Advances on Senescence-associated secretory phenotype regulated by circular RNAs in tumors.

The components that comprise the senescence-associated secretory phenotype (SASP) include growth factors, proteases, chemokines, cytokines, and bioactive lipids. It drives secondary aging and disrupts tissue homeostasis, ultimately leading to tissue repair and regeneration loss. It has a two-way regulatory effect on tumor cells, resisting cancer occurrence and promoting its progression. A category of single-stranded circular non-coding RNA molecules known as circular RNAs (circRNAs) carries out a series of cellular activities, including sequestering miRNAs and modulating gene editing and expression. Research has demonstrated that a large number of circRNAs exhibit aberrant expression in pathological settings, and play a part in the onset and progress of cancer via modulating SASP factors. However, the research related to SASP and circRNAs in tumors is still in its infancy at this stage. This review centers on the bidirectional modulation of SASP and the role of circRNAs in regulating SASP factors across different types of tumors. The aim is to present novel perspectives for the diagnosis and therapeutic management of malignancies.

Construction and validation of a RARRES3-based prognostic signature related to the specific immune microenvironment of pancreatic cancer.

Background: Tumor immune microenvironment (TiME) is prognostically instructive in Pancreatic adenocarcinoma (PAAD). However, the potential value of TiME-related genes in the individualized immunotherapy of PAAD has not been clarified. Methods: Correlation between Immune-Related Genes (IRGs) and immune-related transcription factors (TFs) was performed to prove the immune correlation of selected genes. Immune-related molecular subtypes were identified by consensus clustering. The TiME-score, an immune microenvironment-related prognostic signature for PAAD, was constructed using minimum absolute contraction and selection operator regression (Lasso-Cox). The International Cancer Genome Consortium (ICGC) dataset validated the reliability of TiME-score as external validation. Single-cell samples from GSE197177 confirmed microenvironment differences of TiME-score hub genes between tumor and its paracancer tissues. Then, RARRES3, a hub gene in TiME-score, was further analyzed about its upstream TP53 mutation and the specific immune landscape of itself in transcriptome and Single-cell level. Eventually, TiME-score were validated in different therapeutic cohorts of PAAD mice models. Results: A 14-genes PAAD immune-related risk signature, TiME-score, was constructed based on IRGs. The differences of TiME-score hub genes in single-cell samples of PAAD cancer tissues and adjacent tissues were consistent with the transcriptome. Single-cell samples of cancer tissues showed more pronounced immune cell infiltration. The upstream mutation factor TP53 of RARRES3 was significantly enriched in immune-related biological processes. High RARRES3 expression was correlated with a worse prognosis and high macrophages M1 infiltration. Additionally, the immunohistochemistry of hub genes AGT, DEFB1, GH1, IL20RB, and TRAF3 in different treatment cohorts of mice PAAD models were consistent with the predicted results. The combination of immunotherapy, chemotherapy and targeted therapy has shown significantly better therapeutic effects than single drug therapy in PAAD. Conclusion: TiME-score, as a prognostic signature related to PAAD-specific immune microenvironment constructed based on RARRES3, has predictive value for prognosis and the potential to guide individualized immunotherapy for PAAD patients.

Comparison of different treatment regimens and analysis of prognostic factors in secondary hemophagocytic lymphohistiocytosis in adults: A single-center retrospective study.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease caused by immune hyperactivation. The overall survival (OS) of adults with secondary HLH remains suboptimal and new treatment strategies are needed. OBJECTIVES: This study aimed to compare the efficacy of different regimens in the treatment of secondary HLH in adults and analyze the prognostic factors affecting patient survival. MATERIAL AND METHODS: The clinical data of 245 adults with secondary HLH admitted to our hospital from January 2016 to October 2021 were analyzed retrospectively. The patients were divided into 3 groups according to different treatment regimens: corticosteroids therapy + chemotherapy + supportive treatment group (JHZ group), chemotherapy + supportive treatment group (HZ group) and corticosteroids therapy + supportive treatment group (JZ group). The clinical efficacy was compared among the 3 groups after treatment, and progression-free survival (PFS) and overall survival (OS) were calculated. Additionally, risk factors associated with prognosis were also analyzed with Cox regression analysis. RESULTS: The objective response rate (ORR) in the JHZ group was higher than that in the HZ group and JZ group, but there was no significant difference between the 3 groups. Also, the patients in the JHZ group had the longest OS and median PFS. Further Cox regression analysis suggested that hyperbilirubinemia was an independent risk factor for OS in secondary HLH patients. CONCLUSIONS: A combination of corticosteroids therapy, chemotherapy and supportive therapy is superior to the other 2 regimens in the clinical benefit in the treatment of secondary HLH in adults, and thus may be a preferred and feasible treatment regimen. Moreover, hyperbilirubinemia was a risk factor for prognosis that has crucial guiding significance for clinical treatment of patients with secondary HLH.

