Prognostic analysis of related factors of adverse reactions to immunotherapy in advanced gastric cancer and establishment of a nomogram model

BACKGROUND Immunotherapy for advanced gastric cancer has attracted widespread attention in recent years.However,the adverse reactions of immunotherapy and its relationship with patient prognosis still need further study.In order to determine the association between adverse reaction factors and prognosis,the aim of this study was to conduct a systematic prognostic analysis.By comprehensively evaluating the clinical data of patients with advanced gastric cancer treated by immunotherapy,a nomogram model will be established to predict the survival status of patients more accurately.AIM To explore the characteristics and predictors of immune-related adverse reactions(irAEs)in advanced gastric cancer patients receiving immunotherapy with programmed death protein-1(PD-1)inhibitors and to analyze the correlation between irAEs and patient prognosis.METHODS A total of 140 patients with advanced gastric cancer who were treated with PD-1 inhibitors in our hospital from June 2021 to October 2023 were selected.Patients were divided into the irAEs group and the non-irAEs group according to whether or not irAEs occurred.Clinical features,manifestations,and prognosis of irAEs in the two groups were collected and analyzed.A multivariate logistic regression model was used to analyze the related factors affecting the occurrence of irAEs,and the prediction model of irAEs was established.The receiver operating characteristic(ROC)curve was used to evaluate the ability of different indicators to predict irAEs.A Kaplan-Meier survival curve was used to analyze the correlation between irAEs and prognosis.The Cox proportional risk model was used to analyze the related factors affecting the prognosis of patients.RESULTS A total of 132 patients were followed up,of whom 63(47.7%)developed irAEs.We looked at the two groups’clinical features and found that the two groups were statistically different in age≥65 years,Ki-67 index,white blood cell count,neutrophil count,and regulatory T cell(Treg)count(all P<0.05).Multivariate logistic regression analysis showed that Treg count was a protective factor affecting irAEs occurrence(P=0.030).The ROC curve indicated that Treg+Ki-67+age(≥65 years)combined could predict irAEs well(area under the curve=0.753,95%confidence interval:0.623-0.848,P=0.001).Results of the Kaplan-Meier survival curve showed that progressionfree survival(PFS)was longer in the irAEs group than in the non-irAEs group(P=0.001).Cox proportional hazard regression analysis suggested that the occurrence of irAEs was an independent factor for PFS(P=0.006).CONCLUSION The number of Treg cells is a separate factor that affects irAEs in advanced gastric cancer patients receiving PD-1 inhibitor immunotherapy.irAEs can affect the patients’PFS and result in longer PFS.Treg+Ki-67+age(≥65 years old)combined can better predict the occurrence of adverse reactions.

Prognostic analysis of intramedullary ependymomas in medulla oblongata and cervical cord

Objective To analyze factors affecting operative prognosis of intramedullary ependymomas in medulla oblongata and cervical cord. Methods Thirty patients harboring intramedullary ependymomas in medulla oblongata and cervical cord were operated. The preoperative and postoperative status was taken by follow-up and

Analysis of clinicopathological features and prognostic factors of breast cancer brain metastasis

