CD47 blockade improves the therapeutic effect of osimertinib in non-small cell lung cancer / 医学前沿

The third-generation epidermal growth factor receptor (EGFR) inhibitor osimertinib (OSI) has been approved as the first-line treatment for EGFR-mutant non-small cell lung cancer (NSCLC). This study aims to explore a rational combination strategy for enhancing the OSI efficacy. In this study, OSI induced higher CD47 expression, an important anti-phagocytic immune checkpoint, via the NF-κB pathway in EGFR-mutant NSCLC HCC827 and NCI-H1975 cells. The combination treatment of OSI and the anti-CD47 antibody exhibited dramatically increasing phagocytosis in HCC827 and NCI-H1975 cells, which highly relied on the antibody-dependent cellular phagocytosis effect. Consistently, the enhanced phagocytosis index from combination treatment was reversed in CD47 knockout HCC827 cells. Meanwhile, combining the anti-CD47 antibody significantly augmented the anticancer effect of OSI in HCC827 xenograft mice model. Notably, OSI induced the surface exposure of "eat me" signal calreticulin and reduced the expression of immune-inhibitory receptor PD-L1 in cancer cells, which might contribute to the increased phagocytosis on cancer cells pretreated with OSI. In summary, these findings suggest the multidimensional regulation by OSI and encourage the further exploration of combining anti-CD47 antibody with OSI as a new strategy to enhance the anticancer efficacy in EGFR-mutant NSCLC with CD47 activation induced by OSI.

Histone deacetylase 3 promotes innate antiviral immunity through deacetylation of TBK1

TANK-binding kinase 1 (TBK1), a core kinase of antiviral pathways, activates the production of interferons (IFNs). It has been reported that deacetylation activates TBK1; however, the precise mechanism still remains to be uncovered. We show here that during the early stage of viral infection, the acetylation of TBK1 was increased, and the acetylation of TBK1 at Lys241 enhanced the recruitment of IRF3 to TBK1. HDAC3 directly deacetylated TBK1 at Lys241 and Lys692, which resulted in the activation of TBK1. Deacetylation at Lys241 and Lys692 was critical for the kinase activity and dimerization of TBK1 respectively. Using knockout cell lines and transgenic mice, we confirmed that a HDAC3 null mutant exhibited enhanced susceptibility to viral challenge via impaired production of type I IFNs. Furthermore, activated TBK1 phosphorylated HDAC3, which promoted the deacetylation activity of HDAC3 and formed a feedback loop. In this study, we illustrated the roles the acetylated and deacetylated forms of TBK1 play in antiviral innate responses and clarified the post-translational modulations involved in the interaction between TBK1 and HDAC3.

Research progress on metabolism and efficacy of small molecular prodrug nanosystems responsive to tumor redox microenvironment / 药学学报

Compared with normal tissues and cells, the tumor microenvironment has significant differences. For example, glutathione-related metabolic enzymes and reactive oxygen species are highly expressed in different subcellular structures, resulting in an unbalanced redox state. Aiming at the specific redox state in tumor tissues and cells, a series of small molecule prodrug self-assembled nanoparticles can be designed and connected by intelligent response linkers including disulfide bonds, sulfide bonds, and selenium bonds, thioketal bonds, etc. The in vitro and in vivo efficiency and metabolic mode of these nanoparticles are related to the type of linker. This review will summarize the tumor redox microenvironment, the design of intelligent responsive small molecule prodrug nanoparticles, and the metabolic pathways of small molecule prodrug nanoparticles with different connecting linkers and their relationship with drug efficacy.

