Emerging trends in organ-on-a-chip systems for drug screening

New drug discovery is under growing pressure to satisfy the demand from a wide range of domains, especially from the pharmaceutical industry and healthcare services. Assessment of drug efficacy and safety prior to human clinical trials is a crucial part of drug development, which deserves greater emphasis to reduce the cost and time in drug discovery. Recent advances in microfabrication and tissue engineering have given rise to organ-on-a-chip, an in vitro model capable of recapitulating human organ functions in vivo and providing insight into disease pathophysiology, which offers a potential alternative to animal models for more efficient pre-clinical screening of drug candidates. In this review, we first give a snapshot of general considerations for organ-on-a-chip device design. Then, we comprehensively review the recent advances in organ-on-a-chip for drug screening. Finally, we summarize some key challenges of the progress in this field and discuss future prospects of organ-on-a-chip development. Overall, this review highlights the new avenue that organ-on-a-chip opens for drug development, therapeutic innovation, and precision medicine.

Modeling human hypertrophic scars with 3D preformed cellular aggregates bioprinting.

The therapeutic interventions of human hypertrophic scars (HHS) remain puzzle largely due to the lack of accepted models. Current HHS models are limited by their inability to mimic native scar architecture and associated pathological microenvironments. Here, we create a 3D functional HHS model by preformed cellular aggregates (PCA) bioprinting, firstly developing bioink from scar decellularized extracellular matrix (ECM) and alginate-gelatin (Alg-Gel) hydrogel with suitable physical properties to mimic the microenvironmental factors, then pre-culturing patient-derived fibroblasts in this bioink to preform the topographic cellular aggregates for sequent printing. We confirm the cell aggregates preformed in bioink displayed well defined aligned structure and formed functional scar tissue self-organization after bioprinting, hence showing the potential of creating HHS models. Notably, these HHS models exhibit characteristics of early-stage HHS in gene and protein expression, which significantly activated signaling pathway related to inflammation and cell proliferation, and recapitulate in vivo tissue dynamics of scar forming. We also use the in vitro and in vivo models to define the clinically observed effects to treatment with concurrent anti-scarring drugs, and the data show that it can be used to evaluate the potential therapeutic target for drug testing. The ideal humanized scar models we present should prove useful for studying critical mechanisms underlying HHS and to rapidly test new drug targets and develop patient-specific optimal therapeutic strategies in the future.

Multimodal integrated strategy for the discovery and identification of quality markers in traditional Chinese medicine / 药物分析学报

With the modernization and internationalization of traditional Chinese medicine(TCM),the requirement for quality control has increased.The quality marker(Q-marker)is an important standard in this field and has been implemented with remarkable success in recent years.However,the establishment of Q-markers remains fragmented and the process lacks systematicity,resulting in inconsistent quality control and insufficient correlation with clinical efficacy and safety of TCM.This review introduces four multi-modal integrated approaches that contribute to the discovery of more comprehensive and accurate Q-markers,thus aiding in the establishment of new quality control patterns based on the characteristics and principles of TCM.These include the whole-process quality control strategy,chemical-activity-based screening method,efficacy,safety,and consistent combination strategy,and TCM theory-guided approach.Furthermore,methodologies and representative examples of these strategies are described,and important future directions and questions in this field are also proposed.

Predictive performance of Smart Dose, PharmVan and JPKD on Vancomycin plasma concentration / 中华危重病急救医学

