The purpose of this study is to design push-pull osmotic pump (PPOP) tablets of famotidine using the expert system for the formulation design of osmotic pump of poor water-soluble drug which had been established by the authors. Firstly, the parameters which were requisite of the system input were obtained from literatures and experimental tests. Then the parameters were input into the system, and the program was run. The system displayed the designed formulations sequential. Finally, famotidine PPOP was prepared according to the designed formulations and the in vitro dissolution was carried out. It was found out that the target formulation of famotidine PPOP which could release for 24 hours was obtained in a very short period. Meanwhile, the practicability of the established expert system was proved.

Objective To explore six-degree-of-freedom (6-DF) registration methods between planning and cone beam computed tomography (CBCT) during image-guided radiation therapy (IGRT) in esophageal cancer.Methods Thirty pairs of CBCT images acquired before radiation and the corresponding planning computed tomography (CT) images of esophageal cancer were selected for further investigation.Registration markers for 6-DF image registration were determined and contoured in those images.The results of registration as well as time cost were compared among different registration methods of bone match, gray value match, manual match, and bone plus manual match.Results Contouring bone and spinal canal posterior to the target volume of esophageal carcinoma as registration marker could make 6-DF registration quick and precise.Compared with manual match, set-up errors of v rotation in bone plus manual match (-0.55° vs.-0.88°, t=2.55, P=0.020), of x-axis and v rotation in bone match (0.12 mm vs.-2.33 mm, t=5.75, P=0.000; -0.35° vs.-0.88°, t=3.00, P=0.007), and of x-axis and w rotation in gray value match (7.20 mm vs.-2.33 mm, t=3.10, P=0.006; -0.10° vs.-0.59°, t=2.81, P =0.011) were significantly different.Compared with manual match, the coincidence rate of bone plus manual match was the highest (85.55%), followed by bone match and gray value match (74.45% and 74.45%).The time cost of each registration method from longest to shortest was:6.00 -10.00 minutes for manual match, 1.00 - 5.00 minutes for bone plus manual match, 0.75 - 1.50 minutes for gray value match, and 0.50 - 0.83 minutes for bone match.Conclusions Registration marker is useful for image registration of CBCT and planning CT in patients with esophageal cancer.Bone plus manual match may be the best registration method considering both registration time and accuracy.

AIM To establish an LC-MS/MS method for the simultaneous content determination of paeoniflorin,albiflorin,neochlorogenic acid,chlororogenic acid,catechin,epicatechin,ethyl gallate,danshensu,ferulic acid,caffeic acid,gallic acid,protocatechuic acid,protocatechualdehyde and rosmarinic acid in Yangxue Qingnao Granules (Angelicae sinensis Radix,Chuanxiong Rhizoma,Paeoniae Radix Alba,etc.).METHODS The analysis of methanol extract of this drug was performed on a 20 ℃ thermostatic Waters Symmetry Shield RP C18 column (3.9 mm × 150 mm,5 μm),with the mobile phase comprising of acetonitrile-water (containing 0.1％ formic acid) flowing at 0.4 mL/min in a gradient elution manner.RESULTS Fourteen constituents showed good linear relationships within their own ranges,whose average recoveries were 85.5％-107.0％ with the RSDs of 2.0％-5.0％.CONCLUSION This simple,sensitive,accurate and reproducible method can be used for the quality control of Yangxue Qingnao Granules.

