Multi-systemic melioidosis in a patient with type 2 diabetes in nonendemic areas:A case report and review of literature

BACKGROUND Melioidosis,an infectious disease caused by Burkholderia pseudomallei(B.pseudomallei),occurs endemically in Southeast Asia and Northern Australia and is a serious opportunistic infection associated with a high mortality rate.CASE SUMMARY A 58-year-old woman presented with scattered erythema on the skin of her limbs,followed by fever and seizures.B.pseudomallei was isolated successively from the patient’s urine,blood,and pus.Magnetic resonance imaging showed abscess formation involving the right forehead and the right frontal region.Subsequently,abscess resection and drainage were performed.The patient showed no signs of relapse after 4 months of follow-up visits post-treatment.CONCLUSION We present here a unique case of multi-systemic melioidosis that occurs in nonendemic regions in a patient who had no recent travel history.Hence,it is critical to enhance awareness of melioidosis in non-endemic regions.

Effects of serum inflammatory factors,health index and disease activity scores on ankylosing spondylitis patients with sleep disorder

BACKGROUND Patients with ankylosing spondylitis(AS)frequently suffer from comorbid sleep disorders,exacerbating the burden of the disease and affecting their quality of life.AIM To investigate the clinical significance of serum inflammatory factors,health index and disease activity scores in patients with AS complicated by sleep disorders.METHODS A total of 106 AS patients with comorbid sleep disorders were included in the study.The patients were grouped into the desirable and undesirable prognosis groups in accordance with their clinical outcomes.The serum levels of inflammatory factors,including C-reactive protein,erythrocyte sedimentation rate,interleukin(IL)-6,tumour necrosis factor-αand IL-1β,were measured.Disease activity scores,such as the Bath AS functional index,Bath AS disease activity index,Bath AS metrology index and AS disease activity score,were assessed.The health index was obtained through the Short Form-36 questionnaire.RESULTS The study found significant associations amongst serum inflammatory factors,health index and disease activity scores in AS patients with comorbid sleep disorders.Positive correlations were found between serum inflammatory factors and disease activity scores,indicating the influence of heightened systemic inflammation on disease severity and functional impairment.Conversely,negative correlations were found between disease activity scores and health index parameters,highlighting the effect of disease activity on various aspects of healthrelated quality of life.Logistic regression analysis further confirmed the predictive value of these factors on patient outcomes,underscoring their potential utility in risk assessment and prognostication.CONCLUSION The findings demonstrate the intricate interplay amongst disease activity,systemic inflammation and patientreported health outcomes in AS patients complicated by sleep disorders.The results emphasise the need for comprehensive care strategies that address the diverse needs and challenges faced by these patients and underscore the potential relevance of serum inflammatory factors,health index and disease activity scores as prognostic markers in this patient population.

Successful management of infection and macrophage activation syndrome patient using low-dose etoposide:A case report

BACKGROUND Macrophage activation syndrome(MAS),a sub-type of hemophagocytic lymphohistiocytosis(HLH)secondary to autoimmune rheumatic diseases,is a critical and potentially fatal condition characterized by an excessive inflammatory response.Despite the established efficacy of the HLH-2004 guideline in diagnosing and treating HLH over the years,ongoing discussion persists regarding its application,especially for HLH secondary to complicated conditions,such as autoimmune rheumatic diseases combined with severe infection.Etoposide(VP-16),a topoisomerase II inhibitor that effectively induces DNA damage and subsequent apoptosis in hyperactivated immune cells,has been widely used for the treatment of HLH.However,its suppressive effect on immune system may also cause potential exacerbation of infection in autoimmune rheumatic disease-induced HLH patients complicated with severe infection.Therefore,the use of VP-16 in such cases was inconclusive.CASE SUMMARY In this case study,we propose a potentially effective strategy for managing a patient diagnosed with secondary HLH complicated with systemic lupus erythematosus(SLE)and chronic coronavirus disease 2019 infection.Our approach involves early administration of low-dose VP-16(100 mg twice a week,300 mg in total),combined with methylprednisolone,cyclophosphamide,and cyclosporine A.The administration of etoposide effectively led to improvements in various indices of HLH.CONCLUSION Low dose etoposide proves to be an effective approach in alleviating HLH while mitigating the risk of infection.

