Crohn’s disease(CD)is caused by immune,environmental,and genetic factors.It can involve the entire gastrointestinal tract,and although its prevalence is rapidly increasing its etiology remains unclear.Emerging biolog...Crohn’s disease(CD)is caused by immune,environmental,and genetic factors.It can involve the entire gastrointestinal tract,and although its prevalence is rapidly increasing its etiology remains unclear.Emerging biological and small-molecule drugs have advanced the treatment of CD;however,a considerable proportion of patients are non-responsive to all known drugs.To achieve a breakthrough in this field,innovations that could guide the further development of effective therapies are of utmost urgency.In this review,we first propose the innovative concept of pan-lymphatic dysfunction for the general distribution of lymphatic dysfunction in various diseases,and suggest that CD is the intestinal manifestation of pan-lymphatic dysfunction based on basic and clinical preliminary data.The supporting evidence is fully summarized,including the existence of lymphatic system dysfunction,recognition of the inside-out model,disorders of immune cells,changes in cell plasticity,partial overlap of the underlying mechanisms,and common gut-derived fatty and bile acid metabolism.Another benefit of this novel concept is that it proposes adopting the zebrafish model for studying intestinal diseases,especially CD,as this model is good at presenting and mimicking lymphatic dysfunction.More importantly,the ensuing focus on improving lymphatic function may lead to novel and promising therapeutic strategies for CD.展开更多
Metabolic dysfunction-associated fatty liver disease(MAFLD)is the most prevalent chronic liver condition worldwide.Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment ...Metabolic dysfunction-associated fatty liver disease(MAFLD)is the most prevalent chronic liver condition worldwide.Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment delays.Regarding Chen et al,the risk of developing MAFLD remains elevated even when alanine aminotransferase levels fall within the normal range.Therefore,there is an urgent need for advanced diagnostic techniques and updated algorithms to enhance the accuracy of MAFLD diagnosis and enable early intervention.This paper proposes two potential screening methods for identifying individuals who may be at risk of developing MAFLD:Lowering these thresholds and promoting the use of noninvasive liver fibrosis scores.展开更多
BACKGROUND Colorectal cancer(CRC)ranks among the most prevalent malignant tumors globally.Recent reports suggest that Fusobacterium nucleatum(F.nucleatum)contributes to the initiation,progression,and prognosis of CRC....BACKGROUND Colorectal cancer(CRC)ranks among the most prevalent malignant tumors globally.Recent reports suggest that Fusobacterium nucleatum(F.nucleatum)contributes to the initiation,progression,and prognosis of CRC.Butyrate,a short-chain fatty acid derived from the bacterial fermentation of soluble dietary fiber,is known to inhibit various cancers.This study is designed to explore whether F.nucleatum influences the onset and progression of CRC by impacting the intestinal metabolite butyric acid.AIM To investigate the mechanism by which F.nucleatum affects CRC occurrence and development.METHODS Alterations in the gut microbiota of BALB/c mice were observed following the oral administration of F.nucleatum.Additionally,DLD-1 and HCT116 cell lines were exposed to sodium butyrate(NaB)and F.nucleatum in vitro to examine the effects on proliferative proteins and mitochondrial function.RESULTS Our research indicates that the prevalence of F.nucleatum in fecal samples from CRC patients is significantly greater than in healthy counterparts,while the prevalence of butyrate-producing bacteria is notably lower.In mice colonized with F.nucleatum,the population of butyrate-producing bacteria decreased,resulting in altered levels of butyric acid,a key intestinal metabolite of butyrate.Exposure to NaB can impair mitochondrial morphology and diminish mitochondrial membrane potential in DLD-1 and HCT116 CRC cells.Consequently,this leads to modulated production of adenosine triphosphate and reactive oxygen species,thereby inhibiting cancer cell prolif-eration.Additionally,NaB triggers the adenosine monophosphate-activated protein kinase(AMPK)signaling pathway,blocks the cell cycle in HCT116 and DLD-1 cells,and curtails the proliferation of CRC cells.The combined presence of F.nucleatum and NaB attenuated the effects of the latter.By employing small interfering RNA to suppress AMPK,it was demonstrated that AMPK is essential for NaB’s inhibition of CRC cell proliferation.CONCLUSION F.nucleatum can promote cancer progression through its inhibitory effect on butyric acid,via the AMPK signaling pathway.展开更多
Objective: To carry out empirical research on the role of project-achieving quality control circle (QCC) in constructing a new model of contactless medical service for outpatients. Methods: A QCC, consisting of inform...Objective: To carry out empirical research on the role of project-achieving quality control circle (QCC) in constructing a new model of contactless medical service for outpatients. Methods: A QCC, consisting of information office members from a grade A tertiary hospital in Wenzhou, was established to conduct a research project with the theme “Constructing a new model of contactless medical service based on outpatients’ experience.” According to the ten steps and PDCA cycle, an analysis was carried out before and after the QCC activities, focusing on improving pre-consultation services, providing steward-like services, and facilitating post-consultation management. Results: After the QCC activities, the mobile appointment rate, missed appointment rate, the proportion of smart check-ins, and the average check-in time were 55.68%, 4.02%, 39.75%, and 8.24 ± 3.66 min, respectively;in contrast, before the activities, they were 32.00%, 7.88%, 0.00%, and 14.96 ± 4.98 min, respectively;the difference between the two groups was statistically significant (χ2 = 3480.112, 4994.496;Fisher’s exact probability = 963788.570;t = 5.323, P < 0.001). Many experts have also visited the hospital to learn about this system, thus rendering social and economic benefits. Conclusion: Project-achieving QCC activities are suitable for complex situations, such as constructing a new model of contactless medical service, and can significantly improve outpatient service quality, enhance patients’ experience, and improve the abilities of circle members.展开更多
BACKGROUND In recently diagnosed patients with thyroid cancer,papillary thyroid cancer(PTC),as the most common histological subtype,accounts for 90%of all cases.Although PTC is known as a relatively adolescent maligna...BACKGROUND In recently diagnosed patients with thyroid cancer,papillary thyroid cancer(PTC),as the most common histological subtype,accounts for 90%of all cases.Although PTC is known as a relatively adolescent malignant disease,there still is a high possibility of recurrence in PTC patients with a poor prognosis.Therefore,new biomarkers are necessary to guide more effective stratification of PTC patients and personalize therapy to avoid overtreatment or inadequate treatment.Accumulating evidence demonstrates that microRNAs(miRNAs)have broad application prospects as diagnostic biomarkers in cancer.AIM To explore novel markers consisting of miRNA-associated signatures for PTC prognostication.METHODS We obtained and analyzed the data of 497 PTC patients from The Cancer Genome Atlas.The patients were randomly assigned to either a training or testing cohort.RESULTS We discovered 237 differentially expressed miRNAs in tumorous thyroid tissues compared with normal tissues,which contained 172 up-regulated and 65 downregulated miRNAs.The evaluation of differently expressed miRNAs was conducted using our risk score model.We then successfully generated a fourmiRNA potential prognostic signature[risk score=(-0.001×hsa-miR-181a-2-3p)+(0.003×hsa-miR-138-5p)+(-0.018×hsa-miR-424-3p)+(0.284×hsa-miR-612)],which reliably distinguished patients from high and low risk with a significant difference in the overall survival(P<0.01)and was effective in predicting the five-year disease survival rate with the area under the receiver operating characteristic curve of 0.937 and 0.812 in the training and testing cohorts,respectively.Additionally,there was a trend indicated that high-risk patients had shorter relapse-free survival,although statistical significance was not reached(P=0.082)in our sequencing cohort.CONCLUSION Our results indicated a four-miRNA signature that has a robust predictive effect on the prognosis of PTC.Accordingly,we would recommend more radical therapy and closer follow-ups for highrisk groups.展开更多