Objective To study the changes of trans-diaphragmatic pressure (Ptra) and its correlation with esophageal pressure (Peso) through ARDS piglet model.Methods Five piglets were enrolled in the study.Peso,gastric pressure (Pgas) and intra-thoracic pressure (Pint) was monitored through balloon inserted.The data before ARDS serve as control.ARDS was produced in the piglets through saline lavage.The pressure were observed and the Ptra were calculated.The pressure changes and correlation between Ptra and Peso were analyzed as well.Linear regression with the coefficient of determination and t-test were used as appropriate.Significance was assumed for P ＜ 0.05.Results Peso,Pgas and Pint before ARDS were 7.3 ± 1.9,25.5 ± 2.4,- 1.23 ± 0.21 cmH2O,Ptra was 18.2 ± 1.6 cmH2O.While after ARDS,the data were 4.7 ± 1.4,31.1 ± 3.1 and - 1.79 ± 0.28 cmH2O,and Ptra was 26.4 ± 2.1 cmH2 O,and all these changes were obviously ( P ＜ 0.05 ).The correlation between Pint and Peso,Pint and Ptra (A) and Ptra ( B ) were 0.93 ± 0.025,0.88 ± 0.023 and 0.87 ± 0.37 before ARDS.After ARDS,the correlation changed to be 0.82 ±0.21,0.81 ±0.20 and 0.78 ±0.31.Although a bit decreased,the correlation was still positive (P ＜ 0.01 ).Conclusions There existed good correlations between Peso and Ptra as well as between Pint and Peso before or after ARDS.Ptra was increased obviously after ARDS,which could lead to respiratory muscle fatigue.

Objective To investigate influences of estrogen-related receptor α(ERRα) on pulmonary vascular endothelium of rats undergoing sepsis. Methods Male Sprague-Dawley (SD) rats were divided into four groups according to the random number table method (12 in each group): normal control group (NC group), sham operation group (Sham group), sepsis model caused by cecal ligation and puncture (CLP) group (CLP group), XCT790 intervention group (XCT790 group, given the XCT790 2.5 mg/kg via intraperitoneal injection 30 minutes before CLP). After 24 hours, rats were sacrificed and the organs were harvested. The pathological changes of lung tissue were observed using hematoxylin and eosin (HE) staining, and the ultrastructural changes of lung tissue were observed by double staining of uranium citrate with lead acetate, the degree of apoptosis of pulmonary capillary endothelial cells were observed by TdT-mediated dUTP nike end labeling stain (TUNEL), the permeability of lung vascular endothelial was detected by Evans blue (EB) staining, the levels of serum cytokines were detected by enzyme linked immunosorbent assay (ELISA), and white blood cell count in bronchial alveolar lavage fluid (BALF) was detected. Results Compared with NC group and Sham group, the CLP group and XCT790 group had severe pathological damage and increased lung tissue permeability, the levels of serum cytokines and white blood cell count in BALF were increased. Compared with CLP group, the pathological changes of lung tissue, the degree of ultrastructural damage of lung tissue, the degree of apoptosis of lung capillary endothelial cells in XCT790 group further intensified, the permeability of lung endothelial barrier further increased [the content of EB (μg/g): 116.00±15.46 vs. 60.19±19.79, P < 0.05], and the level of serum cytokines further increased [interleukin-1β(IL-1β, ng/L): 71.38±4.01 vs. 56.58±2.45, interleukin-6 (IL-6, ng/L): 741.62±88.94 vs. 534.22±72.70, tumor necrosis factor-α(TNF-α, ng/L):188.55±7.41 vs. 143.33±11.27, all P < 0.05], the white blood cell count in the BALF increased further (×104/L:193.79±27.46 vs. 99.34±36.41, P < 0.05). Conclusion ERRα can aggravate inflammation in sepsis rats, destroy lung tissue and increase pulmonary permeability.

