Emerging role of exosome-derived non-coding RNAs in tumor-associated angiogenesis of tumor microenvironment.

The tumor microenvironment (TME) is an intricate ecosystem that is actively involved in various stages of cancer occurrence and development. Some characteristics of tumor biological behavior, such as proliferation, migration, invasion, inhibition of apoptosis, immune escape, angiogenesis, and metabolic reprogramming, are affected by TME. Studies have shown that non-coding RNAs, especially long-chain non-coding RNAs and microRNAs in cancer-derived exosomes, facilitate intercellular communication as a mechanism for regulating angiogenesis. They stimulate tumor growth, as well as angiogenesis, metastasis, and reprogramming of the TME. Exploring the relationship between exogenous non-coding RNAs and tumor-associated endothelial cells, as well as their role in angiogenesis, clinicians will gain new insights into treatment as a result.

Emodin improves glucose metabolism and ovarian function in PCOS mice via the HMGB1/TLR4/NF-κB molecular pathway.

In brief: Obese PCOS mice display metabolic and endocrine disorders that manifest as abnormal metabolism of glucose and dysfunctions in the reproductive system. This study demonstrates that emodin alleviates most of these conditions possibly via the HMGB1/TLR4/NF-kB pathway. Abstract: PCOS is a reproductive disorder with an unclear etiology. It affects 5-10% of women worldwide and is largely associated with impaired glucose metabolism and obesity. HMGB1 is a nuclear protein associated with impaired glucose metabolism and PCOS. We sought to investigate the potential therapeutic effects of emodin on glucose metabolism and ovarian functions in PCOS mice via the HMGB1 molecular pathway. A high-fat diet (HFD) and dehydroepiandrosterone (DHEA)- induced PCOS mouse model comprising four experimental groups was established: control, PCOS, PCOS plus emodin, and PCOS plus vehicle groups. Emodin administration attenuated obesity, elevated fasting glucose levels, impaired glucose tolerance, and insulin resistance, and improved the polycystic ovarian morphology of PCOS mice. Additionally, it lowered elevated serum HMGB1, LH, and testosterone levels in PCOS mice. Elevated ovarian protein and mRNA levels of HMGB1 and TLR4 in PCOS mice were also lowered following emodin treatment. Furthermore, emodin lowered high NF-ĸB/65 protein levels in the ovaries of PCOS mice. Immunohistochemical staining of the ovaries revealed strong HMGB1, TLR4, and AR expressions in PCOS mice, which were lowered by emodin treatment. Moreover, emodin significantly increased GLUT4, IRS2, and INSR levels that were lowered by PCOS. Overall, our study showed that emodin alleviated the impaired glucose metabolism and improved ovarian function in PCOS mice, possibly via the HMGB1/TLR4/NF-ĸB signaling pathway. Thus, emodin could be considered a potential therapeutic agent in the management of PCOS.

Corrigendum: Effects of Yulin Tong Bu formula on modulating gut microbiota and fecal metabolite interactions in mice with polycystic ovary syndrome.

[This corrects the article DOI: 10.3389/fendo.2023.1122709.].

Glycyrrhizin ameliorates impaired glucose metabolism and ovarian dysfunction in a polycystic ovary syndrome mouse model.

The aim of this study was to determine the impact of glycyrrhizin, an inhibitor of high mobility group box 1, on glucose metabolic disorders and ovarian dysfunction in mice with polycystic ovary syndrome. We generated a polycystic ovary syndrome mouse model by using dehydroepiandrosterone plus high-fat diet. Glycyrrhizin (100 mg/kg) was intraperitoneally injected into the polycystic ovary syndrome mice and the effects on body weight, glucose tolerance, insulin sensitivity, estrous cycle, hormone profiles, ovarian pathology, glucolipid metabolism, and some molecular mechanisms were investigated. Increased number of cystic follicles, hormonal disorders, impaired glucose tolerance, and decreased insulin sensitivity in the polycystic ovary syndrome mice were reverted by glycyrrhizin. The increased high mobility group box 1 levels in the serum and ovarian tissues of the polycystic ovary syndrome mice were also reduced by glycyrrhizin. Furthermore, increased expressions of toll-like receptor 9, myeloid differentiation factor 88, and nuclear factor kappa B as well as reduced expressions of insulin receptor, phosphorylated protein kinase B, and glucose transporter type 4 were restored by glycyrrhizin in the polycystic ovary syndrome mice. Glycyrrhizin could suppress the polycystic ovary syndrome-induced upregulation of high mobility group box 1, several inflammatory marker genes, and the toll-like receptor 9/myeloid differentiation factor 88/nuclear factor kappa B pathways, while inhibiting the insulin receptor/phosphorylated protein kinase B/glucose transporter type 4 pathways. Hence, glycyrrhizin is a promising therapeutic agent against polycystic ovary syndrome.

