Construction of an immune-related gene signature for overall survival prediction and immune infiltration in gastric cancer

BACKGROUND Treatment options for patients with gastric cancer(GC)continue to improve,but the overall prognosis is poor.The use of PD-1 inhibitors has also brought benefits to patients with advanced GC and has gradually become the new standard treatment option at present,and there is an urgent need to identify valuable biomarkers to classify patients with different characteristics into subgroups.AIM To determined the effects of differentially expressed immune-related genes(DEIRGs)on the development,prognosis,tumor microenvironment(TME),and treatment response among GC patients with the expectation of providing new biomarkers for personalized treatment of GC populations.METHODS Gene expression data and clinical pathologic information were downloaded from The Cancer Genome Atlas(TCGA),and immune-related genes(IRGs)were searched from ImmPort.DEIRGs were extracted from the intersection of the differentially-expressed genes(DEGs)and IRGs lists.The enrichment pathways of key genes were obtained by analyzing the Kyoto Encyclopedia of Genes and Genomes(KEGGs)and Gene Ontology(GO)databases.To identify genes associated with prognosis,a tumor risk score model based on DEIRGs was constructed using Least Absolute Shrinkage and Selection Operator and multivariate Cox regression.The tumor risk score was divided into high-and lowrisk groups.The entire cohort was randomly divided into a 2:1 training cohort and a test cohort for internal validation to assess the feasibility of the risk model.The infiltration of immune cells was obtained using‘CIBERSORT,’and the infiltration of immune subgroups in high-and low-risk groups was analyzed.The GC immune score data were obtained and the difference in immune scores between the two groups was analyzed.RESULTS We collected 412 GC and 36 adjacent tissue samples,and identified 3627 DEGs and 1311 IRGs.A total of 482 DEIRGs were obtained.GO analysis showed that DEIRGs were mainly distributed in immunoglobulin complexes,receptor ligand activity,and signaling receptor activators.KEGG pathway analysis showed that the top three DEIRGs enrichment types were cytokine-cytokine receptors,neuroactive ligand receptor interactions,and viral protein interactions.We ultimately obtained an immune-related signature based on 10 genes,including 9 risk genes(LCN1,LEAP2,TMSB15A mRNA,DEFB126,PI15,IGHD3-16,IGLV3-22,CGB5,and GLP2R)and 1 protective gene(LGR6).Kaplan-Meier survival analysis,receiver operating characteristic curve analysis,and risk curves confirmed that the risk model had good predictive ability.Multivariate COX analysis showed that age,stage,and risk score were independent prognostic factors for patients with GC.Meanwhile,patients in the low-risk group had higher tumor mutation burden and immunophenotype,which can be used to predict the immune checkpoint inhibitor response.Both cytotoxic T lymphocyte antigen4+and programmed death 1+patients with lower risk scores were more sensitive to immunotherapy.CONCLUSION In this study a new prognostic model consisting of 10 DEIRGs was constructed based on the TME.By providing risk factor analysis and prognostic information,our risk model can provide new directions for immunotherapy in GC patients.

Progress on immuno-microenvironment and immune-related therapies in patients with pseudomyxoma peritonei

Pseudomyxoma peritonei(PMP) is an indolent malignant syndrome. The standard treatment for PMP is cytoreductive surgery combined with intraperitoneal hyperthermic chemotherapy(CRS + HIPEC). However, the high recurrence rate and latent clinical symptoms and signs are major obstacles to further improving clinical outcomes. Moreover, patients in advanced stages receive little benefit from CRS + HIPEC due to widespread intraperitoneal metastases. Another challenge in PMP treatment involves the progressive sclerosis of PMP cell-secreted mucus, which is often increased due to activating mutations in the gene coding for guanine nucleotide-binding protein alpha subunit(GNAS). Consequently, the development of other PMP therapies is urgently needed. Several immune-related therapies have shown promise, including the use of bacterium-derived non-specific immunogenic agents, radioimmunotherapeutic agents, and tumor cell-derived neoantigens, but a well-recognized immunotherapy has not been established. In this review the roles of GNAS mutations in the promotion of mucin secretion and disease development are discussed. In addition, the immunologic features of the PMP microenvironment and immune-associated treatments are discussed to summarize the current understanding of key features of the disease and to facilitate the development of immunotherapies.