Objective:To explore the effect of estrogen-related receptor α (ERRα) on lipopolysaccharide (LPS)-induced vascular endothelial cell apoptosis and tight junction protein degradation.Methods:RPMVECs transfected with shERRα were cultured in vitro and divided into four groups: Normal control group (Ctr group); shERRα knockdown group (shERRα group); normal cells + LPS treated group (LPS group): The cells in the six-well plates were cultured in serum-free medium for 12 h, and then treated with 20 μg/mL LPS for 12 h; and shERRα+LPS group: ERRα knockdown cells were treated as the LPS group. ROS fluorescence kit was used to detect the intracellular ROS levels . Apoptosis ratio was detected by TUNEL staining, AnnexinV-FITC and PI. Cell membrane ZO-1 expression was detected by cellular immunofluorescence, and the levels of apoptosis-related proteins Bcl-2, Bax, Smac, Cytochrome c, and tight junction protein ZO-1, as well as the expression of Occludin, JAM-A and E-Ca at molecular level were detected by Western blot.Results:Compared with the Ctr group and the shERRα group, the ROS level, apoptosis rate (TUNEL test: 16.44 ± 2.55; and flow cytometry test: 23.56 ± 2.22), the expression of pro-apoptotic proteins Bax, Smac and Cytochrome c were increased in the LPS group, while the expression of anti-apoptotic proteins Bcl-2 and tight junction protein were decreased. In the LPS group. Cellular immunofluorescence results showed that the ZO-1 was degraded in the cell membrane and the network structure was broken. Compared with the LPS group, inhibition of ERRα in the shERRα+LPS group increased cell damage.Conclusions:ERRα can negatively regulate the apoptosis and affect the function of pulmonary microvascular endothelial cells, thereby regulating sepsis-induced acute lung injury.

Objective To investigate the effect of estrogen-related receptor alpha(ERRα)on lipopolysaccharide-induced inflammatory response in rat pulmonary microvascular endothelial cells (PMVECs) and its mechanism.Methods PMVECs were cultured in vitro.When the cells were in the logarithmic growth phase,the cell were ransfected with lentivirus,and a stable low-expression ERRα cell line was constructed.The cells were divided into four groups:Ctr group (normal control group),Ctr+LPS group (normal celI+LPS treatment group),shERRα1 (shERRα1 gene knockdown group),and shERRα1+LPS group (shERRα1 gene knockdown +LPS treatment group).After 20 μg/mL LPS stimulated cells in the control group and shERRal group for 6,12 and 24 h,cell counting kit-8 (cck-8) was used to detect the cell proliferation ability of each group,and enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of tumor necrosis factor alpha (TNF-α) and Interleukin-1β (IL-1β) in cell culture fluid.After 12 h LPS stimulation,the expression levels of ERRα and NF-κB related proteins (p-p65,p65,P-IKBα,IKBα) were measured by Western blot.Pairwise comparisons were performed with SNK-q test (two-tailed),and multiple-group comparisons were performed with one-way ANOVA.The non-parametric test of rank transformation was used when homogeneity of variance were not met.P value＜0.05 was considered significantly different.Results Compared with the control group,ERRα expression in the shERRα group was significantly decreased (0.09±0.01 vs 0.15±0.01).At 6,12 and 24 h after LPS stimulation,compared with the control group,the cell proliferation ability (％) of the shERRαl+LPS group was significantly reduced (99.68±4.53 vs 48.62±1.60) and the concentration of TNF-α (ng/mL) (15.76±3.38 vs 5 498.91±367.95) and IL-1β (ng/mL) (14.41±3.86 vs 6 014.92±277.33) in the cell culture supematant were significantly increased.The change was most obvious after 12 h stimulation.Meanwhile the expression of p-p65 (0.30±0.50 vs 1.05±0.07) and p-IKBα (0.27±0.04 vs 0.77±0.06) were increased significantly,while the expression of IKBα (0.96±0.07 vs 0.14±0.04) was decreased significantly in the shERRαl+LPS group (all P＜0.05).Conclusion ERRα gene attenuates LPS-induced inflammatory response in rat pulmonary microvascular endothelial cells by inhibiting NF-κB signaling pathway activation.

