)and calcium chloride(CaCl_(2)),we developed a versatile and portable wound healing solution that possesses the ability to scavenge reactive oxygen species(ROS),remarkable biocompatibility,antibacterial properties,and regenerative capabilities.The synthesized SCC hydrogel was comprehensively characterized through advanced microscopic and spectroscopic techniques,revealing a unique nanostructured composition with intrinsic redox capacity.In vitro assessments demonstrated excellent cytocompatibility,hemocompatibility,and potent antibacterial activity against both gram-positive and gramnegative bacteria.In vivo rat wound model experiments further validated the hydrogel's therapeutic efficacy,showing significantly accelerated wound closure,reduced inflammatory responses,and enhanced tissue regeneration.Key innovations include the hydrothermal synthesis of CeO_(2)nanoparticles,a simple spray-induced crosslinking process,and the strategic incorporation of nanoparticles to modulate wound healing mechanisms.The SCC hydrogel exhibited superior performance in promoting granulation tissue formation,collagen deposition,and bacterial elimination,positioning it as a promising candidate for advanced wound management strategies.
基金supported by research grants from the Guangdong Province Basic and Applied Basic Research Fund Project(2022A1515110447)Open Fund Project of the State Key Laboratory of Applied Microbiology in South China(SKLAM006-2022)+1 种基金74th batch of general funding from the China Postdoctoral Science Foundation(2023M740774)Guangdong Provincial People’s Hospital,Postdoctoral Research Launch Fund(BY012022017)。
文摘Epidemiological studies have indicated that branched-chain amino acids(BCAAs)increased and gut microbiota disordered in type 2 diabetes mellitus(T2DM).This study aimed to investigate the mechanism of Lactiplantibacillus plantarum strain 84-3(Lp84-3)combined with Staphylococcus aureus bacteriophage on ameliorating T2DM.Here we perform a case-control study and identify that Staphylococcus_phage was inversely correlated with fasting blood glucose(FBG).It revealed that Lp84-3 could inhibit the growth of S.aureus,and Lp84-3 contains BCAAs degradation enzymes in its genome.Furthermore,Lp84-3 alone or combined with S.aureus bacteriophage interventions can improve blood glucose,insulin resistance,triglycerides,interleukin-1β,tumor necrosis factor-α(TNF-α),BCAAs,and acetyllactate synthase(ALS)in db/db mice.Lp84-3 and S.aureus bacteriophage decreased S.aureus,Malacoplasma iowae,and Oscillibacter sp.,and increased some beneficial such as L.plantarum and Muribaculaceae bacterium.Transcriptomic analyses revealed that Lp84-3 and S.aureus bacteriophage activated the PI3K/AKT/GLUT4 signaling pathway and upregulated key genes of Il22,Hgf,Col6a1,Gh,Itga10,Fgf23,and Prl involved in glucose metabolism in hypothalamus.Collectively,Lp84-3 and S.aureus bacteriophage alleviate T2DM by modulating gut microbiota and enhancing glucose metabolism in hypothalamus,supporting its potential use as a promising functional compound microecological agent for alleviating T2DM.
基金supported by grants from the National Natural Science Foundation of China(82002351,82394442,82130070,82272442)funded by the Innovation Capability Support Program of Shaanxi Province(2024SF-LCZX-16)+2 种基金the Shaanxi Province Health Scientific Research Innovation Ability Promotion Plan(2024PT-12)the Independent Exploration and Innovation Project of Xi’an Jiaotong University(xzy012023121)the project of Xi’an Postdoctoral Innovation Base.