Analysis of status and influencing factors of mental health in patients with systemic lupus erythematosus

BACKGROUND Systemic lupus erythematosus(SLE)is a heterogeneous autoimmune disorder with varied clinical courses and prognoses,not only did the patients suffer from physical impairment,but also various physical and psychiatric comorbidities.Growing evidence have suggested that mental disorders in SLE patients,can lead to various adverse consequences.AIM To explored the features and influencing factors of mental health in patients with SLE and clarifying the correlations between mental health and personality characteristics and perceived social support.The results would provide a basis for psychological intervention in patients with SLE.METHODS The clinical data of 168 patients with SLE admitted at the First Affiliated Hospital of Hainan Medical University between June 2020 and June 2022 were collected.Psychological assessment and correlation analysis were conducted using the Symptom Checklist-90(SCL-90)and Perceived Social Support Scale,and the collected data were compared with the national norms in China.The relevant factors influencing mental health were identified by statistical analysis.A general information questionnaire,the Revised Life Orientation Test,and Short-Form 36-Item Health Survey were employed to assess optimism level and quality of life(QoL),respectively.RESULTS Patients with SLE obtained higher scores for the somatization,depression,anxiety,and phobic anxiety subscales than national norms(P<0.05).A correlation was identified between total social support and total SCL-90 score or each subscale(P<0.05).The factors significantly affecting patients’mental health were hormone dosage and disease activity index(DAI)(P<0.05).The average optimism score of patients with SLE was 14.36±4.42,and 30 cases were in the middle and lower levels.A positive correlation was found between optimism level and QoL scores.CONCLUSION Patients with SLE develop psychological disorders at varying degrees,which are significantly influenced by hormone dosage and DAI.Patients’mental health should be closely monitored during clinical diagnosis and treatment and provided adequate support in establishing positive,healthy thinking and behavior patterns and improving their optimism level and QoL.

A meta-analysis on the clinical efficacy of fire dragon cupping in the treatment of lumbar disc herniation

Background:The incidence of lumbar disc herniation(LDH)is notably high.Consensus among experts highlights non-surgical treatments as the primary therapeutic approach for LDH.Contemporary medicine frequently employs pharmacotherapy and epidural injections in such treatments,which are associated with numerous adverse effects.Prolonged use can severely impair the liver and kidney functions of patients.Hence,the role of safe and effective traditional Chinese medicine techniques becomes pivotal.Among various traditional Chinese medicine approaches for treating LDH,fire dragon cupping,renowned for its remarkable efficacy,cost-effectiveness,and ease of application,is extensively utilised in clinical settings for managing LDH.Nonetheless,there is a scarcity of systematic and standardised evidence from evidence-based medicine studies.Therefore,conducting a meta-analysis is imperative.Methods:A comprehensive computerised search was conducted in databases including China National Knowledge Infrastructure,WanFang Data,VIP,China Biology Medicine disc,PubMed,EMbase,The Cochrane Library,Web of Science,and CINAHL.The search aimed to gather randomised controlled trials on fire dragon cupping therapy for LDH,spanning from the inception of these databases until December 2023.Two researchers independently screened the literature according to inclusion and exclusion criteria,extracted data,and assessed the methodological quality of the studies included,utilising RevMan 5.3 software for meta-analysis.Results:The results show that the fire dragon cupping therapy group had better clinical effectiveness(relative risk=1.23,95%confidence interval(CI)(1.14,1.33),P<0.00001),less pain(standardized mean difference=–1.33,95%CI(–1.49,–1.16),P<0.00001),and some improvement in lumbar function(Japanese Orthopaedic Association scores:mean difference=3.37,95%CI(2.31,4.43),P<0.00001.Conclusion:The fire dragon cupping therapy significantly alleviates LDH,warranting its extensive application.However,considering the limitations in the number and quality of studies included,the aforementioned conclusion necessitates further validation through more high-quality research.

