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.

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.

Objective To investigate the effect of long non-coding small nucleolar RNA host gene 1 (lncRNA-SNHG1) on the proliferation of human hypertrophic scar fibroblasts. Methods The hypertrophic scar tissue and normal skin tissue adjacent to the scar (within 3 cm near the scar) of 22 patients with hypertrophic scar treated and operated in the Department of Burn and Plastic Surgery of the General Hospital of Ningxia Medical University from 2019 to 2021 were collected, and human primary fibroblasts were isolated and cultured from the hypertrophic scar and normal skin tissue adjacent to the scar, while the expression of SNHG1 and miR-382-3p was detected at the tissue and primary cell levels by using qRT-PCR. Proliferative scar fibroblasts were randomly divided into control group, SNHG1 negative control group (adding empty lentivirus vectors), mimic control group (adding control mimic), SNHG1 negative control + mimic control group (adding empty lentivirus vectors and control mimic), SNHG1 overexpression group (adding overexpression lentivirus), miR-382-3p overexpression group (adding miR-382-3p mimics), SNHG1 overexpression + mimic control group (adding overexpression lentivirus and control mimics) and SNHG1 overexpression + miR-382-3p overexpression group (adding overexpression lentivirus and miR-382-3p mimics). qRT-PCR was used to detect the mRNA expression of SNHG1, PCNA, p27 and miR-382-3p in each group; CCK-8 method to detect the proliferation viability of the cells in each group after transfection; EdU staining method to detect the change of proliferation level of each group of cells after transfection;Western blotting to detect the expression levels of p27 and PCNA proteins in each group of cells after transfection. Results SNHG1 presented high expression in hypertrophic scar tissue (3.21±2.65 vs. 1.14±0.61, P<0.001) and primary cells (0.91±0.08 vs. 0.54±0.08, P<0.01), whereas the expression of miR-382-3p was down-regulated (0.53±0.34 vs. 1.15±0.61, P<0.001; 0.84±0.09 vs. 1.01±0.004, P<0.05). Compared with SNHG1 negative control group, the cell proliferation ability of SNHG1 overexpression group increased (0.23±0.03 vs. 0.16±0.01, P<0.001), the percentage of EdU positive cells significantly increased (30.01%±5.70% vs. 7.13%±4.40%, P<0.001), the expression levels of PCNA mRNA and protein increased (mRNA: 2.97±0.33 vs. 0.98±0.25,P<0.01; protein: 2.20±0.09 vs. 0.88±0.20, P<0.05), the expression levels of p27 mRNA and protein decreased (mRNA: 0.30±0.03 vs. 1.42±0.15, P<0.001; protein: 0.47±0.11 vs. 1.13±0.19, P<0.05), and the expression level of miR-382-3p decreased significantly(0.05±0.01 vs. 1.03± 0.12, P<0.001). Compared with SNHG1 overexpression + mimic control group, the cell proliferation ability of SNHG1 overexpression + miR-382-3p overexpression group decreased (0.15±0.02 vs. 0.26±0.01, P<0.001), the percentage of EdU positive cells decreased (5.97%±0.33% vs. 11.70%±0.87%, P<0.001), the expression levels of PCNA mRNA and protein decreased significantly (mRNA: 0.64±0.09 vs. 3.33±0.38, P<0.001; protein: 1.70±0.36 vs. 2.34±0.16, P<0.05), the expression levels of p27 mRNA and protein increased (mRNA: 1.01±0.44 vs. 0.09±0.04, P<0.05; protein: 1.38±0.31 vs. 0.50±0.09, P<0.05). Conclusion SNHG1 presents high expression in hypertrophic scar and can negatively regulate miR-382-3p expression to promote proliferation of primary hypertrophic scar fibroblasts, which may become a potential new target in the treatment of hypertrophic scar.

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 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.

Adipose tissue is inextricably linked to nutritional balance and metabolic diseases, and the way of adipocytes differentiation will directly affect the health of adipose tissue. Preadipocytes are cells that are present at adipose depot and restricted to becoming mature adipocytes specificity. Their favorable differentiation ability to differentiate into healthy mature adipocytes as well as undergo hyperplasia (the expansion of adipose tissue by de novo adipocytes) rather than hypertrophy (the expansion of adipose tissue by increasing the size of already being adipocytes) is crucial for regenerative medicine and obesity-related diseases.Despite much effort has focused on the factors and mechanism about preadipocyte's adipogenic differentiation, the precise regulatory mechanism is still not completely clear. Based on the related research in recent years, this review discusses the ambiguous definition, the origin and terminal differentiation of preadipocytes in brief, summarizes the surface markers of preadipocytes in detail which include stem cell surface markers (such as CD29, CD34, CD38 and SCA1), perivascular markers (such as PDGFRα and PDGFRβ), ZFP423 (zinc-finger protein 423), Pref-1/DLK1 (preadipocyte factor 1). The deep look at preadipocytes provides new ideas for clinical diagnosis and treatment. The clinical application potential of preadipocytes in the treatment of soft tissue defects, obesity-related metabolic diseases, tumors (breast cancer and prostate cancer), and wound healing is further discussed in this review.