Objective:To evaluate the predictive performance of the individualized drug delivery decision-making system including Smart Dose, PharmVan and JPKD on predicting the Vancomycin plasma concentration and to analyze the related factors affecting the predictive performance.Methods:The clinical data of patients who were treated with Vancomycin and received therapeutic drug monitoring (TDM) admitted to the First Affiliated Hospital of Wenzhou Medical University from January 2018 to July 2020 were retrospectively collected. Smart Dose and PharmVan were used to predict the plasma concentration of Vancomycin of the initial regimen. Smart Dose, PharmVan and JPKD were used to predict the plasma concentration of Vancomycin of the adjustment regimen for patients whose initial steady-state trough concentration were not qualified. The relative predictive error (PE) between the measured plasma concentration and predicted plasma concentration was calculated and box plotted. Mann-Whitney U test was used to evaluate the difference of the absolute value of PE (APE) predicted by each software for Vancomycin plasma concentration. The TDM results were divided into accurate prediction group (APE < 30%) and the inaccurate prediction group (APE≥30%) according to the APE value. Patients and disease characteristics including gender, age, body weight complication, Vancomycin medication and TDM results were collected from electronic medical records. Univariate analysis and multivariate Logistic regression analysis were used to screen the related factors that influence the predictive performance of Smart Dose, PharmVan and JPKD; and receiver operating characteristic curve (ROC curve) was drawn to evaluate its predictive value. Results:A total of 185 patients were enrolled, and 258 plasma concentration of Vancomycin were collected, including 185 concentrations of initial regimen and 73 concentration of adjustment regimen. There was no significant difference in the APE of the initial regimen of plasma concentration between Smart Dose and PharmVan. No significant difference in the APE of the adjustment regimen of plasma concentration was found among Smart Dose, PharmVan and JPKD. The accuracy of Smart Dose in predicting the plasma concentration of the adjustment regimen was better than that of the initial regimen [22.94% (10.50%, 36.24%) vs. 29.33% (13.07%, 47.99%), P < 0.05]. The univariate analysis of factors affecting the performance of Smart Dose in predicting the concentration of initial regimen showed that the proportion of patients with hypertension in the accurate prediction group was significantly higher than that in the inaccurate prediction group [43.3% (42/97) vs. 27.3% (24/88), P < 0.05]. The univariate analysis of factors affecting the performance of Smart Dose in predicting the concentration of adjustment regimen showed that the proportion of patients with valvular heart disease in the accurate prediction group was significantly lower than that in the inaccurate prediction group [23.4% (11/47) vs. 46.2% (12/26), P < 0.05]. The univariate analysis of factors affecting the performance of JPKD in predicting the concentration of adjustment regimen showed that the body weight of patients in the accurate prediction group was significantly higher than that in the inaccurate prediction group (kg: 62.8±14.9 vs. 54.8±12.8, P < 0.05). Multivariate Logistic regression analysis indicated that hypertension was a beneficial factor for Smart Dose to predict the initial plasma concentration of Vancomycin [odds ratio ( OR) = 0.526, 95% confidence interval (95% CI) was 0.281-0.983, P = 0.044], and low body weight was an independent risk factor for the inaccurate prediction of JPKD for adjustment regimen ( OR = 1.042, 95% CI was 1.001-1.085 , P = 0.043). ROC curve analysis indicated that the area underROC curve (AUC) of the body weight for evaluating the accuracy of JPKD in predicting Vancomycin plasma concentration was 0.663, and 95% CI was 0.529-0.796 ( P = 0.023). When the body weight was less than 55.95 kg, the risk of inaccurate prediction of JPKD in predicting Vancomycin plasma concentration was increased, and the predictive sensitivityand specificity were 75% and 60% respectively. Conclusions:There is no significant difference in the predictive performance of Smart Dose, PharmVan or JPKD on Vancomycin plasma concentration. Smart Dose had a better predictive performance for the Vancomycin plasma concentration of adjustment regimen than initial regimen. Smart Dose had a better predictive performance when the patient was concomitant with hypertension. JPKD had a poor predictive performance for low-body weight patients. The predictive performance of JPKD was decreased when the body weight was lower than 55.95 kg.

Value of albumin-bilirubin score combined with neutrophil count and procalcitonin in ascites in predicting spontaneous bacterial peritonitis in patients with cirrhotic ascites / 临床肝胆病杂志

Objective To investigate the risk factors for spontaneous bacterial peritonitis (SBP) in patients with cirrhotic ascites, and to establish a new model for predicting the development of SBP. Methods A total of 215 patients who were diagnosed with cirrhotic ascites in Hebei General Hospital from September 2016 to September 2020 were enrolled, and according to the presence or absence of SBP, they were divided into SBP group with 55 patients and non-SBP group with 160 patients. Related clinical data were collected and albumin-bilirubin (ALBI) score, Model for End-Stage Liver Disease (MELD) score, MELD combined with serum sodium concentration (MELD-Na) score, and Child-Pugh score were calculated. The t -test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups; a multivariate logistic regression analysis was used to screen out independent risk factors, and the receiver operating characteristic (ROC) curve was plotted to evaluate the performance of ALBI score, procalcitonin (PCT), polymorphonuclear neutrophil (PMN) count in ascites, and the ALBI-PMN-PCT combined model in the diagnosis of SBP. Results Compared with the SBP group, the non-SBP group had a significantly higher concentration of Na + ( Z =-3.414, P =0.001) and significantly lower total bilirubin ( Z =-2.720, P =0.007), creatinine ( Z =-1.994, P =0.046), urea nitrogen ( Z =-2.440, P =0.015), C-reactive protein ( Z =-9.137, P 0.272 had an increased risk of developing SBP. Conclusion The ALBI-PMN-PCT combined model has a high value in predicting the onset of SBP in patients with cirrhotic ascites.