Prognostic value of sirtuin family members and experimental verification identify SIRT5 as diagnostic biomarkers in clear cell renal cell carcinoma.

Background: The sirtuins (SIRTs) family is a nicotinamide adenine dinucleotide (NAD+) family of dependent deacetylases, which includes SIRT1-7. This family is related to the development and progression of various tumors. However, a comprehensive analysis of the role of SIRTs in clear cell renal cell carcinoma (ccRCC) is still lacking, and there are few reports on the inhibitory role of SIRT5 in ccRCC. Methods: We used immunohistochemical analysis, and several bioinformatic databases to perform an integrated analysis of the expression and prognostic value of SIRT5 and other SIRT family members in ccRCC along with the associated immune cell infiltration. These databases include TIMER, THPA, cell culture, UALCAN, cBioPortal, WebGestalt, Metascape, DiseaseMeth, STRING database, and Cytoscape. Results: The protein expression of SIRT1, 2, 3, 6, and 7 were upregulated in ccRCC for the Human Protein Atlas database, whereas the expression of SIRT4 and SIRT5 was decreased. The expression based on tumor stage, and grade followed a similar trend. Kaplan-Meier analysis showed that high SIRT4 and SIRT5 expression was positively related to better overall survival (OS), whereas SIRT6 and SIRT7 expression was positively related to worse OS. Further, high SIRT3 expression was related to worse relapse-free survival (RFS), whereas high SIRT5 expression was related to better RFS. To explore the mechanism underlying the function of SIRTs in ccRCC, we also used several databases to perform the functional enrichment analysis and explore the relationship between infiltrating immune cells and seven SIRT family members in ccRCC. The results showed that several SIRT family members, and particularly SIRT5, are correlated with the infiltration of some important immune cells. The protein expression of SIRT5 was significantly lower in tumor tissue compared to normal tissue and was negatively related to the age of the patient ccRCC individual tumor stages, and grades. In human ccRCC samples, strong IHC staining expression of SIRT5 was displayed in adjacent normal tissue than in tumor tissues. Conclusion: SIRT5 may be a prognostic marker and a novel strategy for the treatment of ccRCC.

Effects of Yulin Tong Bu formula on modulating gut microbiota and fecal metabolite interactions in mice with polycystic ovary syndrome.

Background: Polycystic ovarian syndrome (PCOS) is a common endocrine disorder characterized by hyperandrogenism, ovarian dysfunction and polycystic ovarian morphology. Gut microbiota dysbiosis and metabolite are associated with PCOS clinical parameters. Yulin Tong Bu formula (YLTB), a traditional Chinese medicine formula, has been recently indicated to be capable of ameliorating polycystic ovary symptoms and correcting abnormal glucose metabolism. However, the therapeutic mechanism of YLTB on PCOS has not been fully elucidated. Methods: A pseudo sterile mouse model was established during this four-day acclimatization phase by giving the animals an antibiotic cocktail to remove the gut microbiota. Here, the therapeutic effects of YLTB on PCOS were investigated using dehydroepiandrosterone plus high-fat diet-induced PCOS mice model. Female prepuberal mice were randomly divided into three groups; namely, the control group, PCOS group and YLTB (38.68 g·kg-1·day-1) group. To test whether this effect is associated with the gut microbiota, we performed 16S rRNA sequencing studies to analyze the fecal microbiota of mice. The relationships among metabolites, gut microbiota, and PCOS phenotypes were further explored by using Spearman correlation analysis. Then, the effect of metabolite ferulic acid was then validated in PCOS mice. Results: Our results showed that YLTB treatment ameliorated PCOS features (ovarian dysfunction, delayed glucose clearance, decreased insulin sensitivity, deregulation of glucolipid metabolism and hormones, etc.) and significantly attenuated PCOS gut microbiota dysbiosis. Spearman correlation analysis showed that metabolites such as ferulic acid and folic acid are negatively correlated with PCOS clinical parameters. The effect of ferulic acid was similar to that of YLTB. In addition, the bacterial species such as Bacteroides dorei and Bacteroides fragilis were found to be positively related to PCOS clinical parameters, using the association study analysis. Conclusion: These results suggest that YLTB treatment systematically regulates the interaction between the gut microbiota and the associated metabolites to ameliorate PCOS, providing a solid theoretical basis for further validation of YLTB effect on human PCOS trials.