文摘Osteoarthritis(OA)is one of the most common degenerative joint diseases in the elderly,increasing in prevalence and posing a substantial socioeconomic challenge,while no disease-modifying treatments available.Better understanding of the early molecular events will benefit the early-stage diagnosis and clinical therapy.Here,we observed the nucleus accumulation of ZBTB20,a member of ZBTB-protein family,in the chondrocytes of early-stage OA.Chondrocytes-specific depletion of Zbtb20 in adult mice attenuated DMM-induced OA progress,restored the balance of extracellular matrix anabolism and catabolism.The NF-κB signaling mediated disturbance of ECM maintenance by ZBTB20 requires its suppression of Pten and consequent PI3K-Akt signaling activation.Furthermore,the subcellular localization of ZBTB20 was modulated by the kinase LATS1.Independent approaches to modulating ZBTB20 via utilizing TRULI and DAPA can restore ECM homeostasis,improving the abnormal behavior and moderating cartilage degeneration.The compounds TRULI and DAPA modulating ZBTB20 may serve as anti-OA drugs.
基金financially supported by Mianyang Science and Technology Bureau(No.2023ZYDF081)the Research topic of Zhongnanshan Youth Science and Technology Innovation Award Fund of China Youth Entrepreneurship and Employment Foundation
文摘Wearable healthcare sensors can convert various physical signals, physiological signals, and electrophysiological activities of the human body into quantifiable resistive or capacitive changes for real-time health monitoring. Gallium(Ga)-based liquid metal(LM) has become an ideal candidate for wearable healthcare sensors due to its excellent physical and chemical properties, such as high stretchability, high electrical conductivity, self-healing and thermal conductivity, and good biocompatibility. However,the high surface tension of LM makes it difficult to be processed. After LM is modified, the LM surface tension is reduced to be able to form LM composites by tightly bonding with the elastomer matrix, and the LM composites exhibit enhanced electromechanical, thermal, and magnetic properties, among others. Here, we review the fabrication methods of LM composites;we describe in detail the composite forms of LM composites and recent advances in tensile, thermal and electrical conductivity, high dielectric constant and biocompatibility. Sensor devices(e.g.,piezoelectric sensors, friction electric sensors, strain sensors, and magnetic sensors) of LM composites for wearable healthcare monitoring are summarized. Finally, challenges and opportunities of LM composites in the neighborhood of wearable healthcare sensors are also discussed.
基金Supported by National Natural Science Foundation of China,No.82172781Shaanxi Health Scientific Research Innovation Team Project,No.2024TD-06.
文摘BACKGROUND Despite the promising prospects of utilizing artificial intelligence and machine learning(ML)for comprehensive disease analysis,few models constructed have been applied in clinical practice due to their complexity and the lack of reasonable explanations.In contrast to previous studies with small sample sizes and limited model interpretability,we developed a transparent eXtreme Gradient Boosting(XGBoost)-based model supported by multi-center data,using patients'basic information and clinical indicators to forecast the occurrence of anastomotic leakage(AL)after rectal cancer resection surgery.The model demonstrated robust predictive performance and identified clinically relevant thresholds,which may assist physicians in optimizing perioperative management.AIM To develop an interpretable ML model for accurately predicting the occurrence probability of AL after rectal cancer resection and define our clinical alert values for serum calcium ions.METHODS Patients who underwent anterior resection of the rectum for rectal carcinoma at the Department of Digestive Surgery,Xijing Hospital of Digestive Diseases,Air Force Medical University,and Shaanxi Provincial People's Hospital,were retrospectively collected from January 2011 to December 2021.Ten ML models were integrated to analyze the data and develop the predictive models.Receiver operating characteristic(ROC)curves,calibration curve,decision curve analysis,accuracy,sensitivity,specificity,positive predictive value,negative predictive value,and F1 score were used to evaluate model performance.We employed the SHapley Additive exPlanations(SHAP)algorithm to explain the feature importance of the optimal model.RESULTS A total of ten features were integrated to construct the predictive model and identify the optimal model.XGBoost was considered the best-performing model with an area under the ROC curve(AUC)of 0.984(95%confidence interval:0.972-0.996)in the test set(accuracy:0.925;sensitivity:0.92;specificity:0.927).Furthermore,the model achieved an AUC of 0.703 in external validation.The interpretable SHAP algorithm revealed that the serum calcium ion level was the crucial factor influencing the predictions of the model.CONCLUSION A superior predictive model,leveraging clinical data,has been crafted by employing the most effective XGBoost from a selection of ten algorithms.This model,by predicting the occurrence of AL in patients after rectal cancer resection,has identified the significant role of serum calcium ion levels,providing guidance for clinical practice.The integration of SHAP provides a clear interpretation of the model's predictions.