Immune-related gene characteristics:A new chapter in precision treatment of gastric cancer

Gastric cancer ranks as the sixth most prevalent cancer worldwide.In recent research within the realm of gastric cancer treatment,the identification and application of immune-related genetic features have emerged as groundbreaking advancements.The study by Ma et al,which developed a prognostic model based on 10 genes,categorizes patients into high and low-risk groups to predict their responsiveness to immune checkpoint inhibitor therapy.This research underscores the potential of immune-related genes as biomarkers for personalized treatment,offering insights into tumor mutation burden and immune phenotype scores.We advocate for further validation,understanding of biological mechanisms,and integration of diverse datasets to enhance the model's predictive accuracy and clinical application,marking a significant step towards personalized and precise treatment for gastric cancer.

Ilizarov technique for treating elbow stiffness caused by myositis ossificans:A case report

BACKGROUND Myositis ossificans(MO)is a rare disease involving the formation of bone outside the musculoskeletal system.While surgical intervention is the main treatment approach,preventing recurrence and standardized rehabilitation are also crucial.Here,we present a surgical strategy to prevent the recurrence of MO.CASE SUMMARY A 28-year-old female patient was admitted for the first time for a comminuted fracture of the left olecranon.However,incorrect postoperative rehabilitation resulted in the development of elbow joint stiffness with ectopic ossification,causing a loss of normal range of motion.The patient was diagnosed with MO based on physical examination,X-ray findings,and clinical presentation.We devised a surgical strategy to remove MO,followed by fixation with an Ilizarov frame,and implemented a scientifically reasonable rehabilitation plan.The surgery lasted for 3 h with an estimated blood loss of 45 mL.A drainage tube was placed after surgery,and fluid was aspirated through ultrasound-guided puncture.The patient experienced a significant reduction in joint stiffness after surgery.In the final follow-up at 9 mouths,there was evident improvement in the range of motion of the elbow joint,and no other symptoms were reported.CONCLUSION The Ilizarov frame is an advantageous surgical technique for facilitating rehabilitation after MO removal.It offers benefits such as passive recovery,individualized treatment,and prompt recovery.

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio:Markers predicting immune-checkpoint inhibitor efficacy and immune-related adverse events

We conducted a comprehensive review of existing prediction models pertaining to the efficacy of immune-checkpoint inhibitor(ICI)and the occurrence of immune-related adverse events(irAEs).The predictive potential of neutrophil-to-lymphocyte ratio(NLR)and platelet-to-lymphocyte ratio(PLR)in determining ICI effectiveness has been extensively investigated,while limited research has been conducted on predicting irAEs.Furthermore,the combined model incor-porating NLR and PLR,either with each other or in conjunction with additional markers such as carcinoembryonic antigen,exhibits superior predictive capabilities compared to individual markers alone.NLR and PLR are promising markers for clinical applications.Forthcoming models ought to incorporate established efficacious models and newly identified ones,thereby constituting a multifactor composite model.Furthermore,efforts should be made to explore effective clinical application approaches that enhance the predictive accuracy and efficiency.