AIM:To estimate and compare the incidence and characteristics of rhegmatogenous retinal detachments(RRDs)in the Wenzhou area in 2015 to 2019.METHODS:All newly developed RRD cases among residents of the Wenzhou area,fr...AIM:To estimate and compare the incidence and characteristics of rhegmatogenous retinal detachments(RRDs)in the Wenzhou area in 2015 to 2019.METHODS:All newly developed RRD cases among residents of the Wenzhou area,from January 2015 to December 2019,were retrospectively retrieved from hospital records.Annual population data were extracted from the Wenzhou Statistical Yearbook.RESULTS:There were 3629 eligible cases.The average incidence of RRD was 7.79 cases per 100000 population(95%confidence interval,7.24-8.34),and the incidences were 7.99 and 7.56 for males and females,respectively.The annual incidence increased gradually from 7.26 cases per 100000 in 2015 to 10.00 cases per 100000 in 2019,with an overall increase of 37.74%.The highest rate of increase occurred in the age group from 60 to 69 years.Of 2750 eyes with axial length(AL)data,1675(60.91%)had an AL greater than 24 mm.CONCLUSION:A trend to increasing RRD incidence is observed in the Wenzhou area over the past 5-year period.展开更多
BACKGROUND The immunosuppressive capacity of mesenchymal stem cells(MSCs)is dependent on the“license”of several proinflammatory factors to express immunosuppressive factors such as programmed cell death 1 ligand 1(P...BACKGROUND The immunosuppressive capacity of mesenchymal stem cells(MSCs)is dependent on the“license”of several proinflammatory factors to express immunosuppressive factors such as programmed cell death 1 ligand 1(PD-L1),which determines the clinical therapeutic efficacy of MSCs for inflammatory or immune diseases.In MSCs,interferon-gamma(IFN-γ)is a key inducer of PD-L1 expression,which is synergistically enhanced by tumor necrosis factor-alpha(TNF-α);however,the underlying mechanism is unclear.AIM To reveal the mechanism of pretreated MSCs express high PD-L1 and explore the application of pretreated MSCs in ulcerative colitis.METHODS We assessed PD-L1 expression in human umbilical-cord-derived MSCs(hUC-MSCs)induced by IFN-γand TNF-α,alone or in combination.Additionally,we performed signal pathway inhibitor experiments as well as RNA interference experiments to elucidate the molecular mechanism by which IFN-γalone or in combination with TNF-αinduces PD-L1 expression.Moreover,we used luciferase reporter gene experiments to verify the binding sites of the transcription factors of each signal transduction pathway to the targeted gene promoters.Finally,we evaluated the immunosuppressive capacity of hUC-MSCs treated with IFN-γand TNF-αin both an in vitro mixed lymphocyte culture assay,and in vivo in mice with dextran sulfate sodium-induced acute colitis.RESULTS Our results suggest that IFN-γinduction alone upregulates PD-L1 expression in hUC-MSCs while TNF-αalone does not,and that the co-induction of IFN-γand TNF-αpromotes higher expression of PD-L1.IFN-γinduces hUCMSCs to express PD-L1,in which IFN-γactivates the JAK/STAT1 signaling pathway,up-regulates the expression of the interferon regulatory factor 1(IRF1)transcription factor,promotes the binding of IRF1 and the PD-L1 gene promoter,and finally promotes PD-L1 mRNA.Although TNF-αalone did not induce PD-L1 expression in hUCMSCs,the addition of TNF-αsignificantly enhanced IFN-γ-induced JAK/STAT1/IRF1 activation.TNF-αupregulated IFN-γreceptor expression through activation of the nuclear factor kappa-B signaling pathway,which significantly enhanced IFN-γsignaling.Finally,co-induced hUC-MSCs have a stronger inhibitory effect on lymphocyte proliferation,and significantly ameliorate weight loss,mucosal damage,inflammatory cell infiltration,and up-regulation of inflammatory factors in colitis mice.CONCLUSION Overall,our results suggest that IFN-γand TNF-αenhance both the immunosuppressive ability of hUC-MSCs and their efficacy in ulcerative colitis by synergistically inducing high expression of PD-L1.展开更多
Objective:To analyze the risk factors of neonatal medical adhesive-related skin injury and put forward targeted preventive measures,so as to provide reference for the care and prevention of neonatal medical adhesive-r...Objective:To analyze the risk factors of neonatal medical adhesive-related skin injury and put forward targeted preventive measures,so as to provide reference for the care and prevention of neonatal medical adhesive-related skin injuries.Methods:Using the convenience sampling method,262 neonates admitted to the neonatal intensive care unit(NICU)of a tertiary general hospital in Wenzhou from April 2021 to May 2022 were selected as the study subjects.The incidence of medical adhesive-related skin injuries in these neonates was retrospectively analyzed.Results:Among the 262 children,43 cases had skin injuries,with an incidence rate of 16.4%.Single factor analysis showed that the occurrence of medical adhesive-related skin injury was related to gestational age,weight,electrocardiogram(ECG)monitoring,venous access,ambient temperature,and mechanical ventilation(P<0.05).Multivariate logistic regression showed that gestational age,ECG monitoring,and ambient temperature were independent risk factors of medical adhesive-related skin injury(OR values were 0.700,0.431,and 6.365,respectively).Conclusion:The high incidence of neonatal medical adhesive-related skin injury may be caused by one or more factors.Clinical measures should be taken,such as selecting the appropriate type of adhesive according to gestational age and using skin-protecting membrane,minimizing ECG monitoring,etc.,to prevent the occurrence of neonatal medical adhesive-related skin injury.展开更多
Objective:CAR-T/NK cells have had limited success in the treatment of solid tumors,such as colorectal cancer(CRC),in part because of the heterogeneous nature of tumor-associated antigens that lead to antigen-negative ...Objective:CAR-T/NK cells have had limited success in the treatment of solid tumors,such as colorectal cancer(CRC),in part because of the heterogeneous nature of tumor-associated antigens that lead to antigen-negative relapse after the initial response.This barrier might be overcome by enhancing the recruitment and durability of endogenous immune cells.Methods:Immunohistochemistry and flow cytometry were used to assess the expression of CD133 antigen in tissue microarrays and cell lines,respectively.Retroviral vector transduction was used to generate CBLB502-secreting CAR133-NK92 cells(CAR133-i502-NK92).The tumor killing capacity of CAR133-NK92 cells in vitro and in vivo were quantified via LDH release,the RTCA assay,and the degranulation test,as well as measuring tumor bioluminescence signal intensity in mice xenografts.Results:We engineered CAR133-i502-NK92 cells and demonstrated that those cells displayed enhanced proliferation(9.0×10^(4)cells vs.7.0×10^(4)cells)and specific anti-tumor activities in vitro and in a xenogeneic mouse model,and were well-tolerated.Notably,CBLB502 secreted by CAR133-i502-NK92 cells effectively activated endogenous immune cells.Furthermore,in hCD133+/hCD133−mixed cancer xenograft models,CAR133-i502-NK92 cells suppressed cancer growth better than the counterparts(n=5,P=0.0297).Greater T-cell infiltration was associated with greater anti-tumor potency(P<0.0001).Conclusions:Armed with a CBLB502 TLR5 agonist,CAR133-NK92 cells were shown to be capable of specifically eliminating CD133-positive colon cancer cells in a CAR133-dependent manner and indirectly eradicating CD133-negative colon cancer cells in a CBLB502-specific endogenous immune response manner.This study describes a novel technique for optimizing CAR-T/NK cells for the treatment of antigenically-diverse solid tumors.展开更多
Triple-negative breast cancer(TNBC)poses a significant challenge due to the lack of reliable prognostic gene signatures and an understanding of its immune behavior.Methods:We analyzed clinical information and mRNA exp...Triple-negative breast cancer(TNBC)poses a significant challenge due to the lack of reliable prognostic gene signatures and an understanding of its immune behavior.Methods:We analyzed clinical information and mRNA expression data from 162 TNBC patients in TCGA-BRCA and 320 patients in METABRIC-BRCA.Utilizing weighted gene coexpression network analysis,we pinpointed 34 TNBC immune genes linked to survival.The least absolute shrinkage and selection operator Cox regression method identified key TNBC immune candidates for prognosis prediction.We calculated chemotherapy sensitivity scores using the“pRRophetic”package in R software and assessed immunotherapy response using the Tumor Immune Dysfunction and Exclusion algorithm.Results:In this study,34 survival-related TNBC immune gene expression profiles were identified.A least absolute shrinkage and selection operator-Cox regression model was used and 15 candidates were prioritized,with a concomitant establishment of a robust risk immune classifier.The high-risk TNBC immune groups showed increased sensitivity to therapeutic agents like RO-3306,Tamoxifen,Sunitinib,JNK Inhibitor VIII,XMD11-85h,BX-912,and Tivozanib.An analysis of the Search Tool for Interaction of Chemicals database revealed the associations between the high-risk group and signaling pathways,such as those involving Rap1,Ras,and PI3K-Akt.The low-risk group showed a higher immunotherapy response rate,as observed through the tumor immune dysfunction and exclusion analysis in the TCGA-TNBC and METABRIC-TNBC cohorts.Conclusion:This study provides insights into the immune complexities of TNBC,paving the way for novel diagnostic approaches and precision treatment methods that exploit its immunological intricacies,thus offering hope for improved management and outcomes of this challenging disease.展开更多