Objective To evaluate the predictors of the occurrence of intramyocardial hemorrhage (IMH) in patients with acute ST-segment elevation myocardial infarction (STEMI) after primary percutaneous coronary intervention. Methods A total of two hundred and four patients, admitted in the First Medical Center of Chinese PLA General Hospital from February, 2014 to March, 2019, diagnosed as STEMI undergoing emergency PCI treatment within the first 12 h of evolution, were screened for our retrospective analysis. IMH lesions were visualized by T₂-weighted sequences on cardiac magnetic resonance (CMR) between days 3 to 7 after PCI. Based on the existence of IMH, all patients were classified into the non-IMH group (n=117) and the IMH group (n=87). We investigate the clinical features between the two groups. Factors influencing were analyzed by logistic regression analysis. Results Compared with the non-IMH group, the ischemia time, admission glucose, admission heart rate, hemoglobin(Hb) reduction, creatine kinase isoenzymes (CK-MB) peak value, troponin T (TnT) peak value, low-density lipoprotein cholesterol, infarct size were significantly higher and the left ventricular ejection fraction (LVEF) was significantly lower in IMH group(P<0.05). Besides, in the IMH group, the proportion of patients with diabetes mellitus history, hyperlipemia history, preprocedural thrombolysis in myocardial infarction (TIMI) flow grades <3, anterior infarction, periprocedural glycoprotein Ⅱb/Ⅲa inhibitor treatment was significantly higher (P<0.05). Logistic regression model presented that diabetes mellitus history (P=0.003, OR=7.782,95%CI 2.009-30.846), ischemia time (P<0.001, OR=1.011, 95%CI 1.007-1.014), admission glucose (P<0.001, OR=1.428, 95%CI 1.182-1.725), admission heart rate (P=0.006, OR=1.041, 95%CI 1.012-1.071), Hb reduction (P<0.001, OR=1.117, 95%CI 1.059-1.178), CK-MB peak value (P=0.007, OR=1.006, 95%CI 1.002-1.010), anterior infarction (P=0.042, OR=2.626, 95%CI 1.037-6.652) and periprocedural glycoprotein Ⅱb/Ⅲa inhibitor treatment (P=0.022, OR=3.362, 95%CI 1.195-9.460) were independent risk factors for IMH in acute STEMI patients undergoing PCI. Conclusion Diabetes mellitus history, ischemia time, admission glucose, admission heart rate, Hb reduction, CK-MB peak value, anterior infarction, periprocedural glycoprotein Ⅱb/Ⅲa inhibitor treatment were independent risk factors for IMH in the patients with acute STEMI undergoing primary PCI. Appropriate strategies for managing acute STEMI patients at high risk for IMH should be taken into consideration.

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.

Objective To explore the effect and potential mechanism of miR-125b-5p targecting ΔNp63α in keratinocyte differentiation. Methods To induce keratinocytes (HaCaT) differentiation, 1.8 mmol/L calcium chloride was added in the culture media. The mRNA level of miR-125b-5p, ΔNp63α, cytokeratin 10 (CK10), involucrin (Inv), transglutaminase 1(TG1), phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), and mammalian target of rapamycin (mTOR) during keratinocyte differentiation were quantified by qRT-PCR (at day 0, 1, 5 and 7). The expression of ΔNp63α was detected by cellular immunofluorescence after treatment for 0 and 5 days. The binding site of miR-125b-5p to ΔNp63α was identified by the bibiserv website. The mimics/inhibitors of miR-125b-5p and the mimics/inhibitors of the negative control were transfected into keratinocytes. After five days of culture, the mRNA and protein expression of ΔNp63α, CK10, Inv, TG1, PI3K, Akt and mTOR were determined by qRT-PCR and Western blotting analysis. Results Compared with calcium chloride treatment for 0 days(1.00±0.02), the relative expression level of miR-125b-5p decreased significantly at 1 (0.17±0.02), 5 (0.08±0.01) and 7 days(0.07±0.02) (P<0.001). Compared with calcium chloride treatment for 0 days, the expression of ΔNp63α, CK10, Inv, TG1, PI3K,Akt and mTOR mRNA increased gradually after calcium chloride treatment for 1, 5 and 7 days (P<0.05). The results of cellular immunofluorescence assay showed that the positive rate of ΔNp63α increased after calcium chloride treatment for five days(96.9%±0.9% vs. 43.2%±8.2%, P<0.001). miR-125b-5p can bind to the 3'-UTR site of ΔNp63α. Compared with negative control mimic group, the mRNA expression levels of ΔNp63α, CK10, Inv, TG1, PI3K, Akt, and mTOR decreased significantly in miR-125b-5p mimic group. In addition, the protein expression levels of ΔNp63α, CK10, Inv, TG1, PI3K, Akt, p-Akt, mTOR, and p-mTOR also decreased significantly (P<0.05). Interestingly, the inhibition of miR-125b-5p could reverse the above effects (P<0.05). Conclusion miR-125b-5p targeting ΔNp63α inhibits keratinocyte differentiation by PI3K/Akt/mTOR signal pathway.

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.