New roles of tumor-derived exosomes in tumor microenvironment

Throughout tumorigenesis, the co-evolution of tumor cells and their surrounding microenvironment leads to the development of malignant phenotypes. Cellular communication within the tumor microenvironment(TME) plays a critical role in influencing various aspects of tumor progression, including invasion and metastasis. The release of exosomes, a type of extracellular vesicle, by most cell types in the body, is an essential mediator of intercellular communication. A growing body of research indicates that tumor-derived exosomes(TDEs) significantly expedite tumor progression through multiple mechanisms, inducing epithelial-mesenchymal transition and macrophage polarization, enhancing angiogenesis, and aiding in the immune evasion of tumor cells. Herein, we describe the formation and characteristics of the TME, and summarize the contents of TDEs and their diverse functions in modulating tumor development. Furthermore, we explore potential applications of TDEs in tumor diagnosis and treatment.

Early adenocarcinoma mixed with a neuroendocrine carcinoma component arising in the gastroesophageal junction: A case report

BACKGROUND Early adenocarcinoma mixed with a neuroendocrine carcinoma(NEC)component arising in the gastroesophageal junctional(GEJ)region is rare and even rarer in young patients.Here,we report such a case in a 29-year-old Chinese man.CASE SUMMARY This patient presented to our hospital with a 3-mo history of dysphagia and regurgitation.Upper endoscopy revealed an elevated nodule in the distal esophagus 1.6 cm above the GEJ line,without Barrett’s esophagus or involvement of the gastric cardia.The nodule was completely resected by endoscopic submu-cosal dissection(ESD).Pathological examination confirmed diagnosis of intra-mucosal adenocarcinoma mixed with an NEC component,measuring 1.5 cm.Immunohistochemically,both adenocarcinoma and NEC components were positive for P53 with a Ki67 index of 90%;NEC was positive for synaptophysin and chromogranin.Next-generation sequencing of 196 genes demonstrated a novel germline mutation of the ERCC3 gene in the DNA repair pathway and a germline mutation of the RNF43 gene,a common gastric cancer driver gene,in addition to pathogenic somatic mutations in P53 and CHEK2 genes.The patient was alive without evidence of the disease 36 mo after ESD.CONCLUSION Early adenocarcinoma with an NEC component arising in the distal esophageal side of the GEJ region showed evidence of gastric origin.

OSW-1 triggers necroptosis in colorectal cancer cells through the RIPK1/RIPK3/MLKL signaling pathway facilitated by the RIPK1- p62/SQSTM1 complex

BACKGROUND Necroptosis has emerged as a novel molecular pathway that can be targeted by chemotherapy agents in the treatment of cancer.OSW-1,which is derived from the bulbs of Ornithogalum saundersiae Baker,exerts a wide range of pharmaco-logical effects.AIM To explore whether OSW-1 can induce necroptosis in colorectal cancer(CRC)cells,thereby expanding its range of clinical applications.METHODS We performed a sequence of functional experiments,including Cell Counting Kit-8 assays and flow cytometry analysis,to assess the inhibitory effect of OSW-1 on CRC cells.We utilized quantitative proteomics,employing tandem mass tag label-ing combined with liquid chromatography-tandem mass spectrometry,to analyze changes in protein expression.Subsequent bioinformatic analysis was conducted to elucidate the biological processes associated with the identified proteins.Transmission electron microscopy(TEM)and immunofluorescence studies were also performed to examine the effects of OSW-1 on necroptosis.Finally,western blotting,siRNA experiments,and immunoprecipitation were employed to evaluate protein interactions within CRC cells.RESULTS The results revealed that OSW-1 exerted a strong inhibitory effect on CRC cells,and this effect was accompanied by a necroptosis-like morphology that was observable via TEM.OSW-1 was shown to trigger necroptosis via activation of the RIPK1/RIPK3/MLKL pathway.Furthermore,the accumulation of p62/SQSTM1 was shown to mediate OSW-1-induced necroptosis through its interaction with RIPK1.CONCLUSION We propose that OSW-1 can induce necroptosis through the RIPK1/RIPK3/MLKL signaling pathway,and that this effect is mediated by the RIPK1-p62/SQSTM1 complex,in CRC cells.These results provide a theoretical foundation for the use of OSW-1 in the clinical treatment of CRC.

