Objective To evaluate the cost-utility of tiotropium/olodaterol in treating Chinese patients with moderate to very severe chronic obstructive pulmonary disease(COPD)and to provide references for selecting more economical inhaled preparations in clinical practice.Methods A four-state lifetime Markov model was established with a 3-month cycle.The health outcomes included life years and quality-adjusted life years.Costs,including direct medical costs,were calculated from the perspective of the Chinese health system.Discontinuation rates were derived from the discontinuation curve using GetData Graph Digitizer.The main output indicator of the model was the incremental cost-utility ratio,which was calculated from the queue simulation results to judge the economy of tiotropium bromide/odataterol.The scenario analysis and sensitivity analyses were carried out to detect the robustness of the base case result.Results Compared with tiotropium bromide,the patient treated with tiotropium bromide/odataterol gained an additional 0.0846 life years,an additional cost of ￥3 201.50,and additional 0.029 6 QALY.The incremental cost-utility ratio was 108 140.11 yuan/QALY,lower than the willingness-to-pay threshold of three times China's per capita GDP in 2021.The costs of tiotropium bromide and tiotropium bromide/odataterol had the greatest impact on the result in the one-way sensitivity analysis.93.8%of the Chinese COPD population was willing to pay for tiotropium bromide/odataterol under the threshold in the probability sensitivity analysis.Conclusion Tiotropium/olodaterol is a cost-effective alternative compared to tiotropium for patients with moderate to very severe COPD in China and the results were robust in the sensitivity analyses.

Objective:To evaluate the predictive value of mechanical power (MP) on the risk of in-hospital mortality in critical ill patients in emergency department.Methods:A total of 105 critical ill patients with invasive mechanical ventilation in the Department of Emergency of Second Affiliated Hospital of Guangzhou Medical University between December 1, 2017 and October 31, 2020 were retrospectively analyzed. Based on the clinical prognosis, the patients were divided into the in-hospital survival group (80 patients) and the in-hospital death group (25 patients). The clinical data and ventilator parameters were recorded, and the MP of the two groups was calculated in order to assess the predictive efficacy of MP on in-hospital death.Results:Compared to the in-hospital death group, the oxygenation index PaO 2/FiO 2 was significantly higher (271 mmHg vs. 217 mmHg, P=0.020) and blood lactate (1.59 mmol/L vs. 2.56 mmol/L, P<0.001) and procalcitonin (0.31 ng/mL vs. 3.55 ng/mL, P=0.028), minute ventilation (7.03 L/min vs.8.32 mmol/L, P=0.013), MP (14.37 J/min vs. 16.12 J/min, P=0.041), SOFA score (5 vs. 8, P=0.001) and APACHE II score (16 vs. 22, P=0.041) were significantly lower in the in-hospital survival group. Multivariate Logistic regression analysis showed that PaO 2/FiO 2( OR=1.015, P=0.044), MP ( OR=1.813, P=0.039) and SOFA score( OR=2.651, P=0.010) were independent risk factors for predicting hospital mortality in patients with mechanical ventilation. The areas under the ROC curves (AUC) were 0.62, 0.63 and 0.75, respectively. Moreover, the MP combined with SOFA score for predicting in-hospital death was significantly higher than that of MP alone (0.77 vs. 0.63, P<0.05). Conclusions:MP is associated with in-hospital death in patients with invasive mechanical ventilation in emergency department. MP combined with SOFA score can enhance its predictive efficacy