Successful rescue of disseminated Nocardia infection with multiple abscesses in a patient with membranous nephropathy after cardiopulmonary resuscitation:A three-year follow-up

Nocardiosis manifests as an opportunistic infection,primarily affecting individuals who are immunocompromised and susceptible to the infection.We present a case study of one patient with nephrotic syndrome and membranous nephropathy,who underwent treatment with prednisone and cyclosporine in 2016.In early 2017,the patient was diagnosed with a"fungal infection"and discontinued the use of cyclosporine.After one month of anti-infection therapy,a cranial magnetic resonance imaging scan showed multiple abscesses in the right temporal region.The diagnosis of nocardiosis was confirmed based on the presence of metastatic abscess masses,multiple lung and brain lesions,and a positive culture of Nocardia in the drainage.We changed the anti-infection therapy to a combination of trimethoprim-sulfamethoxazole(TMP-SMX),minocycline,and voriconazole.However,the patient experienced a sudden cardiac arrest and subsequently recovered after cardiopulmonary resuscitation.During the five-month follow-up period following the discharge,the patient displayed an enhanced nutritional status and stable renal function.The focal infection ultimately resolved during the subsequent three years.Neuro-infection caused by Nocardia should be considered in immunocompromised patients,and TMP-SMX is the preferred initial therapy;however,because of the high mortality rate,a long-term combination therapy with imipenem,cefotaxime,amikacin,and TMP-SMX is suggested.

Mechanism prediction of Astragalus mongholicus Bunge and Angelica sinensis Diels in treating interstitial lung disease based on network pharmacology and molecular docking

Objective:To investigate the mechanism by which Astragalus mongholicus Bunge(AM),and Angelica sinensis Diels(AS)act in interstitial lung disease(ILD)based on computational prediction.Methods:We screened the ingredients of AM and AS in PubMed,the Web of Science,China National Knowledge Infrastructure(CNKI)Databases,etc.Then obtained the potential effective components.By sharing the same molecular with ILD,we got the possible target genes for ILD treatment and constructed components–targets–disease network with Cytoscape software.The CTD(Comparative Toxicogenomics Database)database was used for GO and KEGG enrichment analysis of these target genes.Results:59 active ingredients that can be druggable were chosen from AM,67 active ingredients were chosen from AS.77 overlapping target genes for AM and ILD and 36 overlapping target genes for AS and ILD were acquired.The hub targets of AM were PTGS2,PTGS1,CDK2,MAOA,ESR1,TOP2A,GSK3B,ESR2,PPARG,NOS2,The hub targets of AS were PTGS2,GABRA1,PTGS1,CHRM1,SLC6A2,ADRA1B,ADRAIA,ADRB2,CHRM3,GABRA2,CHRM2.Quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,and 5-Hydroxycoumarin were the main active ingredients which have more effective targets.Prediction of the protein-protein interaction network showed PTGS2,GSK3B,PPARG,etc.,were the important predicted targets.The enriched KEGG pathways,including the Immune System,Metabolism of lipids and lipoproteins,Cytokine Signaling in the Immune system,Generic Transcription Pathway,The interleukin pathway,Metabolism of proteins,PI3K-Akt signaling pathway,Metabolic pathways,Innate Immune System,Neuroactive ligand-receptor interaction,Metabolism,GPCR downstream signaling,Amine ligand-binding receptors,Class A/1,Calcium signaling pathway.Molecular docking showed that quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,5-Hydroxycoumarin had good binding activities with PTGS2 and GSK3B,which mainly mediated PI3K/Akt and other important signaling pathways in the pathogenesis of ILD.Conclusion:The components in AS and AM share some common targets,such as PTGS2.AM and AS may ameliorate ILD through the PI3K-Akt signaling pathway which is mediated by GSK3B.PTGS2,PPARG may also be vital target genes in the treatment of ILD with AM and AS.