BACKGROUND Breast cancer(BC)has become the most common malignancy in women.The incidence and detection rates of BC brain metastasis(BCBM)have increased with the progress of imaging,multidisciplinary treatment techniques and the extension of survival time of BC patients.BM seriously affects the quality of life and survival prognosis of BC patients.Therefore,clinical research on the clinicopathological features and prognostic factors of BCBM is valuable.By analyzing the clinicopathological parameters of BCBM patients,and assessing the risk factors and prognostic indicators,we can perform hierarchical diagnosis and treatment on the high-risk population of BCBM,and achieve clinical benefits of early diagnosis and treatment.AIM To explore the clinicopathological features and prognostic factors of BCBM,and provide references for diagnosis,treatment and management of BCBM.METHODS The clinicopathological data of 68 BCBM patients admitted to the Air Force Medical Center,Chinese People’s Liberation Army(formerly Air Force General Hospital)from 2000 to 2022 were collected.Another 136 BC patients without BM were matched at a ratio of 1:2 based on the age and site of onset for retrospective analysis.Categorical data were subjected to χ^(2) test or Fisher’s exact probability test,and the variables with P<0.05 in the univariate Cox proportional hazards model were incorporated into the multivariate model to identify high-risk factors and independent prognostic factors of BCBM,with a hazard ratio(HR)>1 suggesting poor prognostic factors.The survival time of patients was estimated by the Kaplan-Meier method,and overall survival was compared between groups by log-rank test.RESULTS Multivariate Cox regression analysis showed that patients with stage Ⅲ/Ⅳ tumor at initial diagnosis[HR:5.58,95% confidence interval(CI):1.99–15.68],lung metastasis(HR:24.18,95%CI:6.40-91.43),human epidermal growth factor receptor 2(HER2)-overexpressing BC and triple-negative BC were more prone to BM.As can be seen from the prognostic data,52 of the 68 BCBM patients had died by the end of follow-up,and the median time from diagnosis of BC to the occurrence of BM and from the occurrence of BM to death or last follow-up was 33.5 and 14 mo,respectively.It was confirmed by multivariate Cox regression analysis that patients with neurological symptoms(HR:1.923,95%CI:1.005-3.680),with bone metastasis(HR:2.011,95%CI:1.056-3.831),and BM of HER2-overexpressing and triple-negative BC had shorter survival time.CONCLUSION HER2-overexpressing,triple-negative BC,late tumor stage and lung metastasis are risk factors of BM.The presence of neurological symptoms,bone metastasis,and molecular type are influencing prognosis factors of BCBM.

Efficacy and prognosis of adjuvant treatment of endometrial cancer with medroxyprogesterone acetate COX regression analysis

BACKGROUND Endometrial cancer is one of the most commonly diagnosed gynecological cancers worldwide,and early-stage high-risk endometrial cancer has a poor prognosis.Adjuvant treatments after surgery,such as chemotherapy and radiotherapy,have been widely used in clinical practice to improve patient survival.Medroxyprogesterone acetate is a synthetic progestogen that has been reported to have potential anticancer effects in endometrial cancer.However,its efficacy,safety,and longterm prognostic benefits as an adjuvant treatment for endometrial cancer remain controversial.Therefore,this study aimed to observe the efficacy and prognostic impact of adjuvant medroxyprogesterone acetate treatment in patients with earlystage high-risk endometrial cancer and evaluate its safety.AIM To observe the efficacy and prognosis of adjuvant treatment of endometrial cancer with medroxyprogesterone acetate and to evaluate its safety.METHODS We collected the clinical data of 200 patients with early-stage high-risk endometrial cancer who were admitted to the Department of Obstetrics and Gynecology of our hospital from January 2018 to December 2022.The control group(100 patients)underwent conventional surgical treatment,and the study group(100 patients)was administered adjuvant medroxyprogesterone acetate tablets on top of the control group.The Kaplan-Meier curve analysis and log-rank test were performed to determine the possible factors influencing the 5-year cumulative survival rate in the patients.The Cox regression analysis was performed to identify the factors influencing the survival prognosis of endometrial cancer.RESULTS According to the Cox regression analysis,age[hazard ratio(HR)=4.636,95%confidence interval(95%CI):1.411-15.237],pathological type(HR=6.943,95%CI:2.299-20.977),molecular typing(HR=5.789,95%CI:3.305-10.141),and myometrial infiltration(HR=5.768,95%CI:1.898-17.520)were factors influencing the prognosis of patients with early-stage high-risk endometrial cancer.CONCLUSION Age,pathological type,molecular typing,and myometrial infiltration were all relevant factors affecting the prognosis of early-stage high-risk endometrial cancer.The potential long-term prognostic benefit of adjuvant postoperative radiotherapy in patients with early-stage high-risk endometrial cancer is worthy of clinical consideration.