基金National Natural Science Foundation of China(No.22264013)Hainan Province Clinical Medical Center(No.2021)Hainan Province Science and Technology Special Fund(No.ZDYF2024SHFZ104).
文摘Hypochlorous acid(HClO)is a critical biomolecule in living organisms,playing an essential role in numerous physiological or pathological processes.Abnormal levels of HClO in the body may lead to a series of diseases,for instance,inflammation and cancer.Thus,accurate measurement of HClO levels should be more beneficial for understanding its role in diseases and gaining a deeper insight into the pathogenesis of diseases.In this work,we designed a near-infrared two-photon fluorescent probe(HDM-Cl-HClO)for detecting fluctuations in HClO levels in inflammatory and tumor-bearing mice.Notably,the probe can respond to HClO within 5 s and trigger a brilliant red fluorescence at 660 nm.It exhibits high specificity and sensitivity for HClO.The superior spectral capability of the probe has enabled the detection of HClO levels in cells and zebrafish,as well as achieved the detection of HClO in inflammatory and tumor mice.This work not only provides a novel strategy and tool for HClO imaging in living systems,but also holds great potential for the diagnosis of inflammation and cancer.
基金supported by the National Key Research and Development Program of China(No.82230071)National Natural Science Foundation of China(Nos.82202674,82202334)Wenzhou Science and Technology Project(Nos.Y20220178,Y20220016).
文摘Crucial for mediating inflammation and the perception of pain,the ion channel known as transient receptor potential ankyrin 1(TRPA1)holds significant importance.It contributes to the increased production of cytokines in the inflammatory cells of cartilage affected by osteoarthritis and represents a promising target for the treatment of this condition.By leveraging the unique advantages of liposomes,a composite microsphere drug delivery system with stable structural properties and high adaptability can be developed,providing a new strategy for osteoarthritis(OA)drug therapy.The liposomes as drug reservoirs for TRPA1 inhibitors were loaded into hyaluronic acid methacrylate(HAMA)hydrogels to make hydrogel microspheres via microfluidic technology.An in vitro inflammatory chondrocyte model was established with interleukin-1β(IL-1β)to demonstrate HAMA@Lipo@HC’s capabilities.A destabilization of the medial meniscus(DMM)mouse model was also created to evaluate the efficacy of intra-articular injections for treating OA.HAMA@Lipo@HC has a uniform particle-size distribution and is injectable.The drug encapsulation rate was 64.29%±2.58%,with a sustained release period of 28 days.Inhibition of TRPA1 via HC-030031 effectively alleviated IL-1β-induced chondrocyte inflammation and matrix degradation.In DMM model OA mice,microspheres showed good long-term sustained drug release properties,improved joint inflammation microenvironment,reduced articular cartilage damage and decreased mechanical nociceptive threshold.This research pioneers the creation of a drug delivery system tailored for delivery into the joint cavity,focusing on TRPA1 as a therapeutic target for osteoarthritis.Additionally,it offers a cutting-edge drug delivery platform aimed at addressing diseases linked to inflammation.
基金Supported by Xi’an Municipal Health Commission of China,No.2022qn07 and No.2023ms11.
文摘As a highly invasive carcinoma,esophageal cancer(EC)was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020.Esophageal squamous cell carcinoma(ESCC)is the major histological subtype of EC,and its incidence and mortality rates are decreasing globally.Due to the lack of specific early symptoms,ESCC patients are usually diagnosed with advanced-stage disease with a poor prognosis,and the incidence and mortality rates are still high in many countries,especially in China.Therefore,enormous challenges still exist in the management of ESCC,and novel strategies are urgently needed to further decrease the incidence and mortality rates of ESCC.Although the key molecular mechanisms underlying ESCC pathogenesis have not been fully elucidated,certain promising biomarkers are being investigated to facilitate clinical decision-making.With the advent and advancement of highthroughput technologies,such as genomics,proteomics and metabolomics,valuable biomarkers with high sensitivity,specificity and stability could be identified for ESCC.Herein,we aimed to determine the epidemiological features of ESCC in different regions of the world,especially in China,and focused on novel molecular biomarkers associated with ESCC screening,early diagnosis and prognosis prediction.