Optimization of the Purification Technology of Total Triterpenoids of Ligustrum lucidum by Box-Behnken Re- sponse Surface Methodology / 中国药房

OBJECTIVE：To i mprove the transfer rate and purity of oleanolic acid and ursolic acid in total triterpenoids from Ligustrum lucidum ，so as to optimize the purification technology. METHODS ：Oleanolic acid and ursolic acid were used as representative components of total triterpenoids ，and their contents were determined by HPLC. The determination was performed on Thermo BDS Hypersil C 18 column with mobile phase consisted of methanol- 0.02％ ammonium acetate solution （80∶20，V/V）at the flow rate of 1.0 mL/min. The detection wavelength was set at 210 nm，and column temperature was 30 ℃. The sample size was 20 μ L. In single factor tests，using transfer rate of oleanolic acid and ursolic acid as index ，the effects of water precipitation temperature and time ，the amount of redissolved ethanol on the purification technology was investigated ；using transfer rate and purity of two components as indexes ，the effects of the amount of activated carbon and volume fraction of crystallization ethanol were investigated. Based on it ，using the amount of redissolved ethanol and activated carbon ，volume fraction of crystallization ethanol as factors ，Box-Behnken response surface methodology was used to optimize the purification technology ，and validation tests were performed. RESULTS ：The optimal purification technology was adding 4-fold（mL/g，the same below ）water in L. lucidum concentrated solution ，placing for 2 hours at 0 ℃（water precipitation ）；adding 1-fold ethanol to dissolve （redissolution）； adding 4％ activated carbon （edulcoration）；finally adding water to adjust the volume fraction of ethanol to 80％，placing at 4 ℃ for 12 hours（crystallization），centrifuging and drying. The results of 3 times of validation tests showed that the transfer rates of oleanolic acid and ursolic acid in total triterpenoids prepared by optimized technology were 61.11％ and 65.78％，the purities of them were 53.44％ and 19.79％，and RSDs were both lower than 3％. CONCLUSIONS ：The optimized purification technology has high extraction efficiency and simple operation ，which can be used for industrial production of purification of total triterpenoids from L. lucidum and the development of corresponding preparations.

Down-regulation of HOTAIR Reverses the Resistance of Gefitinib in HCC827 Cells by Increasing the Expression of PTEN / 中国肺癌杂志

BACKGROUND@#Lung cancer is the most common cancer worldwide with the highest morbidity and mortality, in which the non-small cell lung cancer accounts for 80% of all cases. The expression of (HOX transcript antisense RNA) HOTAIR were abnormal in a variety of tumor tissues and is involved in the regulation of the occurrence and development of lung cancer. The purpose of this study is to investigate the effect and mechanism of down-regulation of HOTAIR on gefitinib resistance of lung adenocarcinoma HCC827 cells by targeting PTEN.@*METHODS@#The HOTAIR downstream target gene was predicted by bioinformatics database. The small interfering RNAs (siRNA) which is corresponding to HOTAIR was transfected using Lipofectamine™ 2000. Quantitative real-time PCR (RT-qPCR) and Western blot were used to detect the expression of HOTAIR, PTEN, PI3K and AKT in HCC827 and HCC827GR cells. MTT assay was used to detect the changes in drug resistance of HCC827GR cells. Flow cytometry analysis were used to test the cell proliferation and the rate of apoptosis.@*RESULTS@#The expression of HOTAIR increased in HCC827GR and the serum of NSCLC patients with gefitinib resistance (P<0.05). Transfection of HOTAIR siRNA decreased the expression of HOTAIR (P<0.05), and increased the expressions of PTEN (P<0.05), while the expression of PI3K and AKT were decreased (P<0.05). Compared with the blank control group, down-regulation of HOTAIR increased the sensitivity of HCC827GR cells to gefitinib. The cell proliferation ability was decreased and the apoptosis was promoted apparently (P<0.05).@*CONCLUSIONS@#Down-regulation of HOTAIR can suppress the cell growth and promote the apoptosis, and it can reverse the resistance of HCC827GR cells to gefitinib. Its potential mechanism may be related with the targeting of PTEN/PI3K/AKT pathway.