Biomarkers associated with immune-related adverse events induced by immune checkpoint inhibitors

Immune checkpoint inhibitors(ICIs)constitute a pivotal class of immunotherapeutic drugs in cancer treatment.However,their widespread clinical application has led to a notable surge in immune-related adverse events(irAEs),significantly affecting the efficacy and survival rates of patients undergoing ICI therapy.While conventional hematological and imaging tests are adept at detecting organ-specific toxicities,distinguishing adverse reactions from those induced by viruses,bacteria,or immune diseases remains a formidable challenge.Consequently,there exists an urgent imperative for reliable biomarkers capable of accurately predicting or diagnosing irAEs.Thus,a thorough review of existing studies on irAEs biomarkers is indispensable.Our review commences by providing a succinct over-view of major irAEs,followed by a comprehensive summary of irAEs biomarkers across various dimensions.Furthermore,we delve into innovative methodologies such as machine learning,single-cell RNA sequencing,multiomics analysis,and gut microbiota profiling to identify novel,robust biomarkers that can facilitate precise irAEs diagnosis or prediction.Lastly,this review furnishes a concise exposition of irAEs mechanisms to augment understanding of irAEs prediction,diagnosis,and treatment strategies.

Evidence-Based Nursing Practice of Reducing Immune-Related Skin Toxicity of Tumor Patients Guided by Sensitive Indicators

Purpose research on nursing sensitive indicators in tumor Patients application effect in immune-related skin toxicity management. Method select our hospital April to June, 202360 cases patients with immune therapy settings as the control group. August-October, 2023 60 cases the patients treated with immune therapy were the experimental group. The control group adopted regular nursing methods, while the experimental group sensitive Indicators, evidence-based give preventive care. The social situation, psychological state, physical function, quality of life score, incidence of skin toxicity caused by immune checkpoint inhibitors, moderate and above of the two groups of patients were compared. Incidence of skin toxicity. Result: experience group SAS score, SDS score higher than the control group, the difference was statistically significant (P < 0.05);The incidence of skin toxic reactions caused by immune checkpoint inhibitors and the incidence of moderate and above skin toxic reactions in the experimental group are lower than those in the control group, and the difference is statistically significant (P < 0.05). Conclusion: sensitive indicator guidance evidence-based preventive care can reduce the degree of immune-related skin toxicity, improve the psychological state and quality of life of tumor patients treated with immune therapy and reduce the incidence of adverse reactions, improve nursing quality and patient satisfaction.

Construction of an immune-related prognostic model to predict prognosis and immunotherapy in liver cancer patients with hepatitis B virus-infected

Background:Hepatocellular carcinoma(HCC)appears to be strongly associated with immune-related genes.However,immune-related genes are not well understood as a prognostic marker in HCC caused by the hepatitis B virus(HBV).The purpose of this study was to investigate the prognostic significance of immune-related genes in HBV-infected HCC.Methods:Gene expression data from 114 HBV-infected HCC and 50 normal tissues were integrated into The Cancer Genome Atlas.Differentially expressed immune-associated genes were analyzed to identify immune-associated differential genes associated with overall survival.Least Absolute Shrinkage and Selection Operator and multivariate Cox regressions were used to constructing immunoprognostic models.An independent prognostic factor analysis using multiple Cox regressions was also performed for HBV-infected HCCs.Immunocorrelation analysis markers and immune cell infiltration were also investigated.Results:We found 113 differentially expressed immune-associated genes.Immune-related differential genes were significantly correlated with the overall survival of HCC patients.We constructed an immune-based prognostic model using multivariate Cox regression analysis including seven immune-related genes.According to further analysis,immune-related prognostic factors may serve as independent prognostic indicators in the clinical setting.There is also evidence that the 7-gene prognostic model reflects the tumor immune microenvironment as a result of the risk score model and immune cell infiltration.Conclusions:As a result of our study,we screened immune-related genes for prognosis in HBV-infected HCC and developed a novel immune-based prognostic model.The research not only provides new prognostic biomarkers but also offers insight into the tumor immune microenvironment and lays the theoretical groundwork for immunotherapy.

