Objective: To explore the effects of 17 β-estrogen (E2) and 2-methoxyestradiol (2ME) on hypoxic induced factor-1α (HIF-1α) and alkane hydroxylase (AlkB) in experimental rats with ovariectomy and hypoxic pulmonary hypertension. Methods: A total of 60 healthy female SD rats with castrated surgery were randomly divided into 6 groups:①Routine oxygen group,②Routine oxygen + E2 group, the rats received subcutaneous injection of E2 (20 μg/kg?d),③Routine oxygen + 2ME group, the rats received 2ME (240 μg/kg?d) and④Hypoxia group,⑤Hypoxia + E2 group,⑥Hypoxia + 2ME group.n=10 in each group and all animals were treated for 8 weeks to establish the hypoxic pulmonary hypertension model. The mean pulmonary artery pressure (mPAP) was measured after bloodletting, right ventricle hypertrophy index (RVHI) was calculated and small pulmonary artery remodeling was observed by HE staining. The expression level of HIF-1α and AlkB were examined by RT-PCR and Western blot analysis. Results: Compared with Routine oxygen group, the rats in Hypoxia group had obviously thickened small pulmonary artery wall with narrowed lumen, increased mPAP and RVHI; the above changes in Hypoxia + E2 and Hypoxia + 2ME groups were relatively smaller, their mPAP and RVHI were higher than Routine oxygen group, while mPAP and RVHI were similar between Hypoxia + E2 and Hypoxia + 2ME groups. There were no real morphological changes in small pulmonary vessels in Routine oxygen + E2 and Routine oxygen + 2ME groups. The HIF-1α expression was obviously elevated in Hypoxia group than Routine oxygen group, while the elevation was less in Hypoxia + E2 and Hypoxia + 2ME groups. HIF-1α expression had no real changes in Routine oxygen+E2 and Routine oxygen + 2ME groups. The AlkB expression was obviously reduced in Hypoxia group than Routine oxygen group, while the reduction was less in Hypoxia + E2 and Hypoxia + 2ME groups. AlkB expression had no real changes in Routine oxygen + E2 and Routine oxygen + 2ME groups. Conclusion: Estradiol E2 and 2ME could remit pulmonary hypertension which might be via up-regulating AlkB expression and down-regulating HIF-1α expression in experimental rats with hypoxic pulmonary hypertension.

Objective To introduce a method to aid dental treatment for autistic children; midazolam oral sedation. Methods 10 autistic children who can not be managed under normal dental procedures were administrated oral midazolam (0.5mg/kg) before treatment. Once they were adequately sedated, dental treatment was carried out in outpatient. During the whole course, their finger oxygen saturation and heart rate were inspected. Painless methods were also applied. The duration of each treatment was controlled within 30min. When the procedure ended, the autistic children were inspected until recovery from sedation and then discharged with their parents. Results 10 children aged 4～10y totally underwent 17 visits to complete all dental treatment. The average ages were (6.00?1.89)y, body weight was (28.10?9.36) kg and Houpt scales were (4.71?0.77). They were all successfully sedated and managed and no severe complications were found. Conclusion The oral midazolam sedation showed satisfactory effects on this group of autistic children while studies of large samples are needed to draw a definite conclusion.

Objective:To establish a preoperative forecasting model for the nature of duodenal papillary tumors and to discuss its main predictors.Methods:A case-control study was conducted;the case group included patients with malignant duodenal papillary tumors and the control group included patients with benign duodenal papillary tumors.All the patients were from Changhai Hospital. Data of patients,including the demographic characteristics,clinical symptoms during onset,laboratory findings,and radiological data, were collected by face-to-face interviews or by reviewing the medical history.Chi-square,t-test or ANOVA were employed to performed univariate analysis.All factors with P values less than or equal to 0.25 in the univariate analysis were used as independent variables for multivariate analysis,and a Logistic regression forecasting model for the nature of duodenal papillary tumors was established.Results: Totally 199 patients with pathologically-confirmed duodenal papillary tumors were included in the present study,with 166 in the case group and 33 in the control group.Multivariate analysis showed that hemoglobin(Hb),total bilirubin(Tbil),direct bilirubin(Dbil), aspartate transferase(AST),alkaline phosphatase(AKP),gamma glutamyl transpeptidase(GGT),and carcinoembryonic antigen(CEA) were independent predictors for nature of duodenal papillary tumors,with their odds ratios(95% confidence interval)being 0.981 (0.959,1.003),0.867(0.794,0.948),1.207(1.075,1.355),1.028(1.008,1.048),0.996(0.992,1.000),1.002(1.000,1.004),and 0.974(0.953,0.994),respectively.Conclusion:The Logistic regression model,which takes into consideration of Hb,Tbil,Dbil,AST, AKP,GGT,and CEA,can be used to predict the nature of duodenal papillary tumors,and its clinical value need to be further studied.