Ovarian cancer with intestinal wall invasion and hyperamylasemia: a case report.

Numerous studies have suggested a robust association between amylase and ovarian cancer. however, few amylase-producing ovarian cancers have been reported because amylase is a rare product of ovarian cancer. A case of an elderly female patient with an upper abdominal unfitness, intestinal wall along with uterine adnexal invasion, and high serum and urinary amylase is summarized in this article. The patient was initially suspected of having a gastrointestinal tumor. Initial laboratory findings showed markedly significantly raised serum and urinary amylase levels. Imaging showed invasion of the intestinal wall and uterine adnexa, and histology of the specimen taken through the abdominal wall lump and electron colonoscopy showed ovarian cancer. The patient's blood amylase levels decreased to normal after 4 cycles of neoadjuvant chemotherapy with paclitaxel and carboplatin. Following this, she underwent interval debulking surgery, which included total hysterectomy, bilateral adnexectomy, great omentectomy, appendectomy, resection of pelvic and abdominal lesions, and partial rectal resection. Postoperative pathology and immunohistochemistry staining confirmed a diagnosis of high-grade serous ovarian cancer. This case suggests that in female patients, hyperamylasemia may indicate the presence of ovarian cancer. It is necessary to perform a multisite, multipoint histologic examination to identify the tumor's origin in patients with multiple sites of invasion.

Advances in hyperbaric oxygen to promote immunotherapy through modulation of the tumor microenvironment.

Hyperbaric oxygen therapy is a relatively safe treatment method that has been used for a long time in the clinic. It has been proven that it can enhance the sensitivity of radiotherapy and photodynamic therapy for cancer. However, there are few studies on hyperbaric oxygen and immunotherapy. In this article, we summarize that hyperbaric oxygen therapy regulates the tumor microenvironment through various pathways such as improving tumor hypoxia, targeting hypoxia-inducing factors, and generating reactive oxygen species. The change in the tumor microenvironment ultimately affects the curative effect of immunotherapy. Therefore, hyperbaric oxygen can influence immunotherapy by regulating the tumor microenvironment, providing a direction for the future development of immunotherapy.

Development and validation of cuproptosis-related lncRNAs associated with pancreatic cancer immune microenvironment based on single-cell.

Background: Cuproptosis, a novel mode of cell death associated with the tricarboxylic acid (TCA) cycle, is relevant to the development of cancer. However, the impact of single-cell-based Cuproptosis-associated lncRNAs on the Tumor immune microenvironment (TIME) of Pancreatic adenocarcinoma (PAAD) and its potential value for individualized immunotherapy has not been clarified. Methods: 14 immune-related CRGs were screened by exploring the interaction between differentially expressed Immune-Related Genes (IRGs) and Cuproptosis-Related Genes (CRGs) in PAAD. Next, the expression amount and expression distribution of CRGs in single-cell samples were analyzed by focusing on 7-CRGs with significant expressions. On the one hand, MAP2K2, SOD1, and VEGFA, which were significantly differentially expressed between PAAD sites and normal tissues adjacent to them, were subjected to immunohistochemical validation and immune landscape analysis. On the other hand, from these 7-CRGs, prognostic signatures of lncRNAs were established by co-expression and LASSO-COX regression analysis, and their prognostic value and immune relevance were assessed. In addition, this study not only validated the hub CRGs and the lncRNAs constituting the signature in a PAAD animal model treated with immunotherapy-based combination therapy using immunohistochemistry and qRT-PCR but also explored the potential value of the combination of targeted, chemotherapy and immunotherapy. Results: Based on the screening of 7-CRGs significantly expressed in a PAAD single-cell cohort and their co-expressed Cuproptosis-Related lncRNAs (CRIs), this study constructed a prognostic signature of 4-CRIs named CIR-score. A Nomogram integrating the CIR-score and clinical risk factors was constructed on this basis to predict the individualized survival of patients. Moreover, high and low-risk groups classified according to the median of signatures exhibited significant differences in clinical prognosis, immune landscape, bioenrichment, tumor burden, and drug sensitivity. And the immunohistochemical and qRT-PCR results of different mouse PAAD treatment strategies were consistent with the trend of inter-group variability in drug sensitivity of hub CRGs and CIR-score. The combination of immunotherapy, targeted therapy, and chemotherapy exhibited a better tumor suppression effect. Conclusion: CIR-score, as a Cuproptosis-related TIME-specific prognostic signature based on PAAD single cells, not only predicts the prognosis and immune landscape of PAAD patients but also provides a new strategy for individualized immunotherapy-based combination therapy.