Down-regulation of HOTAIR Reverses the Resistance of Gefitinib in HCC827 Cells by Increasing the Expression of PTEN / 中国肺癌杂志

BACKGROUND@#Lung cancer is the most common cancer worldwide with the highest morbidity and mortality, in which the non-small cell lung cancer accounts for 80% of all cases. The expression of (HOX transcript antisense RNA) HOTAIR were abnormal in a variety of tumor tissues and is involved in the regulation of the occurrence and development of lung cancer. The purpose of this study is to investigate the effect and mechanism of down-regulation of HOTAIR on gefitinib resistance of lung adenocarcinoma HCC827 cells by targeting PTEN.@*METHODS@#The HOTAIR downstream target gene was predicted by bioinformatics database. The small interfering RNAs (siRNA) which is corresponding to HOTAIR was transfected using Lipofectamine™ 2000. Quantitative real-time PCR (RT-qPCR) and Western blot were used to detect the expression of HOTAIR, PTEN, PI3K and AKT in HCC827 and HCC827GR cells. MTT assay was used to detect the changes in drug resistance of HCC827GR cells. Flow cytometry analysis were used to test the cell proliferation and the rate of apoptosis.@*RESULTS@#The expression of HOTAIR increased in HCC827GR and the serum of NSCLC patients with gefitinib resistance (P<0.05). Transfection of HOTAIR siRNA decreased the expression of HOTAIR (P<0.05), and increased the expressions of PTEN (P<0.05), while the expression of PI3K and AKT were decreased (P<0.05). Compared with the blank control group, down-regulation of HOTAIR increased the sensitivity of HCC827GR cells to gefitinib. The cell proliferation ability was decreased and the apoptosis was promoted apparently (P<0.05).@*CONCLUSIONS@#Down-regulation of HOTAIR can suppress the cell growth and promote the apoptosis, and it can reverse the resistance of HCC827GR cells to gefitinib. Its potential mechanism may be related with the targeting of PTEN/PI3K/AKT pathway.

A brief history of burn rehabilitation medicine in China / 中华烧伤杂志

Objective@#Burn rehabilitation medicine in China has made great progress in recent years. This article reviews the development history of burn rehabilitation medicine in China from three stages of the initial period, the starting stage, and the development period by looking back to the history. Besides, the article is written according to the milestone events in the development of burn rehabilitation medicine, such as article publishing, guideline making, monograph publication, establishment of rehabilitation association, rehabilitation conference holding. By summarizing successful experience in the past and analyzing the challenge we face, the authors wish all the colleagues committed to burn prevention and treatment work together to make the burn rehabilitation medicine in China better in the future.

Effects of penehyclidine hydrochloride combined with unilateral high-frequency jet ventilation on pulmonary function and inflammatory response during one-lung ventilation in patients with chronic obstructive pulmonary disease / 中华麻醉学杂志