Unusual presentation of systemic lupus erythematosus as hemophagocytic lymphohistiocytosis in a female patient: A case report

BACKGROUND Hemophagocytic lymphohistiocytosis(HLH) is a rare life-threatening disorder,often resulting in the immune-mediated injury of multiple organ systems,including primary HLH and secondary HLH(sHLH). Among them, sHLH results from infections, malignant, or autoimmune conditions, which have quite poor outcomes even with aggressive management and are more common in adults.CASE SUMMARY We report a rare case of a 36-year-old female manifested with sHLH on background with systemic lupus erythematosus(SLE). During hospitalization, the patient was characterized by recurrent high-grade fever, petechiae and ecchymoses of abdominal skin, and pulmonary infection. Whole exon gene sequencing revealed decreased activity of natural killer cells. She received systematic treatment with Methylprednisolone, Etoposide, and anti-infective drugs. Intravenous immunoglobulin and plasmapheresis were applied when the condition was extremely acute and progressive. The patient recovered and did not present any relapse of the HLH for one year of follow-up.CONCLUSION The case showed sHLH, thrombotic microvascular, and infection in the whole course of the disease, which was rarely reported by now. The treatment of the patient emphasizes that early recognition and treatment of sHLH in SLE patients was of utmost importance to improve the prognosis and survival rate of patients.

Acute flare of systemic lupus erythematosus with extensive gastrointestinal involvement: A case report and review of literature

BACKGROUND Lupus mesenteric vasculitis(LMV)is a serious condition that may occur as an acute manifestation of gastrointestinal(GI)involvement and is not easily diagnosed by physicians.Delayed diagnosis and treatment of LMV may lead to rapid disease progression and can be life threatening.CASE SUMMARY A previously healthy 27-year-old woman presented with abdominal pain following a history of fatigue and consumption of cold water.Laboratory invest-igations,physical examinations,and enhanced abdominal computed tomography(CT)suggested systemic lupus erythematosus complicated by LMV.She received treatments,such as GI decompression,somatostatin,glucocorticoids,and immu-nosuppressants,and was evaluated using color ultrasonography.Twenty days later,the patient reported no stomach discomfort and was able to consume semi-liquid food.Laboratory investigations showed that inflammatory factors decreased to normal levels and complement levels increased slightly.One year after discharged,she recovered with methylprednisolone being tapered to 4 mg per day,mycophenolate mofetil to 0.75 g bid,and hydroxychloroquine to 0.2 g bid;however,only C3 complement level was slightly below the normal level.CONCLUSION Early diagnosis of LMV is essential for successful treatment;this depends on a combination of clinical manifestations,laboratory investigations,and imaging findings.Enhanced CT is preferred,but ultrasonography can be used for prompt screening and follow-up.

Recent developments in application of single-cell RNA sequencing in the tumour immune microenvironment and cancer therapy

The advent of single-cell RNA sequencing(scRNA-seq)has provided insight into the tumour immune microenvironment(TIME).This review focuses on the application of scRNA-seq in investigation of the TIME.Over time,scRNA-seq methods have evolved,and components of the TIME have been deciphered with high resolution.In this review,we first introduced the principle of scRNA-seq and compared different sequencing approaches.Novel cell types in the TIME,a continuous transitional state,and mutual intercommunication among TIME components present potential targets for prognosis prediction and treatment in cancer.Thus,we concluded novel cell clusters of cancerassociated fibroblasts(CAFs),T cells,tumour-associated macrophages(TAMs)and dendritic cells(DCs)discovered after the application of scRNA-seq in TIME.We also proposed the development of TAMs and exhausted T cells,as well as the possible targets to interrupt the process.In addition,the therapeutic interventions based on cellular interactions in TIME were also summarized.For decades,quantification of the TIME components has been adopted in clinical practice to predict patient survival and response to therapy and is expected to play an important role in the precise treatment of cancer.Summarizing the current findings,we believe that advances in technology and wide application of single-cell analysis can lead to the discovery of novel perspectives on cancer therapy,which can subsequently be implemented in the clinic.Finally,we propose some future directions in the field of TIME studies that can be aided by scRNA-seq technology.