Therapeutic strategies targeting the epidermal growth factor receptor signaling pathway in metastatic colorectal cancer

More than 1.9 million new colorectal cancer(CRC)cases and 935000 deaths were estimated to occur worldwide in 2020,representing about one in ten cancer cases and deaths.Overall,colorectal ranks third in incidence,but second in mortality.More than half of the patients are in advanced stages at diagnosis.Treatment options are complex because of the heterogeneity of the patient population,including different molecular subtypes.Treatments have included conventional fluorouracil-based chemotherapy,targeted therapy,immunotherapy,etc.In recent years,with the development of genetic testing technology,more and more targeted drugs have been applied to the treatment of CRC,which has further prolonged the survival of metastatic CRC patients.

Boeravinone B ameliorates allergic nasal inflammation by modulating the GATA-3/T-bet signaling pathway in a mouse model of allergic rhinitis

Objective:To evaluate the anti-allergic effect of boeravinone B against ovalbumin-induced allergic rhinitis in mice and explore its possible mechanism.Methods:For the induction of allergic rhinitis,mice were intraperitoneally sensitized and intranasally challenged with ovalbumin,as well as orally received various concentrations of boeravinone B.Nasal mucosal inflammation,and the levels of nitric oxide,β-hexosaminidase,IFN-γ,LTC-4,myeloperoxidase,Nrf2,HO-1,GATA-3,ROR-γ,T-bet,antioxidant parameters,and allergen-specific cytokines were assessed.Results:Boeravinone B markedly reduced ovalbumin-induced increase in the number of episodes of nasal sneezing,rubbing,and discharge,as well as the levels of IgE,IgG1,andβ-hexosaminidase(P<0.05).It also significantly reduced differential cell count,myeloperoxidase,oxide-nitrosative stress,and the levels of IL-1β,IL-4,IL-5,IL-6,IL-13,IL-17,tumor necrosis factor-α,GATA-3,and ROR-γwhile enhancing the level of T-bet.Conclusions:Boeravinone B is a potential therapeutic agent for allergic rhinitis by modulating various inflammatory mediators and immune responses.

Knockdown of RCN1 contributes to the apoptosis of colorectal cancer via regulating IP3R1

Background:The incidence of colorectal cancer(CRC)has been increasing in recent years.Thus,the discovery of factors that can assist in alleviating CRC is urgently warranted.Methods:To identify a potential factor involved in the development of CRC,we screened the upregulated genes in tumor tissues through four datasets from an online database.The expression of reticulocalbin 1(RCN1),a Ca2+-binding protein,was upregulated in the four datasets.Based on loss-offunction experiments,the effect of RCN1 on cell viability was assessed by Cell Counting Kit-8(CCK-8)assay.The regulatory effect of RCN1 on apoptosis was evaluated through Annexin V-fluorescein 5-isothiocyanate(FITC)/propidium iodide(PI)staining assay and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling(TUNEL)assay in RKO and SW480 cells.Activation of endoplasmic reticulum(ER)stress signaling pathways was confirmed by estimating the phosphorylation and expression of PRKR-like ER kinase(PERK),inositol-requiring kinase-1(IRE1),transcription factor 6(ACT6),and CCAAT/enhancer-binding protein-homologous protein(CHOP).The intracellular Ca2+homeostasis regulated by RCN1 was determined through the detection of Ca2+concentration and mitochondrial membrane potential(MMP)measurement.Moreover,whether inositol 1,4,5-trisphosphate receptor type 1(IP3R1)was involved in the regulation of RCN1 in CRC was verified through the depletion of IP3R1 in RKO cells.Results:Knockdown of RCN1 reduced cell viability and facilitated apoptosis in RKO and SW480 cells.Phosphorylation of PERK and IRE1,activation of ATF6,and upregulation of CHOP were induced by the absence of RCN1,suggesting that the unfolded protein response(UPR)was activated in CRC cells.The concentration of Ca2+in mitochondria was increased after RCN1 depletion,followed by reduction in the MMP and release of cytochrome c from mitochondria to the cytoplasm in RKO and SW480 cells.Moreover,it was demonstrated that IP3R1 mediates the effect of RCN1 on apoptosis induced by ER stress in CRC cells.The downregulation of IP3R1 restored the RCN1 loss-induced apoptosis and the increased Ca2+concentration.Conclusion:Taken together,our results confirmed that silencing of RCN1 disrupted intracellular Ca2+homeostasis and promoted cell apoptosis caused by TG-induced ER stress by regulating IP3R1 and activating the UPR signaling pathways.

