Objective To analyze the expression of circRNA0087432 (hsa_circ_0087432) in serum exosomes of patients with cervical cancer, and explore its possible relationship with cervical cancer metastasis. Methods The cervical cancer tissue and serum of 30 patients, who were diagnosed as cervical squamous cell carcinoma from June 2019 to June 2020 in Guangzhou Panyu District Central Hospital and untreated with radiotherapy and chemotherapy before surgery, were collected as the experimental group.Normal cervical tissue and serum of 30 women without cervical cancer were used as control group. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression level of hsa_circ_0087432 in cervical tissues and serum exosomes of patients with cervical cancer and healthy people; Siha cells were transfected with plasmid to overexpress hsa_circ_0087432. According to different treatments, Siha cells were divided into three groups: control group (untransfected plasmid), vector group (transfected with pLC5-ciR) and hsa_circ_0087432 group (transfected with hsa_circ_0087432-pLC5-ciR). The exosomes were collected and extracted, and the exosyndrome were characterized by transmission electron microscope (TEM), nanoparticle tracking analysis (NTA)and Western blotting; Endothelial cells were divided into three groups according to different treatments: control-Exs group (extracted exosomes from control group), vector-Exs group (extracted exosomes from vector group) and hsa_circ_0087432-Exs group (extracted exosomes from hsa_circ_0087432 group). CCK-8 kit was used to detect the effect of exosomes on proliferation of endothelial cells.The effect of exosomes on the migration of endothelial cells were detected by scratch test and Transwell. Results The results of TEM showed that most of the exosomes of Siha cells were elliptical or round. The particle size analysis showed that their diameters ranged of 30-150 nm. Western blotting showed that the expressions of CD9, CD81 and CD63 in the two groups of vesicles were positive. The qPCR results showed that the expression level of hsa_circ_0087432 in cervical tissue was significantly higher in experimental group than that in control group (4.03±1.51 vs. 1.00±0.26, P<0.01), and the expression level of hsa_circ_0087432 in serum exosomes was also obviously higher in experimental group than that in control group (1.97±0.04 vs. 1.02±0.23, P<0.01); CCK-8 results showed that, compared with the control-Exs group, the proliferation of human umbilical vein endothelial cells was significantly promoted in hsa_circ_0087432-Exs group (1.57±0.04 vs. 1.09±0.11, P<0.05). Scratch experiments showed that, 12 hours after treatment, the healing degree was better in hsa_circ_0087432-Exs group than that in control-Exs group (24.66%±2.92% vs. 15.01%±3.12%, P<0.05); and 24 hours after scratching, the healing degree was even better in hsa_circ_0087432-Exs group than that in control-Exs group (74.84%±13.22% vs. 38.70%±2.12%, P<0.01). Transwell also showed that the counted number of endothelial cells increased obviously in hsa_circ_0087432-Exs group than that in vector-Exs group and control-Exs group (1755.00±97.35 vs. 1218.00±103.53 vs. 1044.00±103.79) with significant difference (P<0.05). Conclusion The hsa_circRNA 0087432 is highly expressed in serum exosomes of patients with cervical cancer, and the exosomes derived from cervical cancer cells which over-pressing the hsa_circ_0087432 can promote the proliferation and migration of human umbilical vein endothelial cells.

Activated transcription factor 6 (ATF6) is a transmembrane glycoprotein located in the endoplasmic reticulum.It exists widely in various tissues including myocardium and participates in endoplasmic reticulum stress (ERS) by regulating the unfolded protein response (UPR) signal pathway, which has become one of the major regulators of organs/tissues homeostasis and is of great significance in signal transduction, gene expression and protein synthesis. A number of studies have shown that ATF6 plays an important regulatory role in the occurrence and development of atherosclerosis, myocardial infarction, cardiac hypertrophy, diabetic cardiomyopathy, arrhythmia and other common cardiovascular diseases (CVD). At present, some studies have proved that ATF6 can regulate its activity and function to intervene the occurrence and development of some CVD. As a result, whether a small molecule regulator can be designed to treat some CVD by regulating ATF6 has become a research hot-spot. ATF6-based therapies have made great progress and have shown promising efficacy in small animal models of CVD and other systemic protein-based diseases. The small molecule regulator to ATF6 has a broad application prospect in cardiovascular disease, but further basic and clinical studies are still needed to lay the theoretical and practical foundation for its application. In present paper, the structure, classification and correlation of ATF6 with CVD are reviewed in order to provide references for experimental researches, clinical diagnoses and treatments of CVD.