Anchoring super-enhancer-driven oncogenic lncRNAs for anti-tumor therapy in hepatocellular carcinoma.

Super-enhancer (SE) plays a vital role in the determination of cell identity and fate. Up-regulated expression of coding genes is frequently associated with SE. However, the transcription dysregulation driven by SE, from the viewpoint of long non-coding RNA (lncRNA), remains unclear. Here, SE-associated lncRNAs in HCC are comprehensively outlined for the first time. This study integrally screens and identifies several novel SE-associated lncRNAs that are highly abundant and sensitive to JQ1. Especially, HSAL3 is identified as an uncharacterized SE-driven oncogenic lncRNA, which is activated by transcription factors HCFC1 and HSF1 via its super-enhancer. HSAL3 interference negatively regulates NOTCH signaling, implying the potential mechanism of its tumor-promoting role. The expression of HSAL3 is increased in HCC samples, and higher HSAL3 expression indicates an inferior overall survival of HCC patients. Furthermore, siHSAL3 loaded nanoparticles exert anti-tumor effect on HCC in vitro and in vivo. In conclusion, this is the first comprehensive survey of SE-associated lncRNAs in HCC. HSAL3 is a novel SE-driven oncogenic lncRNA, and siHSAL3 loaded nanoparticles are therapeutic candidates for HCC. This work sheds lights on the merit of anchoring SE-driven oncogenic lncRNAs for HCC treatment.

Prognostic implications of left ventricular torsion measured by feature-tracking cardiac magnetic resonance in patients with ST-elevation myocardial infarction.

AIMS: The prognostic implication of left ventricular (LV) torsion on ST-elevation myocardial infarction (STEMI) is unclear. METHODS AND RESULTS: We analysed cardiovascular magnetic resonance (CMR) findings of 420 patients from a registry study (NCT03768453). These patients received CMR examination within 1 week after timely primary percutaneous coronary intervention. LV torsion and other CMR indexes were measured. Compared with healthy control subjects, STEMI significantly decreased patients' LV torsion (1.04 vs. 1.63°/cm, P < 0.001). During follow-up (median, 52 months), the reduction of LV torsion was greater in patients with than without composite major adverse cardiac and cerebrovascular events (MACCEs, 0.79 vs. 1.08°/cm, P < 0.001). The risk of MACCEs would increase to 1.125- or 1.092-fold, and the risk of 1-year LV remodelling would increase to 1.110- or 1.082-fold for every 0.1°/cm reduction in LV torsion after adjustment for clinical or CMR parameters respectively. When divided dichotomously, patients with LV torsion≤ 0.802°/cm had significantly higher risk of MACCEs (40.2 vs. 12.3%, P < 0.001) and more remarkable LV remodelling (46.1 vs. 11.9%, P < 0.001) than patients with better LV torsion. The addition of LV torsion to conventional prognostic factors such as the LV ejection fraction and infarction size led to a better risk classification model of patients for both MACCEs and LV remodelling. Finally, tobacco use, worse post-PCI flow, and greater microvascular obstruction size were presumptive risk factors for reduced LV torsion. CONCLUSION: LV torsion measured by CMR is closely associated with the prognosis of STEMI and would be a promising indicator to improve patients' risk stratification. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT03768453.

