Objective To investigate the effect and mechanisms of celecoxib on right heart function in mice with acute high-altitude hypoxia exposure.Methods Male C57BL/6J mice(7 weeks old)were housed in a hypobaric chamber simulating an altitude of 5 800 m for 2 d to establish an animal model of acute hypobaric hypoxia.①Eighteen mice were randomly assigned to plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S),and high-altitude hypoxia exposure+celecoxib(H+Cel).Body weight and routine blood indicators were measured,and cardiac ultrasound examination were performed for heart rate(HR),pulmonary artery acceleration time to ejection time ratio(AT/ET),tricuspid annular plane systolic excursion(TAPSE),tricuspid annular systolic velocity(S'),and left ventricular ejection fraction(LVEF)and fractional shortening(FS).Targeted metabolomic profiling was applied to detect the cardiac arachidonic acid(AA)metabolite levels.The contents of 12,13-dihydroxy-9Z-octadecenoic acid(12,13-diHOME)in the heart,liver,brown adipose tissue,and plasma were quantified by ELISA.② Eighteen mice were randomly assigned into plain+saline(P+S),high-altitude hypoxia exposure+saline(H+S)and high-altitude hypoxia exposure+12,13-diHOME(H+di)groups.Body weight,routine blood tests,and echocardiography were performed as above.③ Thirty-two mice were randomly divided into high-altitude hypoxia exposure+saline(H+S),high-altitude hypoxia exposure+celecoxib(H+Cel),high-altitude hypoxia exposure+soluble epoxide hydrolase inhibitor(sEHI)(H+sEHI),and high-altitude hypoxia exposure+sEHI+celecoxib(H+sEHI+Cel)groups.Body weight,routine blood tests,and echocardiography were performed as above.Cardiac and plasma contents of 12,13-diHOME and epoxyeicosatrienoic acids(EETs)were measured by ELISA.Results ① Compared to the P+S group,the H+S group exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.001),increased counts of white blood cells(WBC)and neutrophils(P<0.01)and decreased TAPSE,S'and AT/ET both at resting state and under stress(P<0.01,P<0.001).Compared to the H+S group,the H+Cel group exhibited significantly increase of cardiac 12,13-diHOME level(P<0.05),reduced WBC and lymphocyte counts(P<0.01,P<0.05)and improved TAPSE and S'levels at resting state and under stress(P<0.01,P<0.001).② Compared to the H+S group,the H+di group demonstrated significantly improvement of TAPSE at basal and under stress(P<0.001)and a trend towards improved TAPSE at resting state(P=0.0532),but no obvious differences was observed in WBC and neutrophil counts between the H+di group and the H+S group.③ Compared to the H+Cel group,both the H+sEHI and H+sEHI+Cel groups exhibited significantly reduction of cardiac 12,13-diHOME level(P<0.01,P<0.05)though no statistical changes in cardiac function indicators.Compared to the H+S group,WBC counts and lymphocyte were decreased,and serum EETs level was incrased in the H+Cel group,H+sEHI group and H+sEHI+Cel group(P<0.01,P<0.001).Conclusion Celecoxib can elevate cardiac level of 12,13-diHOME and improves right heart function in mice after acute high-altitude hypoxia exposure through the CYP450-sEH metabolic pathway.