BACKGROUND Current approaches for the therapy of diabetic retinopathy(DR),which was one of leading causes of visual impairment,have their limitations.Animal experiments revealed that restructuring of intestinal microb...BACKGROUND Current approaches for the therapy of diabetic retinopathy(DR),which was one of leading causes of visual impairment,have their limitations.Animal experiments revealed that restructuring of intestinal microbiota can prevent retinopathy.AIM To explore the relationship between intestinal microbiota and DR among patients in the southeast coast of China,and provide clues for novel ways to prevention and treatment methods of DR.METHODS The fecal samples of non-diabetics(Group C,n=15)and diabetics(Group DM,n=30),including 15 samples with DR(Group DR)and 15 samples without DR(Group D),were analyzed by 16S rRNA sequencing.Intestinal microbiota compositions were compared between Group C and Group DM,Group DR and Group D,as well as patients with proliferative diabetic retinopathy(PDR)(Group PDR,n=8)and patients without PDR(Group NPDR,n=7).Spearman correlation analyses were performed to explore the associations between intestinal microbiota and clinical indicators.RESULTS The alpha and beta diversity did not differ significantly between Group DR and Group D as well as Group PDR and Group NPDR.At the family level,Fusobacteriaceae,Desulfovibrionaceae and Pseudomonadaceae were significantly increased in Group DR than in Group D(P<0.05,respectively).At the genera level,Fusobacterium,Pseudomonas,and Adlercreutzia were increased in Group DR than Group D while Senegalimassilia was decreased(P<0.05,respectively).Pseudomonas was negatively correlated with NK cell count(r=-0.39,P=0.03).Further,the abundance of genera Eubacterium(P<0.01),Peptococcus,Desulfovibrio,Acetanaerobacterium and Negativibacillus(P<0.05,respectively)were higher in Group PDR compared to Group NPDR,while Pseudomonas,Alloprevotella and Tyzzerella(P<0.05,respectively)were lower.Acetanaerobacterium and Desulfovibrio were positively correlated with fasting insulin(r=0.53 and 0.61,respectively,P<0.05),when Negativibacillus was negatively correlated with B cell count(r=-0.67,P<0.01).CONCLUSION Our findings indicated that the alteration of gut microbiota was associated with DR and its severity among patients in the southeast coast of China,probably by multiple mechanisms such as producing short-chain fatty acids,influencing permeability of blood vessels,affecting levels of vascular cell adhesion molecule-1,hypoxia-inducible factor-1,B cell and insulin.Modulating gut microbiota composition might be a novel strategy for prevention of DR,particularly PDR in population above.展开更多
Dear Editor,Autophagy is an evolutionarily conserved catabolic process that involves the sequestration and transport of organelles,macromolecules,or invading microorganisms to lysosomes for degradation[1].Sequestosome...Dear Editor,Autophagy is an evolutionarily conserved catabolic process that involves the sequestration and transport of organelles,macromolecules,or invading microorganisms to lysosomes for degradation[1].Sequestosome 1(p62/SQSTM1)was the first protein shown to bind target-associated ubiquitin(Ub)and LC3 conjugated to the phagophore membrane,thus,acting as an important autophagy receptor for ubiquitinated targets[2].展开更多
The cell membrane structure is closely related to the occurrence and progression of many metabolic bone diseases observed in the clinic and is an important target to the development of therapeutic strategies for these...The cell membrane structure is closely related to the occurrence and progression of many metabolic bone diseases observed in the clinic and is an important target to the development of therapeutic strategies for these diseases.Strong experimental evidence supports the existence of membrane microdomains in osteoclasts(OCs).However,the potential membrane microdomains and the crucial mechanisms underlying their roles in OCs have not been fully characterized.Membrane microdomain components,such as scaffolding proteins and the actin cytoskeleton,as well as the roles of individual membrane proteins,need to be elucidated.In this review,we discuss the compositions and critical functions of membrane microdomains that determine the biological behavior of OCs through the three main stages of the OC life cycle.展开更多
Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis.To provide clinical practice recommendations on the immune function in sepsis,an expert consensus focusing ...Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis.To provide clinical practice recommendations on the immune function in sepsis,an expert consensus focusing on the monitoring and treatment of sepsis-induced immunosuppression was developed.Literature related to the immune monitoring and treatment of sepsis were retrieved from PubMed,Web of Science,and Chinese National Knowledge Infrastructure to design items and expert opinions were collected through an online questionnaire.Then,the Delphi method was used to form consensus opinions,and RAND appropriateness method was developed to provide consistency evaluation and recommendation levels for consensus opinions.This consensus achieved satisfactory results through two rounds of questionnaire survey,with 2 statements rated as perfect consistency,13 as very good consistency,and 9 as good consistency.After summarizing the results,a total of 14 strong recommended opinions,8 weak recommended opinions and 2 non-recommended opinions were produced.Finally,a face-to-face discussion of the consensus opinions was performed through an online meeting,and all judges unanimously agreed on the content of this consensus.In summary,this expert consensus provides a preliminary guidance for the monitoring and treatment of immunosuppression in patients with sepsis.展开更多
In this editorial,we examined a recent article in the World Journal of Gastroenterology that focused on sepsis-associated liver injury(SLI)and its treatment.SLI is a serious complication of sepsis,primarily caused by ...In this editorial,we examined a recent article in the World Journal of Gastroenterology that focused on sepsis-associated liver injury(SLI)and its treatment.SLI is a serious complication of sepsis,primarily caused by microcirculatory disturbances,the gut-liver axis,and inflammatory responses.Specific treatment recommendations for SLI are lacking.The gut-liver axis represents a potential therapeutic target,with metformin showing promise in modulating the gut microbiome and enhancing intestinal barrier function.Although immunomodulatory therapies are being explored,anti-tumor necrosis factor agents and interleukin-1 receptor antagonists have not demonstrated significant clinical benefits.Statins may reduce liver inflammation and prevent injury in sepsis,but their clinical application is limited.Reduced D-related human leucocyte antigen expression on monocytes and lymphocytes suggests immune suppression in patients,indicating that corticosteroids could reverse clinical deterioration in severe infections and address adrenal cortical insufficiency.Current large-scale studies on glucocorticoid therapy for sepsis have yielded mixed results,likely due to inadequate assessment of the immune status of the host.Future research should prioritize the development of personalized immunotherapy tailored to patients’immune profiles,focusing on identifying novel indicators of immune status and advancing immunomodulatory targets and therapeutics for septic patients.展开更多
Liver fibrosis is primarily driven by the activation of hepatic stellate cells(HSCs),a process associated with ferroptosis.Ginsenoside Rb1(GRb1),a major active component extracted from Panax ginseng,inhibits HSC activ...Liver fibrosis is primarily driven by the activation of hepatic stellate cells(HSCs),a process associated with ferroptosis.Ginsenoside Rb1(GRb1),a major active component extracted from Panax ginseng,inhibits HSC activation.However,the potential role of GRb1 in mediating HSC ferroptosis remains unclear.This study examined the effect of GRb1 on liver fibrosis both in vivo and in vitro,using CCl4-induced liver fibrosis mouse model and primary HSCs,LX-2 cells.The findings revealed that GRb1 effectively inactivated HSCs in vitro,reducing alpha-smooth muscle actin(a-SMA)and type I collagen(Col1A1)levels.Moreover,GRb1 significantly alleviated CCl4-induced liver fibrosis in vivo.From a mechanistic standpoint,the ferroptosis pathway appeared to be central to the antifibrotic effects of GRb1.Specifically,GRb1 promoted HSC ferroptosis both in vivo and in vitro,characterized by increased glutathione depletion,malondialdehyde production,iron overload,and accumulation of reactive oxygen species(ROS).Intriguingly,GRb1 increased Beclin 1(BECN1)levels and decreased the System Xc-key subunit SLC7A11.Further experiments showed that BECN1 silencing inhibited GRb1-induced effects on HSC ferroptosis and mitigated the reduction of SLC7A11 caused by GRb1.Moreover,BECN1 could directly interact with SLC7A11,initiating HSC ferroptosis.In conclusion,the suppression of BECN1 counteracted the effects of GRb1 on HSC inactivation both in vivo and in vitro.Overall,this study highlights the novel role of GRb1 in inducing HSC ferroptosis and promoting HSC inactivation,at least partly through its modulation of BECN1 and SLC7A11.展开更多