Factors impacting the benefits and pathogenicity of Th17 cells in the tumor microenvironment.

Tumor development is closely associated with a complex tumor microenvironment, which is composed of tumor cells, blood vessels, tumor stromal cells, infiltrating immune cells, and associated effector molecules. T helper type 17 (Th17) cells, which are a subset of CD4+ T cells and are renowned for their ability to combat bacterial and fungal infections and mediate inflammatory responses, exhibit context-dependent effector functions. Within the tumor microenvironment, different molecular signals regulate the proliferation, differentiation, metabolic reprogramming, and phenotypic conversion of Th17 cells. Consequently, Th17 cells exert dual effects on tumor progression and can promote or inhibit tumor growth. This review aimed to investigate the impact of various alterations in the tumor microenvironment on the antitumor and protumor effects of Th17 cells to provide valuable clues for the exploration of additional tumor immunotherapy strategies.

Association of Prefrailty and Frailty With All-Cause Mortality, Acute Exacerbation, and Hospitalization in Patients With Chronic Obstructive Pulmonary Disease: A Meta-Analysis.

OBJECTIVE: To evaluate the impact of prefrailty and frailty on all-cause mortality, acute exacerbation, and all-cause hospitalization in patients with chronic obstructive pulmonary disease (COPD). DESIGN: Meta-analysis. SETTING AND PARTICIPANTS: Two authors independently searched PubMed, Web of Science, and Embase databases until December 27, 2022，to identify studies that reported the predictive value of prefrailty and frailty in COPD patients. MEASUREMENTS: All-cause mortality, acute exacerbation, and all-cause hospitalization. RESULTS: Ten studies reporting on 11 articles enrolling 13,203 patients with COPD were included. The prevalence of frailty ranged from 6.0% to 51%. When compared with nonfrailty, the pooled adjusted hazard ratio (HR) of all-cause mortality was 1.48 (95% CI 0.92-2.40) for prefrailty and 2.64 (95% CI 1.74-4.02) for frailty, respectively. The pooled adjusted odds ratio (OR) of all-cause hospitalization was 1.35 (95% CI 1.05-1.74) for prefrailty and 1.65 (95% CI 1.05-2.61) for frailty. In addition, frailty significantly predicted all acute exacerbation (OR 2.20, 95% CI 1.26-3.81) but not moderate to severe acute exacerbation (OR 1.42, 95% CI 0.94-2.17) in patients with stable COPD. However, the pooled results of all-cause hospitalization were not reliable in leave-1-out sensitivity analyses. CONCLUSIONS AND IMPLICATIONS: Frailty significantly predicts all-cause mortality in patients with COPD, even after adjustment for common confounding factors. Assessment of frail status in COPD patients may improve secondary prevention and allow early intervention. However, future studies are warranted to validate the impact of frailty defined by a standardized definition of frailty on acute exacerbation and all-cause hospitalization.

Identification of RNA Methylation-Related lncRNAs Signature for Predicting Hot and Cold Tumors and Prognosis in Colon Cancer.