Objective To study the warning indicators and clinical value of coagulopathy related to traumatic lung injury(TLI). Methods The data of 159 patients with TLI from September 2015 to November 2019 in the intensive care unit of the 908th Hospital of Chinese PLA Logistical Support Force were analyzed retrospectively, including their hemoglobin (HGB), platelet (PLT), fibrinogen (FIB), activated partial thromboplastin time (APTT), prothrombin time (PT), international normalized ratio (INR), thrombin time (TT), D-dimer (D-D), antithrombin Ⅲ (AT-Ⅲ), fibrin degradation product (FDP) and thromboelastography.According to the 90-d prognosis of patients with TLI, they were divided into survival group (n=141) and death group (n=18). COX regression analysis and ROC curve analysis were carried out, and the risk factors INR were screened out. The patients were divided into INR≥1.36 group (n=49) and INR<1.36 group (n=110) for analysis. Results In survival group, INR, lactate (Lac), and injury severe score (ISS) score were significantly lower than those in death group (Z=–4.493, –3.481, –3.177, P<0.01); APTT, PT, R time and K time were much shorter than death group (Z=–3.275, –4.325, –3.300, –2.278, P<0.01); Oxygenation index, PLT, HGB, AT-Ⅲ, blood clots maximum intensity (MA), blood clot formation dynamics (Angle) and coagulation index (CI) were significantly better than those in death group (Z/t=–4.053, –2.764, 0.269, –2.159, –3.058, –3.294, –3.016, P<0.01). Cox regression analysis showed that INR (RR=2.18, 95%CI 1.07-4.43, P=0.031) were significantly correlated with the death of TLI patients. ROC curve analysis showed that the area under the curve for INR to judge the death of TLI patients was 0.826 (P<0.0001), the cut-off value was 1.36 (P<0.0001)and the sensitivity and specificity were 0.788 and 0.752, respectively. The survival rate in INR<1.36 group was significantly higher than that in INR≥1.36 group (P<0.0001). Compared with INR<1.36 group, in INR≥1.36 group, the Lac and ISS score significantly increased (P<0.05); APTT, PT and K time significantly prolonged (P<0.05); the oxygenation index, PLT, HGB, AT-Ⅲ, MA, Angle and CI decreased significantly (P<0.05). Conclusions TLI patients with INR≥1.36 can be used as an early warning indicator of TLI-related coagulopathy, and the risk of death of TLI related coagulation disease patients is significantly increased.

Objective To construct a prediction model based on machine learning algorithm for cirrhosis-related hepatic encephalopathy. Methods A cross-sectional survey was conducted in 1498 patients from 7 medical institutions in Chongqing from June 2019 to June 2020, who were divided into hepatic encephalopathy group (n=285) and non-hepatic encephalopathy group(n=1213) according to whether hepatic encephalopathy occurred. 70% (1048 in total) of the data collected from 1498 patients was randomly chosen as the training set for establishing the prediction model and the rest 30% (450 in total) was used for internal verification. Univariate logistic regression was used to filter input indicators. Logistic regression, random forest, decision tree and XGBoost algorithm based on machine learning were used to construct a diagnostic predictive model. The models constructed by the four methods were compared for predictive and diagnostic value of cirrhosis-related hepatic encephalopathy. Results Logistic regression, random forest, decision tree and XGBoost models all suggested prothrombin activity (OR=0.933, 95%CI 0.921-0.946), age (OR=1.045, 95%CI 1.029-1.061), blood sodium (OR=0.964, 95%CI 0.928-1.000) and urea nitrogen (OR=1.063, 95%CI 1.022-1.105) are important influencing factors of hepatic encephalopathy. The sensitivities of the four models were 0.843, 0.904, 0.759 and 0.892; the specificities were 0.785, 0.695, 0.717 and 0.706; the area under the curve (AUC) were 0.875, 0.883, 0.767 and 0.847 respectively. Conclusions The risk prediction model of cirrhosis-related hepatic encephalopathy established based on machine learning has high diagnostic value. The diagnostic effects of logistic and random forest models are better than those of decision tree and XGBoost models.