Clinical features and prognostic analysis of high-risk acute promyelocytic leukemia patients

<正>Objective To investigate the clinical features and outcomes of high-risk acute promyelocytic leukemia(APL)patients.Methods A retrospective analysis was conducted to compare the clinical characteristics and prognosis of 118 high-risk APL patients(WBC≥10×10~9/L)and 234 low and intermedia-risk patients(WBC<10×10~9/L)from January 2003 to April 2015。

Mechanisms and potential applications of COPS6 in pan-cancer therapy

The COP9 signalosome subunit 6(COPS6)is abnormally overexpressed in many malignancies,yet its precise role in carcinogenesis is unknown.To gain a better understanding of COPS6's role,the authors conducted a pan-cancer analysis using various bioinformatics techniques such as differential expression patterns,prognostic value,gene mutations,immune infiltration,correlation analysis,and functional enrichment assessment.Results showed that COPS6 was highly correlated with prognosis,immune cell infiltration level,tumor mutation burden,and microsatellite instability in patients with a range of tumor types.This suggests that COPS6 may be a potential target for cancer treatment.Overall,this research provides insight into COPS6's role in cancer development and its potential therapeutic applications.

Computational exploration of the significance of COPS6 in cancer:Functional and clinical relevance across tumor types

BACKGROUND The COP9 signalosome subunit 6(COPS6)has been implicated in cancer progression,while its precise role in most types of cancer remains elusive.AIM To investigate the functional and clinical relevance of COPS6 across various tumor types using publicly available databases.METHODS We used R software and online analysis databases to analyze the differential expression,prognosis,mutation and related functions of COPS6 in pan-cancer.RESULTS Differential expression analysis and survival analysis demonstrated that COPS6 was highly expressed and associated with high-risk profiles in the majority of cancer types.Possible associations between COPS6 expression level and prognostic outcomes were found using data from public databases.Mutational analysis revealed that missense mutations were the predominant type of COPS6 mutation.Additionally,positive correlations were identified between COPS6 expression level and tumor mutational burden and microsatellite instability in most types of cancer.Immune infiltration analysis demonstrated a negative correlation between COPS6 expression level and CD8+T cell infiltration in certain types of cancer.The correlation between COPS6 expression level and cancerassociated fibroblast infiltration exhibited heterogeneity,in which a positive correlation was found in head and neck squamous cell carcinoma and tenosynovial giant cell tumor,and a negative correlation was identified in diffuse large B-cell lymphoma and thymoma.The correlation between COPS6 expression level and macrophage infiltration was closely related to macrophage type.Gene co-expression and enrichment analysis highlighted transcription elongation factor B polypeptide 2 and G protein pathway suppressor 1 were significantly and positively associated with COPS6 expression level.These genes were predominantly involved in processes,such as ubiquitin-mediated proteolysis and human immunodeficiency virus 1 infection.CONCLUSION In conclusion,this study systematically explored the significance of COPS6 across different tumor types,providing a solid foundation for considering COPS6 as a novel biomarker in cancer research.

The clinical,radiological and prognostic factor analysis of medullary infarction

Objective To investigate the clinical and radiological features of medullary infarction(MI),and to compare the clinical characteristics of lateral medullary infarction(LMI)and medial medullary infarction(MMI).Methods Patients diagnosed as acute MI who were treated from January 2009 to December 2014 in Department of Neurology,Peking University Third Hospital。