N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), and 7-methylguanosine (m7G) are the major forms of RNA methylation modifications, which are closely associated with the development of many tumors. However, the prognostic value of RNA methylation-related long non-coding RNAs (lncRNAs) in colon cancer (CC) has not been defined. This study summarised 50 m6A/m1A/m5C/m7G-related genes and downloaded 41 normal and 471 CC tumor samples with RNA-seq data and clinicopathological information from The Cancer Genome Atlas (TCGA) database. A total of 1057 RNA methylation-related lncRNAs (RMlncRNAs) were identified with Pearson correlation analysis. Twenty-three RMlncRNAs with prognostic values were screened using univariate Cox regression analysis. By consensus clustering analysis, CC patients were classified into two molecular subtypes (Cluster 1 and Cluster 2) with different clinical outcomes and immune microenvironmental infiltration characteristics. Cluster 2 was considered to be the "hot tumor" with a better prognosis, while cluster 1 was regarded as the "cold tumor" with a poorer prognosis. Subsequently, we constructed a seven-lncRNA prognostic signature using the least absolute shrinkage and selection operator (LASSO) Cox regression. In combination with other clinical traits, we found that the RNA methylation-related lncRNA prognostic signature (called the "RMlnc-score") was an independent prognostic factor for patients with colon cancer. In addition, immune infiltration, immunotherapy response analysis, and half-maximum inhibitory concentration (IC50) showed that the low RMlnc-score group was more sensitive to immunotherapy, while the high RMlnc-score group was sensitive to more chemotherapeutic agents. In summary, the RMlnc-score we developed could be used to predict the prognosis, immunotherapy response, and drug sensitivity of CC patients, guiding more accurate, and personalized treatment regimens.

Integrated Analysis of Necroptosis-Related Genes for Prognosis, Immune Microenvironment Infiltration, and Drug Sensitivity in Colon Cancer.

Background: Necroptosis, is intimately linked to tumor development and prognosis and has been considered as a target for anticancer therapy. However, the role of necroptosis-related genes (NRGs) in colon cancer is unclear. Methods: In the present study, we screened 76 NRGs from previous studies and described the landscape of transcriptomic and genetic variation of NRGs in colon cancer (CC) patient samples. Molecular subtypes of necroptosis in colon cancer were identified by clustering analysis, and these molecular subtypes were linked to patient prognosis and TME cell infiltration characteristics. Then, the NRS-score for predicting overall survival (OS) was built based on the TCGA database and validated in the GSE39582 cohort for its predictive power in CC patients. Besides, the ESTIMATE and CIBERSORT algorithms were applied to explore the relationship between NRS-score and tumor immune microenvironment. Results: We identified two molecular subtypes associated with necroptosis in CC, which have diverse prognosis and immune microenvironment characteristics. Based on the differentially expressed genes between the two molecular subtypes, we further developed a necroptosis risk score signature, referred to as NRS-score. High NRS-score was associated with poor prognosis in CC through immunosuppressive microenvironment and immune escape mechanisms. The nomogram based on NRS-score showed excellent ability to predict prognosis. In addition, NRS-score presented a positive correlation with tumor mutational burden (TMB) and immune checkpoint blockade (ICB) expression and was closely correlated with multiple anticancer agent susceptibility. Conclusion: This work revealed a close relationship between necroptosis and the prognosis and immune microenvironment of colon cancer. The NRS-score based on the 8-gene signature may be used to predict the sensitivity of immunotherapy and chemotherapy in colon cancer patients, and provides a foundation for future studies targeting necroptosis and its immune microenvironment.

Characteristics and prognostic value of pleural effusion in secondary hemophagocytic lymphohistiocytosis.