Construction of sports and medical integration intervention program in phase Ⅱ cardiac rehabilitation for patients with acute myocardial infarction / 中国实用护理杂志

Objective:To construct an intervention program of sports and medical integration for patients with acute myocardial infarction (AMI) in phase Ⅱ cardiac rehabilitation, so as to provide reference for the effective implementation of physical activity behavior change in AMI patients during phase Ⅱ cardiac rehabilitation.Methods:Before the research, we browsed relevant literature and guidelines published from July 2016 to June 2021, made a retrospective study on the influencing factors of cardiac rehabilitation behavior for AMI patients, and carried out a qualitative interview on cognitive and compliance motivations for AMI patients. Furthermore based on trans-theoretical model, the first draft of the intervention program was developed and and the expert consultation questionnaire was formed. From February to April 2022, Delphi method was used in 16 experts from 10 hospitals and 1 nursing college in 4 provinces. After 2 rounds of expert consultations on the importance and operability of items, the intervention program was finally determined.Results:The effective recovery rates of the 2 rounds of expert consultations questionnaires were both 16/16. The authority coefficient of expert consultation was 0.90, the judgment basis coefficient was 0.96, and the familiarity degree was 0.84. After the second round of expert consultation, the coefficient of variation of the importance of each item was (0.0-13.4)%, and the coefficient of variation of operability was (0.0-18.1)%. The final intervention program of sports and medical integration for patients with AMI in phase Ⅱ cardiac rehabilitation had 37 items, containing precontemplation stage (8 items), contemplation stage (7 items), preparation stage (5 items), action stage (9 items) and maintenance stage (8 items).Conclusions:The construction process of the intervention program of sports and medical integration for patients with AMI in phase Ⅱ cardiac rehabilitation is scientific and feasible. The content is focused on the patient-centred conception and the whole-process management for the exercise rehabilitation of AMI patients in phase Ⅱ cardiac rehabilitation. This intervention program may improve the safety, feasibility, participation and compliance in phase Ⅱ cardiac rehabilitation in patients with AMI. So it is recommended to be popularized and used in phase Ⅱ cardiac rehabilitation.

Prognostic value and immune infiltration of the gasdermin family in lung adenocarcinoma.

Background: The GSDM family includes six members, GSDMA, GSDMB, GSDMC, GSDMD, GSDME (DFNA5), and PJVK (Pejvakin, DFNB59), which can induce pyroptosis, thereby regulating the tumorigenesis of various cancers. However, the clinical characteristics and role of the GSDM family in LUAD are not well understood. Methods: In this study, several important bioinformatics databases were used to integrate the analysis of the expression, prognostic value, and immune infiltration of GSDMs in LUAD. These databases include UALCAN, DiseaseMeth, GEPIA, THPA, cBioPortal, TIMER, WebGestalt, STRING database, and Cytoscape. Results: The findings from the UALCAN database revealed that the expression of all six GSDMs based on the tumor stage in LUAD was increased (particularly GSDMD). Our IHC results verified it. Additionally, the DiseaseMeth database showed that the methylation levels of GSDMA, GSDMB, GSDMC, and GSDMD were decreased. The expression of six GSDMs was related to shorter overall survival in patients with LUAD, according to the GEPIA database. The cBioPortal database was further used to explore the alteration rate and correlated genes in LUAD. Subsequently, these genes were subjected to functional enrichment and protein-protein interaction network analyses. We identified that the GSDM family regulate several signaling pathways, including immune-associated signaling pathways. According to tumor-infiltrating immune cell analysis from the TIMER database, GSDM family members are associated with the infiltration of important immune cells and their signature markers. Conclusions: GSDM family may be prognostic markers and novel strategies for the treatment of LUAD.

Autophagy-related long non-coding RNA prognostic model predicts prognosis and survival of melanoma patients.