Myositis and rhabdomyolysis in scrub typhus infection: A case report

Rationale:Fever with myositis and rhabdomyolysis is a medical emergency requiring prompt diagnosis and management.Scrub typhus associated myositis with rhabdomyolysis is rare.Patient concerns:A 36-year-old female presented with intermittent fever up to 38.6℃,jaundice and progressive weakness of all four limbs.Diagnosis:Scrub typhus associated myositis and rhabdomyolysis.Intervention:Doxycycline 100 mg twice daily and injection of ceftriaxone 1 gm twice daily along with continuous intravenous fluids.Outcome:Fever resolved with normalization of liver function and recovery of muscle power.Lessons:Presence of myositis and rhabdomyolysis is uncommon in scrub typhus;high clinical suspicion should be kept in patients with atypical manifestations of scrub typhus.

Intra-abdominal myositis ossificans-a clinically challenging disease:A case report

BACKGROUND Myositis ossificans(MO)is an uncommon disorder characterized by heterotopic ossification within soft tissues.Only a few cases of intra-abdominal MO(IMO)have been described in the literature.Histology could be difficult to understand and a wrong diagnosis could lead to an improper cure.CASE SUMMARY We herein report the case of IMO in a healthy 69-year-old man.The patient presented with an abdominal mass in the left lower quadrant.A computed tomography scan showed an inhomogeneous mass with multiple calcifications.The patient underwent radical excision of the mass.Histopathological findings were compatible with MO.Five months later the patient showed a recurrence causing hemorrhagic shock due to intractable intralesional bleeding.The patients eventually died within three months since recurrence.CONCLUSION The case described could be classified as post-traumatic MO that developed close to the previously fractured iliac bone.The subsequent surgical procedure was ineffective and the disease rapidly recurred.The misleading intraoperative diagnosis led to improper surgical treatment with a dramatic evolution.

Correlation between immune-related adverse events and long-term outcomes in pembrolizumab-treated patients with unresectable hepatocellular carcinoma:A retrospective study

BACKGROUND Although immune checkpoint inhibitor(ICI)therapy has improved the prognosis of unresectable hepatocellular carcinoma(HCC),it has also resulted in unique immune-related adverse events(irAEs).The relationship between irAE and treatment outcomes in ICI-treated unresectable HCC patients remains unknown.AIM To elucidate the correlation between immune-related toxic effects and prognosis in patients with unresectable HCC treated with pembrolizumab.METHODS From March 2019 to February 2021,a total of 190 unresectable HCC(Barcelona Clinic Liver Cancer C)patients receiving pembrolizumab treatment were retrospectively reviewed.Overall survival(OS)was the primary endpoint,while objective response rate(ORR),disease control rate(DCR),and time to progression(TTP)were secondary evaluation indexes.We assessed demographics,irAEs,and outcomes by retrospective review.RESULTS One hundred and forty-three males and 47 females were included in the study.The ORR and DCR were 12.1%(23/190)and 52.1%(99/190),respectively.The median OS was 376 d[95%confidence interval(CI):340-411 d]and the median TTP was 98 d(95%CI:75-124 d).The overall incidence of treatment-related adverse events was 72.6%(138/190)and 10.0%of them were severe irAEs(grade≥3).Child-Pugh B class,portal vein tumor thrombus,extrahepatic metastasis,and hypothyroidism were the independent risk factors for survival.Patients with hypothyroidism showed a longer OS[517 d(95%CI:423-562)vs 431 d(95%CI:412-485),P=0.011]and TTP[125 d(95%CI:89-154)vs 87 d(95%CI:61-98),P=0.004]than those without irAEs.CONCLUSION Pembrolizumab-treated patients with unresectable HCC who experienced hypothyroidism have promising ORR and durable response.Hypothyroidism,an irAE,may be used as a clinical evaluation parameter of response to ICIs in unresectable HCC.