ObjectiveTo assess the value of the area of ground glass opacities (GGOs) in lungs displayed by high-resolution computed tomography (HRCT) in paraquat (PQ) poisoned patients in evaluating prognosis. Methods Clinical and imaging data of 137 patients with acute PQ poisoning admitted to Affiliated Hospital of the Medical College of Chinese People's Armed Police Forces from January 2012 to August 2014 were analyzed retrospectively. The plasma concentration of PQ on admission and the area of GGOs were compared between two groups. The lung HRCT within 10 days of poisoning was performed every 3 days, and the areas of GGOs were evaluated on five levels, including aortic arch, aortic pulmonary window, left upper lobe bronchial, right inferior pulmonary vein, and left diaphragmatic dome. Receiver operating characteristic curve (ROC) was plotted to evaluate the value of all the parameters for prognosis.Results Among 137 patients, 45 died within 28 days after poisoning, with the mortality rate of 32.85%. The plasma PQ level in the non-survivors was significantly higher than that in the survivors (mg/L:7.06±0.67 vs. 3.51±0.34,t = 5.280,P = 0.000). The areas of GGOs at three time points in the non-survivors were significantly higher than those in the survivors [1-3 days: (32.0±5.0)% vs. (2.5±0.4)%,t = 7.860,P = 0.000;4-6 days: (45.5±5.7)% vs. (2.8±0.5)%,t = 12.420,P = 0.000; 7-10 days: (68.0±4.8)% vs. (3.0±0.6)%, t = 23.950,P = 0.000]. ROC analysis demonstrated that the area under the ROC curve (AUC) of GGOs in 7-10 days was 1.000, which could be used to determine the prognosis, but it was too late for the treatment. The AUC of GGOs in 4-6 days was 0.979, with the threshold of> 12.0%, the specificity of 96.15%, the sensitivity of 85.19%, the positive predictive value of 88.46%, and the negative predictive value of 94.94%, which presented good effect in predicting prognosis in the early stage of acute PQ intoxication. But plasma PQ concentration was relatively poor for determining prognosis, AUC was 0.821, with the threshold of> 1.95 mg/L, the specificity of 34.52%, the sensitivity of 88.64%, the positive predictive value of 41.49%, and the negative predictive value of 85.29%.Conclusions The area of GGOs displayed by HRCT can be used to evaluate the fully developed acute PQ lung injury, and it is superior to plasma PQ concentration. The area of GGOs displayed by HRCT 4-6 days after intoxication can be used for the evaluation of PQ induced pulmonary injury in the early stage and the evaluation of clinical prognosis.

AIM:To detect the expression of basic fibroblast growth factor (bFGF) and matrix metalloprotei-nase 9 (MMP9) in nasopharyngeal carcinoma (NPC) and its correlation with clinicopathological features and prognosis of the patients.METHODS:The expression of bFGF and MMP9 was detected by the method of SP immunohistochemical staining in biopsy tissues of NPC patients.The relationship between the expression and the clinical significance was analyzed as well.RESULTS:In 289 cases of NPC patients, the positive rates of bFGF and MMP9 were 71.3% and 61.6%, respectively.Correlation analysis demonstrated that the expression rates of bFGF and MMP9 were both positively associated with N stage and clinical stage in NPC patients.The high expression rates of both bFGF and MMP9 were associated with poor overall survival and progression-free survival of NPC patients.Furthermore, the positive rate of bFGF was positively correlated with that of MMP9, and over-expression of both bFGF and MMP9 was correlated with the poorest survival outcomes in NPC patients.CONCLUSION:bFGF and MMP9 are over-expressed in NPC tissues and significantly associated with NPC recurrence and poor outcome.The combined interpretation of bFGF and MMP9 expression levels leads to refinement of the risks for the NPC patients and could be chosen as the prognostic biomarkers.