Objective To evaluate the effects of penehyclidine hydrochloride (PHCD) combined with high-frequency jet ventilation (HFJV) of the operated lungs on pulmonary function and inflammatory response during one-lung ventilation (OLV) in patients with chronic obstructive pulmonary disease (COPD).Methods Sixty American Society of Anesthesiologists physical status Ⅱ or Ⅲ patients of both sexes with COPD,aged 40-64 yr,with body mass index of 17-26 kg/m2,scheduled for elective video-assisted thoracoscopic surgery under general anesthesia,were divided into 4 groups (n =15 each) using a random number table method:conventional group (group C),PHCD group (group P),HFJV group (group H) and PHCD combined with HFJV group (group PH).After induction of anesthesia,the patients were intubated with a double-lumen tube and then mechanically ventilated,with inspired oxygen concentration 100％,oxygen flow rate 2 L/min,tidal volume 6-8 ml/kg,respiratory rate 10-14 breaths/min,and respiratory rate was set at 12-16 breaths/min and PETCO2 was maintained at 40-45 mmHg during OLV.PHCD 0.01 mg/kg was intravenously injected before intubation in P and PH groups.The ventilation mode was changed to OLV after beginning of skin incision in each group.Ventilation of the lung on the operated side was performed by means of HFJV (driving pressure 0.5 kg/cm2) during OLV in P and PH groups.The pneumodynamic parameters such as airway peak pressure (Ppeak),airway plateau pressure (Pplat),airway resistance (Raw) and dynamic lung compliance (Cdyn) were monitored immediately before skin incision (T1) and at 60 and 120 min of OLV (T2,3).Arterial blood samples were obtained at T2 for blood gas analysis,and oxygenation index (OI),respiratory index (RI),physiologic dead space fraction (VD/Vr)and alveolar-arterial oxygen gradiant (A-aDO2) were calculated.Venous blood samples were drawn at T3 for determination of the serum concentrations of tumor necrosis factor-alpha (TNF-α),interleukin-6 (IL-6)and IL-8 by enzyme-linked immunosorbent assay.The occurrence of pulmonary complications was recorded within 72 h after operation.Results Compared with group C,the serum concentrations of TNF-α,IL-6 and IL-8,Ppeak,Pplat,Raw,RI,VD/VT,A-aDO2 and incidence of pulmonary complications were significantly decreased,and Cdyn and OI were increased in group P and group PH (P＜0.05),and the serum concentrations of TNF-α,IL-6 and IL-8,RI,VD/VT,A-aDO2 and incidence of pulmonary complications were significantly decreased,and OI was increased in group H (P＜0.05).Compared with group P or group H,the serum concentrations of TNF-α,IL-6 and IL-8,RI,VD/VT,A-aDO2 and incidence of pulmonary complications were significantly decreased,and OI was increased in group PH (P＜0.05).Conclusion PHCD combined with HFJV of the operated lung produces better efficacy in improving respiratory function,inhibiting inflammatory responses,reducing lung injury and is more helpful in improving prognosis than either alone in the patients with COPD.

Effect of curcumin on intestinal mucosal mechanical barrier in rats with non-alcoholic fatty liver disease / 中华肝脏病杂志

Objective@#To investigate the effect of curcumin on intestinal mucosal mechanical barrier in rats with non-alcoholic fatty liver disease.@*Methods@#A total of 30 male Sprague-Dawley rats were equally divided into normal control group, model group, and curcumin intervention group. The rats in the model group and the curcumin intervention group were given high-fat feed for 16 weeks, and those in the curcumin intervention group were given curcumin 200 mg/kg/day by gavage once a day after 8 weeks of high-fat feeding. The rats were sacrificed at the end of week 16. A light microscope was used to observe pathological changes in the liver, an electron microscope was used to observe the tight junction of the intestinal mucosa, an automatic biochemical analyzer was used to measure the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), chromogenic substrate Limulus amebocyte lysate assay was used to measure plasma lipopolysaccharide (LPS) level, spectrophotometric method was used to measure the activity of serum diamine oxidase, ELISA was used to measure the serum level of tumor necrosis factor-α (TNFα), and immunohistochemistry was used to measure the expression of the tight junction protein occludin. One-way ANOVA test and SNK-q test were used for statistical analysis.@*Results@#Under the light microscope, the control group had no hepatocyte steatosis, the model group had significant hepatocyte steatosis and inflammatory cell infiltration, and the curcumin intervention group had reduced hepatocyte steatosis and inflammatory cell infiltration. Under the electron microscope, the control group had a clear and complete structure of the tight junction of the intestinal mucosa and normal structures of mitochondria and endoplasmic reticulum; in the model group, the structure of the tight junction of the intestinal mucosa was destroyed, the intercellular space was widened, the desmosomes had a loose structure, there was edema in some mitochondria, and the endoplasmic reticulum was dilated; the curcumin intervention group had improvements in the structure of tight junction of the intestinal mucosa, intercellular space, edema in the mitochondria, and dilation of the endoplasmic reticulum. Compared with the control group, the model group had significant increases in the serum levels of AST, ALT, DAO, TNFα, and LPS (q = -15.918, -14.402, -33.700, -8.944, and -10.832, P < 0.05); compared with the model group, the curcumin intervention group had significant reductions in the serum levels of AST, ALT, DAO, TNFα, and LPS (q = 10.457, 7.752, 18.802, 5.202, and 4.279, P < 0.05). In the control group, occludin showed a linear distribution along the top of small intestinal mucosal epithelial cells. The model group had a significant reduction in positive staining compared with the control group, and the curcumin intervention group had a significant increase in positive staining compared with the model group. The relative expression of occludin was 0.29±0.03 in the control group, 0.12±0.02 in the model group, and 0.21±0.02 in the curcumin intervention group (P < 0.05).@*Conclusion@#Intestinal mucosal mechanical barrier is impaired in rats with NAFLD. Curcumin can reduce such damage, and its mechanism of action may be related to up-regulating the expression of occludin in the intestinal mucosa and reducing the levels of TNFα and LPS.

