Latest ArticlesObjective 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.
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 study the mechanism of +Gz environment exposure induced neck muscle injury in rabbits. Methods A total of 20 male rabbits were randomized into the negative control group, +Gz exposure group, +Gz exposure plus neck loading group, and +Gz exposure plus neck loading plus fixation group (5 in each group). The animal centrifuge was used to simulate the +Gz exposure environment. Rabbits in the +Gz exposure group, +Gz exposure plus neck loading group, and +Gz exposure plus neck loading plus fixation group were exposed for 4 weeks in a +6 Gz environment. Before and after the experiment, the rabbits in each group were photographed by X-ray. At the time of 0-, 1-, 2-, 3- and 4-week exposure, ear vein blood was collected from rabbits in each group, and ELISA was performed to detected plasma leveles of lactate dehydrogenase (LDH), creatine kinase (CK) and reactive oxygen species (ROS). After exposure, the trapezius muscle of rabbits was taken for HE staining to detect the muscle morphology.The apoptosis level was detected by TUNEL in the paraffin section of the rabbit trapezius muscle. The expressions of apoptosis-related proteins Bax and Bcl-2 in the trapezius muscle of rabbits were detected by Western blotting. The rabbit's neck trapezius muscle was taken to conduct proteomics testing, select differentially expressed proteins, and perform protein function cluster analysis. Results There was no significant difference in the morphology of the cervical vertebra in each group before and after+Gz exposure. Compared with negative control group, plasma levels of LDH, CK, and ROS in +Gz exposure group, +Gz exposure plus neck loading group, and +Gz exposure plus neck loading plus fixation group significantly increased (P<0.05). Compared with negative control group, the ratio of apoptosis protein Bax/Bcl-2 in +Gz exposure group significantly increased (P<0.05), the number of positive apoptosis cells detected by TUNEL significantly increased (P<0.05). Compared with +Gz exposure group, the+Gz exposure plus neck loading group showed an increased Bax/Bcl-2 ratio (P<0.05) and more TUNEL positive cells (P<0.05).Compared with +Gz exposure plus neck loading group, the ratio of apoptosis protein Bax/Bcl-2 and the positive number of apoptosis were decreased in +Gz exposure plus neck loading plus fixation group, but there were no statistically significant differences (P>0.05).A total of 600 proteins were significantly altered in +Gz exposure group compared to negative control group, and GO functional clustering analysis of the differential proteins revealed significant enrichment of proteins associated with mitochondrial function. Conclusion Exposure to the +Gz environment can cause neck muscle injury and cell apoptosis in rabbits. The muscle injury symptoms can be improved by fixing the stress link of the rabbit neck. Cell apoptosis induced by +Gz exposure may be related to mitochondrial function.
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.
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 investigate the changes of serum markers of cardiovascular disease risk in patients with acromegaly and the effect of six months of treatment with long-acting octreotide on them. Methods The clinical data of 63 patients with acromegaly (acromegaly group) and 69 healthy people (control group) treated in the First Affiliated Hospital of Chongqing Medical University from May 2012 to January 2021 were collected and analyzed retrospectively. According to the blood glucose level, the patients with acromegaly were divided into three subgroups: normal glucose metabolism (NGT) group (n=25), Impaired glucose regulation (IGR) group (n=11) and diabetes mellitus (DM) group (n=27). The age, body mass index (BMI), blood pressure, growth hormone (GH), blood glucose, blood lipid, high-sensitivity C-reactive protein (hs-CRP), fibrinogen and plasma atherogenic index(AIP) between acromegaly group and control group and three glucose metabolism subgroups were compared, and the relationship between age, BMI, blood pressure, fibrinogen, hs-CRP, blood lipid and AIP was analyzed by Spearman correlation analysis.In addition, 16 of 63 patients with acromegaly who finally completed 6-month long-acting octreotide treatment were studied longitudinally, and the changes of the