Data-driven modeling on anisotropic mechanical behavior of brain tissue with internal pressure

Brain tissue is one of the softest parts of the human body,composed of white matter and grey matter.The mechanical behavior of the brain tissue plays an essential role in regulating brain morphology and brain function.Besides,traumatic brain injury(TBI)and various brain diseases are also greatly influenced by the brain's mechanical properties.Whether white matter or grey matter,brain tissue contains multiscale structures composed of neurons,glial cells,fibers,blood vessels,etc.,each with different mechanical properties.As such,brain tissue exhibits complex mechanical behavior,usually with strong nonlinearity,heterogeneity,and directional dependence.Building a constitutive law for multiscale brain tissue using traditional function-based approaches can be very challenging.Instead,this paper proposes a data-driven approach to establish the desired mechanical model of brain tissue.We focus on blood vessels with internal pressure embedded in a white or grey matter matrix material to demonstrate our approach.The matrix is described by an isotropic or anisotropic nonlinear elastic model.A representative unit cell(RUC)with blood vessels is built,which is used to generate the stress-strain data under different internal blood pressure and various proportional displacement loading paths.The generated stress-strain data is then used to train a mechanical law using artificial neural networks to predict the macroscopic mechanical response of brain tissue under different internal pressures.Finally,the trained material model is implemented into finite element software to predict the mechanical behavior of a whole brain under intracranial pressure and distributed body forces.Compared with a direct numerical simulation that employs a reference material model,our proposed approach greatly reduces the computational cost and improves modeling efficiency.The predictions made by our trained model demonstrate sufficient accuracy.Specifically,we find that the level of internal blood pressure can greatly influence stress distribution and determine the possible related damage behaviors.

An Enhanced Multiview Transformer for Population Density Estimation Using Cellular Mobility Data in Smart City

This paper addresses the problem of predicting population density leveraging cellular station data.As wireless communication devices are commonly used,cellular station data has become integral for estimating population figures and studying their movement,thereby implying significant contributions to urban planning.However,existing research grapples with issues pertinent to preprocessing base station data and the modeling of population prediction.To address this,we propose methodologies for preprocessing cellular station data to eliminate any irregular or redundant data.The preprocessing reveals a distinct cyclical characteristic and high-frequency variation in population shift.Further,we devise a multi-view enhancement model grounded on the Transformer(MVformer),targeting the improvement of the accuracy of extended time-series population predictions.Comparative experiments,conducted on the above-mentioned population dataset using four alternate Transformer-based models,indicate that our proposedMVformer model enhances prediction accuracy by approximately 30%for both univariate and multivariate time-series prediction assignments.The performance of this model in tasks pertaining to population prediction exhibits commendable results.

Exploring the vital role of microglial membrane receptors in Alzheimer’s disease pathogenesis: a comprehensive review

Neurodegenerative diseases constitute a broad category of diseases caused by the degeneration of the neurons.They are mainly manifested by the gradual loss of neuron structure and function and eventually can cause death or loss of neurons.As the global population ages rapidly,increased people are being diagnosed with neurodegenerative diseases.It has been established that the onset of Alzheimer’s disease(AD)is closely linked with increasing age and its major pathological features include amyloid-beta plaques(Aβ),Tau hyperphosphorylation,Neurofibrillary tangles(NFTs),neuronal death as well as synaptic loss.The involvement of microglia is crucial in the pathogenesis and progression of AD and exhibits a dual role.For instance,in the early stage of AD,microglia surface membrane proteins or receptors can participate in immunophagocytosis,and anti-inflammatory functions and act as a physical barrier after recognizing various ligands such as Aβand NFTs.However,in the later stage of the disease,membrane receptors on the surface of microglia can cause its activation to release a substantial quantity of pro-inflammatory factors.Which can amplify the neuroinflammatory response.The rapid decline of normal immune phagocytosis can result in the continuous accumulation of abnormal proteins,leading to neuronal dysfunction and destruction of the formed physical barrier as well as the neurovascular microenvironment.It can also increase the transformation of microglia from anti-inflammatory phenotype M2 to pro-inflammatory phenotype M1,induce severe neuronal injury or apoptosis,and aggravate the progression of AD.Due to few articles have focused on the AD-related membrane protein receptors on microglia,thus in this paper,we have reviewed several representative microglial membrane proteins or receptors about their specific roles and functions implicated in AD,and expect that there will be more in-depth research and scientific research results in the treatment of AD by targeted regulation of microglia membrane protein receptors in the future.