BACKGROUND Acute pancreatitis(AP),the initially triggered inflammatory process in the pancreas,can be life-threatening.It has been reported that 15-lipoxygenase may promote the removal of damaged intracellular compone...BACKGROUND Acute pancreatitis(AP),the initially triggered inflammatory process in the pancreas,can be life-threatening.It has been reported that 15-lipoxygenase may promote the removal of damaged intracellular components,maintain intracellular homeostasis,and promote apoptosis by upregulating the activity of caspases.Despite an increased understanding of the lipoxygenase pathway in inflammation and immune diseases,the role of the Alox15 gene product in modulating the inflammatory changes during AP is not well defined.AIM To investigate the effect of Alox15 expression in cerulein-induced AP in rats.METHODS Model rats were transfected with Alox15 by injecting a recombinant lentivirus vector encoding Alox15 into the left gastric artery before inducing AP.The expression of Alox15 was then assessed at the mRNA and protein levels.RESULTS Our in vivo results showed that serum amylase activity and pancreatic tissue water content were significantly reduced in Alox15-transfected rats.Further,the mRNA expression levels of tumor necrosis factor alpha,interleukin(IL)-1β,IL-6,and monocyte chemoattractant protein-1,as well as the protein expression of nuclear factor kappa B in pancreatic tissue were reduced.Additionally,we observed an upregulation of cleaved caspase-3 that implies an induction of apoptosis in pancreatic cells.The transfection of Alox15 resulted in a lower number of autophagic vacuoles in AP.CONCLUSION Our findings demonstrate a regulatory role of Alox15 in apoptosis and autophagy,making it a potential therapeutic target for AP.展开更多
This review compiles information from the literature on the chemical composition,pharmacological effects,and molecular mechanisms of earthworm extract(EE)and suggests possibilities for clinical translation of EE.We al...This review compiles information from the literature on the chemical composition,pharmacological effects,and molecular mechanisms of earthworm extract(EE)and suggests possibilities for clinical translation of EE.We also consider future trends and concerns in this domain.We summarize the bioactive components of EE,including G-90,lysenin,lumbrokinase,antimicrobial peptides,earthworm serine protease(ESP),and polyphenols,and detail the antitumor,antithrombotic,antiviral,antibacterial,anti-i nflammatory,analgesic,antioxidant,wound-healing,antifibrotic,and hypoglycemic activities and mechanisms of action of EE based on existing in vitro and in vivo studies.We further propose the potential of EE for clinical translation in anticancer and lipid-modifying therapies,and its promise as source of a novel agent for wound healing and resistance to antibiotic tolerance.The earthworm enzyme lumbrokinase embodies highly effective anticoagulant and thrombolytic properties and has the advantage of not causing bleeding phenomena due to hyperfibrinolysis.Its antifibrotic properties can reduce the excessive accumulation of extracellular matrix.The glycolipoprotein extract G-90 can effectively scavenge reactive oxygen groups and protect cellular tissues from oxidative damage.Earthworms have evolved a well-developed defense mechanism to fight against microbial infections,and the bioactive agents in EE have shown good antibacterial,fungal,and viral properties in in vitro and in vivo experiments and can alleviate inflammatory responses caused by infections,effectively reducing pain.Recent studies have also highlighted the role of EE in lowering blood glucose.EE shows high medicinal value and is expected to be a source of many bioactive compounds.展开更多
Objective:To study the clinical effect of targeted infusion safety nursing during infusion of inpatients with cancer.Methods:From January 1,2020,to January 1,2023,a total of 6,614 infusion patients were treated in The...Objective:To study the clinical effect of targeted infusion safety nursing during infusion of inpatients with cancer.Methods:From January 1,2020,to January 1,2023,a total of 6,614 infusion patients were treated in The First Affiliated Hospital of Wenzhou Medical University,and 300 inpatients with cancer were selected as the research objects and randomly divided into the observation group and the control group,with 150 patients in each group.The control group received routine infusion nursing,and the observation group received targeted infusion safety nursing.The targeted infusion safety nursing was judged by comparing the nursing quality assessment,incidence of adverse events,patient compliance,and patients’mastery of infusion knowledge between the two groups.clinical effect.Results:After the targeted infusion safety nursing was given to the patients in the observation group,the patients in this group recognized the nursing quality,and the statistical score was higher than that in the control group;the incidence of adverse events in the observation group was lower than that in the control group.The compliance of the observation group was higher than that of the control group.The mastery of health knowledge in the observation group was also higher than that in the control group and the difference was statistically significant(P<0.02).Conclusion:After implementing targeted infusion safety nursing for inpatients with cancer,it can effectively prevent the occurrence of adverse events,improve patient compliance,and increase the mastery of relevant knowledge of patients.展开更多
BACKGROUND Competitive endogenous RNA(ceRNA)is an innovative way of gene expression modulation,which plays a crucial part in neoplasia.However,the intricacy and behavioral characteristics of the ceRNA network in hepat...BACKGROUND Competitive endogenous RNA(ceRNA)is an innovative way of gene expression modulation,which plays a crucial part in neoplasia.However,the intricacy and behavioral characteristics of the ceRNA network in hepatocellular carcinoma(HCC)remain dismal.AIM To establish a cyclin dependent kinase inhibitor 2A(CDKN2A)-related ceRNA network and recognize potential prognostic indicators for HCC.METHODS The mutation landscape of CDKN2A in HCC was first explored using the cBioPortal database.Differential expression analysis was implemented between CDKN2Ahigh and CDKN2Alow expression HCC samples.The targeted microRNAs were predicted by lncBasev3.0,and the targeted mRNAs were predicted by miRDB,and Targetscan database.The univariate and multivariate analysis were utilized to identify independent prognostic indicators.RESULTS CDKN2A was frequently mutated and deleted in HCC.The single-cell RNA-sequencing analysis revealed that CDKN2A participated in cell cycle pathways.The CDKN2A-related ceRNA network-growth arrest specific 5(GAS5)/miR-25-3p/SRY-box transcription factor 11(SOX11)was successfully established.GAS5 was recognized as an independent prognostic biomarker,whose overexpression was correlated with a poor prognosis in HCC patients.The association between GAS5 expression and methylation,immune infilt-ration was explored.Besides,traditional Chinese medicine effective components targeting GAS5 were obtained.CONCLUSION This CDKN2A-related ceRNA network provides innovative insights into the molecular mechanism of HCC formation and progression.Moreover,GAS5 might be a significant prognostic biomarker and therapeutic target in HCC.展开更多
文摘Crohn’s disease(CD)is caused by immune,environmental,and genetic factors.It can involve the entire gastrointestinal tract,and although its prevalence is rapidly increasing its etiology remains unclear.Emerging biological and small-molecule drugs have advanced the treatment of CD;however,a considerable proportion of patients are non-responsive to all known drugs.To achieve a breakthrough in this field,innovations that could guide the further development of effective therapies are of utmost urgency.In this review,we first propose the innovative concept of pan-lymphatic dysfunction for the general distribution of lymphatic dysfunction in various diseases,and suggest that CD is the intestinal manifestation of pan-lymphatic dysfunction based on basic and clinical preliminary data.The supporting evidence is fully summarized,including the existence of lymphatic system dysfunction,recognition of the inside-out model,disorders of immune cells,changes in cell plasticity,partial overlap of the underlying mechanisms,and common gut-derived fatty and bile acid metabolism.Another benefit of this novel concept is that it proposes adopting the zebrafish model for studying intestinal diseases,especially CD,as this model is good at presenting and mimicking lymphatic dysfunction.More importantly,the ensuing focus on improving lymphatic function may lead to novel and promising therapeutic strategies for CD.
