Heart failure is the end state of various cardiovascular diseases, accompanied by a seriesof energy metabolism changes including transformation of energy substrates, mitochondrial dysfunction, and depletion of high-energy phosphate compounds, etc. In normal heart, fatty acid is the main energy metabolism substrate. However, myocardial substrate metabolism is damaged during heart failure, and metabolic substrate conversion characterized by ketone body occurred. It is of great significance to better understand the metabolism substrate selection during heart failure, regulatory mechanism and its pathophysiological significance for developing novel therapeutics targeting heart failure. The research progress on the changes of myocardial energy metabolism substrates in heart failure, especially the latest progress of ketone body as the substrate in recent years were reviewed in present paper.

Objective To report a case of granulomatous polyangiitis (GPA) with breast involvement, and perform a literature review to better understand this disorder. Methods Retrospectively analyze the data of a case of GPA with breast involvement, to summarize the clinical characteristics of GPA with breast involvement by searching the database (CNKI, Wanfang Data, PubMed) and comprehensively analyze the literature results. Results A case of 53-year-old woman was admitted to the Department of Rheumatology and Immunology of the First Medical Center of Chinese PLA General Hospital because of "inflamed eyelids for 8 months, hearing loss for 6 months, breast induration for 4 months". The symptoms of mammary gland were bilateral-painful breast induration with ulceration. The patient was diagnosed with GPA by positive proteinase 3 (PR3) antibody and biopsy.After treatment with prednisone and cyclophosphamide, the patient experienced a relapse and then was treated with rituximab.By March 2021 (searching CNKI, Wanfang Data and PubMed), a total of 28 English cases of GPA with breast involvement and no Chinese case were found by searching literature. The disorder often occurs in women aged 40 to 60 (60.7%, 17/28), and the typical manifestation was unilateral breast (75.0%, 21/28) involvement. Positive PR3 antibody (69.2%, 9/13) is common. Pathological characteristics of the mammary are infiltration of lymphocyte, vasculitis and granulomatosis lesion. Conclusions The disorder of GPA with breast involvement is rare with non-specific breast symptoms. Detection of anti-neutrophil cytoplasmic antibodies and pathological examination can assist the diagnosis.

Patients with polycystic ovary syndrome (PCOS) have impaired follicular development and maturation. Ovarian granulosa cells play an important regulatory role in the initiation, growth and development of primordial follicles, in which the mitochondria of granulosa cells are involved in the regulation of cell cycle, metabolism, and signal transduction, and provide energy support for oocyte meiosis, fertilization, and up to early embryonic development through energy metabolic pathways. Studying the mitochondrial function of granulosa cells is one of the best non-invasive methods to study the pathological mechanisms in PCOS patients and to evaluate oocyte quality and embryonic developmental potential. A large number of evidences have shown that PCOS is associated with mitochondrial dysfunction in ovarian granulosa cells by mechanisms including altered mitochondrial DNA(mtDNA) copy number and mutations in the mtDNA gene. Some studies have explored the improvement of mitochondrial function in PCOS granulosa cells to improve the impaired follicular development and maturation in PCOS. Therefore, the relevant research progress in recent years have been reviewed in present paper about mitochondrial dysfunction in PCOS granulosa cells, for exploring the mechanism of mitochondrial dysfunction in PCOS granulosa cells, and the ways and methods of improvement.

Objective To explore the impact of severe calcification on the abnormal hemodynamics based on CT-fractional flow reserve (CT-FFR) diagnosis, and evaluate the diagnostic significance of pericoronary fat attenuation index (FAI) on the abnormal hemodynamics of severely calcified coronary artery. Methods The clinical data of patients were retrospectively analyzed who underwent a coronary computed tomography angiography (CCTA) examination within one month before an invasive FFR examination from January 2017 to December 2019 in the First Medical Center of Chinese PLA General Hospital. Regarding invasive FFR≤0.8 as the gold standard of hemodynamically abnormal coronary artery disease (CAD), patients were assigned to FFR≤0.8 group and FFR>0.8 group. The coronary artery calcium score (CACS), degree of major coronary branch stenosis, pericoronary FAI and CT-FFR were measured and compared. Invasive FFR≤0.8 represents the presence of lesion-specific hemodynamic significant CAD. According to the quartiles of CACS, patients were further divided into mildly-moderately calcified (1st-3rd quartiles) and severely calcified (4th quartile) stratification. The diagnostic efficacy for abnormal coronary hemodynamics was analyzed only with CT-FFR and combined with pericoronary FAI detection between the two groups. Results A total of 99 patients with 124 main coronary arteries were included (37 in FFR≤0.8 group, and 87 in FFR>0.8 group). In terms of vascular characteristics, statistically significant differences existed between FFR≤0.8 group and FFR>0.8 group in CACS (85.80, 95%CI 6.750~0.977 vs. 42.50, 95%CI 0.600~110.200, P<0.05), degree of major coronary branch stenosis (63.8%±9.9% vs. 57.6%±9.5%, P<0.01), pericoronary FAI(–73.3±9.5 vs. –80.6±7.5, P<0.01) and CT-FFR (0.77±0.04 vs. 0.86±0.04, P<0.01). The diagnostic efficacy of CT-FFR was lower for severe calcified vessels than for the vessels with mild to moderate calcification (AUC=0.767, 95%CI 0.581~0.899 vs.AUC=0.936, 95%CI 0.865~0.976, P<0.05), while the pericoronary FAI showed good diagnostic efficacy for the severe calcified vessels (AUC=0.850, 95%CI 0.676~0.952). CT-FFR combined with pericoronary FAI improved the diagnostic efficacy than using CT-FFR alone (AUC=0.917, 95%CI 0.760~0.985 vs. AUC=0.767, 95%CI 0.581~0.899, P=0.046). Conclusion For severe calcified vessels, the effectiveness declined of CT-FFR in the diagnosis of significant coronary ischemia, while combined implementation of FAI may improve the diagnosis of CAD with abnormal hemodynamics.