Identification of TMEM159 as a biomarker of glioblastoma progression based on immune characteristics

Background:Glioblastoma multiforme(GBM)is the most general malignancy of the primary central nervous system that is characterized by high aggressiveness and lethality.Transmembrane protein 159(TMEM159)is an endoplasmic reticulum protein that can form oligomers with seipin.The TMEM159-seipin complex decides the site of lipid droplet(LD)formation,and the formation of LDs is a marker of GBM.However,the role of TMEM159 in the progression of GBM has not been investigated to date.Methods:In this study,we examined the genes that may be associated with patient prognosis in GBM by bioinformatics analyses,and identified the key genes that affect the development of GBM using single-cell RNA sequencing technology.The biological functions of TMEM159 in GBM cells were additionally assessed by clone formation and transwell assays as well as using a model of chick embryo chorioallantois membrane(CAM)and western blotting.The association between TMEM159 and epidermal growth factor receptor(EGFR)was finally analyzed in GBM cells.Results:A prognostic model was established and validated for predicting the prognosis.Survival curve analysis showed a critical difference in the prognosis of the high-and low-risk groups predicted by the prognostic model.The results demonstrated that TMEM159 affected the proliferation and invasion of GBM cells.The chick embryo CAM assays demonstrated that the inhibition of TMEM159 expression reduced angiogenesis in the CAM model.Conclusions:The prognostic model achieved good predictive potential for high-risk patients.The findings also revealed that TMEM159 might be an important prognostic factor for GBM,indicating that the protein may be a promising therapeutic target for suppressing the development of GBM.

The role of FMO3 in metabolic diseases

Flavin containing monooxygenase 3(FMO3)is a member of the flavin monooxygenase family,which can oxidize the precursor Trimethylamine(TMA)provided from food to produce Trimethylamine N-oxide(TMAO).The autosomal recessive inherited disease caused by partial functional loss of Fmo3 gene,which leads to excessive excretion of TMA in body fluids and emits fishy odor,is called Fish Odor Syndrome or Trimethylaminuria.This disease has been documented for 3,000 years ago and was first reported in the case report in 1970.FMO3 mainly exists in the liver and can participate in the TMA-TMAO metabolic balance in intestinal microorganisms,liver,and kidneys,closely related to insulin resistance,diabetes,cholesterol metabolism,and cardiovascular disease.Due to its wide range of catalytic substrates and low susceptibility to metabolite accumulation,its role in drug metabolism,new drug development,and discovery of new drug targets are increasingly valued.This review will summarize the research progress on the metabolic process and localization of FMO3,congenital genetic defects,metabolic diseases,and its related possible mechanisms.

Circulating proteomic biomarkers for diagnosing sporadic amyotrophic lateral sclerosis:a cross-sectional study