Clinical value of ankle flexion and extension exercises combined with a psychological intervention in knee osteoarthritis

BACKGROUND Considering the limited effectiveness of clinical interventions for knee osteoarthritis(KOA),it is necessary to continue to explore appropriate and effective treatment strategies to improve the condition of KOA patients.AIM To clarify the influence of ankle flexion and extension exercises combined with a psychological intervention on the psychological status and activities of daily living(ADLs)of patients with KOA.METHODS The research participants were 116 KOA patients admitted to The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine between May 2019 and May 2022,including 54 patients receiving routine treatment,care and psychological intervention(control group)and 62 patients additionally treated with ankle flexion and extension exercises(research group).The two groups were comparatively analyzed in terms of psychological status(Self-rating Anxiety/Depression Scale,SDS/SAS),ADLs,knee joint function(Lysholm Knee Scoring Scale),pain(Visual Analog Scale,VAS),fatigue(Multidimensional Fatigue Inventory,MFI),and quality of life(QoL;Short-Form 36 Item Health Survey,SF-36).RESULTS After evaluation,it was found that the postinterventional SDS,SAS,VAS,and MFI scores in the research group were significantly reduced compared with the baseline(before the intervention)values and those of the control group,while the postinterventional Lysholm,ADL and SF-36 scores were markedly elevated.CONCLUSION Therefore,ankle flexion and extension exercises are highly effective in easing negative psychological status,enhancing ADLs,daily living ability,knee joint function and QoL,and relieving pain and fatigue in KOA patients,thus warranting clinical promotion.

Single-cell analyses reveal cannabidiol rewires tumor microenvironment via inhibiting alternative activation of macrophage and synergizes with anti-PD-1 in colon cancer

Colorectal tumors often create an immunosuppressive microenvironment that prevents them from responding to immunotherapy.Cannabidiol(CBD)is a non-psychoactive natural active ingredient from the cannabis plant that has various pharmacological effects,including neuroprotective,antiemetic,anti-inflammatory,and antineoplastic activities.This study aimed to elucidate the specific anticancer mechanism of CBD by single-cell RNA sequencing(scRNA-seq)and single-cell ATAC sequencing(scATAC-seq)technologies.Here,we report that CBD inhibits colorectal cancer progression by modulating the suppressive tumor microenvironment(TME).Our single-cell transcriptome and ATAC sequencing results showed that CBD suppressed M2-like macrophages and promoted M1-like macrophages in tumors both in strength and quantity.Furthermore,CBD significantly enhanced the interaction between M1-like macrophages and tumor cells and restored the intrinsic anti-tumor properties of macrophages,thereby preventing tumor progression.Mechanistically,CBD altered the metabolic pattern of macrophages and related anti-tumor signaling pathways.We found that CBD inhibited the alternative activation of macrophages and shifted the metabolic process from oxidative phosphorylation and fatty acid oxidation to glycolysis by inhibiting the phosphatidylinositol 3-kinase-protein kinase B signaling pathway and related downstream target genes.Furthermore,CBD-mediated macrophage plasticity enhanced the response to anti-programmed cell death protein-1(PD-1)immunotherapy in xenografted mice.Taken together,we provide new insights into the anti-tumor effects of CBD.

Menstrual and Reproductive Characteristics of Patients with Primary Sjogren’s Syndrome:A 7-year Single-center Retrospective Study

Objective Primary Sjogren’s syndrome(pSS)is a systemic autoimmune disease that mainly affects the exocrine gland,especially in women.Currently,the results of studies on the menstruation or fertility of pSS patients remain controversial.This study aimed to examine the menstrual and reproductive characteristics of pSS patients.Methods Clinical data of 449 pSS patients who were admitted to Tongji Hospital in Hubei,China,from January 2015 to November 2021 were obtained and their menstrual and reproductive information analyzed.In addition,the clinical features of pSS patients with premenopausal or postmenopausal onset were compared.Results The spontaneous abortion rate of pSS patients was not higher than the reported rate of the general population and that the age of menarche,menstrual cycle,and menstrual period of pSS patients did not significantly differ from those reported in the general population;however,early menopause seemed to be more common in pSS patients.Skin involvement(27.96%vs.15.00%,P=0.005)and hyperglobulinemia(10.64%vs.4.16%,P=0.033)were more common in patients with premenopausal pSS onset,but patients with postmenopausal onset had a significantly greater incidence of interstitial lung disease(32.50%vs.17.02%,P=0.0004).Also,erythropenia(47.00%vs.31.25%,P=0.002),hypoalbuminemia(19.49%vs.8.22%,P=0.0009),and prevalence of high hypersensitive C-reactive protein levels(21.67%vs.10.94%,P=0.005)were more common in pSS patients with postmenopausal onset.Notably,the rate of abnormal pregnancy was significantly greater in patients with premenopausal onset(9.72%vs.2.50%,P=0.011).Conclusion Patients with pSS onset before or after menopause may have different risks in pulmonary involvement and laboratory manifestations.