The clinical features of patients with secondary hemophagocytic lymphohistiocytosis (sHLH) complicated with pleural effusion have rarely been evaluated. We retrospectively analyzed 203 patients newly diagnosed with sHLH from July 2015 to July 2019 according to the HLH-2004 protocol. Baseline characteristics, laboratory results, and imaging were reviewed. Pleural effusion was found in 58.6% of the studied sHLH population, and characteristic imaging findings were minimal volume and bilaterality. Patients with pleural effusion had lower PLT counts, HB levels and ALB levels as well as higher sCD25 levels than those without pleural effusion (all p values < 0.05). Multivariate analyses showed that lg(sCD25) and PLT ≤ 65 × 109/L were significant risk factors for developing pleural effusion in sHLH. Regarding prognostic value, survival analysis showed a lower survival probability for patients with pleural effusion than for those without pleural effusion (median OS, 90 vs. 164 days, p = 0.028). In multivariate analysis, pleural effusion was an independent prognostic factor for overall survival (OS) (HR 2.68; 95% CI 1.18-6.11, p = 0.019). Pleural effusion is frequently found in patients with sHLH and is associated with greater inflammation and worse outcomes.

The prevalence and prognosis of hyponatraemia in non-Hodgkin lymphoma-associated hemophagocytic lymphohistiocytosis.

Non-Hodgkin lymphoma associated hemophagocytic lymphohistiocytosis (NHL-HLH) in adult secondary HLH is a common and universally highly lethal critical disorder. Hyponatraemia is the most common electrolyte disorder in the critical illness setting and acts as a negative prognostic factor. The aim of our study was to evaluate the prognostic role of hyponatraemia among patients with NHL-HLH. The results showed that 81 (52.9%) patients had hyponatraemia. After a median follow up 47 (range 14-180) days, there were 72 (88.9%) cumulative deaths in hyponatraemia group while 50 (69.4%) in normonatremia group. After adjustment for confounders, multivariate analysis revealed that hyponatraemia was an independent prognostic factor for OS (HR:1.51, 95% CI: 1.03-2.20; p = 0.033). Restricted cubic spline confirmed a linear and positive association between serum sodium and the risk of mortality. Hyponatraemia is relatively frequent in NHL-HLH. As a readily available biomarker in clinical routine, it was a promising prognostic predictor for NHL-HLH.

Preoperative Serum Prealbumin Level and Adverse Prognosis in Patients With Hepatocellular Carcinoma After Hepatectomy: A Meta-Analysis.

BACKGROUND: Prealbumin is a sensitive indicator of liver function and nutritional status. OBJECTIVES: This meta-analysis aimed to examine the association of the serum prealbumin level with the prognosis of patients with hepatocellular carcinoma (HCC) undergoing hepatectomy. METHODS: We comprehensively searched the PubMed, Embase, Wanfang, China Academic Journals (CNKI), and SinoMed databases up to September 1, 2021. Eligible studies should report the association of the serum prealbumin level with prognosis and provide the multivariable-adjusted risk estimates of the outcomes of interest in HCC patients undergoing hepatectomy. RESULTS: A total of 11 studies with 7,442 HCC patients were identified and analyzed. Meta-analysis of a fixed effects model showed that a low serum prealbumin level was associated with poor overall survival [hazard ratio (HR) = 1.54, 95% confidence interval (CI) = 1.42-1.68], recurrence-free survival (HR = 1.34, 95% CI = 1.17-1.52), and a higher risk of postoperative hepatic insufficiency (HR = 2.21; 95% CI = 1.36-3.60) in HCC patients. Sensitivity and subgroup analyses confirmed the robustness of low serum prealbumin in predicting poor overall survival. CONCLUSIONS: This meta-analysis indicated that a low preoperative serum prealbumin level was significantly associated with adverse prognosis in HCC patients undergoing hepatectomy.

Predictive Value of Geriatric Nutritional Risk Index in Patients With Coronary Artery Disease: A Meta-Analysis.

Background: Low Geriatric Nutritional Risk Index has been identified as an index of impaired nutritional state. The objective of the meta-analysis was to assess the association of the Geriatric Nutritional Risk Index (GNRI) with adverse outcomes in patients with coronary artery disease (CAD). Methods: Relevant studies were identified by comprehensively searching PubMed and Embase databases in May 2021. Studies assessing the association of GNRI with all-cause mortality or major adverse cardiovascular events (MACEs) in patients with CAD were included. The predictive value of GNRI was summarized by pooling multivariable adjusted risk ratios (RR) with 95% confidence intervals (CI) per GNRI point decrease or the lowest vs. the highest GNRI group. Results: A total of eight studies involving 9277 patients with CAD were analyzed. Meta-analysis showed that the lowest GNRI was associated with a higher risk of all-cause mortality (RR 2.10; 95% CI 1.68-2.63) and MACEs (RR 2.84; 95% CI 1.56-5.16), respectively. Furthermore, per point decrease in GNRI was associated with 8 and 10% additional risk of all-cause mortality and MACEs. Subgroup analysis indicated that the value of low GNRI in predicting all-cause mortality was not affected by subtype of patients or follow-up duration. Conclusion: Low GNRI score at baseline was associated with a higher risk of all-cause mortality and cardiovascular events in patients with CAD. The nutritional state estimated by the GNRI score could provide important predictive information in patients with CAD.