METHODS: Rat BMSCs were isolated, cultured and identified. The time-dependent expressions of TSP-2 and Sox9 in BMSCs under a dynamic mechanical pressure of 0–120 kPa at 0.1 Hz for 1 h were tested by qPCR and Western blotting. The role of TSP-2 in chondrogenic differentiation of BMSCs under mechanical pressure was validated by using small interfering RNA. The impact of TSP-2 and mechanical pressure on chondrogenesis were detected and the downstream signaling molecules were explored using Western blotting. RESULTS: Mechanical pressure stimulation of 0–120 kPa for 1 h significantly upregulated the expression of TSP-2 in BMSCs. The expression of the chondrogenesis markers Sox9, Aggrecan, and Col-II were all upregulated under dynamic mechanical pressure or TSP-2 stimulation. Additional exogenous TSP-2 may potentiate the chondrogenic effect of mechanical stimulation. After knock down TSP-2, the upregulation of Sox9, Aggrecan and Col-II under mechanical pressure was inhibited. The NF-jB signaling pathway responded to both dynamic pressure and TSP-2 stimulation, and the cartilage-promoting effect was blocked by an NF-jB signaling inhibitor. CONCLUSION TSP-2 plays an essential role in the chondrogenic differentiation of BMSCs under mechanical pressure. NF-jB signaling is involved in the mechano-chemical coupling of TSP-2 and mechanical pressure for the chondrogenic differentiation of BMSCs.

Patients with Crohn's disease (CD) are often complicated with malnutrition and enteral nutrition is the preferred option for nutritional support. Enteral nutrition is the first-line therapy to induce remission of CD in children, but its application in adults has not been well established. In recent years, studies have found that enteral nutrition can not only improve the nutritional status in adult CD patients, but also induce and maintain CD remission through various mechanisms. Given its favorable nutritional efficacy and safety, enteral nutrition has been considered as the basic treatment for adult CD patients and often used in combination with other treatment approaches. However, any combination therapy should be assessed in terms of benefit and risk. This review aims to describe the efficacy and safety of enteral nutrition combined with other treatment approaches in adult CD patients and enumerate common applicable clinical settings, so as to better inform clinical treatment.

Anxiety and depression are common in patients with inflammatory bowel disease (IBD), especially in patients with complex and active disease. IBD promotes the occurrence of anxiety and depression, while anxiety and depression also affect the progression of IBD. However, the pathogenesis has not been fully clarified, which is related mainly to inflammation, immune activation and brain-gut axis. Clinically, psychological disorders could be screened and identified by quantifiable assessment tools. Appropriate psychotherapy and psychiatric drugs can reduce the level of anxiety and depression and improve the quality of life of patients. This article reviewed the anxiety and depression related to IBD and its intervention.

Objective:To analyze the sepsis related long non-coding RNA (lncRNA) and mRNA expression profiles based on Gene Expression Omnibus (GEO) datasets and bioinformatic analysis, and to analyze the sepsis-associated competing endogenous RNA (ceRNA) network based on microRNA (miRNA) database.Methods:The sepsis-related lncRNA dataset was downloaded from the GEO database, and the differential expression analysis was conducted by Bioconductor on the sepsis dataset to obtain differentially expressed lncRNA (DElncRNA) and differentially expressed mRNA (DEmRNA), and cluster heat map was drawn. miRNA combined with DElncRNA were predicted by miRcode. mRNA targeted by miRNA was simultaneously met by three databases: TargetScan, miRDB, and mirTarBase. The interaction relationship of lncRNA-miRNA-mRNA was obtained. The regulatory network visualization software CytoScape was used to draw ceRNA networks. DEmRNA in the ceRNA networks were imported into the Search Tool for the Retrieval of Interacting Genes Database (STRING) online database to draw the protein-protein interaction (PPI) map. The gene ontology (GO) function annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of DEmRNA were performed.Results:Dataset GSE89376 and GSE145227 were found from GEO database. Difference analysis showed there were 14 DElncRNA and 359 DEmRNA in the elderly group of GSE89376; 8 DElncRNA and 153 DEmRNA in the adult group of GSE89376; 1 232 DElncRNA and 1 224 DEmRNA in the children group of GSE145227. Clustering heatmap showed that there were significant differences in the expression of lncRNA and mRNA between the sepsis group and the control group. The ceRNA networks were constructed with miRNA. Several DElncRNA and multiple DEmRNA participated in the ceRNA network of sepsis. The PPI diagram demonstrated that several genes encoding proteins interacted with each other and form a multi-node interaction network with multiple genes encoding proteins. Functional annotation and enrichment analysis demonstrated that there might be a crosstalk mechanism on functionally related genes such as nuclear receptor activity, ligand-activated transcription factor activity, and steroid hormone receptor activity, and played a role in the occurrence and development of diseases through forkhead box transcription factor O (FoxO) signaling pathway, Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway, p53 signaling pathway, and phosphateidylinositol 3-kinase (PI3K)/Akt signaling pathway.Conclusion:Through sepsis-related lncRNA-miRNA-mRNA ceRNA network and combining with KEGG pathway analysis, there were several lncRNA and mRNA participating in the ceRNA network related sepsis, which played an important role in several signal pathways.