Objective To explore the impact of Shexiang Baoxin Pill(SXBXP,a traditional Chinese patent medicine,broadly applied for the treatment of cardiovascular diseases)on coronary microvascular disease(CMD)and investigate the role and underlying mechanisms of muscone,a key bioactive component of the pills,in the treatment.Methods A total of 16 ob/ob mice(8 weeks old)were randomly and equally divided into an ob/ob-SXBXP group and a ob/ob-Control group,receiving 10 mg/kg·d SXBXP or PBS via oral gavage,and another 8 wild-type mice with the same genetic background(WT group)were subjected as a negative control group.Cell model of CMD was established based on mouse coronary microvascular endothelial cells(MCMEC)under ischemia and hypoxic(HI)condition,and the cells were further treated with 20 μg/mL SXBXP(HI+SX)and 30 μmol/L muscone(HI+Muscone),respectively.Echocardiography was carried out for coronary flow reserve(CFR)and left ventricular function,and laser speckle imaging was applied to evaluate myocardial blood flow(MBF).Microvascular density in the heart was evaluated with CD31 immunofluorescence staining.The expression levels of vascular endothelial growth factor(VEGF)in cardiac microvascular endothelial cells of both mouse and cell models were detected by immunofluorescence staining and Western blot analysis.The proliferation and angiogenesis of MCMEC were observed by 5-ethynyl-2'-deoxyuridine staining and angiogenesis experiments.Results In the ob/ob-Control group of mice,the levels of CFR,MBF,and cardiac microvascular density were significantly lower than those in the WT group(P<0.05),and these indicators were significantly improved in the ob/ob-SXBXP group when compared with the ob/ob-Control group(P<0.05),which indicates that SXBXP improves the CMD phenotype.The expression level of VEGF in cardiac microvascular endothelial cells was significantly lower in the ob/ob-Control mice than the WT mice(P<0.05),while the level in the ob/ob-SXBXP group was significantly higher than that in the ob/ob-Control group(P<0.05),illustrating that SXBXP may ameliorate CMD through VEGF-mediated microvascular angiogenesis.In vitro experiments further revealed that the VEGF expression level and the proliferation and angiogenesis abilities in MCMEC were significantly lower in the HI group than the cells under the normoxia control condition(P<0.05).Both SXBXP and muscone treatment resulted in enhanced expression of VEGF and improved proliferative and angiogenesis abilities of MCMEC(P<0.05).These results suggest that muscone could improve CMD by VEGF-mediated microvascular angiogenesis.Conclusion SXBXP can improve CMD.Muscone,as a key component of SXBXP,promotes microvascular angiogenesis by inducing the expression of VEGF,then enhances myocardial perfusion,and consequently alleviates CMD.

Objective To investigate the mechanism of inhibitory effect of mollugin on hepatocellular carcinoma based on the ferroptosis pathway.Methods HepG2 cells were cultured in vitro and divided into control group,mollugin low-(10 μmol/L),medium-(20 μmol/L),and high-dosage(40 μmol/L)groups based on the inhibitory concentration of 50%.The cell viability was detected by CCK-8 method,cytotoxicity was detected by LDH kit,and the ability of cell colony formation was observed by clone formation assay,the contents of GSH,MDA,ROS,SOD,superoxide,lipid peroxide and MMP were detected,the protein expression of ferroptosis suppressor protein 1(FSP1),GTP cyclohydrolase 1(GCH1),dihydroorotate dehydrogenase(DHODH)and glutathione peroxidase 4(GPX4)were detected by Western blot,the mRNA expression of FSP1,DHODH,GCH1 and GPX4 were detected using RT-qPCR.The effect of mollugin on cell viability and GSH,MDA contents of hepatocellular carcinoma cells were observed under overexpression and silencing of GPX4 by mollugin.Results The medium-and high-dose of mollugin could reduce the number of clone formation in HepG2 cells,decrease the GSH content and SOD activity of cells,increase the content of MDA,superoxide,lipid peroxides and ROS,and decreased MMP(P<0.001).The intervention of mollugin had no significant effect on the expressions of FSP1,GCH1,DHODH protein and mRNA in HepG2 cells,but could decrease the expression of GPX4 protein and mRNA(P<0.001).Overexpression and silencing experiments confirmed that GPX4 was the core target for the regulation of ferroptosis by mollugin.Conclusion Mollugin mainly exerts its anti-liver cancer effect by regulating GPX4 mediated ferroptosis.

Objective:To explore artificial intelligence technology and propose an algorithm for automatic identification of dicentric chromosomes to realize fast and high-throughput biodosimetry. In order to solve the time-consuming and laborious problem of manual analysis of dicentric chromosomes.Methods:Combining artificial intelligence technology and image processing technology, based on MATLAB software, algorithms like image preprocessing, threshold segmentation algorithm, binarization processing, area identification algorithm, convolutional neural network algorithm and double centripetal recognition algorithm were applied. A fuzzy membership function was defined to describe the degree of each chromosome belonging to a dicentric chromosome, and the discrimination threshold was set to realize the automatic identification of dicentric chromosomes.Results:Through the test on 1 471 chromosome images, compared with manual recognition, the detection rate of dicentric chromosomes cells of this algorithm reached 70.7%.Conclusions:This algorithm method carries out a preliminary study on the automatic identification of dicentric chromosomes with good result.