Objective To summarize the clinical characteristics of patients suffering from invasive pulmonary aspergillosis(IPA) associated with pulmonary nocardiosis (PN) for improving the level in diagnosis and treatment of the disease. Methods The clinical characteristics, diagnosis and treatment of one patient diagnosed with IPA and PN in the First Medical Center of Chinese PLA General Hospital in January 2017 were reported. Wanfang, CNKI, PubMed, Web of Science and Embase databases were searched, and the clinical characteristics and diagnosis and treatment process of patients with IPA and PN were analyzed together with this patient. Results This patient was a 66-year-old male. His underlying disease was nephrotic syndrome, and long-term treatment with hormones and other immunosuppressive agents. The clinical manifestations were cough, yellow sputum, fever. Chest CT showed multiple nodules in both lungs. Aspergillus and Nocardia were found in the sputum. The patient was clearly diagnosed as "invasive pulmonary aspergillosis combined with pulmonary nocardiosis". After targeted anti-infective treatment, the patient recovered. Combined with the literature, a total of 24 cases of patient, including 16 males and 8 females, were analyzed; except for one patient who was infected after drowning, the other 23 patients had immunological impairment; all the patients received anti-infective treatment against Aspergillus and Nocardia, and a total of 6 deaths. Conclusions Patients with IPA may be associated with PN, and it is prone to occur in immunosuppressed patients. Attention should be paid to differential diagnosis during clinical diagnosis and treatment. Early diagnosis and treatment may have a positive effect on improving the prognosis.

Objective To investigate the effect of oleanolic acid (OA) in the maturation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) through switching pyruvate kinase type M isoforms. Methods HiPSC-CMs were derived from human induced pluripotent stem cells (hiPSCs), through sequential activation and inhibition of the Wnt signaling pathway. On day 19 hiPSC-CMs were divided into control group (RPMI 1640+B27), DMSO group (RPMI 1640+B27+2 μl DMSO), and 10 μmol/L OA group (RPMI 1640+B27+2 μl 5 mmol/L OA) and treated for 7 days, and the medium was changed every 2 days. Immunofluorescence or RT-qPCR were used to detect the expression of stem factor in hiPSCs and cardiac specific markers in hiPSC-CMs. Western blotting was used to detect the expression of PK and mitofusin 2 (MFN2). Mito-Tracker staining showed the morphology of mitochondria, and transmission electron microscope (TEM) showed the ultrastructure of mitochondria. EDU staining was used to detect cell proliferation, and flow cytometry was used to detect cell cycle. Results Immunofluorescence showed that hiPSCs expressed Nanog and Sox2, and hiPSC-CMs expressed myocardial specific markers cTnT, Cx43 and α-actinin.RT-qPCR showed that, compared with hiPSCs, significant differences (P<0.05 or P<0.01) existed in hiPSC-CMs expressed troponin I3 (TNNI3), myosin heavy chain 6 (MYH6), and myosin heavy chain 7 (MYH7). Immunofluorescence showed that, compared with control group and DMSO group, the cell area increased, sarcomere length increased, and the cell circularity decreased in hiPSC-CMs cultured with OA, and the differences were statistically significant (P<0.05); Western blotting showed that, compared with control group and DMSO group, the ratio of PKM1/PKM2 and the expression of MFN2 increased obviously, and the differences were statistically significant (P<0.05 or P<0.01), the fusion lengthening of mitochondria was observed under electron microscope, and Mito-Tracker staining showed that mitochondria formed more mature structure; EDU staining showed a decreased cell proliferation in hiPSC-CMs cultured with OA group compared with control group and DMSO group, all differences were statistically significant(P<0.05). The flow cytometry results indicated that the number of coenocytes increased in hiPSC-CMs cultured with OA group compared with control group and DMSO group. Conclusion OA can promote the maturation of cell structure, mitochondrial structure and morphology, and also can promote cell multinucleation. OA can promote hiPSC-CMs' maturation by switching pyruvate kinase type M isoforms.