Objective:To investigate the effect of lipopolysaccharide (LPS) on primary neonatal rat cardiomyocytes (CMs) and human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs).Methods:The hiPS-CMs and primary neonatal rat CMs were treated with different concentrations of LPS for 24 to 48 h. Then the cellular viability was analyzed by the xCELLigence RTCA Cardio system. The measurement of NPPB gene was studied by qRT-PCR and the gene expression analysis was performed by the qPCR array, in order to evaluate the cardiac inflammation effect induced by LPS.Results:The LPS exposure led to dysfunction in the primary neonatal rat CMs, which shown as an increase in beating rate and a decrease in contraction amplitude ( P<0.01), accompanied by an increased NPPB mRNA level ( P<0.01). There was no significant alteration in beating rate and the contraction amplitude in the corresponding concentration of the primary neonatal rat CMs ( P>0.05), as well as the NPPB mRNA level ( P>0.05). However, the expression of NPPB mRNA in hiPS-CMs was significantly different at a higher concentration of LPS (5 μg/mL~40 μg/mL) ( P<0.01), but the beating rate and the contraction amplitude showed no significant change, even the concentration of LPS up to 40 μg/mL ( P>0.05). Finally, the genes of C3, Gpnmb, Atf3, Il6r and Ly96 upregulated to 1.5 folds in the primary neonatal rat CMs. In comparison with primary neonatal rat CMs, the AK4, TOLLIP, SPP1, FABP1, IL6R, LY96 and C3 were over expression to 1.5 folds in the hiPS-CMs. Conclusions:In comparison with primary neonatal rat CMs, hiPS-CMs are markedly less injured by LPS and show a different pattern of inflammation gene expression.

Objective:To compare the difference and effect of fat grafting assisted by adjustable external volume expansion (EVE) and fat grafting only in female patients who chose autologous fat grafting for breast reconstruction after a breast cancer operation.Methods:A retrospective analysis was carried out in 17 patients in the past four years. The patients in the experimental group wore EVE 10 hours daily for four weeks before surgery, and the negative pressure value was -60 mmHg. From the second week after the operation, they continued to wear EVE 10 hours every day, and the initial negative pressure value was -40 mmHg. After one week, the negative pressure was adjusted to -20 mmHg, and the EVE was worn for four weeks after surgery. Both the experimental group and the control group chose classical Coleman fat for breast reconstruction.Results:The number of operations in the experimental and control groups was 3.0±0.8 and 3.9±1.2, respectively ( t=2.193; P<0.05). The single fat injection volume of the experimental group and the control group was (228.60±15.34) ml and (198.20±12.01) ml, respectively ( t=4.861; P<0.01). The single fat volume preservation rate of the experimental group and the control group was (31.6±5.8)% and (25.8±6.2)%, respectively ( t=2.226; P<0.05). For postoperative complications, there were 3 cases in the experimental group (10 cases in total) and 3 cases in the control group (7 cases in total). Conclusions:For breast cancer patients who choose autologous fat grafting for breast reconstruction, wearing EVE can reduce the number of operations, improve the single fat injection volume and postoperative fat preservation rate, and reduce postoperative complications.