Musculoskeletal Ultrasonography for the Assessment of Combined Drug Therapy for Rheumatoid Arthritis

Background: To evaluate the effect of treatment on musculoskeletal ultrasound (MSUS) and explore whether MSUS are associated with therapeutic response in rheumatoid arthritis (RA) patients treated with Tofacitinib in combination with methotrexate (MTX). Methods: We enrolled 102 RA patients treated with Tofacitinib in combination with MTX from a multicenter, exploratory, short-term, prospective and observational ultrasound cohort study of patients who received biologic or targeted synthetic disease-modifying antirheumatic drug (DMARD) therapy. We evaluated the patients’ clinical disease activity and musculoskeletal ultrasound (MSUS) scores. The serum concentrations of two venous blood inflammatory indicators were evaluated (c-reactive protein [CRP], erythrocyte sedimentation rate [ESR]) by multiplex bead assays at baseline, 3, and 6?months: the change over 6?months was defined as the P value. Before MSUS score treatment, an associate chief physician tested the wrist joints of each patient at the first treatment, and the attending physician with 3 years of MSUS experience and 7 years of work experience also performed semi-quantitative scores on the same RA patients and tested the consistency of the results. Results: Tofacitinib in combination with MTX significantly improved the clinical disease activity and MSUS score over 6?months. Serum ESR and CRP were significantly elevated at 6?months after the Tofacitinib in combination with MTX introduction (P P P Conclusions: MSUS scores may be useful for predicting RA patients’ therapeutic responses to abatacept.

Vascular endothelial growth factor B improves impaired glucose tolerance through insulin-mediated inhibition of glucagon secretion

BACKGROUND Impaired glucose tolerance(IGT)is a homeostatic state between euglycemia and hyperglycemia and is considered an early high-risk state of diabetes.When IGT occurs,insulin sensitivity decreases,causing a reduction in insulin secretion and an increase in glucagon secretion.Recently,vascular endothelial growth factor B(VEGFB)has been demonstrated to play a positive role in improving glucose metabolism and insulin sensitivity.Therefore,we constructed a mouse model of IGT through high-fat diet feeding and speculated that VEGFB can regulate hyperglycemia in IGT by influencing insulin-mediated glucagon secretion,thus contributing to the prevention and cure of prediabetes.AIM To explore the potential molecular mechanism and regulatory effects of VEGFB on insulin-mediated glucagon in mice with IGT.METHODS We conducted in vivo experiments through systematic VEGFB knockout and pancreatic-specific VEGFB overexpression.Insulin and glucagon secretions were detected via enzyme-linked immunosorbent assay,and the protein expression of phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)was determined using western blot.Further,mRNA expression of forkhead box protein O1,phosphoenolpyruvate carboxykinase,and glucose-6 phosphatase was detected via quantitative polymerase chain reaction,and the correlation between the expression of proteins was analyzed via bioinformatics.RESULTS In mice with IGT and VEGFB knockout,glucagon secretion increased,and the protein expression of PI3K/AKT decreased dramatically.Further,in mice with VEGFB overexpression,glucagon levels declined,with the activation of the PI3K/AKT signaling pathway.CONCLUSION VEGFB/vascular endothelial growth factor receptor 1 can promote insulin-mediated glucagon secretion by activating the PI3K/AKT signaling pathway to regulate glucose metabolism disorders in mice with IGT.