BACKGROUND: Melanomas are malignant tumors that can occur in different body parts or tissues such as the skin, mucous membrane, uvea, and pia mater. Long non-coding RNAs (lncRNAs) are key factors in the occurrence and development of many malignant tumors, and are involved in the prognosis of some patients. AIM: To identify autophagy-related lncRNAs in melanoma that are crucial for the diagnosis, treatment, and prognosis of melanoma patients. METHODS: We retrieved transcriptome expression profiles and clinical information of 470 melanoma patients from The Cancer Genome Atlas (TCGA) database. Then, we identified autophagy-related genes in the Human Autophagy Database. Using R, coexpression analysis of lncRNAs and autophagy-related genes was conducted to obtain autophagy-related lncRNAs and their expression levels. We also performed univariate and multivariate Cox proportional risk analyses on the obtained datasets, to systematically evaluate the prognostic value of autophagy-related lncRNAs in melanoma. Fifteen autophagy-related lncRNAs were identified and an autophagy-related prognostic signature for melanoma was established. The Kaplan-Meier and univariate and multivariate Cox regression analyses were used to calculate risk scores. Based on the risk scores, melanoma patients were randomly divided into high- and low-risk groups. Receiver operating characteristic curve analysis, dependent on time, was performed to assess the accuracy of the prognostic model. At the same time, we also downloaded the melanoma data sets GSE65904, GSE19234, and GSE78220 from the GENE EXPRESSION OMNIBUS database for model verification. Finally, we performed Gene Set Enrichment Analysis functional annotation, which showed that the low and the high-risk groups had different enriched pathways. RESULTS: The co-expression network for autophagy-related genes was constructed using R, and 936 lncRNAs related to autophagy were identified. Then, 52 autophagy-related lncRNAs were significantly associated with TCGA melanoma patients' survival by univariate Cox proportional risk analysis (P < 0.01). Further, the 52 autophagy-related lncRNAs mentioned above were analyzed by multivariate Cox analysis with R. Fifteen lncRNAs were selected: LINC01943, AC090948.3, USP30-AS1, AC068282.1, AC004687.1, AL133371.2, AC242842.1, PCED1B-AS1, HLA-DQB1-AS1, AC011374.2, LINC00324, AC018553.1, LINC00520, DBH-AS1, and ITGB2-AS1. The P values in all survival analyses using these 15 lncRNAs were < 0.05. These lncRNAs were used to build a risk model based on the risk score. Negative correlations were observed between risk scores and overall survival rate in melanoma patients over time. Additionally, the melanoma risk curve and scatter plot analyses showed that the death number increased along with the increase in the risk score. Overall, we identified and established a new prognostic risk model for melanoma using 15 autophagy-related lncRNAs. The risk model constructed with these lncRNAs can help and guide melanoma patient prognosis predictions and individualized treatments in the future. CONCLUSION: Overall, the risk model developed based on the 15 autophagy-related lncRNAs can have important prognostic value and may provide autophagy-related clinical targets for melanoma treatment.

Ovarian inflammatory mRNA profiles of a dehydroepiandrosterone plus high-fat diet-induced polycystic ovary syndrome mouse model.

RESEARCH QUESTION: What is the expression pattern of inflammatory mRNA profiles of a dehydroepiandrosterone (DHEA) plus high-fat diet (HFD)-induced polycystic ovary syndrome (PCOS) mouse model? DESIGN: RNA sequencing was performed to investigate the mRNA expression profiles in the ovarian tissues of a DHEA plus HFD-induced PCOS mouse model. Six samples were divided into two groups (control and PCOS), with three biological replicates in each group. This was followed by hierarchical clustering, gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. The relative expression levels of nine inflammatory genes were validated via quantitative reverse-transcription polymerase chain reaction. RESULTS: A total of 436 genes were differentially expressed between the control and PCOS mice. Out of these, 137 genes were up-regulated while 299 genes were down-regulated. Gene ontology analysis indicated that differentially expressed mRNA were associated with T cell-mediated cytotoxicity and homocysteine metabolic processes. Pathway analysis further showed that these abnormally expressed mRNA were associated with signalling pathways, such as NF-kB signalling, tyrosine metabolism and phenylalanine metabolism. All these pathways are involved in chronic inflammation and PCOS. CONCLUSION: The differentially expressed genes are potentially involved in the inflammation that is evident in PCOS, and so could serve as therapeutic options against the disease. Nevertheless, prospective studies are needed to test this hypothesis.

A decrease in cluster of differentiation 2 expression on natural killer cells is associated with polycystic ovary syndrome but not influenced by metformin in a mouse model†.