Immune-related adverse events induced by programmed death protein-1 inhibitors from the perspective of lymphoma immunotherapy

Lymphoma,which is highly malignant,stems from lymph nodes and lymphoid tissue.Lymphoma cells express programmed death-ligand 1/2(PD-L1/PD-L2),which binds with programmed cell death 1 protein(PD-1)to establish inhibitory signaling that impedes the normal function of T cells and allows tumor cells to escape immune system surveillance.Recently,immune checkpoint inhibitor immunotherapies such as PD-1 inhibitors(nivolumab and pembrolizumab)have been introduced into the lymphoma treatment algorithm and have shown remarkable clinical efficacy and greatly improve prognosis in lymphoma patients.Accordingly,the number of lymphoma patients who are seeking treatment with PD-1 inhibitors is growing annually,which results in an increasing number of patients developing immune-related adverse events(irAEs).The occurrence of irAEs inevitably affects the benefits provided by immunotherapy,particularly when PD-1 inhibitors are applied.However,the mechanisms and characteristics of irAEs induced by PD-1 inhibitors in lymphoma need further investigation.This review article summarizes the latest research advances in irAEs during treatment of lymphoma with PD-1 inhibitors.A comprehensive understanding of irAEs incurred in immunotherapy can help to achieve better efficacy with PD-1 inhibitors in lymphoma.

Integrated bioinformatics analysis identifies immune-related epithelial-mesenchymal transition prognostic biomarkers and immune infiltrates in patients with lung adenocarcinoma

Background:Lung cancer,particularly lung adenocarcinoma(LUAD),is highly lethal.Understanding the critical interaction between epithelial-mesenchymal transition(EMT)and the immune status of patients is imperative for clinical assessment.Methods:We conducted bioinformatics analysis to identify potential immune-related EMT(iEMT)prognostic genes and explored the immune status in LUAD.Using data from The CancerGenome Atlas andGSE68465,differentially expressed genes,were identified,and a risk modelwas constructed.Cluster analysis was conducted using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways.Results:Our findings revealed 69 differentially expressed iEMT genes,with risk values demonstrating independent prognostic significance for both The Cancer Genome Atlas and GSE68465 samples.The risk value was positively correlated with tumor stage.Immune cell infiltration analysis showed a significant decrease in resting dendritic cells and an increase in CD4 memory T cells in high-risk groups with poor survival prognoses.The immunotherapy analysis revealed weak immunotherapeutic effects in the high-risk group.Conclusions:This study provides insights into potential aberrant differential iEMT genes and risk models and explores immune landscapes that inform personalized immunotherapy in patients with LUAD.

Identification of an immune-related gene-based signature to predict prognosis of patients with gastric cancer

BACKGROUND Gastric cancer(GC)is the most commonly diagnosed malignancy worldwide.Increasing evidence suggests that it is necessary to further explore genetic and immunological characteristics of GC.AIM To construct an immune-related gene(IRG)signature for accurately predicting the prognosis of patients with GC.METHODS Differentially expressed genes(DEGs)between 375 gastric cancer tissues and 32 normal adjacent tissues were obtained from The Cancer Genome Atlas(TCGA)GDC data portal.Then,differentially expressed IRGs from the ImmPort database were identified for GC.Cox univariate survival analysis was used to screen survival-related IRGs.Differentially expressed survival-related IRGs were considered as hub IRGs.Genetic mutations of hub IRGs were analyzed.Then,hub IRGs were selected to conduct a prognostic signature.Receiver operating characteristic(ROC)curve analysis was used to evaluate the prognostic performance of the signature.The correlation of the signature with clinical features and tumor-infiltrating immune cells was analyzed.RESULTS Among all DEGs,70 hub IRGs were obtained for GC.The deletions and amplifications were the two most common types of genetic mutations of hub IRGs.A prognostic signature was identified,consisting of ten hub IRGs(including S100A12,DEFB126,KAL1,APOH,CGB5,GRP,GLP2R,LGR6,PTGER3,and CTLA4).This prognostic signature could accurately distinguish patients into highand low-risk groups,and overall survival analysis showed that high risk patients had shortened survival time than low risk patients(P<0.0001).The area under curve of the ROC of the signature was 0.761,suggesting that the prognostic signature had a high sensitivity and accuracy.Multivariate regression analysis demonstrated that the prognostic signature could become an independent prognostic predictor for GC after adjustment for other clinical features.Furthermore,we found that the prognostic signature was significantly correlated with macrophage infiltration.CONCLUSION Our study proposed an immune-related prognostic signature for GC,which could help develop treatment strategies for patients with GC in the future.