Biomarke rs are required for the early detection,prognosis prediction,and monitoring of amyotrophic lateral sclerosis,a progressive disease.Proteomics is an unbiased and quantitative method that can be used to detect neurochemical signatures to aid in the identification of candidate biomarke rs.In this study,we used a label-free quantitative proteomics approach to screen for substantially differentially regulated proteins in ten patients with sporadic amyotrophic lateral scle rosis compared with five healthy controls.Su bstantial upregulation of serum proteins related to multiple functional clusters was observed in patients with spo radic amyotrophic lateral sclerosis.Potential biomarke rs were selected based on functionality and expression specificity.To validate the proteomics profiles,blood samples from an additional cohort comprising 100 patients with sporadic amyotrophic lateral sclerosis and 100 healthy controls were subjected to enzyme-linked immunosorbent assay.Eight substantially upregulated serum proteins in patients with spora dic amyotrophic lateral sclerosis were selected,of which the cathelicidin-related antimicrobial peptide demonstrated the best discriminative ability between patients with sporadic amyotrophic lateral sclerosis and healthy controls(area under the curve[AUC]=0.713,P<0.0001).To further enhance diagnostic accuracy,a multi-protein combined discriminant algorithm was developed incorporating five proteins(hemoglobin beta,cathelicidin-related antimicrobial peptide,talin-1,zyxin,and translationally-controlled tumor protein).The algo rithm achieved an AUC of 0.811 and a P-value of<0.0001,resulting in 79%sensitivity and 71%specificity for the diagnosis of sporadic amyotrophic lateral scle rosis.Subsequently,the ability of candidate biomarkers to discriminate between early-stage amyotrophic lateral sclerosis patients and controls,as well as patients with different disease severities,was examined.A two-protein panel comprising talin-1 and translationally-controlled tumor protein effectively distinguished early-stage amyotrophic lateral sclerosis patients from controls(AUC=0.766,P<0.0001).Moreove r,the expression of three proteins(FK506 binding protein 1A,cathelicidin-related antimicrobial peptide,and hemoglobin beta-1)was found to increase with disease progression.The proteomic signatures developed in this study may help facilitate early diagnosis and monitor the progression of sporadic amyotrophic lateral sclerosis when used in co mbination with curre nt clinical-based parameters.

Successful splenic artery embolization in a patient with Behçet’s syndrome-associated splenic rupture:A case report

BACKGROUND Splenic rupture associated with Behçet’s syndrome(BS)is extremely rare,and there is no consensus on its management.In this case report,a patient with BSassociated splenic rupture was successfully treated with splenic artery embolization(SAE)and had a good prognosis after the intervention.CASE SUMMARY The patient was admitted for pain in the left upper abdominal quadrant.He was diagnosed with splenic rupture.Multiple oral and genital aphthous ulcers were observed,and acne scars were found on his back.He had a 2-year history of BS diagnosis,with symptoms of oral and genital ulcers.At that time,he was treated with oral corticosteroids for 1 month,but the symptoms did not alleviate.He underwent SAE to treat the rupture.On the first day after SAE,the patient reported a complete resolution of abdominal pain and was discharged 5 d later.Three months after the intervention,a computed tomography examination showed that the splenic hematoma had formed a stable cystic effusion,suggesting a good prognosis.CONCLUSION SAE might be a good choice for BS-associated splenic rupture based on good surgical practice and material selection.

A food-grade and senescent cell-targeted fisetin delivery system based on whey protein isolate-galactooligosaccharides Maillard conjugate

Cellular senescence is the results of aging and age-related diseases,and the development of anti-aging methods may improve health and extend longevity.The natural flavonol fisetin has been shown to antagonize senescence in vitro and increases longevity in vivo,but has poor water solubility and limited bioavailability.In this study,a food-grade and senescent cell-targeted delivery system for fisetin was developed based on whey protein isolate-galactooligosaccharides(WPI-GOS)Maillard conjugate,which could recognize senescence associatedβ-galactosidase in senescent cells.The fisetin nanoparticles possessed a high encapsulation efficiency,excellent dispersibility in water,good storage stability and well biocompatibility.Moreover,they could effectively accumulate and retain in senescent cells with excellent senescent cell-targeting efficacy,and inhibit the oxidative stress-induced cellular senescence in vitro.Thus,this novel nanoparticle system based on WPI-GOS Maillard conjugate showed promise to deliver hydrophobic bioactive ingredients like fisetin to senescent cells to improve their bioavailability and anti-senescence effect.

Glucose metabolic reprogramming-related parameters for the prediction of 28-day neurological prognosis and all-cause mortality in patients after cardiac arrest:a prospective single-center observational study