Circular RNAs' cap-independent translation protein and its roles in carcinomas.

Circular RNAs a kind of covalently closed RNA and widely expressed in eukaryotes. CircRNAs are involved in a variety of physiological and pathological processes, but their regulatory mechanisms are not fully understood. Given the development of the RNA deep-sequencing technology and the improvement of algorithms, some CircRNAs are discovered to encode proteins through the cap-independent mechanism and participate in the important process of tumorigenesis and development. Based on an overview of CircRNAs, this paper summarizes its translation mechanism and research methods, and reviews the research progress of CircRNAs translation in the field of oncology in recent years. Moreover, this paper aims to provide new ideas for tumor diagnosis and treatment through CircRNAs translation.

The Interaction Between N6-Methyladenosine Modification and Non-Coding RNAs in Gastrointestinal Tract Cancers.

N6-methyladenosine (m6A) is the most common epigenetic modification of eukaryotic RNA, which can participate in the growth and development of the body and a variety of physiological and disease processes by affecting the splicing, processing, localization, transport, translation, and degradation of RNA. Increasing evidence shows that non-coding RNAs, particularly microRNA, long non-coding RNA, and circular RNA, can also regulate the RNA m6A modification process by affecting the expression of m6A-related enzymes. The interaction between m6A modification and non-coding RNAs provides a new perspective for the exploration of the potential mechanism of tumor genesis and development. In this review, we summarize the potential mechanisms and effects of m6A and non-coding RNAs in gastrointestinal tract cancers.

Utility of Elevated Pentraxin-3 Level as Inflammatory Marker for Predicting Adverse Outcomes in Patients With Acute Coronary Syndrome: A Meta-Analysis.

BACKGROUND: Vascular inflammation plays an important role in the pathogenesis and development of acute coronary syndrome (ACS). However, studies on the association between elevated pentraxin-3 level and adverse outcomes in patients with ACS have yielded controversial results. The purpose of this meta-analysis was to assess the value of elevated pentraxin-3 level as an inflammatory marker for predicting adverse outcomes in patients with ACS. METHODS: Two authors systematically searched the articles indexed in PubMed, Embase, CNKI, Wanfang, and VIP databases up to March 31, 2021. Studies reporting the association of elevated pentraxin-3 level at the acute phase with cardiovascular mortality, all-cause mortality, or cardiac events (cardiac death, non-fatal myocardial infarction, revascularization, or heart failure) in patients with ACS were included. RESULTS: A total of 8,775 ACS patients from 12 studies were identified and analyzed. When compared the lowest pentraxin-3 level, ACS patients with the highest pentraxin-3 level conferred an increased risk of cardiovascular mortality [risk ratio (RR) 2.10; 95% CI 1.44-3.06], all-cause mortality (RR 1.99; 95% CI 1.46-2.71), and cardiac events (RR 1.74; 95% CI 1.32-2.29), even after adjustment for some important confounders. Subgroup analysis indicated that the association of elevated pentraxin-3 level with cardiac events appeared to be stronger in ST-segment elevation myocardial infarction patients (RR 2.72; 95% CI 1.69-4.36) than in all patients with ACS (RR 1.59; 95% CI 1.10-2.29). CONCLUSIONS: Elevated pentraxin-3 level is possibly an independent predictor of adverse outcomes in patients with ACS. Assessment of pentraxin-3 level at the acute phase can provide important information for early risk stratification of ACS.

Analysis of N6-Methyladenosine Methylome in Adenocarcinoma of Esophagogastric Junction.