Effects of Rab7 gene silencing on cytokine and MAPK signal pathway activated by R848 in macrophage / 中国免疫学杂志

Objective:To investigate the effect of Rab7 on cytokine induced by TLR7 (Toll like receptor-7) R848 activated in Raw264.7,and discusses the influence of Rab7 on MAPK signal transduction.Methods: TLR7 downstream cytokines such as TNF-α,IL-6,IFN-α,IFN-β and IP-10 activated by R848 were detected through Q-PCR in Rab7 silenced mouse macrophages,and then analysis of phosphorylation of MAPK determined with Western blot showed the effect of Rab7 on signal transduction of MAPK.Results: Rab7 inhibit production of cytokine activated by TLR7,and also,Rab7 had an inhibitory effect on MAPK signal pathway.Conclusion: The experimental results further illustrate that the Rab7 is the TLR7 signal transduction pathway negative regulatory factor,and to participate in MAPK signaling pathway.

Rab5a promotes expression of pro-inflammatory cytokines and type Ⅰ IFN in CpG induced macrophages / 中国免疫学杂志

Objective:Using the macrophage cell lines RAW264.7 stably expressing Rab5a and its dominant negative mutant Rab5aN133I as models to analyze the effect and the mechanism of Rab 5a,Rab5aN133I on CpG-induced production of pro-inflammatory cytokines and type Ⅰ IFN.Methods: The eukaryotic expression vectors of Rab5a and Rab5aN133I were transfected into RAW264.7 cells by liposome,and screened with G418.The G418-resistant colonies were obtained and amplified.The transformed cell lines were i-dentified by RT-PCR,Real time-PCR and Western blot.The production of cytokines were measured after transformed cell lines of Rab5a and Rab5aN133I was stimulation with CpG for 8 h.Results: Rab5a expression in transfected cells was significantly higher than the control cell group (P<0.05).Overexpression of Rab5a significantly promoted the production of TNF -α,IL1-β(P<0.01) and IFN-β( P<0.05) in CpG stimulated RAW264.7.The production of cytokines was restored in Rab 5aN133I transfected cell line.Conclusion:Rab 5a promotes CpG-induced pro-inflammatory cytokines and typeⅠIFN in macrophages,it may be act as a positive regulator in TLR9 signaling pathway.

GLP-1 down-regulates mRNA expression of SOCS-3 and SREBP-1c in rats with nonalcoholic fatty liver disease / 中国病理生理杂志

AIM:To investigate the effects of glucagon-like peptide-1 (GLP-1) on mRNA expression of SOCS-3 and SREBP-1c in the rats with nonalcoholic fatty liver disease.METHODS:Male SD rats were randomly divided into normal control ( NC) group, high fat ( HF) group and HF+liraglutide ( Lira) group.The rats in HF group and HF+Lira group were given high-fat diet for 16 weeks.After 12 weeks of high-fat diet feeding in HF+Lira group, Lira (600μg? kg-1? d-1 ) was intraperitoneally injected for 4 weeks.At the end of the 16th week, the rats were killed.The pathologi-cal changes of the liver were observed under optical microscope.The serum levels of alanine aminotransferase ( ALT) , as-partate aminotransferase ( AST) , triglyceride ( TG) and total cholesterol ( TC) were detected by automatic biochemical an-alyzer.TG contents of liver were measured by GPO-PAP method.The fasting insulin ( FINS) was determined by ELISA, and insulin resistance index was assessed by homeostasis mode assessment ( HOMA-IR) .The mRNA expression of SOCS-3 and SREBP-1c in the liver tissues was detected by RT-qPCR.RESULTS:Compared with NC group, HOMA-IR, TG of liver, and the serum levels of ALT, AST, TG, TC and FINS in HF group were obviously increased (P duce TG of liver through decreasing the mRNA expression of SOCS-3 and SREBP-1c, so as to play a therapeutic role in nonalcoholic fatty liver disease.