indexes above were compared before and after treatment. Results Compared with the control group, the levels of BMI, blood pressure, fibrinogen, fasting blood glucose (FPG), triglyceride (TG), lipoprotein a [Lp (a)]and AIP were significantly higher, and of hs-CRP, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were significantly lower (P<0.05) in acromegaly group. For subgroup analysis, the TG level was significantly higher in DM group than that in IGR group and NGT group (P<0.05), while the difference between IGR group and NGT group was not statistically significant; The AIP level was significantly higher in DM group than that in NGT group (P<0.05), and no significant difference existed among the other groups. In correlation analysis, AIP was positively correlated with BMI, fibrinogen, FPG, TG, apolipoprotein B (Apo B), non-high density lipoprotein cholesterol (Non-HDL-C), TC/HDL-C, LDL-C/HDL-C, APO B/APO A-1, and Non-HDL-C/HDL-C, but negatively correlated with HDL-C and apolipoprotein A-1 (Apo A-1). After subgroup analysis, AIP was still correlated with the indexes mentioned above, and the difference was statistically significant (P<0.05). The levels of TG and AIP decreased significantly, but of hs-CRP increased significantly (P<0.05) in patients with acromegaly after 6 months of long-acting octreotide treatment compared with that before treatment. Conclusions The cardiovascular risk of patients with acromegaly is increased. Long acting octreotide treatment can reduce the risk of cardiovascular disease in patients with acromegaly.
Objective To evaluate the diagnostic value of magnetic resonance imaging (MRI) and mammography (MG)in clustered calcification of breast lesions. Methods The imaging and pathological data of 62 patients with clustered calcification breast lesions in the Chinese PLA General Hospital was retrospectively analyzed to compare the diagnostic efficacy of MRI and MG. Results Of 62 clustered calcification lesions, 20 were benign according to pathologic result, and 42 were malignant. In MRI examination, 14 cases (22.6%) were classified as 1-3, 11 cases (17.7%) as 4, and 37 cases (59.7%) as 5. In MG examination, 10 cases (16.1%) were classified as 1-3, 30 cases (48.4%) as 4, and 22 cases (35.5%) as 5. The consistency between MRI and MG was poor (Kappa=0.346). The diagnostic efficacy of MRI (AUC=0.940, 95%CI 0.850-1.000) was higher than that of MG (AUC=0.800,95%CI 0.686-0.914), and the sensitivity, accuracy, positive predictive value, negative predictive value of MRI (85.7%, 88.7%, 97.3%,76.0%) were higher than those of MG (50.0%, 64.5%, 95.5%, 47.5%). Conclusion For clustered calcification of breast lesions, the diagnostic value of MRI is higher than that of MG.
Objective To explore the promoting effect and its mechanism of shikonin on wound healing and neovascularization of rats with chronic skin ulcer. Methods Fifty of 60 male SD rats were selected to establish the rat model of chronic skin ulcer, of which 40 rats were done successfully and randomly divided into the model group, positive control group, and low- and high-dose shikonin groups (10 rats each). The other 10 rats served as the control group. The wound surfaces in low-and high-dose shikonin group were evenly smeared with 4 mg/cm2 and 8 mg/cm2 shikonin suspension, in positive control group with 1890 U/cm2 recombinant bovine basic fibroblast growth factor gel to smear the wound, and in model group and positive control group were given the equal volume of normal saline for external application. The wound healing was observed on the 3rd,7th and 14th day of intervention. The abdominal aortic blood and wound granulation tissue of rats were taken after intervention, the histopathological changes of wound granulation were observed by HE staining, and the neovascularization was observed by immunohistochemical staining; the content of hydroxyproline (HyP) in granulation tissue was detected by hydrolysis method, the expression of Notch1 pathway related protein in granulation tissue was detected by Western blotting; and the levels of serum inflammatory factors were detected by ELISA. Results The wound healing rate of skin ulcer in each group increased with time and in a time-dependent manner (P<0.05). The wound healing rate decreased in low- and high-dose shikonin groups than in positive control group, and decreased in low-dose shikonin group than in high-dose shikonin group on