Objective To explore the relationship between platelet function and disease progression and prognosis in patients with cerebral hemorrhage without antiplatelet agents. Methods A retrospective analysis was performed on the clinical data of 129 patients with intracerebral hemorrhage who were admitted to the Neurosurgical Department, the First Affiliated Hospital of Chongqing Medical University from January 2015 to December 2019. These patients were divided into two groups: rebleeding group after intracerebral hemorrhage (n=53) and non-rebleeding group (n=76). The relation of thrombelastograph parameters including R value, K value, Angle of view, and the inhibition rates of arachidonic acid (AA) and adenosine diphosphate (ADP) under the condition without use of antiplatelet drugs at admission and their correlation with Glasgow Coma Scale score were compared between the two groups. Results The AA inhibition rate (P=0.015) and ADP inhibition rate (P=0.025) in rebleeding group were statistically higher than those in non-rebleeding group. AA inhibition rate of platelet function (P=0.022) and ADP inhibition rate (P=0.030) in rebleeding death group were statistically higher than those in survival group. AA inhibition rate (r=–0.183,P=0.038) and ADP inhibition rate (r=–0.175, P=0.047) were negatively correlated with Glasgow Coma Scale score. Conclusions Thrombelastographic detection of platelet function can be used as an early warning indicator to assist the assessment of the risk of rebleeding and prognosis in patients with intracerebral hemorrhage.

Objective To investigate the effect of psoralen on the degeneration of human nucleus pulposus cells (HNPCs)induced by interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) and its mechanism. Methods HNPCs were cultured in vitro, and HNPCs were stimulated by 10 ng/ml IL-1β and 50 ng/ml TNF-α for 24 hours to induce degeneration. Cells were divided into control group, IL-1β+TNF-α group, psoralen (10 μmol/L, 25 μmol/L and 50 μmol/L) group, psoralen (25 μmol/L) + S-phase kinase-associated protein 2 (SKP2) interference or over-expression group, psoralen + parathyroid hormone-related protein (PTHrP)recombinant protein (100 nmol/L) group, psoralen + PTHrP recombinant protein (100 nmol/L) + silent information regulator 1 (SIRT1) activator SRT1720 (1 μmol/L) group. The apoptosis of nucleus pulposus cells was detected by flow cytometry; the levels of IL-6, MMP-3 and MMP-13 in nucleus pulposus cells were detected by ELISA; the level of reactive oxygen species (ROS)in nucleus pulposus cells was detected by the DCFDA probe method. Western blotting was used to detect the expression levels of SKP2, PTHrP, SIRT1 and extracellular matrix (ECM) related protein [type II collagen (COL II) and proteoglycan protein]. Co-immunoprecipitation (Co-IP) experiment was used to verify the binding of SKP2 and PTHrP, ubiquitination experiment was used to analyze the effect of psoralen on SKP2-mediated PTHrP ubiquitination. Results Psoralen significantly inhibited cell apoptosis,the production of IL-6, MMP-3, MMP-13 and ROS (P<0.05 or P<0.01), and promoted the expression of SKP2 and ECM-related proteins of HNPCs after IL-1β and TNF-α induction in a dose-dependent manner (P<0.05). Compared with psoralen + scramble group, the expression levels of SKP2 and ECM-related proteins were significantly reduced (P<0.05), and the apoptosis rate, the levels of IL-6, MMP-3, MMP-13 and ROS were significantly increased in psoralen + SKP2 interference group (P<0.05 or P<0.01).The results of the Co-IP experiment showed that SKP2 is directly bound to PTHrP. The results of the ubiquitination experiment showed that, compared with psoralen + empty vector group, the expression level of PTHrP protein was significantly decreased, and the expression level of SKP2 protein was significantly increased in psoralen + SKP2 over-expression group (P<0.05). Compared with psoralen group, the expression levels of SIRT1 and ECM-related proteins were significantly reduced (P<0.05), and the apoptosis rate,the levels of IL-6, MMP-3, MMP-13 and ROS were significantly increased in psoralen + PTHrP recombinant protein group (P<0.05).Compared with psoralen + PTHrP recombinant protein group, the expression level of PTHrP protein did not change significantly(P>0.05), and the expression levels of SIRT1 and ECM-related proteins were significantly increased (P<0.05), the apoptosis rate,the levels of IL-6, MMP-3, MMP-13 and ROS were significantly decreased in psoralen + PTHrP recombinant protein + SRT1720 group (P<0.05). Conclusion Psoralen can promote SKP2-mediated PTHrP ubiquitination, activate SIRT1, and alleviate NP cell apoptosis in an inflammatory environment.