Background: From previous studies, we found that there are more than 100 types of RNA modifications in RNA molecules. m6A methylation is the most common. The incidence rate of adenocarcinoma of the esophagogastric junction (AEG) at home and abroad has increased faster than that of stomach cancer at other sites in recent years. Here, we systematically analyze the modification pattern of m6A mRNA in adenocarcinoma at the esophagogastric junction. Methods: m6A sequencing, RNA sequencing, and bioinformatics analysis were used to describe the m6A modification pattern in adenocarcinoma and normal tissues at the esophagogastric junction. Results: In AEG samples, a total of 4,775 new m6A peaks appeared, and 3,054 peaks disappeared. The unique m6A-related genes in AEG are related to cancer-related pathways. There are hypermethylated or hypomethylated m6A peaks in AEG in differentially expressed mRNA transcripts. Conclusion: This study preliminarily constructed the first m6A full transcriptome map of human AEG. This has a guiding role in revealing the mechanism of m6A-mediated gene expression regulation.

Clinical features of 47 secondary hemophagocytic lymphohistiocytosis patients complicated with capillary leak syndrome.

The clinical features of patients with secondary hemophagocytic lymphohistiocytosis (sHLH) complicated with capillary leak syndrome (CLS) remain controversial. The data of 259 sHLH patients were retrospectively analyzed. The clinical manifestations, laboratory findings, treatment, and prognosis of the CLS-sHLH group and non-CLS-sHLH group were compared. The levels of fibrinogen, albumin, and serum calcium in the CLS-sHLH group were lower than in the non-CLS-sHLH group, and serum triglycerides in the CLS-sHLH group were higher than in the non-CLS-sHLH group (P < 0.05). Univariate analysis showed that fibrinogen level was an independent prognostic factor in sHLH patients complicated with CLS. The median survival time was significantly shorter in patients with fibrinogen ≤ 1.3 g/L than in patients with fibrinogen > 1.3 g/L (P < 0.05). Patients with improved CLS conditions in the CLS-sHLH group had significantly increased albumin and serum calcium after treatment (P < 0.05); patients without improved conditions in the CLS-sHLH group also had significantly increased albumin after treatment (P < 0.05), but the serum calcium did not change significantly (P > 0.05). sHLH patients complicated with CLS had significantly worse prognosis than without CLS. Significant reduction in fibrinogen may be an independent prognostic factor for poor prognosis in sHLH patients complicated with CLS.

The Prognosis Role of AST/ALT (De Ritis) Ratio in Patients with Adult Secondary Hemophagocytic Lymphohistiocytosis.

PURPOSE: Secondary hemophagocytic lymphohistiocytosis (sHLH) accompanied by liver involvement, characterized by hepatomegaly and increased liver enzymes, is usually associated with elevated mortality. However, the magnitude of these associations remains unknown. Our objective was to assess the associations of the aspartate transaminase/alanine transaminase (AST/ALT, De Ritis) ratio with overall survival among adult patients with sHLH. METHODS: A retrospective analysis was performed on 289 patients aged 18-86 years with complete serum transaminase data at diagnosis of sHLH. Multivariate Cox regression analyses and restricted cubic splines were conducted to address the association between the De Ritis ratio and the risk of mortality. RESULTS: The median De Ritis ratio for the entire study population was 1.34 (IQR: 0.84-2.29). After a median follow-up time of 60 (range 17-227.5) days, 205 deaths occurred. After fully adjusting for hepatomegaly, albumin, fibrinogen, EBV, ferritin, etiologies, and treatment strategies, the adjusted hazard ratios (HRs) with corresponding confidence intervals (CIs) of mortality for the 2 st tertile and 3 st tertile were 1.2 (0.8-1.7) and 1.6 (1.1-2.2), respectively (P < 0.01 for trends). Restricted cubic spline confirmed a linear association between the log2-transformed De Ritis ratio and the risk of mortality. Moreover, this trend persisted in subgroups with MHLH, hyperferrinaemia, sCD25 ≤ 20,000 ng/L, patients without EBV infection, and those received treatment. CONCLUSIONS: The De Ritis ratio is a strong and independent predictor for overall survival in patients with sHLH. As a readily available biomarker in routine clinical practice, it is used to identify patients with sHLH with inferior overall survival.