Inhibitory effects of seabuckthorn polysaccharide on oxidative stress in mice with actue liver injury and modulatory effect on BCL-2/Bax and PPAR-γexpression / 中国免疫学杂志

Objective:To explore the inhibitory effects of seabuckthorn polysaccharide on hepatic oxidative stress in a mice model of acute liver injury induced by intraperitoneal injection of LPS and D -GalN and detect the expression on hepatic BCL-2/Bax and PPAR-γ.Methods: C57BL/6 male mice were randomly divided into six groups:control group ( CTRL), model group ( L/G), dexamethasone positive control group ( DXM ) , low ( SPL ) , medium ( SPM ) and high dose group ( SPH ) of seabuckthorn polysaccharide.Mice in the SPL,SPM and SPH group were gavaged with 50,100 and 200 mg/kg seabuckthorn polysaccharide for 14 days respectively.Acute liver injury model were established by intraperitoneal injection of LPS (10 μg/kg) and D-GalN (700 mg/kg) .Serum and liver samples were collected 4 h after model establishment .Serum levels of ALT and AST and the content of MDA were de-tected.Hepatic expression of SOD 2 BCL-2 and Bax was determined by Western blot and the expression of PPAR-γwas detected by im-munohistochemistry .Results:ALT and AST levels significantly increased in the model group and decreased dose-dependently after pre-treatment with seabuckthorn polysaccharide .The level of MDA in the model group increased significantly as compared with the control group and decreased in seabuckthorn polysaccharide groups ,while the level of SOD 2 decreased in the model group and recovered in sea-buckthorn polysaccharide groups .The expression of Bax decreased after pretreatment with seabuckthorn polysaccharide .There was no obvious effect on BCL-2 expression after sea buckthorn polysaccharide supplementation .The expression of PPAR-γreduced in the sea-buckthorn polysaccharide group as compared with the model group .Conclusion:Seabuckthorn polysaccharide protects against LPS /D-GalN-induced liver injury.The effect is associated with an upregulation of SOD 2 and downregulation of Bax .

A review of nursing care of pressure ulcer at different stage / 中国实用护理杂志

Pressure ulcer care were always the focus and difficulty of nursing work.Timely and effective care were helpful to promote the repair of pressure ulcer.This article described and compared the different stages of system pressure sores assessment.This article mainly summarized the effective nursing methods at every stage of pressure ulcer at present,which were helpful to carry out evidence-based care and improve the quality of nursing.

Principal Items Respond to Activities of Daily Living for Persons with Physical Disability / 中国康复理论与实践

@#Objective To investigate the principal indicators of self-care ability in activities of daily living for the persons with physical disability. Methods Persons with physical disability were asked to select the top 3 items out of 27 items of activities of daily living in 3 levels. Results A total of 1960 questionnaires were send out, and 1862 were returned. For all the subjects, the items related with personal hygiene, such as toileting, self-cleaning and bathing, were selected 899 times (16.1%). The items related with personal health, as visiting community clinics and community exercising, were selected 570 times (10.2%). The items related with social interaction, as making a telephone and chatting, were selected 500 times (9.0%). For the persons with physical disability of first grade, the major items most selected were eating, entertaining, self-cleaning and transferring; and self-cleaning and housework for those of second grade; self-cleaning, community activities and housework for those of third grade; and community and interaction for those of fourth grade. Conclusion The persons with physical disability mostly focused on the activities related with personal hygiene, health and social interaction, and varied with the severity of disability, from self-cleaning to housework and social participation.

