Objective To investigate the interventional effect of anwulignan on pulmonary fibrosis and the underlying mechanism. Methods Sixty-five male ICR mice were randomly divided into control group, bleomycin (BLM) model group, anwuzhisu low dose group (1 mg/kg), anwuzhisu high dose group (4 mg/kg) and N-acetylcysteine group (150 mg/kg), with 13 mice in each group. Mouse pulmonary fibrosis model was induced by intratracheal perfusion of 5 mg/kg BLM. The serum and lung tissues were collected, and the pathological changes of lung tissues were observed by HE staining and Masson trichrome staining; serum oxidative stress index and hydroxyproline (HYP) content in lung tissue were measured by kit; the expression level of iron death pathway related genes was detected by Western blotting and qRT-PCR. Take the logarithmic growth phase HFL-1 cells, (1) set the control group and anwuzhisu administration group (0.3125, 0.625, 1.25, 2.5, 5, 10, 20,40, 80 μmol/L), and CCK-8 method was used to detect the toxic effect of anwuzhi on HFL-1 cells. (2) Set the control group, transforming growth factor (TGF)-β₁ model group, anwuzhisu low dose group (5 μmol/L) and anwuzhisu high dose group(10 μmol/L), with TGF-β₁ induced pulmonary fibrosis cell model. The oxidative stress index and reactive oxygen species(ROS) level were measured by kit; the expression level of iron death pathway related genes was detected by Western blotting and qRT-PCR. Results HE staining, Masson trichrome staining and the increase of HYP content indicated that the BLM-induced pulmonary fibrosis model was successfully constructed, and the pulmonary fibrosis phenotype was significantly improved after the administration of anwulignan. CCK-8 assay showed that the concentration of anwulignan <20 μmol/L had no significant effect on the proliferation activity of HFL-1 cells (P>0.05). Compared with model group, the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT) and the levels of glutathione (GSH) in lung tissues of mice and HFL-1 cells were significantly increased after the administration of anwulignan, while the levels of malondialdehyde(MDA) were significantly decreased (P<0.01 or P<0.001). Compared with TGF-β₁ model group, 10 μmol/L anwulignan could decrease the level of ROS in HFL-1 cells (P<0.01). Western blotting and qRT-PCR results showed that anwulignan could significantly up-regulate the expressions of ferroptosis pathway related genes in lung tissues of mice and HFL-1 cells including glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11) and transferrin (TF), and significantly down-regulate the expression of transferrin receptor 1 (TFR1) (P<0.05, P<0.01 or P<0.001). Conclusion Anwulignan can improve pulmonary fibrosis by inhibiting oxidative stress and ferroptosis, laying a foundation for the development of clinical drugs for pulmonary fibrosis.

The purpose of Bacillus Calmette-Guérin (BCG) vaccination is to prevent Mycobacterium tuberculosis infection, but studies have shown that BCG activates innate immunity, causes epigenetic reprogramming and metabolic changes of myeloid cells, and forms innate immune memory or trained immunity. When bone marrow-like cells are stimulated by pathogens again, they show enhanced immune response and promote the host's nonspecific defense ability. Innate immune memory is also called training immunity. In recent years, BCG-induced innate immune memory has attracted much attention, and it will guide the design of novel vaccine. This article reviews the application of BCG in prevention and treatment of corone virus disease 2019, the non-specific protection and mechanism of BCG-mediated trained immunity.