Objective: To investigate the difference of the temporomandibular joint between patients with anterior open-bite and normal overbite with cone beam CT (CBCT). Methods : Fifty-four patients with anterior open bites and 54 patients with normal overbites were selected from the Department of Orthodontics, Nanjing Stomatological Hospital, Medical School of Nanjing University from June 2014 to August 2020. Sagittal and coronal images of the temporomandibular joint were reconstructed with multiplanar reconstruction techique. The Kamelchuk method was used to measure the superior, posterior and anterior space of the temporomandibular joint, and the condylar morphology was divided into two types: normal and abnormal. The joint space and condylar morphology of the anterior open-bite group and the normal overbite group were statistically analyzed. The anterior open-bite group was divided into 3 subgroups: ① Ⅰ° open-bite (open bite distance < 3 mm), ② Ⅱ° open-bite (open bite distance ≥ 3 mm and ≤ 5 mm) and ③ Ⅲ° open-bite (open bite distance > 5 mm). The difference of overbite spaces of the temporomandibular joint was compared among these three subgroups. Results: Compared to the normal group, no significant differences were found for the anterior and superior space of the temporomandibular joint in the anterior open-bite group (P > 0.05), but the posterior space increased significantly (P < 0.01). A total of 52.8% of patients in the anterior open-bite group had abnormal condyles, whereas 21.3% of patients in the normal group, overbite significant differences was found between the two groups (P < 0.01). Compared with patients with Ⅰ° and Ⅱ° openbite, the condyle of patients with III° open bites was more forward in the fossa (P < 0.05). Conclusion The position of the condyle in the fossa of patients with anterior open bites is more forward, and abnormal condylar bone is more common found.

To evaluate the safety and effectiveness of Shenbei Guchang capsules in treatment of diarrhea type irritable bowel syndrome (yang deficiency of spleen and kidney) under widely used conditions, an open, multicenter, controlled, phase Ⅳ clinical trial was conducted in the drug clinical trial centers of 16 domestic hospitals. 2 123 patients from June 10, 2011 to November 29, 2012 were enrolled in the trial. Drug clinical trial was approved by Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital Ethics Committee before implementation. Before the start of trial, subjects were selected according to the research scheme and inclusion criteria, then they would step into the 14 d study after signing Informed Consent Form. All subjects were treated according to the research scheme, evaluated the conditions and filled in CFR sheet, to provide the evaluation data and information on safety and efficacy of Shenbei Guchang capsules. Shenbei Guchang capsules were used to treat diarrhea type irritable bowel syndrome in widely used conditions (2 123 cases), and 2 029 cases of them entered FAS set, cure+markedly effective in 1 921 cases, with a comprehensive curative effect rate of 94.68%; 2 010 cases of them entered PPS set, cure+markedly effective in 1 906 cases, with a comprehensive curative effect rate of 94.83%. The primary symptoms of IBS were abdominal pain and diarrhea. After treatment, both abdominal pain and diarrhea were improved, with significant differences (P<0.000 1). There were significant differences in traditional Chinese medicine symptom scores on both post-treatment day 7 and day 14 as compared with the conditions before treatment (P<0.000 1). 35 cases of adverse events occurred during the trial with an incidence of 1.65%, including 12 cases of drug-related adverse events (adverse reaction) with an incidence of 0.57%, mainly manifested as nausea, abdominal distension and dry mouth, most of which would be spontaneously relieved without any measures. No serious adverse events occurred. The commercially available Shenbei Guchang capsules are proved safe and effective for the treatment of diarrhea type irritable bowel syndrome (yang deficiency of spleen and kidney) under widely used conditions (2 123 cases), and can be continued for clinical promotion and application.

Objective To study the dynamic changes of plasma C-reactive protein (CRP) and cortisol (COR) and their clinical value in prognosis of patients with sepsis. Methods Daily CRP and COR detection was conducted to record the dynamic changes of CRP and COR for cases of sepsis patients in ICU then the rela-tionship between dynamic changes of serum CRP and COR and prognosis were analyzed. Results Serum CRP and COR levels of dead patients were significantly higher than those of survival patients after treatment (P <0.05). According to the difference of the dynamic changes of CRP and COR, the data were divided into typeⅠ:sustained elevated type , typeⅡ: up-and-down type , type Ⅲ: fluctuated type and type Ⅳ: normal or mild ele-vation type. The mortality of CRP typeⅠ patients was significantly higher than that of type Ⅱ and type Ⅳ(P <0.001). The mortality of COR typeⅠ and COR Ⅲ patients was significantly higher than that in COR Ⅱand COR Ⅳ (P < 0.001). Further analysis showed that the mortality of group with significant elevation of CRP and COR were obviously higher than that of group with significant increase of CRP or COR and that of group with no significant elevation of CRP and COR (P < 0.001); the mortality of group with significant increase of CRP or COR was also significantly higher than that of group with no significant elevation of CRP and COR (P < 0.001). Conclusions The dynamic changes of COR and CRP in patients with sepsis present certain regularity and monitor-ing the dynamic changes of the two provides accurate assessment of the prognosis of sepsis.