the 3rd, 7th and 14th day of intervention (P<0.05). HE staining showed that new granulation tissue with a large number of inflammatory cell infiltration could be seen in model group. Compared with model group, old granulation tissue and inflammatory cell infiltration were observed in low- and high-dose shikonin groups and positive control group, and the inflammatory cell infiltration decreased in turn. Compared with that in positive control group, the IOD value of wound granulation tissue decreased in low- and high-dose shikonin groups(104 725.45±2062.45 vs. 197 585.23±2478.42, P<0.05; 149 752.54±2441.86 vs. 197 585.23±2478.42, P<0.05), and the content of HyP decreased [(3.62±0.12) μg/mg vs. (6.48±0.14) μg/mg, P<0.05; (4.94±0.15) μg/mg vs. (6.48±0.14) μg/mg, P<0.05].The IOD value and HyP content of wound granulation tissue were higher in high-dose shikonin group than in low-dose shikonin group (P<0.05). Western blotting results showed that the relative expressions of vascular endothelial growth factor (VEGF) and transforming growth factor β1 (TGF-β1) in wound granulation tissue increased, and of Notch1 protein decreased in low- and high-dose shikonin groups than in model group (P<0.05), while the relative expression of VEGF and TGF-β1 increased and of Notch1 protein decreased in wound granulation tissue of high-dose shikonin group than in low-dose shikonin group (P<0.05). ELISA results showed that the levels of serum IL-8 and TNF-α decreased in positive control group and low- and high-dose shikonin groups than in model group (P<0.05), but increased in low- and high-dose shikonin groups than in positive control group (P<0.05), and decreased in the high-dose shikonin group than in low-dose shikonin group (P<0.05). Conclusion Shikonin may promote the wound healing and neovascularization of rats with chronic skin ulcer by regulating Notch1 signaling pathway.
Female urethral stricture is considered to be one of the important causes of female lower urinary tract symptoms, but it is relatively rare in clinical practice and lacks relevant diagnostic and therapeutic guidelines. In the past, urethral dilation was used as the first-line treatment option for this disease. However, due to its low success rate, high recurrence rate of stricture, and with the development of research on the structure of the female urethra, a variety of urethroplasty procedures have been applied. The success rate of urethroplasty is high, but it is not clear which procedure is more superior. This article reviews the research progress in the etiology, diagnosis and treatment of female urethral stricture to provide a reference for urologists to carry out a variety of treatment methods, and to promote the clinical application of related diagnosis and treatment.
Objective To investigate the effect of fatty acid binding protein 4 (FABP4) in cardiomyocyte pyroptosis induced by homocysteine (Hcy). Methods The cultured rat cardiomyocytes were divided into two groups: control group(0 mmol/L Hcy) and Hcy group (3 mmol/L Hcy). The expression of FABP4 and pyroptosis related proteins [NOD-like receptor protein 3 (NLRP3), caspase-1, interleukin-1β (IL-1β)] were detected by Western blotting. The expression level of FABP4 mRNA was detected by qRT-PCR. The changes of expression of pyroptosis associated proteins were detected by immunofluorescence staining. The cultured cardiomyocytes were treated with FABP4 inhibitor (BMS-309403), and then divided into control group (0 mmol/L Hcy), Hcy group (3 mmol/L Hcy) and Hcy+BMS-309403 group (3 mmol/L Hcy and 50 μmol/L BMS-309403), and the expression levels of pyroptosis related proteins were then re-detected. Results Compared with control group, Western blotting showed that the expression levels of FABP4, NLRP3, caspase-1 and IL-1β in Hcy group increased significantly (P<0.05); Compared with control group, qRT-PCR results showed that the expression of FABP4 in Hcy group increased significantly (P<0.05); Compared with control group, immunofluorescence staining results showed that the fluorescence intensity of NLRP3, caspase-1 and IL-1β in Hcy group increased significantly. After adding FABP4 inhibitor (BMS-309403) and Hcy treatment, the expression levels of FABP4, NLRP3, caspase-1 and IL-1β in Hcy+BMS-309403 group decreased significantly compared with Hcy group (P<0.05 or P<0.01). Conclusion FABP4 may promote cardiomyocytes pyroptosis induced by homocysteine.