The outbreak of coronavirus disease 2019 (COVID-19) has become a global pandemic. The pathogen responsible for this disease is a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It belongs to coronavirus family, a pathogen similar to SARS and Middle East respiratory syndrome (MERS), and manifests strong infectivity and pathogenicity to progress into severe pneumonia. Till now, there is no specific therapeutic drug targeting against this virus. With the rapid spread and deterioration of the epidemic situation, vaccination has become an urgent need. This review introduces the immune defense mechanism of human body against coronavirus briefly, set forth the key viral spike protein for coronavirus vaccine development, and then summarize the recent advances/progresses and potential challenges in safety and efficacy of vaccine development for SARS-CoV-2.

Male breast cancer (MBC) is a rare disease for which almost no prospective studies have focused on its diagnosis and treatment. MBC is more likely to be positive for hormone receptor while the ratio of triple negative and human epidermal growth factor receptor 2 (HER2) positive is very low. Most men have undergone radical mastectomy and modified radical mastectomy after diagnosis of breast cancer during past decades and sentinel lymph node biopsy has been gradually used in recent years. The indications of postoperative adjuvant radiotherapy refer to female breast cancer (FBC). Tamoxifen is the first choice of adjuvant endocrine therapy for MBC and chemotherapy can also improve MBC patients' prognosis. Anti-HER2 therapy is recommended for patients with high risks, though there is no definite evidence for its application. Data for the use of new drugs in MBC are lacking,whereas it may be a reasonable approach for metastatic MBC. In general, the overall prognosis of MBC is worse than FBC, but a few studies showed that MBC and FBC had similar survival rates after adjustment for demographic characteristics, disease stage, and treatment. Most of published articles are retrospective studies including small cohorts of MBC patients, which have been reviewed in this article. The review summarizes current data on the epidemiology of MBC, pathological and clinical characteristics, prognosis and treatment, and data published in our country during the past decade.

Objective To explore the correlation of the serum C-reactive protein/albumin ratio (CRP/ALB, CAR) and homocysteine/high-density lipoprotein cholesterol (HCY/HDL-C) to the morbid change of coronary artery disease. Methods A total of 577 patients who underwent coronary angiography in the Department of Cardiology of the 904th Hospital of PLA Joint Logistics Support Force from January 2018 to December 2019 were divided into two groups according to the results of coronary angiography: non-coronary heart group (n=245) and coronary atherosclerotic heart disease group (coronary heart disease group,n=332). The coronary heart disease group was further divided into two subgroups: mild coronary artery disease subgroup (Gensini score <30, n=183) and severe coronary artery disease subgroup (Gensini score ≥30, n=149). The serum levels of CRP, ALB, HCY,HDL-C and other indicators of patients in each group were detected, and CAR and HCY/HDL-C were calculated, and then the logistic regression analysis, Pearson correlation analysis and receiver operating characteristic (ROC) curve analysis were carried out to analyze the independent risk factors for coronary heart disease and severe coronary artery lesion. Results The levels of CAR and HCY/HDL-C were significantly higher in coronary heart disease group than those in non-coronary heart disease group with statistically significant difference (P<0.05). Multivariate logistic regression analysis showed that CAR, HCY/HDL-C, age, hypertension, and gender were the independent risk factors for coronary heart disease and severe coronary artery disease. Pearson correlation analysis showed that CAR and HCY/HDL-C were positively correlated with Gensini score (r=0.427, P<0.01; r=0.247,P<0.01). The results of ROC curve analysis showed that CAR, HCY/HDL-C and both their combination had predictive values for severe coronary heart disease, and the AUC of combined the both factors was statistically higher than that of any single factor alone(P<0.05). Conclusions Elevated levels of CAR and HCY/HDL-C may predict the severe coronary artery disease. The diagnostic value of combined the two factors is better than a single factor alone, so can be used for the diagnosis and condition evaluation of coronary artery disease.

Ferroptosis suppressor protein 1 (FSP1), confirmed as a ferroptosis-resistant factor recently, plays a key role in the oncogenesis and progress of human diseases, such as breast cancer, ovarian cancer, lung cancer, hepatocellular carcinoma,melanoma, lymphoma, leukemia, copper resistance, severe acute pancreatitis, and diabetes. FSP1 is regarded as a double-edged sword according to previous studies. Mechanically, FSP1 triggers caspase-independent apoptosis via its C-terminal fragments,nuclear translocation, or over-expression, and inhibits ferroptosis through FSP1-CoQ₁₀-NAD(P)H axis, being independent of the glutathione (GSH)-GPX4 axis. The research progress in action mechanism of FSP1 in human diseases is briefly described in this review for providing novel preventative and therapeutic target molecules for human diseases.