Transcriptome analysis reveals tumor antigen and immune subtypes of melanoma

Purpose:To screen potential tumor antigens for melanoma vaccine development and identify different immune subtypes.Methods:Transcriptional data(HTSEQ-FPKM)and clinical information of a 472 Melanoma cohort GDC TCGA Melanoma(SKCM)were downloaded from the UCSC XENA website(http://xena.ucsc.edu/).Subsequently,transcriptome data and clinical information of 210 melanoma cohort GSE65904 were downloaded from Gene Expression Omnibus(GEO),a large global public database.All the transcriptome expression data matrices were log2 transformed for subsequent analysis.GEPIA,TIMER,and IMMPORT databases are also used for analysis.Cell function experiments were performed to validate the role of the IDO1 gene in melanoma cell line A375.Results:Our study provides potential tumor antigens for vaccine development in melanoma patients:GZMB,GBP4,CD79A,APOBEC3F,IDO1,JCHAIN,LAG3,PLA2G2D,XCL2.In addition,we divide melanoma patients into two immune subtypes that have significant differences in tumor immunity and may have different responses to vaccination.In view of the unclear role of IDO1 in melanoma,we selected IDO1 for cell assay validation.Cell function assay showed that IDO1 was significantly overexpressed in the melanoma A375 cell line.After IDO1 knockdown,the activity,invasion,migration and healing ability of A375 cell lines were significantly decreased.Conclusion:Our study could provide a reference for the development of vaccines for melanoma patients.

Mechanism prediction of Astragalus mongholicus Bunge and Angelica sinensis Diels in treating interstitial lung disease based on network pharmacology and molecular docking

Objective:To investigate the mechanism by which Astragalus mongholicus Bunge(AM),and Angelica sinensis Diels(AS)act in interstitial lung disease(ILD)based on computational prediction.Methods:We screened the ingredients of AM and AS in PubMed,the Web of Science,China National Knowledge Infrastructure(CNKI)Databases,etc.Then obtained the potential effective components.By sharing the same molecular with ILD,we got the possible target genes for ILD treatment and constructed components–targets–disease network with Cytoscape software.The CTD(Comparative Toxicogenomics Database)database was used for GO and KEGG enrichment analysis of these target genes.Results:59 active ingredients that can be druggable were chosen from AM,67 active ingredients were chosen from AS.77 overlapping target genes for AM and ILD and 36 overlapping target genes for AS and ILD were acquired.The hub targets of AM were PTGS2,PTGS1,CDK2,MAOA,ESR1,TOP2A,GSK3B,ESR2,PPARG,NOS2,The hub targets of AS were PTGS2,GABRA1,PTGS1,CHRM1,SLC6A2,ADRA1B,ADRAIA,ADRB2,CHRM3,GABRA2,CHRM2.Quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,and 5-Hydroxycoumarin were the main active ingredients which have more effective targets.Prediction of the protein-protein interaction network showed PTGS2,GSK3B,PPARG,etc.,were the important predicted targets.The enriched KEGG pathways,including the Immune System,Metabolism of lipids and lipoproteins,Cytokine Signaling in the Immune system,Generic Transcription Pathway,The interleukin pathway,Metabolism of proteins,PI3K-Akt signaling pathway,Metabolic pathways,Innate Immune System,Neuroactive ligand-receptor interaction,Metabolism,GPCR downstream signaling,Amine ligand-binding receptors,Class A/1,Calcium signaling pathway.Molecular docking showed that quercetin,kaempferol,daidzein,pavilion,7-Hydroxycoumarin,5-Hydroxycoumarin had good binding activities with PTGS2 and GSK3B,which mainly mediated PI3K/Akt and other important signaling pathways in the pathogenesis of ILD.Conclusion:The components in AS and AM share some common targets,such as PTGS2.AM and AS may ameliorate ILD through the PI3K-Akt signaling pathway which is mediated by GSK3B.PTGS2,PPARG may also be vital target genes in the treatment of ILD with AM and AS.