Objective To report a case of atrial septal defect (ASD) with congenital fibrinogen deficiency (CFD), and review the literature. Methods A case of secondary ASD with CFD treatment in Xuanwu Hospital of Capital Medical University was reported, and the defect was repaired under CPB on beating heart. The management experience of cardiac surgery under CPB in patients with CFD was summarized by means of PubMed database and literature analysis. Results This patient was female,30 years old. She was admitted to the hospital with the complaint that ASD was found for 8 months after physical examination. On admission, echocardiography showed that the atrial septum was interrupted by about 34 mm. Color Doppler flow imaging(CDFI) detection indicated systolic left to right shunt, the pressure difference of tricuspid regurgitation was 66 mmHg, systolic pulmonary artery pressure (SPAP) was 76 mmHg, ejection fraction (EF) was 64%. Coagulation function: Prothrombin time was>120 s, thrombin time >240 s, activated partial thrombin time >180 s, and fibrinogen <0.6 g/L. Preoperative continuous intravenous infusion of fibrinogen 4 g per day was to maintain the plasma fibrinogen >1.5 g. Three days later ASD repair was performed under CPB on beating heart. Infusion of fibrinogen 2 g was performed by venous injection during operation, and another fibrinogen 2 g was given after heparin was neutralized by protamine. Operation time was 3.5 hours, and CPB time was 45min. Fibrinogen 4 g per day was supplemented postoperatively for 5 days. At the 3rd day chest drainage tube was removed. The patient was discharged at the 7th day. There were no hemorrhage and thrombosis complications. After 3 months, outpatient follow-up showed the surgical incision healed well, echocardiography showed no residual shunt in the atrial septum, and EF value was 67%. A total of 8 English literatures were obtained after searching PubMed database and manually screening, including 875 patients with hypofibrinogenemia after CPB cardiac surgery. Among them, 604 were males (69.0%) and 271 were females (31.0%). There were 6 case reports, including 1 infant(5 days old, weight 2.5 kg) and 5 adult cases, and they were all male. Patients with abnormal afibrinogenemia may have both bleeding and thromboembolic symptoms. Patients with fibrinogen deficiency who undergo CPB cardiac surgery need to be supplemented with fibrinogen, cryoprecipitation or fresh frozen plasma during the perioperative period to prevent severe postoperative bleeding complications. Conclusion Patients with fibrinogen deficiency should be given a individualized perioperative management plan according to the quantitative and other coagulation indexes of fibrinogen in plasma for cardiac surgery under CPB.

Objective To investigate the effects of Schisandrin C (SchC) on hydrogen peroxide (H₂O₂) treated human immortalized keratinocyte cells (HaCaT) and to understand its potential mechanisms on ageing. Methods HaCaT cells were cultured in vitro and divided into control group, H₂O₂ model group, and SchC treatment group. Cell viability was evaluated by CCK-8 assay. The levels of superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) were determined by WST-1 assay. The level of reactive oxygen species (ROS) was determined by chemical fluorescence assay. The mRNA expression of matrix metalloproteinase, cyclooxygenase-2 (COX-2) and apoptosis-related genes were detected by qRT-PCR. The expression of COX-2, matrix metalloproteinase, apoptosis-related protein, ageing-related protein, transcription factor NF-E₂ related factor 2 (Nrf-2), heme oxygenase (HO-1), cytoplasmic transcription factor-κB (NF-κB) and p-NF-κB was detected by Western blotting. Results SchC at the concentration of less than 100 μmol/L had no significant effects on the proliferation of HaCaT cells; while cell viability decreased to (57.0±3.0)% (P<0.001) after treated with 800 μmol/L H₂O₂. Compared with the H₂O₂ model group, the cell viability, SOD, and GSH levels were significantly increased; MDA and ROS levels were significantly decreased (P<0.05 or P<0.01). Western blotting results showed that the expression of P16, P21 and p-NF-κB were significantly down-regulated, and the expression of Nrf-2 and HO-1 were up-regulated by SchC (P<0.05 or P<0.01). qRT-PCR and Western blotting results showed that SchC could up-regulate the expression of caspase-3 and caspase-9, and down-regulate the expression of Bcl-2, matrix metalloproteinase (MMP-1, MMP-9) and inflammatory factor COX-2 by regulating NF-κB pathway (P<0.05 or P<0.01). Conclusion SchC had a protective effect on the aging model of oxidative stress damage of H₂O₂-induced HaCaT cells, which could lay a foundation for the development of anti-ageing products of Schisandra C.