Myocardial infarction (MI) is cardiomyocyte necrosis caused by myocardial ischemia and hypoxia, and is the leading cause of death and disability in the world. Although direct percutaneous coronary intervention (PCI) can restore epicardial coronary blood flow and reduce the mortality of MI, some patients with MI will still develop into chronic heart failure. As an important complication caused by reperfusion therapy, intramyocardial hemorrhage (IMH) is defined as red blood cell extravasation caused by severe microvascular injury, and can be used as an independent predictor of the adverse ventricular remodeling after myocardial infarction, which is the pathological basis of heart failure after myocardial infarction. At present, the main evaluation method for IMH is cardiac magnetic resonance imaging (MRI), especially the qualitative and quantitative evaluation of intracardial bleeding can be achieved by T₂* sequence. It has been shown that iron deposition after degradation of IMH exacerbates the inflammatory response, leading to the aggregation of macrophages and secretion of matrix metalloproteinases, which are involved in subsequent adverse ventricular remodeling. The recent progress of clinical and basic research on the relationship between IMH and the adverse ventricular remodeling after MI are reviewed in present paper, hoping to be helpful for the prevention and treatment of IMH in the future.

Pulmonary arterial hypertension (PAH) is a progressive disease with poor prognosis, which may lead to right heart dysfunction, resulting in a series of clinical symptoms and even death, and there is still a lack of effective treatment. The etiology of PAH is complex, in which epigenetic changes play an important role in its pathogenesis. Histone acetylation modification is one of the most widely and deeply studied epigenetic modifications. The histone acetylation is mainly regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), which play a key role in chromatin and gene regulation, and is closely related to the occurrence of PAH. Targeted histone acetylation pathway has a certain therapeutic potential for PAH. This article reviews the research progress on the effect of HDACs on PAH, in order to further understand the pathogenesis of PAH and provide a new direction of treatment.

Objective To investigate the clinical value of serum iron in diagnostic and prognostic evaluation of sepsis. Methods Retrospectively analyzed 85 cases of sepsis patients and 50 sex- and age-matched non-septic patients admitted to the ICU of the First Affiliated Hospital of Dali University from September 2018 to September 2019. According to the prognosis at 28 d, 85 sepsis patients were divided into survival group (n=51) and non-survival group (n=34). Serum iron levels were compared between the two groups. Correlation analysis between serum iron and these indices as erythrocytes, hemoglobin, C-reactive protein (CRP), procalcitonin (PCT), interleukin-1β (IL-1β), sequential organ failure assessment (SOFA) scores were performed. The receiver operating characteristic curves (ROC) were plotted to evaluate the ability of serum iron in the diagnosis and prognosis evaluation of sepsis. Kaplan-Meier survival analysis was conducted comparing the survival rates between the patients with different levels of serum iron. Cox proportional hazards regression model was used to screen the risk factors for prognosis of the patients with sepsis. Results The serum iron levels were much lower in the septic patients [8.55(4.80, 15.53) μmol/L] than those in the controls [5.30(3.15,7.90) μmol/L]. And a significantly reduced serum iron level was observed in septic patients who died [4.45(1.80, 6.88) μmol/L]than survival patients [6.30(3.80, 9.50) μmol/L]. ROC analysis indicated that the serum iron exhibited the capability to identify individuals with sepsis, with an area under curve (AUC) of 0.71, and estimated prognosis of sepsis patients, with an AUC of 0.70.Kaplan-Meier survival analysis showed that lower serum iron levels (<2.5 μmol/L) were correlated with poor 28-day survival in septic patients (P=0.003). Spearman correlation analysis suggested a significant negative correlation between serum iron levels and IL-1β levels (r=–0.51, P<0.001). Additionally, univariate Cox proportional hazards regression model suggested that lower serum iron level was a risk factor for sepsis (HR=0.86, P=0.009). Conclusion Serum iron is useful in predicting the 28-day mortality among sepsis patients, especially those with serum iron less than <2.5 μmol/L.