Treatment outcomes of occult breast carcinoma and prognostic analyses

Background The surgical management of occult breast cancer is controversial.We compared the outcomes of different treatments of occult breast cancer and evaluated the potential prognostic factors for overall survival and recurrence.Methods We retrospectively reviewed 77 patients who presented to our hospital from 1968 to 2011 with a diagnosis of occult breast cancer.Patients were divided into three groups：42 patients （63％） were treated with modified radical mastectomy＋axillary lymph node dissection （ALND）,16 patients （24％） were treated with ALND＋postoperative radiotherapy,and 9 patients （13％） with only ALND.Survival analyses were undertaken to compare the efficacy of these three treatments.Results Of the 77 patients with occult breast cancer,2 patients were lost to follow-up and 8 patients refused surgical treatment：67 patients （90.4％） were included in this analysis.The median follow-up was 62.2 （0.6-328.0）months.Kaplan-Meier analyses showed no significant difference in overall survival and recurrence-free survival between the three groups （P=0.494 and 0.397,respectively）.The prevalence of local recurrence was 11.9％ for the mastectomy＋ALND,18.8％ for ALND＋radiotherapy,and 11.1％ for ALND-only groups,and those for distant recurrence were 2.4％,12.5％,and 11.1％,respectively.Compared with progesterone receptor-negative subjects,progesterone receptor-positive patients had better overall survival and lower recurrence rates （P=0.057 and 0.062,respectively）.Conclusions There was no significant difference in outcomes between mastectomy and breast-preserving surgery.Expression of the progesterone receptor should be taken into account when evaluating the prognosis of occult breast cancer.

Genomics-based Approach and Prognostic Stratification Significance of Gene Mutations in Intermediate-risk Acute Myeloid Leukemia

Objective： Intermediate-risk acute myeloid leukemia （IR-AML）, which accounts for a substantial number of AML cases, is highly heterogeneous. We systematically summarize the latest research progress on the significance ofgene mutations for prognostic stratification of IR-AML. Data Sources： We conducted a systemic search from the PubMed database up to October, 2014 using various search terms and their combinations including IR-AML, gene mutations, mutational analysis, prognosis, risk stratification, next generation sequencing （NGS）. Study Selection： Clinical or basic research articles on NGS and the prognosis of gene mutations in 1R-AML were included. Results： The advent of the era of whole-genome sequencing has led to the discovery of an increasing number of molecular genetics aberrations that involved in leukemogenesis, and some of them have been used for prognostic risk stratification. Several studies have consistently identified that some gene mutations have prognostic relevance, however, there are still many controversies for some genes because of lacking sufficient evidence. In addition, tumor cells harbor hundreds of mutated genes and multiple mutations often coexist, therefore, single mutational analysis is not sufficient to make accurate prognostic predictions. The comprehensive analysis of multiple mutations based on sophisticated genomic technologies has raised increasing interest in recent years. Conclusions： NGS represents a pioneering and helpful approach to prognostic risk stratification of 1R-AML patients. Further large-scale studies for comprehensive molecular analysis are needed to provide guidance and a theoretical basis for IR-AML prognostic stratification and clinical management.

A novel testability model for health management of heading attitude system

Prognostics and health management （PHM） is very important to guarantee the reliability and safety of aerospace systems, and sensing and test are the precondition of PHM. Integrating design for testability into early design stage of system early design stage is deemed as a fundamental way to improve PHM performance, and testability model is the base of testability analysis and design. This paper discusses a hierarchical model-based approach to testability modeling and analysis for heading attitude system health management. Quantified directed graph, of which the nodes represent components and tests and the directed edges represent fault propagation paths, is used to describe fault-test dependency, and quantitative testability information is assigned to nodes and directed edges. The fault dependencies between nodes can be obtained by functional fault analysis methodology that captures the physical architecture and material flows such as energy, heat, data, and so on. By incorporating physics of failure models into component, the dynamic process of a failing or degrading component can be projected onto system behavior, i.e., system symptoms. Then, the analysis of extended failure modes, mechanisms and effects is utilized to construct fault evolution-test dependency. Using this integrated model, the designers and system analysts can assess the test suite＇s fault detectability, fault isolability and fault predictability. And heading attitude system application results show that the proposed model can support testability analysis and design for PHM very well.