基金Supported by Xi’an Health Commission Residential Training Base Construction Project,No.2023zp09.
文摘BACKGROUND Acute non-variceal upper gastrointestinal bleeding(ANVUGIB)constitutes a prevalent emergency within Gastroenterology,encompassing 80%-90%of all gastrointestinal hemorrhage incidents.This condition is distinguished by its abrupt onset,swift progression,and notably elevated mortality rate.AIM To gather clinical data from patients with ANVUGIB at our hospital in order to elucidate the clinical characteristics specific to our institution and analyze the therapeutic effectiveness of endoscopic hemostasis.METHODS We retrospectively retrieved the records of 532 patients diagnosed with ANVUGIB by endoscopy at our hospital between March 2021 and March 2023,utilizing our medical record system.Data pertaining to general patient information,etiological factors,disease outcomes,and other relevant variables were meticulously collected and analyzed.RESULTS Among the 532 patients diagnosed with ANVUGIB,the male-to-female ratio was 2.91:1,with a higher prevalence among males.Notably,43.6%of patients presented with black stool as their primary complaint,while 27.4%had hematemesis as their initial symptom.Upon admission,17%of patients exhibited both hematemesis and black stool,while most ANVUGIB patients primarily complained of overt gastrointestinal bleeding.Urgent routine blood examinations at admission revealed that 75.8%of patients had anemia,with 63.4%experiencing moderate to severe anemia,and 1.5%having extremely severe anemia(hemoglobin<30 g/L).With regard to etiology,53.2%of patients experienced bleeding without a definitive trigger,24.2%had a history of using gastric mucosa-irritating medications,24.2%developed bleeding after alcohol consumption,2.8%attributed it to improper diet,1.7%to emotional excitement,and 2.3%to fatigue preceding the bleeding episode.Drug-induced ANVUGIB was more prevalent in the elderly than middle-aged and young individuals,while bleeding due to alcohol consumption showed the opposite trend.Additionally,diet-related bleeding was more common among the young age group compared to the middle-aged group.Gastrointestinal endoscopy identified peptic ulcers as the most frequent cause of ANVUGIB(73.3%),followed by gastrointestinal malignancies(10.9%),acute gastric mucous lesions(9.8%),and androgenic upper gastrointestinal bleeding(1.5%)among inpatients with ANVUGIB.Of the 532 patients with gastrointestinal bleeding,68 underwent endoscopic hemostasis,resulting in an endoscopic treatment rate of 12.8%,with a high immediate hemostasis success rate of 94.1%.
基金Supported by Xi’an Municipal Health Commission of China,No.2022qn07 and No.2023ms11.
文摘As a highly invasive malignancy,esophageal cancer(EC)is a global health issue,and was the eighth most prevalent cancer and the sixth leading cause of cancerrelated death worldwide in 2020.Due to its highly immunogenic nature,emerging immunotherapy approaches,such as immune checkpoint blockade,have demonstrated promising efficacy in treating EC;however,certain limitations and challenges still exist.In addition,tumors may exhibit primary or acquired resistance to immunotherapy in the tumor immune microenvironment(TIME);thus,understanding the TIME is urgent and crucial,especially given the importance of an immunosuppressive microenvironment in tumor progression.The aim of this review was to better elucidate the mechanisms of the suppressive TIME,including cell infiltration,immune cell subsets,cytokines and signaling pathways in the tumor microenvironment of EC patients,as well as the downregulated expression of major histocompatibility complex molecules in tumor cells,to obtain a better understanding of the differences in EC patient responses to immunotherapeutic strategies and accurately predict the efficacy of immunotherapies.Therefore,personalized treatments could be developed to maximize the advantages of immunotherapy.