基金the National Natural Science Foundation of China,No.82070588 and No.82370577.
文摘Metabolic dysfunction-associated fatty liver disease(MAFLD)is the most prevalent chronic liver condition worldwide.Current liver enzyme-based screening methods have limitations that may missed diagnoses and treatment delays.Regarding Chen et al,the risk of developing MAFLD remains elevated even when alanine aminotransferase levels fall within the normal range.Therefore,there is an urgent need for advanced diagnostic techniques and updated algorithms to enhance the accuracy of MAFLD diagnosis and enable early intervention.This paper proposes two potential screening methods for identifying individuals who may be at risk of developing MAFLD:Lowering these thresholds and promoting the use of noninvasive liver fibrosis scores.
基金Supported by the Key Discipline of Zhejiang Province in Medical Technology(First Class,Category A)and the Health Project of the Science and Technology Department of Wenzhou,No.Y20220029.
文摘BACKGROUND Colorectal cancer(CRC)ranks among the most prevalent malignant tumors globally.Recent reports suggest that Fusobacterium nucleatum(F.nucleatum)contributes to the initiation,progression,and prognosis of CRC.Butyrate,a short-chain fatty acid derived from the bacterial fermentation of soluble dietary fiber,is known to inhibit various cancers.This study is designed to explore whether F.nucleatum influences the onset and progression of CRC by impacting the intestinal metabolite butyric acid.AIM To investigate the mechanism by which F.nucleatum affects CRC occurrence and development.METHODS Alterations in the gut microbiota of BALB/c mice were observed following the oral administration of F.nucleatum.Additionally,DLD-1 and HCT116 cell lines were exposed to sodium butyrate(NaB)and F.nucleatum in vitro to examine the effects on proliferative proteins and mitochondrial function.RESULTS Our research indicates that the prevalence of F.nucleatum in fecal samples from CRC patients is significantly greater than in healthy counterparts,while the prevalence of butyrate-producing bacteria is notably lower.In mice colonized with F.nucleatum,the population of butyrate-producing bacteria decreased,resulting in altered levels of butyric acid,a key intestinal metabolite of butyrate.Exposure to NaB can impair mitochondrial morphology and diminish mitochondrial membrane potential in DLD-1 and HCT116 CRC cells.Consequently,this leads to modulated production of adenosine triphosphate and reactive oxygen species,thereby inhibiting cancer cell prolif-eration.Additionally,NaB triggers the adenosine monophosphate-activated protein kinase(AMPK)signaling pathway,blocks the cell cycle in HCT116 and DLD-1 cells,and curtails the proliferation of CRC cells.The combined presence of F.nucleatum and NaB attenuated the effects of the latter.By employing small interfering RNA to suppress AMPK,it was demonstrated that AMPK is essential for NaB’s inhibition of CRC cell proliferation.CONCLUSION F.nucleatum can promote cancer progression through its inhibitory effect on butyric acid,via the AMPK signaling pathway.
文摘Objective: To carry out empirical research on the role of project-achieving quality control circle (QCC) in constructing a new model of contactless medical service for outpatients. Methods: A QCC, consisting of information office members from a grade A tertiary hospital in Wenzhou, was established to conduct a research project with the theme “Constructing a new model of contactless medical service based on outpatients’ experience.” According to the ten steps and PDCA cycle, an analysis was carried out before and after the QCC activities, focusing on improving pre-consultation services, providing steward-like services, and facilitating post-consultation management. Results: After the QCC activities, the mobile appointment rate, missed appointment rate, the proportion of smart check-ins, and the average check-in time were 55.68%, 4.02%, 39.75%, and 8.24 ± 3.66 min, respectively;in contrast, before the activities, they were 32.00%, 7.88%, 0.00%, and 14.96 ± 4.98 min, respectively;the difference between the two groups was statistically significant (χ2 = 3480.112, 4994.496;Fisher’s exact probability = 963788.570;t = 5.323, P < 0.001). Many experts have also visited the hospital to learn about this system, thus rendering social and economic benefits. Conclusion: Project-achieving QCC activities are suitable for complex situations, such as constructing a new model of contactless medical service, and can significantly improve outpatient service quality, enhance patients’ experience, and improve the abilities of circle members.
基金Supported by the Foundation of Wenzhou Municipal Science and Technology Bureau,No.Y20190209 and No.Y2020739the Hospital Research Incubation Program,No.FHY2019075。
文摘BACKGROUND In recently diagnosed patients with thyroid cancer,papillary thyroid cancer(PTC),as the most common histological subtype,accounts for 90%of all cases.Although PTC is known as a relatively adolescent malignant disease,there still is a high possibility of recurrence in PTC patients with a poor prognosis.Therefore,new biomarkers are necessary to guide more effective stratification of PTC patients and personalize therapy to avoid overtreatment or inadequate treatment.Accumulating evidence demonstrates that microRNAs(miRNAs)have broad application prospects as diagnostic biomarkers in cancer.AIM To explore novel markers consisting of miRNA-associated signatures for PTC prognostication.METHODS We obtained and analyzed the data of 497 PTC patients from The Cancer Genome Atlas.The patients were randomly assigned to either a training or testing cohort.RESULTS We discovered 237 differentially expressed miRNAs in tumorous thyroid tissues compared with normal tissues,which contained 172 up-regulated and 65 downregulated miRNAs.The evaluation of differently expressed miRNAs was conducted using our risk score model.We then successfully generated a fourmiRNA potential prognostic signature[risk score=(-0.001×hsa-miR-181a-2-3p)+(0.003×hsa-miR-138-5p)+(-0.018×hsa-miR-424-3p)+(0.284×hsa-miR-612)],which reliably distinguished patients from high and low risk with a significant difference in the overall survival(P<0.01)and was effective in predicting the five-year disease survival rate with the area under the receiver operating characteristic curve of 0.937 and 0.812 in the training and testing cohorts,respectively.Additionally,there was a trend indicated that high-risk patients had shorter relapse-free survival,although statistical significance was not reached(P=0.082)in our sequencing cohort.CONCLUSION Our results indicated a four-miRNA signature that has a robust predictive effect on the prognosis of PTC.Accordingly,we would recommend more radical therapy and closer follow-ups for highrisk groups.
基金Supported by Zhejiang Provincial Highlevel Health Talents Training Project(No.CZ-RC2022010)Wenzhou Basic Medical and Health Technology Project(No.Y20220779)。
文摘AIM:To estimate and compare the incidence and characteristics of rhegmatogenous retinal detachments(RRDs)in the Wenzhou area in 2015 to 2019.METHODS:All newly developed RRD cases among residents of the Wenzhou area,from January 2015 to December 2019,were retrospectively retrieved from hospital records.Annual population data were extracted from the Wenzhou Statistical Yearbook.RESULTS:There were 3629 eligible cases.The average incidence of RRD was 7.79 cases per 100000 population(95%confidence interval,7.24-8.34),and the incidences were 7.99 and 7.56 for males and females,respectively.The annual incidence increased gradually from 7.26 cases per 100000 in 2015 to 10.00 cases per 100000 in 2019,with an overall increase of 37.74%.The highest rate of increase occurred in the age group from 60 to 69 years.Of 2750 eyes with axial length(AL)data,1675(60.91%)had an AL greater than 24 mm.CONCLUSION:A trend to increasing RRD incidence is observed in the Wenzhou area over the past 5-year period.