Objective To analyze the significance and biological role of MAGEA6 expression in gastric cancer. Methods The tissue microarray samples of 90 cases of gastric cancer resected surgically in the hospital sample bank from December 2009 to June 2010 were collected. The expression of MAGEA6 in gastric cancer tissue microarray was detected by immunohistochemical staining, and the relationship between MAGEA6 expression and clinicopathological features of gastric cancer was analyzed.Kaplan-Meier analyzed the relationship between the expression of MAGEA6 and the prognosis of gastric cancer. BGC-823 gastric cancer cell line was cultured in vitro. Set si-MAGEA6 group (transfected with si-MAGEA6) and si-Ctrl group (transfected with vector), the cell proliferation ability and apoptosis rate were detected by CCK-8 and flow cytometry. Western blotting detected the expression of MAGEA6, apoptosis-related proteins [b lymphoma-2 gene (Bcl-2), bcl-2 related X protein (Bax)], autophagy-related proteins [microtubule associated protein light chain 3-Ⅱ (LC3-Ⅱ), p62 protein (p62), autophagy-related gene 5 (Atg5) protein, yeast Atg6 homolog (Beclin 1)], Akt/mTOR signaling pathway-related proteins [protein kinase B (Akt), phosphorylated protein kinase B (p-Akt), mammalian target of rapamycin (mTOR), phosphorylated mammalian target of rapamycin (p-mTOR)]. The autophagy flow and autophagosome formation were observed by laser confocal microscope and electron microscope. Results The immunohistochemical score of MAGEA6 in gastric cancer tissues was higher than that in adjacent tissues [(3.77±1.50) points vs.(2.58±1.11) points, P<0.05]. Patients with high expression of MAGEA6 were significantly related to age and TNM stage (P<0.05).The cell viability of gastric cancer cells in si-MAGEA6 group was lower than that in si-Ctrl group (P<0.05). The apoptosis rate of gastric cancer cells in si-MAGEA6 group was higher than that in si-Ctrl group (14.97%±0.86% vs. 4.63%±0.55%, P<0.05). The protein expression levels of MAGEA6, Bcl-2, p62, p-Akt, and p-mTOR in si-MAGEA6 group were lower than those in si-Ctrl group, the protein expression levels of Bax, Atg5, Beclin 1, and LC3-Ⅰ/LC3-Ⅱ were higher than those in si-Ctrl group (P<0.05). In the si-MAGEA6 group, autophagy bodies increased significantly, and autophagy bodies and lysosomes formed autophagy lysosomes. Conclusions Gastric cancer tissues showed a significantly increased level of MAGEA6. Silencing MAGEA6 expression inhibits the proliferation of gastric cancer cells, suggesting that MAGEA6 may be an effective biomarker and potential therapeutic target for gastric cancer.

Objective To explore the risk factors of persistent ectopic pregnancy (PEP) in patients with fallopian tubal pregnancy after tubal pregnancy surgery. Methods A total of 38 patients, who underwent the tubal pregnancy surgery in International Peace Maternity and Child Health Hospital affiliated to Medical College of Shanghai Jiao Tong University from January 2000 to December 2020, were selected as the research subjects and included into PEP group; and another 152 patients undergone the same operation during the same period and recovered well were selected as control group. The clinical data of the two groups were analyzed retrospectively. The age, gravidity, body mass index (BMI), menopause duration, previous fallopian tube surgery history, postoperative serum β-human chorionic gonadotropin (β-HCG) decline rate, tubal pregnancy site, ectopic pregnancy focus, and intraoperative pelvic adhesion etc. of all patients were recorded and analyzed. The clinical baseline data of the two groups were analyzed. The chi square test was used to analyze the risk factors of PEP after tubal pregnancy surgery, and Poisson regression analysis was performed to do the multivariate analysis. The independent risk factors of PEP after tubal pregnancy surgery were screened, and then the treatment method of PEP after tubal pregnancy surgery was analyzed. Results There were no significant differences between PEP group and control group in terms of age, gravidity, BMI and menopause duration. Univariate analysis showed that the PEP after tubal pregnancy surgery was related to emergency/elective surgery, pelvic adhesion and the rupture of ectopic pregnancy lesions/abortion, and the difference was statistically significant (P<0.05), while no obvious relation to the operation method, the location of tubal pregnancy and the size of ectopic pregnancy focus. Poisson regression analysis showed that the pelvic adhesion and the rupture of ectopic pregnancy lesions/abortion were the independent risk factors of PEP. The cure rates with methotrexate (MTX) treatment was 95% for PEP patient after tubal pregnancy surgery. Conclusion The pelvic adhesion and the rupture of ectopic pregnancy lesions/abortion were the independent risk factors of PEP after the tubal pregnancy surgery.