Adult ; Aged ; Carcinoma, Squamous Cell ; genetics ; metabolism ; Esophageal Neoplasms ; genetics ; metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Genes, p53 ; Humans ; Loss of Heterozygosity ; Male ; Middle Aged ; Point Mutation ; Tumor Suppressor Protein p53 ; genetics ; metabolism

Objective:Osteoprotegerin (OPG) is a key molecule negatively regulating osteoclast differentiation and activation; and the conserved mycobacterial heat shock 70 (HSP70) peptide p111-125 has also been found to inhibit inflammation reactions in chronic arthritis. BaculoDirectTM baculovirus expression system was selected to express recombinant OPG-HSP70 in insect cells.Methods:The human functional fragment (p22-194) of OPG and functional fragment (p111-125) of mycobacterial HSP70 gene were cloned into the transfer vector pENTRTM/SD/D-TOPO. The recombinant plasmid was performed an LR reaction with the BaculoDirectTM Linear DNA to generate recombinant baculovirus DNA. The cultured Sf9 insect cells were directly transferred with the recombinant baculovirus DNA,and the pure recombinant baculovirus was obtained. Then recombinant baculovirus was infected Sf9 insect cells again to express the OPG-HSP70 gene.Results:The target protein was detected at the time of 48h post infection,reached at highest yield at the time of 72h post-infection. A 28kDa protein immunostaining band was detected by Western blotting from lysate of those cells.And the purified protein was obtained by using Ni-NTA system. Functional stuies on the fusion protein showed it significantly reduce osteoclast cell number[(3.10?0.640) cells under each microscope field in treatment group by comparing to (10.70?0.817)cells in the control group] in the osteoclast inhibition test,and reduce the inflammation reaction in a delayed type hypersensitivity (DTH) mice model (P

Dysfunction in tyrosine kinase activity disrupts the nor-mal control of cellular phosphorylation signaling pathways,which plays a vital role in genesis and development of various tumors, and makes tyrosine kinases a class of targets of many anti-tumor drugs. Currently most approved tyrosine kinase inhibitors ( TKIs) are based on irreversible binding mechanisms, making them poorly selective, not potent or sustained enough regarding pharmacological effects and prone to triggering resistance. In the past decade, much progress has been made in the development of
a new class of TKIs which irreversibly inhibit their target proteins via the formation of covalent bonds, overcoming the drawbacks of irreversible TKIs. Several irreversible TKIs have entered markets or clinical research phases. This review is to summarize the structural, pharmacological and medicinal chemical properties of investigational and marketed irreversible TKIs as well as their re-cent developments.

Objective: To analyze the influencing factors for hospitalization costs among stroke patients with different subtypes, so as to provide the reference for reducing the economic burden of patients. Methods: Data of patients with hemorrhagic or ischemic stroke who were discharged from hospitals in Nanshan District, Shenzhen City from January 1, 2016 to December 31, 2021 were collected through Hospital Information System. Hospitalization costs were analyzed between hemorrhagic and ischemic stroke patients, and factors affecting hospitalization costs among stroke patients with different subtypes were identified using a structural equation model. Results: A total of 10 298 patients with stroke were recruited, including 2 820 patients with hemorrhagic stroke (27.38%) and 7 478 patients with ischemic stroke (72.62%). The patients with hemorrhagic stroke had a median duration of hospital stay of 19.00 (interquartile range, 18.00) d, and a median hospitalization cost of 26 759.48 (interquartile range, 51 000.87) Yuan. The patients with ischemic stroke had a median duration of hospital stay of 12.00 (interquartile range, 10.00) d, and a median hospitalization cost of 12 199.87 (interquartile range, 13 290.20) Yuan. Structural equation model analysis showed that department of hospitalization, discharge status, ways of leaving hospital, surgery and hypertension had direct effects on hospitalization costs and indirect effects on hospitalization costs through duration of hospital stay among hemorrhagic stroke patients, and duration of hospital stay had the highest total effect (0.684), followed by surgery (0.632). Employment status, admission route, department of hospitalization, ways of leaving hospital, payment mode, surgery and dyslipidemia had direct effects on hospitalization costs and indirect effects on hospitalization costs through duration of hospital stay among ischemic stroke patients, and duration of hospital stay (0.746), surgery (0.424) and department of hospitalization (0.151) ranked the top three in total effects. Conclusion The hospitalization cost is relatively high among stroke patients in Nanshan District, and duration of hospital stay and surgery have great influence on hospitalization costs among stroke patients with different subtypes.