基金Supported by the National Natural Science Foundation of China,No.81871568,No.32100643COVID-19 Infection and Prevention Emergency Special Project of Chongqing Education Commission,No.KYYJ202009.
文摘BACKGROUND The immunosuppressive capacity of mesenchymal stem cells(MSCs)is dependent on the“license”of several proinflammatory factors to express immunosuppressive factors such as programmed cell death 1 ligand 1(PD-L1),which determines the clinical therapeutic efficacy of MSCs for inflammatory or immune diseases.In MSCs,interferon-gamma(IFN-γ)is a key inducer of PD-L1 expression,which is synergistically enhanced by tumor necrosis factor-alpha(TNF-α);however,the underlying mechanism is unclear.AIM To reveal the mechanism of pretreated MSCs express high PD-L1 and explore the application of pretreated MSCs in ulcerative colitis.METHODS We assessed PD-L1 expression in human umbilical-cord-derived MSCs(hUC-MSCs)induced by IFN-γand TNF-α,alone or in combination.Additionally,we performed signal pathway inhibitor experiments as well as RNA interference experiments to elucidate the molecular mechanism by which IFN-γalone or in combination with TNF-αinduces PD-L1 expression.Moreover,we used luciferase reporter gene experiments to verify the binding sites of the transcription factors of each signal transduction pathway to the targeted gene promoters.Finally,we evaluated the immunosuppressive capacity of hUC-MSCs treated with IFN-γand TNF-αin both an in vitro mixed lymphocyte culture assay,and in vivo in mice with dextran sulfate sodium-induced acute colitis.RESULTS Our results suggest that IFN-γinduction alone upregulates PD-L1 expression in hUC-MSCs while TNF-αalone does not,and that the co-induction of IFN-γand TNF-αpromotes higher expression of PD-L1.IFN-γinduces hUCMSCs to express PD-L1,in which IFN-γactivates the JAK/STAT1 signaling pathway,up-regulates the expression of the interferon regulatory factor 1(IRF1)transcription factor,promotes the binding of IRF1 and the PD-L1 gene promoter,and finally promotes PD-L1 mRNA.Although TNF-αalone did not induce PD-L1 expression in hUCMSCs,the addition of TNF-αsignificantly enhanced IFN-γ-induced JAK/STAT1/IRF1 activation.TNF-αupregulated IFN-γreceptor expression through activation of the nuclear factor kappa-B signaling pathway,which significantly enhanced IFN-γsignaling.Finally,co-induced hUC-MSCs have a stronger inhibitory effect on lymphocyte proliferation,and significantly ameliorate weight loss,mucosal damage,inflammatory cell infiltration,and up-regulation of inflammatory factors in colitis mice.CONCLUSION Overall,our results suggest that IFN-γand TNF-αenhance both the immunosuppressive ability of hUC-MSCs and their efficacy in ulcerative colitis by synergistically inducing high expression of PD-L1.
基金the Basic Medical and Health Technology Project of Wenzhou Science and Technology Bureau(Y20190308).
文摘Objective:To analyze the risk factors of neonatal medical adhesive-related skin injury and put forward targeted preventive measures,so as to provide reference for the care and prevention of neonatal medical adhesive-related skin injuries.Methods:Using the convenience sampling method,262 neonates admitted to the neonatal intensive care unit(NICU)of a tertiary general hospital in Wenzhou from April 2021 to May 2022 were selected as the study subjects.The incidence of medical adhesive-related skin injuries in these neonates was retrospectively analyzed.Results:Among the 262 children,43 cases had skin injuries,with an incidence rate of 16.4%.Single factor analysis showed that the occurrence of medical adhesive-related skin injury was related to gestational age,weight,electrocardiogram(ECG)monitoring,venous access,ambient temperature,and mechanical ventilation(P<0.05).Multivariate logistic regression showed that gestational age,ECG monitoring,and ambient temperature were independent risk factors of medical adhesive-related skin injury(OR values were 0.700,0.431,and 6.365,respectively).Conclusion:The high incidence of neonatal medical adhesive-related skin injury may be caused by one or more factors.Clinical measures should be taken,such as selecting the appropriate type of adhesive according to gestational age and using skin-protecting membrane,minimizing ECG monitoring,etc.,to prevent the occurrence of neonatal medical adhesive-related skin injury.
基金supported by the Technology Innovation and Application Developnent Key Program of Chongqing(Grant No.CSTC2021jscx-gksb-N0026)the National Natural Science Foundation of China(Grant No.31540016)+1 种基金the Basic Research and Frontier Exploration Projects of Chongqing(Grant No.cstc2018jcyjAX0075)the Subsidy Fund for the Development of National Silk in Chongqing(Grant No.CQ2018JSCE05).
文摘Objective:CAR-T/NK cells have had limited success in the treatment of solid tumors,such as colorectal cancer(CRC),in part because of the heterogeneous nature of tumor-associated antigens that lead to antigen-negative relapse after the initial response.This barrier might be overcome by enhancing the recruitment and durability of endogenous immune cells.Methods:Immunohistochemistry and flow cytometry were used to assess the expression of CD133 antigen in tissue microarrays and cell lines,respectively.Retroviral vector transduction was used to generate CBLB502-secreting CAR133-NK92 cells(CAR133-i502-NK92).The tumor killing capacity of CAR133-NK92 cells in vitro and in vivo were quantified via LDH release,the RTCA assay,and the degranulation test,as well as measuring tumor bioluminescence signal intensity in mice xenografts.Results:We engineered CAR133-i502-NK92 cells and demonstrated that those cells displayed enhanced proliferation(9.0×10^(4)cells vs.7.0×10^(4)cells)and specific anti-tumor activities in vitro and in a xenogeneic mouse model,and were well-tolerated.Notably,CBLB502 secreted by CAR133-i502-NK92 cells effectively activated endogenous immune cells.Furthermore,in hCD133+/hCD133−mixed cancer xenograft models,CAR133-i502-NK92 cells suppressed cancer growth better than the counterparts(n=5,P=0.0297).Greater T-cell infiltration was associated with greater anti-tumor potency(P<0.0001).Conclusions:Armed with a CBLB502 TLR5 agonist,CAR133-NK92 cells were shown to be capable of specifically eliminating CD133-positive colon cancer cells in a CAR133-dependent manner and indirectly eradicating CD133-negative colon cancer cells in a CBLB502-specific endogenous immune response manner.This study describes a novel technique for optimizing CAR-T/NK cells for the treatment of antigenically-diverse solid tumors.
文摘Triple-negative breast cancer(TNBC)poses a significant challenge due to the lack of reliable prognostic gene signatures and an understanding of its immune behavior.Methods:We analyzed clinical information and mRNA expression data from 162 TNBC patients in TCGA-BRCA and 320 patients in METABRIC-BRCA.Utilizing weighted gene coexpression network analysis,we pinpointed 34 TNBC immune genes linked to survival.The least absolute shrinkage and selection operator Cox regression method identified key TNBC immune candidates for prognosis prediction.We calculated chemotherapy sensitivity scores using the“pRRophetic”package in R software and assessed immunotherapy response using the Tumor Immune Dysfunction and Exclusion algorithm.Results:In this study,34 survival-related TNBC immune gene expression profiles were identified.A least absolute shrinkage and selection operator-Cox regression model was used and 15 candidates were prioritized,with a concomitant establishment of a robust risk immune classifier.The high-risk TNBC immune groups showed increased sensitivity to therapeutic agents like RO-3306,Tamoxifen,Sunitinib,JNK Inhibitor VIII,XMD11-85h,BX-912,and Tivozanib.An analysis of the Search Tool for Interaction of Chemicals database revealed the associations between the high-risk group and signaling pathways,such as those involving Rap1,Ras,and PI3K-Akt.The low-risk group showed a higher immunotherapy response rate,as observed through the tumor immune dysfunction and exclusion analysis in the TCGA-TNBC and METABRIC-TNBC cohorts.Conclusion:This study provides insights into the immune complexities of TNBC,paving the way for novel diagnostic approaches and precision treatment methods that exploit its immunological intricacies,thus offering hope for improved management and outcomes of this challenging disease.