BACKGROUND:We aimed to observe the dynamic changes in glucose metabolic reprogrammingrelated parameters and their ability to predict neurological prognosis and all-cause mortality in cardiac arrest patients after the restoration of spontaneous circulation(ROSC).METHODS:Adult cardiac arrest patients after ROSC who were admitted to the emergency or cardiac intensive care unit of the First Aflliated Hospital of Dalian Medical University from August 1,2017,to May 30,2021,were enrolled.According to 28-day survival,the patients were divided into a non-survival group(n=82) and a survival group(n=38).Healthy adult volunteers(n=40) of similar ages and sexes were selected as controls.The serum levels of glucose metabolic reprogrammingrelated parameters(lactate dehydrogenase [LDH],lactate and pyruvate),neuron-specific enolase(NSE) and interleukin 6(IL-6) were measured on days 1,3,and 7 after ROSC.The Acute Physiology and Chronic Health Evaluation II(APACHE II) score and Sequential Organ Failure Assessment(SOFA) score were calculated.The Cerebral Performance Category(CPC) score was recorded on day 28 after ROSC.RESULTS:Following ROSC,the serum LDH(607.0 U/L vs.286.5 U/L),lactate(5.0 mmol/L vs.2.0 mmol/L),pyruvate(178.0 μmol/L vs.70.9 μmol/L),and lactate/pyruvate ratio(34.1 vs.22.1) significantly increased and were higher in the non-survivors than in the survivors on admission(all P<0.05).Moreover,the serum LDH,pyruvate,IL-6,APACHE II score,and SOFA score on days 1,3 and 7 after ROSC were significantly associated with 28-day poor neurological prognosis and 28-day all-cause mortality(all P<0.05).The serum LDH concentration on day 1 after ROSC had an area under the receiver operating characteristic curve(AUC) of 0.904 [95% confidence interval [95% CI]:0.851–0.957]) with 96.8% specificity for predicting 28-day neurological prognosis and an AUC of 0.950(95% CI:0.911–0.989) with 94.7% specificity for predicting 28-day all-cause mortality,which was the highest among the glucose metabolic reprogramming-related parameters tested.CONCLUSION:Serum parameters related to glucose metabolic reprogramming were significantly increased after ROSC.Increased serum LDH and pyruvate levels,and lactate/pyruvate ratio may be associated with 28-day poor neurological prognosis and all-cause mortality after ROSC,and the predictive eflcacy of LDH during the first week was superior to others.

Impaired implicit emotion regulation in patients with panic disorder:An event-related potential study on affect labeling

BACKGROUND Panic disorder(PD)involves emotion dysregulation,but its underlying mechanisms remain poorly understood.Previous research suggests that implicit emotion regulation may play a central role in PD-related emotion dysregulation and symptom maintenance.However,there is a lack of studies exploring the neural mechanisms of implicit emotion regulation in PD using neurophysiological indicators.AIM To study the neural mechanisms of implicit emotion regulation in PD with eventrelated potentials(ERP).METHODS A total of 25 PD patients and 20 healthy controls(HC)underwent clinical evaluations.The study utilized a case-control design with random sampling,selecting participants for the case group from March to December 2018.Participants performed an affect labeling task,using affect labeling as the experimental condition and gender labeling as the control condition.ERP and behavioral data were recorded to compare the late positive potential(LPP)within and between the groups.RESULTS Both PD and HC groups showed longer reaction times and decreased accuracy under the affect labeling.In the HC group,late LPP amplitudes exhibited a dynamic pattern of initial increase followed by decrease.Importantly,a significant group×condition interaction effect was observed.Simple effect analysis revealed a reduction in the differences of late LPP amplitudes between the affect labeling and gender labeling conditions in the PD group compared to the HC group.Furthermore,among PD patients under the affect labeling,the late LPP was negatively correlated with disease severity,symptom frequency,and intensity.CONCLUSION PD patients demonstrate abnormalities in implicit emotion regulation,hampering their ability to mobilize cognitive resources for downregulating negative emotions.The late LPP amplitude in response to affect labeling may serve as a potentially valuable clinical indicator of PD severity.

Potential pharmacological mechanisms of digallate in the treatment of enteritis based on network pharmacology and molecular docking

Background:In order to investigate the possible pharmacological mechanism of digallate in Galla Chinensis for treating enteritis,providing reference for the search and exploration of effective drugs for treating enteritis.Method:Traditional Chinese Medicines Systems Pharmacology Database and Analysis Platform,PharmMapper,DisGeNET,DrugBank,and GeneCards databases were used to obtain drug and disease-related target information.Gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment were performed,and the main therapeutic pathways and targets were identified by combining protein-protein interaction networks and cytoHubba plug-in.Molecular docking was used to validate the results.Result:297 drug related targets,2436 disease related targets,and 66 target points related to digallate were predicted to be associated with enteritis.10 related signal pathways and 10 key genes were identified.Conclusion:Digallate may be utilized to treat enteritis by acting on similar pathways,such those related to pathways in cancer,lipid and atherosclerosis,proteoglycans in cancer,Rap1 signaling pathway,PI3K-Akt signaling pathway and other targets such as IGF1,EGFR,SRC,IGF1R,PPARG.