Coagulation dysfunction occurs in more than 40% of severe patients. The adverse bleeding events, blood transfusion volume and mortality of severe patients with coagulation dysfunction may be increased by more than 4 times. Early recognition of the coagulation dysfunction and accurate evaluation of coagulation function are the premise and guarantee of correcting the coagulation dysfunction as soon as possible. However, there is still a lack of standards for rapid and accurate evaluation of coagulation dysfunction in severe patients at home and abroad. Therefore, the People's Liberation Army Professional Committee of Critical Care Medicine and Chinese Society on Thrombosis, Hemostasis and Critical Care of China Medicine Education Association jointly formulate this consensus. The related concepts, evaluation methods and diagnostic criteria of coagulation dysfunction in severe patients have been included in the present paper in order to provide corresponding guidance for clinical work.

At present, there is a relatively complete guideline for heart failure with ejection fraction reduction (HFrEF), but there is still a lack of evidence-based medical evidence for heart failure with preserved ejection fraction (HFpEF) treatment criteria.In recent years, a large amount of evidence has emerged that a new oral hypoglycemic drug sodium-glucose cotransporter 2 inhibitor(SGLT2i) can significantly reduce the risk of cardiovascular death and the hospitalization rate of heart failure in patients with type 2 diabetes mellitus, and improve the prognosis of HFrEF. However, there is still a lack of overall understanding of the mechanism and research progress of SGLT2i in the treatment of HFpEF. This article reviews the pathological mechanism of HFpEF, the mechanism of action of SGLT2i and the related research on the treatment of HFpEF, in order to provide reference for the clinical drug treatment of HFpEF.

Objective To investigate the relationship between autoantibodies and biochemical responses to different doses of ursodeoxycholic acid (UDCA) in the treatment of primary biliary cholangitis (PBC). Methods Clinical data of 122 patients with PBC admitted to the Department of Gastroenterology, the Second Affiliated Hospital of Kunming Medical University from January 2013 to August 2020 were retrospectively analyzed. According to the treatment dose of UDCA, they were divided into >15 mg/(kg.d)UDCA group (n=71)and ≤15 mg/(kg.d) UDCA group (n=51). The relationship between antibody typing and treatment response to different doses of UDCA group and the effects of different doses of UDCA on biochemical indexes and immune indexes of PBC patients were analyzed. Results Baseline anti-SSA positive PBC patients were associated with >15 mg/(kg.d) UDCA response (P<0.05); Pathological stage Ⅱ was associated with ≤15 mg/(kg.d) UDCA response (P<0.05). The level of alanine transaminase (ALT), aspartase aminotransferase (AST), alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT), total bilirubin (TBIL), IgM and the positivity rates of antinuclear antibodies (ANA) in>15 mg/(kg.d) UDCA group were significantly decreased after 1 year of treatment, and the pre-albumin was significantly increased (P<0.05).The levels of ALP and GGT and the positivity rates of anti-mitochondrial antibody type 2 (AMA-M2) in UDCA group ≤15 mg/(kg.d)after one year of treatment were significantly lower than those before treatment, and the pre-albumin level was significantly decreased (P<0.05).From the perspective of pathological stages, the >15 mg/(kg.d) UDCA group was dominated by stages Ⅲ and Ⅳ, and the ≤15 mg/(kg.d)UDCA group by stages Ⅰ and Ⅱ. The positivity rate of anti-gp210 was higher in non-response group than that in response group regardless of dose. Conclusions Both large and small doses of UDCA can improve the biochemical and immune indices of PBC patients, but for patients with severe disease and advanced pathological stage, high-dose UDCA therapy is recommended.