Non Traumatic Myositis Ossificans Mimicking a Malignant Neoplasm: A Case Report

Myositis ossificans is a benign self limiting condition that usually related to trauma. Despite a clinically and histologically distinct entity, myositis ossificans still causes considerable difficulties in diagnosis. A 33-year-old Moroccan woman presented with a 2-month history of left inguinal inflammatory pain with limping gait, MRI examination suggested a malignant neoplasm such as soft tissue osteosarcoma. A diagnosis of myositis ossificans was made by incisional biopsy. Conservative management with clinical and radiological follow up of 19 months confirm the diagnosis. The symptoms resolved within seven months. Myositis ossificans should be considered by clinicians as a possible diagnosis for a soft tissue lesion.

Giant nontraumatic myositis ossificans in a child:A case report

BACKGROUND Nontraumatic myositis ossificans is a rare disease whose specific pathogenesis is unclear.Early diagnosis of this disease is very difficult in children because of difficulties in determining medical history and nonspecific early clinical manifestations,which may lead to the failure of timely and effective diagnosis and treatment in some patients.We report the diagnosis and treatment of a child with nontraumatic myositis ossificans and summarize the clinical characteristics and diagnosis and treatment of the disease.CASE SUMMARY An 8-year-old girl first came to our hospital for more than a week with pain in the right lower limb.There was no history of trauma or strenuous activities.On physical examination,no mass on the right thigh was found,and the movement of the right lower extremity was limited.Ultrasonography showed synovitis of the hip,and bed rest was recommended.Three days later,the child’s pain persisted and worsened,accompanied by fever and other discomforts.She came to our hospital again and a mass was found on the right thigh with redness and swelling on the surface.The images showed a soft tissue tumor on the right thigh with calcification.Routine blood tests revealed that the inflammation index was significantly increased.In case of infection,the patient was given antibiotics,and the pain was relieved soon after,without fever.However,the right thigh mass persisted and hardened.The patient underwent incision biopsy more than 1 mo later,and the postoperative pathology showed nontraumatic myositis ossificans.After approximately 9 mo of observation,the tumor still persisted,which affected the life of the child,and then resection was performed.Since follow-up,there has been no recurrence.CONCLUSION Due to the difficulty in discerning a child’s medical history and the diverse early manifestations,it is difficult to diagnose nonossifying muscle disease in children in its early stage.Measures such as timely follow-up and periodic image monitoring are conducive to early diagnosis of the disease.The disease has a certain degree of self-limitation,and it can be observed and treated first.If the tumor persists in the later stage or affects functioning,then surgery is considered.

Proposed criteria to differentiate heterogeneous eosinophilic gastrointestinal disorders of the esophagus, including eosinophilic esophageal myositis