Deliberate self-harm among pediatric psychiatric inpatients in China:A single-center retrospective study

BACKGROUND For children and adolescents,deliberate self-harm(DSH)is becoming a mental health problem of concern.Despite several studies on the prevalence and factors of DSH in the world,there is little information on DSH among children and adolescents in China.This study explores the prevalence,types,associated risk factors and tendency of DSH in pediatric psychiatric inpatients in China.AIM To understand the situation of DSH among hospitalized children and adolescents and its related factors.METHODS In this study,we retrospectively studied 1414 hospitalized children and adolescents with mental illness at Xiamen Mental Health Center from 2014 to 2019,extracted the demographic and clinical data of all patients,and analyzed clinical risk factors of DSH.RESULTS A total of 239(16.90%)patients engaged in at least one type of DSH in our study.Cutting(n=115,48.12%)was the most common type of DSH.Females(n=171,71.55%)were more likely to engage in DSH than males(n=68,28.45%).DSH was positively associated with depressive disorders[OR=3.845(2.196-6.732);P<0.01],female[OR=2.536(1.815-3.542);P<0.01],parental marital status[OR=5.387(2.254-12.875);P<0.01]and negative family history of psychiatric illness[OR=7.767(2.952-20.433);P<0.01],but not with occupation,substance use and history of physical abuse.CONCLUSION Our findings suggest that for patients with depression,females,an abnormal marriage of parents,and no history of mental illness,attention should be paid to the occurrence of DSH.

Exploring the impact of non-small cell lung cancer tumor microbiome on the efficacy of chemotherapy and immune checkpoint inhibitors

Background:This study aimed to investigate the potential of intratumoral microbiota,gut microbiome,peripheral blood T-cell subsets,and inflammatory markers as predictive biomarkers for antitumor efficacy in patients with non-small cell lung cancer.Methods:This study observed patients with metastatic non-driver mutation non-small cell lung cancer who were initially diagnosed at the First Affiliated Hospital of Dalian Medical University’s Department of Oncology from August 2021 to July 2022 and completed at least four cycles of chemotherapy combined with immune checkpoint inhibitor treatment.Lung biopsy tissues,fecal,and peripheral blood samples were collected from these patients.Based on the efficacy of the combined chemotherapy and immunotherapy,patients were divided into an effective group and an ineffective group.The tumor microbiota,gut microbiome,peripheral blood T-cell subsets,and inflammatory markers were compared between the two groups.The lung and fecal microbiota were analyzed using 16S rRNA high-throughput sequencing.Flow cytometry was used to detect T-cell subsets,and enzyme-linked immunosorbent assay was employed to measure inflammatory factors.Results:A total of 21 patients were observed.There were significant differences in the tumor microbiota between the responsive and non-responsive groups,particularly the proportion of the genera Sphingomonas and Pseudomonas.The gut microbiome composition changed after treatment,but there were no differences between the two groups before treatment.There were no significant differences in T-cell subsets and inflammatory markers between the responsive and non-responsive groups.Conclusion:The composition of intratumoral microbiota in non-small cell lung cancer patients may serve as an indicator of response to chemotherapy combined with immunotherapy.The predictive value of gut microbiota,T-cell subsets,and inflammatory markers appears limited.Future research should further validate the predictive role of changes in gut microbiota on treatment outcomes.

A Study on the Problems and Solution Paths in the Conduct of Elderly Competency Assessment

Exploring the problems existing in the process of carrying out an elderly competency assessment aims to provide useful references for its improvement.Starting from the importance of elderly competency assessment in the field of elderly services,this paper analyses the problems in the process of carrying out elderly competency assessment and explores the corresponding solutions.The analysis finds that problems in the process of carrying out elderly competency assessment are inevitable,but as long as the study continues to explore and innovate and actively seek solution paths,the study will be able to overcome these difficulties and provide the elderly with better and more efficient elderly services.