PROBLEM: Natural killer (NK) cells from the peripheral blood and spleen represent the source from which various tissues replenish their immune cell populations. Hyperandrogenism and high interleukin-2 (IL-2) levels are factors present in polycystic ovary syndrome (PCOS). These factors and metformin, one of the commonest medications used in treating PCOS, may have an impact on NK cells. However, this is presently unknown. Here, we aimed to assess the distribution of peripheral blood and splenic NK cells and their CD2 and CD94 expression patterns in a PCOS mouse model and test whether metformin could reverse these effects. METHOD OF STUDY: Four mouse groups were designed as follows (n = 15/group): control, PCOS, PCOS plus vehicle, PCOS plus metformin. Dehydroepiandrosterone and a high-fat diet were administered to induce the PCOS mouse model. Flow cytometry was used to analyze the expressions of CD2 and CD94 on peripheral blood and splenic NK cells. RESULTS: PCOS mice had a low surface-density of CD2 on peripheral blood NK cells and a decreased percentage of CD2+ splenic NK cells. Metformin administration did not significantly influence these changes; however, it reduced the splenic NK cell counts. CONCLUSIONS: Our findings proved the association of PCOS with an altered expression of CD2 on peripheral blood and splenic NK cells and that of metformin with a lowered splenic NK cell reserve in PCOS conditions. These findings could further unlock key mechanisms in PCOS pathophysiology and in the mechanism of action of metformin, towards improving PCOS management.

Low-frequency and rare coding variants of NUS1 contribute to susceptibility and phenotype of Parkinson's disease.

NUS1 has been recently identified as a candidate gene for Parkinson's disease (PD). Few studies have examined the association of NUS1 variants with PD susceptibility and phenotypes. In the first cohort, whole-exome sequencing was performed to identify variants in NUS1 exon-coding and exon-intron regions in 1542 cases and 1625 controls. 13 variants were totally detected, of which 10 rare variants and 3 low-frequency variants. Burden analysis showed that rare NUS1 variants significantly enriched in PD (p=0.016). We also performed a meta-analysis based on previous and our studies to correlate NUS1 mutations with PD susceptibility. Integrating our previous cohort (3210 cases and 2807 controls) and the first cohort identified the significant association of rs539668656 with PD risk (odds ratio (OR) = 2.82, p = 0.016). The genotype-phenotype association analysis showed that patients carrying rare variants, or rs539668656 were significantly associated with earlier onset age, depression, emotional impairment and severe disease condition. Our results support the role of NUS1 rare variants and rs539668656 towards PD susceptibility and phenotype.

Development of evaluation index system for community screening and referral procedure of patients with chronic heart failure / 中华全科医师杂志

Objective:To develop an evaluation index system for community screening and referral procedure of patients with chronic heart failure.Methods:Experts in fields of medical education, health administration and various clinical specialties were selected from Shanghai through the purpose sampling method. Two rounds of expert consultation with Delphi method were conducted during October 2020 to February 2021, the contents of consultation included the importance and availability of the index system. According to the consultation results, the index system for community screening and referral procedure of patients with chronic heart failure was developed.Results:A total of 16 experts participated in the consultation, among whom 15 held senior or associate senior titles and 14 had worked for 20 years. The recovery rates of valid questionnaires of two rounds expert of consultation were 16/16. The familiarity and judgment coefficient were 0.82 and 0.90 in the first round of expert consultation, and 0.86 and 0.90 in the second round. The expert consultation coordination coefficient of the importance in the community screening and referral procedure were 0.652 and 0.462 for the first consultation; 0.741 and 0.525 for the second consultation. In the final version of the evaluation index system there were 7 first-level indicators, 15 secondary indicators and 3 conditions for screening; and 2 first-level indicators, 5 secondary indicators and 1 condition for referral.Conclusion:In this study the positivity coefficient and authority degree of experts are high; the opinions are relatively concentrated. The consultation results have a high rationality and feasibility, which would be applicable for assessment of community screening and referral procedure of patients with chronic heart failure.

Development and Validation of a Random Forest Diagnostic Model of Acute Myocardial Infarction Based on Ferroptosis-Related Genes in Circulating Endothelial Cells.