Nutritional status efficacy of early nutritional support in gastrointestinal care: A systematic review and meta-analysis

BACKGROUND Gastrointestinal surgery is a complicated process used to treat many gastrointestinal diseases,and it is associated with a large trauma:Most patients often have different degrees of malnutrition and immune dysfunction before surgery and are prone to various infectious complications during postoperative recovery,thus affecting the efficacy of surgical treatment.Therefore,early postoperative nutritional support can provide essential nutritional supply,restore the intestinal barrier and reduce complication occurrence.However,different studies have shown different conclusions.AIM To assess whether early postoperative nutritional support can improve the nutritional status of patients based on literature search and meta-analysis.METHODS Articles comparing the effect of early nutritional support and delayed nutritional support were retrieved from PubMed,EMBASE,Springer Link,Ovid,China National Knowledge Infrastructure,China Biology Medicine databases.Notably,only randomized controlled trial articles were retrieved from the databases(from establishment date to October 2022).The risk of bias of the included articles was determined using Cochrane Risk of Bias V2.0.The outcome indicators,such as albumin,prealbumin,and total protein,after statistical intervention were combined.RESULTS Fourteen literatures with 2145 adult patients undergoing gastrointestinal surgery(1138 patients(53.1%)receiving early postoperative nutritional support and 1007 patients(46.9%)receiving traditional nutritional support or delayed nutritional support)were included in this study.Seven of the 14 studies assessed early enteral nutrition while the other seven studies assessed early oral feeding.Furthermore,six literatures had"some risk of bias,"and eight literatures had"low risk".The overall quality of the included studies was good.Meta-analysis showed that patients receiving early nutritional support had slightly higher serum albumin levels,than patients receiving delayed nutritional support[MD(mean difference)=3.51,95%CI:-0.05 to 7.07,Z=1.93,P=0.05].Also,patients receiving early nutritional support had shorter hospital stay(MD=-2.29,95%CI:-2.89 to-1.69),Z=-7.46,P<0.0001)shorter first defecation time(MD=-1.00,95%CI:-1.37 to-0.64),Z=-5.42,P<0.0001),and fewer complications(Odd ratio=0.61,95%CI:0.50 to 0.76,Z=-4.52,P<0.0001)than patients receiving delayed nutritional support.CONCLUSION Early enteral nutritional support can slightly shorten the defecation time and overall hospital stay,reduce complication incidence,and accelerate the rehabilitation process of patients undergoing gastrointestinal surgery.

Advances in the biological function of interleukin 38 and its study in immune diseases

IL-38 is a newly discovered anti-inflammatory cytokine that belongs to the IL-1 family's IL-36 subfa+mily.Nonetheless,recent studies have shown that it can interact with multiple receptors to impede downstream signaling pathway activation,thereby restraining the differentiation and maturation of Th17 cells.While IL-38 enhances the immunosuppressive activity of Treg by inhibiting the transformation of CD4+T cells to Th17 cells,it can also exert its immune regulatory role by binding to the corresponding IL-38 receptor on the cell surface,which in turn inhibits classical signaling pathways such as NF-κB,P38,or JNK activation.IL-38 has been shown to alleviate disease progression in Rheumatoid Arthritis(RA),Systemic lupus erythematosus(SLE),cardiovascular disease(CVD),and other diseases by reducing the production of inflammatory cytokines and limiting the inflammatory response that is dependent on T cell subsets.Moreover,an increasing body of evidence suggests that IL-38 is a promising therapeutic target for these diseases.This article primarily reviews the immunological function of IL-38 and its involvement in related diseases,providing insights and theoretical support for chronic inflammatory and autoimmune diseases.

Advances in Diagnosis and Treatment of Lupus Nephritis(Class V)

Membranous lupus nephritis(MLN),class V,is a distinct LN characterized by immune complex deposition on subepithelial kidney biopsy.MLN is often associated with nephrotic syndrome.The histology of MLN is very similar to idiopathic(primary)membranous nephropathy(pMN).However,MLN usually has abundant mesa-glomerular deposits absent in primary membranous nephropathy.The clinical manifestations,management,and prognosis of MLN differ from other types of LN(type III,IV,or mixed type III/IV+V).Although immunosuppressive therapy is often necessary for MLN,the optimal treatment regimen is yet to be determined.This review summarizes the progress in the diagnosis and treatment of MLN and discusses the selection of immunosuppressants for MLN.