Protective effects of sea buckthorn polysaccharide extracts on LPS/D-GalN-induced liver injury in mice and modulation on TLR4,SOCS3 expression / 中国免疫学杂志

Objective:To study the protective effects of sea buckthorn polysaccharide extracts on lipopolysaccharide( LPS)/D-galactosa mine ( D-GalN )-induced liver injury in mice and investigate the regulation on hepatic TLR4 and SOCS3 expression.Methods:C57BL/6 male mice were randomly divided into six groups:control group,model group,dexamethasone positive control group, low, medium and high dose group of sea buckthorn polysaccharide.Mice in the sea buckthorn polysaccharides low, medium and high dose group were gavaged with 50, 100 and 200 mg/kg sea buckthorn polysaccharide extracts for 14 days respectively.Acute liver injury model were established by intraperitoneal injection of LPS(10 μg/kg) and D-GalN (700 mg/kg).The mice in the dexamethasone positive control group were intraperitoneally injected with dexamethasone (10 mg/kg) before model estab-lishment.Serum and liver samples were collected after model establishment for 4 h .Serum levels of ALT and AST were detected.Histological changes of liver tissue were observed by HE staining.Hepatic expression of TLR4 and SOCS3 was detected by Western blot.Results:Sea buckthorn polysaccharide significantly inhibited LPS/D-GalN-induced elevation in serum levels of ALT and AST.It also alleviated liver cell injury and inflammatory infiltration.Western blot results showed that sea buckthorn polysaccharide inhibited LPS/D-GalN-induced TLR4 expression.SOCS3 expression was not dramatically influenced by sea buckthorn polysaccharide supplementation.Conclusion:Sea buckthorn polysaccharide protects against LPS/D-GalN-induced liver injury.This protective effects may be achieved by inhibiting the expression of TLR4 but not associated with modulation on SOCS3 expression.

The value of pulmonary rehabilitation in patients with acute exacerbation of chronic obstructive pulmonary disease / 天津医药

Objective To observe the effect of early pulmonary rehabilitation (PR) on patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). Methods AECOPD patients (n=97) were randomly distributed into two groups:control group (n=39) and rehabilitation group (n=58). Patients in both groups were assessed when symptom im?proved from acute phase (baseline, T1). Then patients in control group only received pharmaco-therapy and rehabilitation ed?ucation without PR. When symptom was relieved and stable (T2), they were given 12 weeks PR (T3). On the other hand, pa?tients in rehabilitation group underwent a 12-week PR after T1 directly (T2). The lung function parameters, 6 min walking distance (6MWD), MRC scores and CAT scores were observed and analyzed in two groups. Results Until the end of the 12-weeks observation, the value of lung function showed no statistic differences between two groups(either T1 in control group vs T1 in PR group or T2 in PR group vs T2 and T3 in control group. In control group, the value of 6MWD scores of T3 was bet?ter than that of T1 and T2, in PR group(F6MWD=8.762,FMRC=4.432,FCAT=10.266,P<0.05)while MRC, CAT value in T3 of control group were higher than those in T1 and T2 of PR group. At T1, parameters does not demonstrate significant difference between these two groups. Value of 6MWD was higher while MRC and CAT were lower in T2 of PR group than that in T2 and T3 of control group. Conclusion Early pulmonary rehabilitation could improve the mobility and qulity of life, as well as ameliorate the severity of dyspnea in AECOPD patients.

Clinic significance of four clinical scoring systems in evaluating prognosis of acute pancreatitis / 天津医药

Objective To compare the clinic significance of four clinical scoring systems in evaluating prognosis of acute pancreatitis: bedside index for severity in acute pancreatitis(BISAP), acute physiology and chronic health evaluation (APACHEⅡ), Ranson’s scoring system, computed tomography severity index (CTSI) in AP. Methods Patients visited our clinic with AP (n=114) in recent 2 years were retrospectively analyzed. BISAP and APACHEⅡscores were obtained at 24 hours after admission; Ranson ’s score was obtained at 48 hours after admission and CTSI are obtained was obtained at 72 hours after admission. Results of four scoring system were compared under different causes and different severity of the dis?ease. Correlation between BISAP score and the other three scores were analyzed and the predicative value of all four scoring systems for severity of AP and death were also compared. Results The mean values of four scoring systems show no signifi?cant difference in AP patients with different etiology (P>0.05). The BISAP score is positively correlated with APACHE-Ⅱ, Ranson ’s score and CTSI score (P<0.01). The four scoring systems all present good predictive value on the severity of AP and death (P<0.01). Conclusion The four scoring systems can all be applied to grading and prognosis for AP of various causes. BISAP is a simple, prompt, economical scoring system in clinical practice.