The high incidence and mortality of acute myocardial infarction (MI) drastically threaten human life and health. In the past few decades, the rise of reperfusion therapy has significantly reduced the mortality rate, but the MI diagnosis is still by means of the identification of myocardial injury markers without highly specific biomarkers of microcirculation disorders. Ferroptosis is a novel reported type of programmed cell death, which plays an important role in cancer development. Maintaining iron homeostasis in cells is essential for heart function, and its role in the pathological process of ischemic organ damages remains unclear. Being quickly detected through blood tests, circulating endothelial cells (CECs) have the potential for early judgment of early microcirculation disorders. In order to explore the role of ferroptosis-related genes in the early diagnosis of acute MI, we relied on two data sets from the GEO database to first detect eight ferroptosis-related genes differentially expressed in CECs between the MI and healthy groups in this study. After comparing different supervised learning algorithms, we constructed a random forest diagnosis model for acute MI based on these ferroptosis-related genes with a compelling diagnostic performance in both the validation (AUC = 0.8550) and test set (AUC = 0.7308), respectively. These results suggest that the ferroptosis-related genes might play an important role in the early stage of MI and have the potential as specific diagnostic biomarkers for MI.

Impact of Concomitant Impairments of the Left and Right Ventricular Myocardial Strain on the Prognoses of Patients With ST-Elevation Myocardial Infarction.

Background: The impact of concomitant impairments of left and right ventricular (LV and RV) strain on the long-term prognosis of acute ST-elevation myocardial infarction (STEMI) is not clear. Methods: We analyzed CMR images and followed up 420 first STEMI patients from the EARLY Assessment of MYOcardial Tissue Characteristics by CMR in STEMI (EARLY-MYO-CMR) registry (NCT03768453). These patients received timely primary percutaneous coronary intervention (PCI) within 12 h and CMR examination within 1 week (median, 5 days; range, 2-7 days) after infarction. Global longitudinal strain (GLS), global radial strain (GRS), and global circumferential strain (GCS) of both ventricles were measured based on CMR cine images. Conventional CMR indexes were also assessed. Primary clinical outcome was composite major adverse cardiac and cerebrovascular events (MACCEs) including cardiovascular death, re-infarction, re-hospitalization for heart failure and stroke. In addition, CMR data from 40 people without apparent heart disease were used as control group. Results: Compared to controls, both LV and RV strains were remarkably reduced in STEMI patients. During follow-up (median: 52 months, interquartile range: 29-68 months), 80 patients experienced major adverse cardiac and cerebrovascular events (MACCEs) including cardiovascular death, re-infarction, heart failure, and stroke. LV-GCS > -11.20% was an independent predictor of MACCEs (P < 0.001). RV-GRS was the only RV strain index that could effectively predict the risk of MACCEs (AUC = 0.604, 95% CI [0.533, 0.674], P = 0.004). Patient with RV-GRS ≤ 38.79% experienced more MACCEs than those with preserved RV-GRS (log rank P < 0.001). Moreover, patients with the concomitant decrease of LV-GCS and RV-GRS were more likely to experience MACCEs than patients with decreased LV-GCS alone (log rank P = 0.010). RV-GRS was incremental to LV-GCS for the predictive power of MACCEs (continuous NRI: 0.327; 95% CI: 0.095-0.558; P = 0.006). Finally, tobacco use (P = 0.003), right coronary artery involvement (P = 0.002), and LV-GCS > -11.20% (P = 0.012) was correlated with lower RV-GRS. Conclusions: The concomitant decrease of LV and RV strain is associated with a worse long-term prognosis than impaired LV strain alone. Combination assessment of both LV and RV strain indexes could improve risk stratification of patients with STEMI. Trial Registration: ClinicalTrials.gov, NCT03768453. Registered 7 December 2018 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03768453.

Characterizing cellular and molecular variabilities of peripheral immune cells in healthy inactivated SARS-CoV-2 vaccine recipients by single-cell RNA sequencing

We systematically investigated the transcriptomes of the peripheral immune cells from 6 inactivated vaccine, BBIBP-CorV recipients at 4 pivotal time points using single-cell RNA-seq technique. First, the significant variation of the canonical immune-responsive signals of both humoral and cellular immunity, as well as other possible symptom-driver signals were evaluated in the specific cell types. Second, we described and compared the common and distinct variation trends across COVID-19 vaccination, disease progression, and flu vaccination to achieve in-depth understandings of the manifestation of immune response in peripheral blood under different stimuli. Third, the expanded T cell and B cell clones were correlated to the specific phenotypes which allowed us to characterize the antigen-specific ones much easier in the future. At last, other than the coagulopathy, the immunogenicity of megakaryocytes in vaccination were highlighted in this study. In brief, our study provided a rich data resource and the related methodology to explore the details of the classical immunity scenarios.