基金Supported by Wenzhou Science and Technology Bureau,No.Y20190129 and No.Y2020263.
文摘BACKGROUND Current approaches for the therapy of diabetic retinopathy(DR),which was one of leading causes of visual impairment,have their limitations.Animal experiments revealed that restructuring of intestinal microbiota can prevent retinopathy.AIM To explore the relationship between intestinal microbiota and DR among patients in the southeast coast of China,and provide clues for novel ways to prevention and treatment methods of DR.METHODS The fecal samples of non-diabetics(Group C,n=15)and diabetics(Group DM,n=30),including 15 samples with DR(Group DR)and 15 samples without DR(Group D),were analyzed by 16S rRNA sequencing.Intestinal microbiota compositions were compared between Group C and Group DM,Group DR and Group D,as well as patients with proliferative diabetic retinopathy(PDR)(Group PDR,n=8)and patients without PDR(Group NPDR,n=7).Spearman correlation analyses were performed to explore the associations between intestinal microbiota and clinical indicators.RESULTS The alpha and beta diversity did not differ significantly between Group DR and Group D as well as Group PDR and Group NPDR.At the family level,Fusobacteriaceae,Desulfovibrionaceae and Pseudomonadaceae were significantly increased in Group DR than in Group D(P<0.05,respectively).At the genera level,Fusobacterium,Pseudomonas,and Adlercreutzia were increased in Group DR than Group D while Senegalimassilia was decreased(P<0.05,respectively).Pseudomonas was negatively correlated with NK cell count(r=-0.39,P=0.03).Further,the abundance of genera Eubacterium(P<0.01),Peptococcus,Desulfovibrio,Acetanaerobacterium and Negativibacillus(P<0.05,respectively)were higher in Group PDR compared to Group NPDR,while Pseudomonas,Alloprevotella and Tyzzerella(P<0.05,respectively)were lower.Acetanaerobacterium and Desulfovibrio were positively correlated with fasting insulin(r=0.53 and 0.61,respectively,P<0.05),when Negativibacillus was negatively correlated with B cell count(r=-0.67,P<0.01).CONCLUSION Our findings indicated that the alteration of gut microbiota was associated with DR and its severity among patients in the southeast coast of China,probably by multiple mechanisms such as producing short-chain fatty acids,influencing permeability of blood vessels,affecting levels of vascular cell adhesion molecule-1,hypoxia-inducible factor-1,B cell and insulin.Modulating gut microbiota composition might be a novel strategy for prevention of DR,particularly PDR in population above.
基金supported by the Ministry of Science and Technology of China (2019YFA0802103)the National Natural Science Foundation of China (31900804, 31960179)+1 种基金the Department of Science and Technology of Zhejiang Province (2021C03104)the Science and Technology Commission of Shanghai Municipality (19140903500)
文摘Dear Editor,Autophagy is an evolutionarily conserved catabolic process that involves the sequestration and transport of organelles,macromolecules,or invading microorganisms to lysosomes for degradation[1].Sequestosome 1(p62/SQSTM1)was the first protein shown to bind target-associated ubiquitin(Ub)and LC3 conjugated to the phagophore membrane,thus,acting as an important autophagy receptor for ubiquitinated targets[2].
基金supported by the National Nature Science Fund of China(Grant No.82102313)Zhejiang Province Traditional Chinese Medicine Science and Technology Plan Project(Grant No.2023ZL497)+1 种基金Zhejiang Province Medical and Health Science and Technology Project(Grant No.2022519563)National Health and Medical Research Council of Australia(Grant No.app1107828,app1163933)。
文摘The cell membrane structure is closely related to the occurrence and progression of many metabolic bone diseases observed in the clinic and is an important target to the development of therapeutic strategies for these diseases.Strong experimental evidence supports the existence of membrane microdomains in osteoclasts(OCs).However,the potential membrane microdomains and the crucial mechanisms underlying their roles in OCs have not been fully characterized.Membrane microdomain components,such as scaffolding proteins and the actin cytoskeleton,as well as the roles of individual membrane proteins,need to be elucidated.In this review,we discuss the compositions and critical functions of membrane microdomains that determine the biological behavior of OCs through the three main stages of the OC life cycle.
基金supported by grants from the National Natural Science Foundation of China(81730057,82130062)the Key Project of Military Medical Innovation Program of Chinese PLA(18CXZ026)+1 种基金the Guangdong Clinical Research Center for Critical Care Medicine(2020B1111170005)the Sun Yat?sen University Clinical Research Program 5010(2019002)。
文摘Emerged evidence has indicated that immunosuppression is involved in the occurrence and development of sepsis.To provide clinical practice recommendations on the immune function in sepsis,an expert consensus focusing on the monitoring and treatment of sepsis-induced immunosuppression was developed.Literature related to the immune monitoring and treatment of sepsis were retrieved from PubMed,Web of Science,and Chinese National Knowledge Infrastructure to design items and expert opinions were collected through an online questionnaire.Then,the Delphi method was used to form consensus opinions,and RAND appropriateness method was developed to provide consistency evaluation and recommendation levels for consensus opinions.This consensus achieved satisfactory results through two rounds of questionnaire survey,with 2 statements rated as perfect consistency,13 as very good consistency,and 9 as good consistency.After summarizing the results,a total of 14 strong recommended opinions,8 weak recommended opinions and 2 non-recommended opinions were produced.Finally,a face-to-face discussion of the consensus opinions was performed through an online meeting,and all judges unanimously agreed on the content of this consensus.In summary,this expert consensus provides a preliminary guidance for the monitoring and treatment of immunosuppression in patients with sepsis.
基金The Zhejiang Medical and Health Science and Technology Program,China,No.2021KY205 and No.2024KY139The Wenzhou Science and Technology Plan Project,China,No.Y2023111.
文摘In this editorial,we examined a recent article in the World Journal of Gastroenterology that focused on sepsis-associated liver injury(SLI)and its treatment.SLI is a serious complication of sepsis,primarily caused by microcirculatory disturbances,the gut-liver axis,and inflammatory responses.Specific treatment recommendations for SLI are lacking.The gut-liver axis represents a potential therapeutic target,with metformin showing promise in modulating the gut microbiome and enhancing intestinal barrier function.Although immunomodulatory therapies are being explored,anti-tumor necrosis factor agents and interleukin-1 receptor antagonists have not demonstrated significant clinical benefits.Statins may reduce liver inflammation and prevent injury in sepsis,but their clinical application is limited.Reduced D-related human leucocyte antigen expression on monocytes and lymphocytes suggests immune suppression in patients,indicating that corticosteroids could reverse clinical deterioration in severe infections and address adrenal cortical insufficiency.Current large-scale studies on glucocorticoid therapy for sepsis have yielded mixed results,likely due to inadequate assessment of the immune status of the host.Future research should prioritize the development of personalized immunotherapy tailored to patients’immune profiles,focusing on identifying novel indicators of immune status and advancing immunomodulatory targets and therapeutics for septic patients.
基金supported by Wenzhou Municipal Science and technology Bureau,China(Grant No.:Y20220023)the Key Laboratory of Clinical Laboratory Diagnosis and Translational Research of Zhejiang Province,China(Grant No.:2022E10022)the Project of Wenzhou Medical University Basic Scientific Research,China(Grant No.:KYYW201904).