Objective To investigate the changes of cognitive function in early stage of severe heatstroke (HS) in a rat model, and analyze the metabolic changes of central nervous system by ¹H NMR-based metabonomics. Methods Twenty-five male Sprague-Dawley rats were randomly divided into control group (n=11) and HS group (n=14). The rats in HS group were exposed to 40 ℃ heat chamber. When the core temperature reached 42 ℃, they were taken out and rewarmed for 3 h. The rats in control group were placed at (25.0±0.5) ℃. The rats in HS group were evaluated for neurological deficits before modeling and 0 and 3 h after the rewarm by the modified neurological severity score (mNSS); the tissues of the control group (n=3) and HS group (n=3) were taken and HE staining was used to detect the pathological changes; the brain tissues of the rats in control group (n=8) and HS group (n=11)were taken and the MestReNova software (v9.0.1) was used to perform ¹H NMR detection in the NMR spectrometer. The related mechanism of early HS brain injury in rats was expounded from the perspective of metabolomics. Results In the early stage of HS, nerve cell necrosis and apoptosis can be seen in pathological observation. The escape latency time and distance was significantly increased in the HS group compared with control group [(33.14±1.51) s vs. (53.14±2.14) s, P<0.05; (360.79±13.50) cm vs.(693.29±28.63) cm, P<0.05]; the number of platform-crossing and the activity time of target quadrant was significantly reduced in the HS group compared with control [(6.36±0.84) times vs. (2.64±0.75) times, P<0.05; (65.78%±1.06%) vs. (35.81%±1.14%), P<0.05]. The metabolic patterns of central nervous system were significantly changed in early stage of severe heatstroke. Compared to the control group, glutamine, glutamate, lactate and succinate were distinctly increased, while the levels of aspartate, glycine, glutathione and pyruvate were markedly decreased. Conclusions The neurological impairment and cognitive dysfunction can occur in the early stage of severe heat stroke, and the metabolic pattern of central nerve system is changed, resulting disorders of neurotransmitters as amino acids and energy metabolism and oxidative stress.

Objective To investigate the clinical characteristics of severe coronavirus disease 2019 (COVID-19) and explore the relevant risk factors that affect outcomes of the patients. Methods A retrospective analysis was performed on the data of the patients with severe COVID-19 admitted to the ICU of Huoshenshan Hospital of Wuhan City during the period from February to April, 2019. The patients were classified into survival group and death group. The general data, clinical manifestations, laboratory examinations, and treatments were compared between the 2 groups. Results A total of 122 severe COVID-19 patients were included in the study, 56 died and the fatality rate was 45.9%. The proportion of comorbidities of coronary heart disease in death group was significantly higher than that in the survival group [19.6%(11/56) vs. 7.6%(5/66), P=0.049]. Compared with patients in the survival group, the platelet count in the death group decreased [190.1(132.3, 245.0)×10⁹/L vs. 217.0(176.0,262.3)×10⁹/L, P=0.015] and the levels of C-reactive protein and brain natriuretic peptide in the death group increased [37.4(4.3,125.6) mg/L vs. 8.9(2.7, 51.4) mg/L, P=0.027 and 65.17(18.84, 167.71) pg/ml vs. 16.60(0.01, 67.68) pg/ml, P=0.007]. The prothrombin time and thrombin time in the death group were longer than those in the survival group [14.20(13.22, 15.86) s vs.13.27(12.16, 14.27) s, P<0.01 and 16.32(15.11, 18.02) s vs. 15.75(14.81, 16.62) s, P=0.037]. Dynamic observation data showed that there were significant differences in neutrophil count, lymphocyte count, neutrophil/lymphocyte ratio and levels of both lactate dehydrogenase and α-hydroxybutyrate dehydrogenase (α-HBDH) between the two groups. ROC curve analysis showed that LDH and α-HBDH were of high value in predicting outcome, and the area under the curve was more than 0.7. Conclusions We should pay close attention to the changes of blood routine, LDH, and α-HBDH for older patients with underlying diseases. This will help us to identify the patients with high risk of death in the early stage, and take effective treatment measures as early as possible to improve the prognosis.