Objective:To explore the role of bedside cardiopulmonary ultrasound in the evaluation of non-invasive positive pressure ventilation (NPPV) in patients with cardiaogenic pulmonary edema in emergency department.Methods:The clinical data and characteristics of bedside rapid cardiopulmonary ultrasound in patients withcardiaogenic pulmonary edema treated with NPPV in the emergency department were retrospectively analyzed. The following ultrasound parameters, including lung ultrasound score, the ratio of lung consolidation, diameter of inferior vena cava, left ventricular ejection fraction (LVEF), the mitral annular systolic displacement (MAPSE) and tricuspid annular systolic displacement (TAPSE), the peak Doppler velocities of the early diastolic mitral (E), the tissue velocity imaging of left ventricular and right ventricular (Sm), the tissue Doppler of the early diastolic velocity of the mitral annulus (e’), the average E/e’ ratio of left ventricular, systolic pulmonary artery pressure (SPAP) and the ratio of atrial fibrillation,, were determined. All of the parameters combined with clinical parameters were compared between the non-invasive ventilation success group and non-invasive ventilation failure group. Univariate and multivariate logistic regression analysis were used to screen out the risk factors by taking the failure of NPPV treatment as the dependent variable. The area under the receiver operating characteristic (ROC) curve was used to analyze the predictive value of the indicators above.Results:A total of 66 patients, included 44 (66.%) of NPPV success and 22 (33.3%) of NPPV failure revealed by bedside cardiopulmonary ultrasound. In comparison with the NPPV success group, the lung ultrasound score, ratio of lung consolidation, E/e’ of LV , SPAP, the ratio of right ventricular dysfunction, the ratio of atrial fibrillation and the level of Ccr were significantly evaluated, but the Sm of right ventricular and PaO2/FiO2 were significantly lower in the NPPV failure group (all P< 0.05). There were no differences in LVEF, MAPSE, TPASE, diameter of inferior vena cava and the Sm of left ventricular between groups (all P> 0.05). Multivariate logistic regression analysis showed that lung ultrasound score, E/e’ and SPAP were independent predictors of NPPV failure in patients with cardiaogenic pulmonary edema. The AUCs of lung ultrasound score, E/e’ of LV and SPAP for predicting NPPV failure was 0.802, 0.783 and 0.852, respectively. . Conclusions:The lung ultrasound score, right ventricular diastolic function and SPAP evaluated by bedside cardiopulmonary ultrasound could provide predictive values for the non-invasive positive ventilation failure in patients with cardiaogenic pulmonary edema.

Objective To compare the performance of colitis induced by dextran sulfate sodium (DSS) between Lnk-knockout mice and wild-type mice. Methods The C57 BL/6 mice with similar week age were divided into wild type group (WT), wild type mouse with colitis group (WT +DSS), Lnk-knockout group (KO) and Lnk-knockout mouse with colitis group (KO + DSS). WT and KO mice were admitted to drink water freely, WT + DSS and KO + DSS mice was allowed to drink2. 5％ DSS aqueous solution freely. The experiment was carried out for 7 days to observe daily weight change, fecal texture (soft or hardness) and intestinal hemorrhage in mice, and to evaluate the disease activity index (DAI). After 7 days, the peripheral blood was collected to detect the regulatory B-cell (Breg) frequency by flow cytometry in the peripheral blood of WT mice and KO mice. The mouse was sacrificed, and the bowel was taken to observe the shape, color and measure the length of the intestine. The colonic tissue was produced by histological sections and HE staining, and histological changes were observed under the microscope. Results The bowel movement was normal in WT group and KO group, and the mice in KO + DSS group and the WT + DSS group had manifestation of earlier diarrhea and blood-draining. In the experimental period, the weight of KO + DSS group was significantly lower than the other 3 groups, and DAI in the KO + DSS group increased significantly with time. Breg cells frequency in KO group was significantly lower than WT group. In the KO +DSS group, colon obviously shortened, microscopic examination of HE tissue section showed erosive bleeding congestion, multiple lesions shallow ulcer, inflammatory cell infiltration mucosa and submucosa with involvement of the muscle layer, which indicated increased inflammatory response.Conclusion Lnk deficiency can aggravate the performance of DSS-induced colitis in mice, which may be related to the decrease of Breg cells frequency and negative regulation of inflammatory response in Lnk KO mice.