文摘Liver fibrosis is primarily driven by the activation of hepatic stellate cells(HSCs),a process associated with ferroptosis.Ginsenoside Rb1(GRb1),a major active component extracted from Panax ginseng,inhibits HSC activation.However,the potential role of GRb1 in mediating HSC ferroptosis remains unclear.This study examined the effect of GRb1 on liver fibrosis both in vivo and in vitro,using CCl4-induced liver fibrosis mouse model and primary HSCs,LX-2 cells.The findings revealed that GRb1 effectively inactivated HSCs in vitro,reducing alpha-smooth muscle actin(a-SMA)and type I collagen(Col1A1)levels.Moreover,GRb1 significantly alleviated CCl4-induced liver fibrosis in vivo.From a mechanistic standpoint,the ferroptosis pathway appeared to be central to the antifibrotic effects of GRb1.Specifically,GRb1 promoted HSC ferroptosis both in vivo and in vitro,characterized by increased glutathione depletion,malondialdehyde production,iron overload,and accumulation of reactive oxygen species(ROS).Intriguingly,GRb1 increased Beclin 1(BECN1)levels and decreased the System Xc-key subunit SLC7A11.Further experiments showed that BECN1 silencing inhibited GRb1-induced effects on HSC ferroptosis and mitigated the reduction of SLC7A11 caused by GRb1.Moreover,BECN1 could directly interact with SLC7A11,initiating HSC ferroptosis.In conclusion,the suppression of BECN1 counteracted the effects of GRb1 on HSC inactivation both in vivo and in vitro.Overall,this study highlights the novel role of GRb1 in inducing HSC ferroptosis and promoting HSC inactivation,at least partly through its modulation of BECN1 and SLC7A11.
基金National Health Commission Research Fund,No.WKJ-ZJ-2342National Natural Science Foundation of China,No.81900583Science and Technology Plan Project of Wenzhou,No.Y20180103.
文摘BACKGROUND Acute pancreatitis(AP),the initially triggered inflammatory process in the pancreas,can be life-threatening.It has been reported that 15-lipoxygenase may promote the removal of damaged intracellular components,maintain intracellular homeostasis,and promote apoptosis by upregulating the activity of caspases.Despite an increased understanding of the lipoxygenase pathway in inflammation and immune diseases,the role of the Alox15 gene product in modulating the inflammatory changes during AP is not well defined.AIM To investigate the effect of Alox15 expression in cerulein-induced AP in rats.METHODS Model rats were transfected with Alox15 by injecting a recombinant lentivirus vector encoding Alox15 into the left gastric artery before inducing AP.The expression of Alox15 was then assessed at the mRNA and protein levels.RESULTS Our in vivo results showed that serum amylase activity and pancreatic tissue water content were significantly reduced in Alox15-transfected rats.Further,the mRNA expression levels of tumor necrosis factor alpha,interleukin(IL)-1β,IL-6,and monocyte chemoattractant protein-1,as well as the protein expression of nuclear factor kappa B in pancreatic tissue were reduced.Additionally,we observed an upregulation of cleaved caspase-3 that implies an induction of apoptosis in pancreatic cells.The transfection of Alox15 resulted in a lower number of autophagic vacuoles in AP.CONCLUSION Our findings demonstrate a regulatory role of Alox15 in apoptosis and autophagy,making it a potential therapeutic target for AP.
基金supported by the National Key R&D Program of China(2021YFC2502100,2023YFC3603404,2019YFA0111900)National Natural Science Foundation of China(82072506,82272611,92268115)+7 种基金Hunan Provincial Science Fund for Distinguished Young Scholars(2024JJ2089)Hunan Young Talents of Science and Technology(2021RC3025)Provincial Clinical Medical Technology Innovation Project of Hunan(2023SK2024,2020SK53709)Provincial Natural Science Foundation of Hunan(2020JJ3060)National Natural Science Foundation of Hunan Province(2023JJ30949)National Clinical Research Center for Geriatric Disorders,Xiangya Hospital(2021KFJJ02,2021LNJJ05)the Hunan Provincial Innovation Foundation for Postgraduate(CX20230308,CX20230312)the Independent Exploration and Innovation Project for Postgraduate Students of Central South University(2024ZZTS0163)。
文摘This review compiles information from the literature on the chemical composition,pharmacological effects,and molecular mechanisms of earthworm extract(EE)and suggests possibilities for clinical translation of EE.We also consider future trends and concerns in this domain.We summarize the bioactive components of EE,including G-90,lysenin,lumbrokinase,antimicrobial peptides,earthworm serine protease(ESP),and polyphenols,and detail the antitumor,antithrombotic,antiviral,antibacterial,anti-i nflammatory,analgesic,antioxidant,wound-healing,antifibrotic,and hypoglycemic activities and mechanisms of action of EE based on existing in vitro and in vivo studies.We further propose the potential of EE for clinical translation in anticancer and lipid-modifying therapies,and its promise as source of a novel agent for wound healing and resistance to antibiotic tolerance.The earthworm enzyme lumbrokinase embodies highly effective anticoagulant and thrombolytic properties and has the advantage of not causing bleeding phenomena due to hyperfibrinolysis.Its antifibrotic properties can reduce the excessive accumulation of extracellular matrix.The glycolipoprotein extract G-90 can effectively scavenge reactive oxygen groups and protect cellular tissues from oxidative damage.Earthworms have evolved a well-developed defense mechanism to fight against microbial infections,and the bioactive agents in EE have shown good antibacterial,fungal,and viral properties in in vitro and in vivo experiments and can alleviate inflammatory responses caused by infections,effectively reducing pain.Recent studies have also highlighted the role of EE in lowering blood glucose.EE shows high medicinal value and is expected to be a source of many bioactive compounds.
文摘Objective:To study the clinical effect of targeted infusion safety nursing during infusion of inpatients with cancer.Methods:From January 1,2020,to January 1,2023,a total of 6,614 infusion patients were treated in The First Affiliated Hospital of Wenzhou Medical University,and 300 inpatients with cancer were selected as the research objects and randomly divided into the observation group and the control group,with 150 patients in each group.The control group received routine infusion nursing,and the observation group received targeted infusion safety nursing.The targeted infusion safety nursing was judged by comparing the nursing quality assessment,incidence of adverse events,patient compliance,and patients’mastery of infusion knowledge between the two groups.clinical effect.Results:After the targeted infusion safety nursing was given to the patients in the observation group,the patients in this group recognized the nursing quality,and the statistical score was higher than that in the control group;the incidence of adverse events in the observation group was lower than that in the control group.The compliance of the observation group was higher than that of the control group.The mastery of health knowledge in the observation group was also higher than that in the control group and the difference was statistically significant(P<0.02).Conclusion:After implementing targeted infusion safety nursing for inpatients with cancer,it can effectively prevent the occurrence of adverse events,improve patient compliance,and increase the mastery of relevant knowledge of patients.
基金Supported by the Zhejiang Province Major Science and Technology Project for Medicine and Health,No.WKJ-ZJ-2329.
文摘BACKGROUND Competitive endogenous RNA(ceRNA)is an innovative way of gene expression modulation,which plays a crucial part in neoplasia.However,the intricacy and behavioral characteristics of the ceRNA network in hepatocellular carcinoma(HCC)remain dismal.AIM To establish a cyclin dependent kinase inhibitor 2A(CDKN2A)-related ceRNA network and recognize potential prognostic indicators for HCC.METHODS The mutation landscape of CDKN2A in HCC was first explored using the cBioPortal database.Differential expression analysis was implemented between CDKN2Ahigh and CDKN2Alow expression HCC samples.The targeted microRNAs were predicted by lncBasev3.0,and the targeted mRNAs were predicted by miRDB,and Targetscan database.The univariate and multivariate analysis were utilized to identify independent prognostic indicators.RESULTS CDKN2A was frequently mutated and deleted in HCC.The single-cell RNA-sequencing analysis revealed that CDKN2A participated in cell cycle pathways.The CDKN2A-related ceRNA network-growth arrest specific 5(GAS5)/miR-25-3p/SRY-box transcription factor 11(SOX11)was successfully established.GAS5 was recognized as an independent prognostic biomarker,whose overexpression was correlated with a poor prognosis in HCC patients.The association between GAS5 expression and methylation,immune infilt-ration was explored.Besides,traditional Chinese medicine effective components targeting GAS5 were obtained.CONCLUSION This CDKN2A-related ceRNA network provides innovative insights into the molecular mechanism of HCC formation and progression.Moreover,GAS5 might be a significant prognostic biomarker and therapeutic target in HCC.