A plateform for management of atrial fibrillation based on internet and medical concortium / 中华全科医师杂志

In order to provide efficient medical care to atrial fibrillation patients in the community, the Huamu Community Health Service Center in association with its medical consortium, Renji Hospital have developed a novel atrial fibrillation management system. With the collaboration of general practitioners and specialist team from the tertiary hospital, a special clinic for atrial fibrillation has been set up in the community health service center, which is based on the internet technology and the medical consortium platform. This article introduces the development of this novel system and the initial outcome of the measures, to provide a reference for the management of atrial fibrillation patients in the community.

Effect of Modified Huangqi Biejiatang Combined with Auricular Acupressure on Diabetic Peripheral Neuropathy of Qi-Yin Deficiency Syndrome and Serum MyD88/IκB Signaling Pathway / 中国实验方剂学杂志

Objective:To observe the effects of modified Huangqi Biejiatang combined with auricular acupressure on diabetic peripheral neuropathy （DPN） due to Qi and Yin deficiency and serum myeloid differentiation factor 88/inhibitor of nuclear factor-<italic>κ</italic>B （MyD88/I<italic>κ</italic>B） signaling pathway. Method:One hundred and forty cases were randomly divided into an observation group （<italic>n</italic>=70） and a control group （<italic>n</italic>=70）. In addition to routine treatments like dietary intervention and the regulation of fasting blood glucose （FBG） and blood pressure， the modified Huangqi Biejiatang combined with auricular acupressure was further provided in the observation group， while mecobalamine was administered in the control group. After four-week intervention， the toronto clinical scoring system （TCSS） score， traditional Chinese medicine （TCM） syndrome score， the conduction velocities of motor and sensory nerves （median nerve， common peroneal nerve， tibial nerve， and ulnar nerve）， glucose metabolism indexes ［fasting plasma glucose （FPG）， 2 h postprandial blood glucose （2 h PG）， and hemoglobin A1c （HbA1c）］， intestinal genera （<italic>Clostridium</italic>， <italic>Prauserella</italic>， <italic>Bacteroides</italic>， and <italic>Faecalibacterium</italic>）， as well as the serum MyD88， I<italic>κ</italic>B<italic>α</italic>， and phosphorylated I<italic>κ</italic>B<italic>α </italic>（p-I<italic>κ</italic>B<italic>α</italic>） levels in the MyD88/I<italic>κ</italic>B signaling pathway before and after treatment were observed in the two groups， for comparing their clinical efficacy and safety. Result:The total effective rate of the observation group was 85.3% （58/68）， which was higher than 48.5% （32/66） of the control group （<italic>χ</italic>²=6.143， <italic>P</italic><0.05）. The comparison with the control group revealed that the scores of TCSS and TCM syndrome， the levels of FPG， 2 h PG， HbA1c， MyD88， and p-I<italic>κ</italic>B<italic>α</italic>， as well as the abundances of <italic>Clostridium</italic> and <italic>Prauserella</italic> in the observation group were decreased （<italic>P</italic><0.05）， while the conduction velocities of motor and sensory nerves （median nerve， common peroneal nerve， tibial nerve， and ulnar nerve） were significantly accelerated （<italic>P</italic><0.05）. Besides， the abundances of <italic>Bacteroides</italic> and <italic>Faecalibacterium</italic> and I<italic>κ</italic>B<italic>α</italic> level were significantly elevated （<italic>P</italic><0.05）. The incidence of adverse reactions in the observation group was 1.5% （1/68）， lower than 12.1% （8/66） in the control group （<italic>χ</italic>²=4.328， <italic>P</italic><0.05）. Conclusion:The modified Huangqi Biejiatang combined with auricular acupressure alleviates DPN due to Qi and Yin deficiency， which may be attributed to the regulation of serum MyD88/I<italic>κ</italic>B signaling pathway.