Objective:To explore the early application effect of the bedside sitting respiratory training in patients with respiratory failure and noninvasive positive pressure ventilation of the acute exacerbation of chronic obstructive pulmonary disease(AECOPD).Methods:A total of 102 patients with respiratory failure and noninvasive positive pressure ventilation of the AECOPD treated in Shanghai Public Health Clinical Center from June 2018 to December 2019 were selected and divided into the control group and the research group by random digits table method with 51 cases in each group. The control group was given the conventional treatment and nursing measures; and the research group was given the bedside sitting respiratory training. Pulmonary functional and blood -gas analysis parameters, clinical outcome of patients, etc. before and after the intervention between the two groups were compared. Results:After the intervention, the forced expiratory volume in one second (FEV 1), forced vital capacity(FVC), FEV 1/FVC were (1.79±0.22) L, (3.09±0.28) L, (62.16±5.94)% in the research group, and (1.43±0.18) L, (2.66±0.23) L, (53.48±5.31)% in the control group, the differences were statistically significant(t values were 8.36, 8.00, 7.19, P<0.01). Arterial partial pressure of carbon dioxide (PaCO 2) and arterial partial pressure of oxygen (PaO 2) in blood gas analysis were (51.14±3.79) mmHg(1 mmHg=0.133 kPa), (71.07±5.49) mmHg in the research group, and (57.52±3.86) mmHg, (65.62±5.27) mmHg in the control group, the differences were statistically significant ( t values were -7.78, 4.72, P<0.01). The non-invasive positive pressure ventilation time, hospital stays were (7.41±1.76) d, (11.27±2.41) d in the research group, and (9.79±2.11) d, (15.46±3.12) d in the control group, the differences were statistically significant ( t values were -5.71, -6.70, P<0.01). The incidence of adverse events was 3 cases in the research group, 1 case in the control group, the difference was no statistically significant ( P>0.05). Conclusions:The application of the bedside sitting respiratory training in patients with respiratory failure and noninvasive positive pressure ventilation of the AECOPD can effectively improve the pulmonary physiological function, shorten the noninvasive positive pressure ventilation time and hospitalization time, which has clinical application value.

Objective To investigate the effect of central lymph node dissection on the clinical efficacy and prognostic quality of life for differentiated thyroid carcinoma patients.Methods A total of 100 differentiated thyroid carcinoma patients in our hospital for unilateral thyroidectomy and isthmus,contralateral resection underwent central lymph node dissection were as research objects.The lymph node metastasis rate of the patients was statistically analyzed,and the related factors,prognostic quality of life were observed and analyzed.Results Lymph node metastasis was correlated to age and tumor diameter (P ＜ 0.05).Patients in Ⅵ area had the highest rate of metastasis among 100 patients with central lymph node dissection,which showed a significant difference (P ＜ 0.05).Recurrent laryngeal nerve,surrounded by thyroid papillary carcinoid tissue,was injured in 1 patient,and there were 4 cases with subcutaneous hemorrhage,5 with hoarseness.All were discharged after treatment,and there were no died and tracheal collapse patients.The quality of life score was significantly higher than preoperation (P ＜ 0.05).Conclusion Central lymph node dissection can eliminate lymph node and occult lymph nodes with high metastasis rate,and improve the quality of life of differentiated thyroid cancer patients.

Objective To investigate the effect of central lymph node dissection on the clinical efficacy and prognostic quality of life for differentiated thyroid carcinoma patients.Methods A total of 100 differentiated thyroid carcinoma patients in our hospital for unilateral thyroidectomy and isthmus,contralateral resection underwent central lymph node dissection were as research objects.The lymph node metastasis rate of the patients was statistically analyzed,and the related factors,prognostic quality of life were observed and analyzed.Results Lymph node metastasis was correlated to age and tumor diameter (P ＜ 0.05).Patients in Ⅵ area had the highest rate of metastasis among 100 patients with central lymph node dissection,which showed a significant difference (P ＜ 0.05).Recurrent laryngeal nerve,surrounded by thyroid papillary carcinoid tissue,was injured in 1 patient,and there were 4 cases with subcutaneous hemorrhage,5 with hoarseness.All were discharged after treatment,and there were no died and tracheal collapse patients.The quality of life score was significantly higher than preoperation (P ＜ 0.05).Conclusion Central lymph node dissection can eliminate lymph node and occult lymph nodes with high metastasis rate,and improve the quality of life of differentiated thyroid cancer patients.