AIM To define clinical criteria to differentiate eosinophilic gastrointestinal disorder(Eo GD) in the esophagus. METHODS Our criteria were defined based on the analyses of the clinical presentation of eosinophilic esophagitis(Eo E), subepithelial eosinophilic esophagitis(s Eo E) and eosinophilic esophageal myositis(Eo EM), identified by endoscopy, manometry and serum immunoglobulin E levels(s-Ig E), in combination with histological and polymerase chain reaction analyses on esophageal tissue samples.RESULTS In five patients with Eo E, endoscopy revealed longitudinal furrows and white plaques in all, and fixed rings in two. In one patient with s Eo E and four with Eo EM, endoscopy showed luminal compression only. Using manometry, failed peristalsis was observed in patients with Eo E and s Eo E with some variation, while Eo EM was associated with hypercontractile or hypertensive peristalsis, with elevated s-Ig E. Histology revealed the following eosinophils per high-power field values. Eo E = 41.4 ± 7.9 in the epithelium and 2.3 ± 1.5 in the subepithelium; s Eo E = 3 in the epithelium and 35 in the subepithelium(conventional biopsy); Eo EM = none in the epithelium, 10.7 ± 11.7 in the subepithelium(conventional biopsy or endoscopic mucosal resection) and 46.8 ± 16.5 in the muscularis propria(peroral esophageal muscle biopsy). Presence of dilated epithelial intercellular space and downward papillae elongation were specific to Eo E. Eotaxin-3, IL-5 and IL-13 were overexpressed in Eo E.CONCLUSION Based on clinical and histological data, we identified criteria, which differentiated between Eo E, s Eo E and Eo EM, and reflected a different pathogenesis between these esophageal Eo GDs.

Left abdominal wall proliferative myositis resection and patch repair:A case report

BACKGROUND Proliferative myositis is a rare benign tumor that is typically self-limiting and does not become malignant.It can be cured by simple resection without reported recurrence.Due to its rapid growth,hard structure and ill-defined borders,it can however be mistaken for malignant tumors such as sarcomas.CASE SUMMARY We investigate the case of a 64-year-old male with proliferative myositis of the abdominal wall,who was preoperatively administered a needle aspiration biopsy and given a simple excision and patch repair.We then compared it with other similar cases to determine the effectiveness of this treatment method.CONCLUSION Resection with follow-up observation has shown to be an effective treatment method for proliferative myositis.To avoid unnecessarily extended or destructive resection,a thorough and conclusive diagnosis is crucial,which requires adequate imaging and pathological knowledge.

Use of traditional Chinese medicine in the treatment of immune-related adverse events of cancer immunotherapy

Immune checkpoint inhibitors(ICPI)have shown considerable promise in the treatment of tumors.However,immune-related adverse events(irAEs)caused by ICPI have been reported in nearly every organ system.Whilst this represents a new challenge in the field of cancer treatment,traditional Chinese medicine(TCM)provides benefits in the treatment of irAEs.This article reviews the studies of the treatment of immune-related gastrointestinal diseases and dermatosis with TCM and introduces the collaborative efforts between China and France in the implementation of TCM for the treatment of irAEs.

Inflammatory Cytokine Secretion Status of Bone Marrow Cells and Clinical Significance in Immune-related Hematocytopenia

Objective To observe the expression of inlfammatory molecules in bone marrow immune cells of patients with immune-related hematocytopenia (IRH), and to investigate the immune mechanism and clinical signiifcance of the disease. Methods Total of 36 IRH patients were selected as observation group and 30 healthy people were taken as control group. Serum cytokines levels, activity of immunocytes and expression of HLA-DR were detected. Immune lfuorescence was applied to observe the expression state of immunologic molecules and cytokines in IRH patients. Results Serum cytokines were elevated in various degrees in observation group. Compared with the control group, the cytokines levels were significantly higher (P < 0.05). After treatement with immunosuppressive drugs, the serum levels of cytokines in observation group reduced to a level close to the control group. HLA-DR were upregulated in activated tissue basophils, eosinophils, dendritic cells (DC) and macrophages of bone marrow in IRH patients, and POX activity in these immunocytes of IRH was higher than that of the control group. Immune molecules were highly expressed in eosinophils, DC and macrophages. Conclusions It is demonstrated that antibodies or self-reactive lymphocytes were produced in IRH marrow, which would cause lesions of hemocytes, and lead to pathological process ifnally. Structure of hematopoietic cells mutated and these cells might be acted as target cells of immunocytes in the pathological process. Immunocytes could secrete inlfammatory factors and lead to immunologic injury of hemocyte.