Analysis of related factors of epilepsy secondary to aneurysmal subarachnoid hemorrhage in the elderly / 中国基层医药

Objective:To explore the related factors of epilepsy secondary to aneurysmal subarachnoid hemorrhage in the elderly.Methods:From January 2015 to January 2019, 213 elderly patients with aneurysmal subarachnoid hemorrhage admitted to Wuhan Hospital of Traditional Chinese Medicine were divided into epilepsy group(46 cases) and non-epilepsy group(167 cases) according to whether secondary epilepsy.Univariate analysis was used to analyze the related factors affecting epilepsy secondary to aneurysmal subarachnoid hemorrhage in the elderly, and multivariate logistic regression was used to analyze the risk factors of epilepsy secondary to aneurysmal subarachnoid hemorrhage in the elderly.The investigation factors included sex, age, hypertension, diabetes mellitus, smoking history, location of responsible aneurysms, number of aneurysms, intracranial hematoma, hydrocephalus and neurological sequelae.Results:Univariate analysis showed that there were no statistically significant differences in sex, age, history of diabetes mellitus and smoking between the two groups(all P>0.05). There were statistically significant differences between the epilepsy group and non epilepsy group in hypertension(15 cases vs.22 cases), location of responsible aneurysms in middle cerebral artery(22 cases vs.24 cases), number of aneurysms(23 cases vs.41 cases), intracranial hematoma(15 cases vs.26 cases), hydrocephalus(15 cases vs.21 cases) and neurological sequelae(14 cases vs.20 cases)(χ 2=9.491, 23.840, 11.113, 6.737, 10.306, 9.161, all P<0.05). The results of multivariate analysis showed that hypertension, middle cerebral artery, multiple aneurysms, intracranial hematoma, hydrocephalus and neurologic sequelae were risk factors for epilepsy secondary to aneurysmal subarachnoid hemorrhage in the elderly[ OR(95% CI)2.361(1.476-3.421), 3.012(1.935-1.845), 1.494(1.027-1.845), 2.785(1.684-3.982), 1.920(1.283-2.984), 1.637(1.171-2.316)]. Conclusion:There are many factors influencing secondary epilepsy in elderly patients with aneurysmal subarachnoid hemorrhage.In order to reduce the incidence of secondary epilepsy, preventive measures should be taken against the above risk factors.

Tryptanthrin derivative CY-1-4 nanoparticle induces ferroptosis in B16-F10 cells / 药学学报

CY-1-4 is a tryptanthrin derivative exhibiting antitumor activity. The solubility of CY-1-4 was poor and the corresponding mechanism needs further study. To solve this problem, we prepared nanoparticles encapsulated with CY-1-4 (CY-1-4 NPs) by nanoprecipitation method using poly(caprolactone) (PCL) and poly(ethylene glycol)-co-poly(ε-caprolactone) (PEG-PCL) as carriers to improve solubility. We then explored whether CY-1-4 NPs induced B16-F10 cytotoxicity via ferroptosis by determining the effect of CY-1-4 NPs on reactive oxygen (ROS) levels, repairing efficacy of lipid reactive oxygen inhibitor ferrostatin-1 and iron chelator deferoxamine (DFO), and potentiation of protoporphyrin (PPIX) induced B16-F10 cell death. The results showed that nanoparticlated strategy significantly improved solubility of CY-1-4. With the particle size about 116 nm, encapsulating efficacy was about 83% and the drug loading capacity was about 4.80%. Ferroptosis mechanistic studies indicated that CY-1-4 NPs could improve the ROS level in B16-F10 cells, whereas ferrostatin-1 and DFO could partly inhibited the cytotoxicity and PPIX could potentiated the cytotoxicity of CY-1-4 NPs in B16-F10 cells. These results showed that ferroptosis was one of the cell death mechanisms induced by tryptanthrin derivative CY-1-4 nanoparticle.

Epidemiological characteristics and related risk factors on placental abruption in Hebei province / 中华流行病学杂志

Objective The aim of this study was to assess the risk factors and epidemiological characteristics of placental abruption (PA) in Hebei province.Methods A cross-sectional survey was conducted to collect data on 218 880 pregnant women who were hospitalized in 22 hospitals which were under a monitoring program,in Hebei province,from January 1,2013 to December 31,2016.Data regarding epidemiological characteristics as time distribution,population distribution and related risk factors of placental abruption were gathered and analyzed.Results In this cohort study,218 880 women were included,with 669 (0.31％) of the pregnant women having PA.The overall prevalence rates were higher in the South than in the north parts of the area and higher in more developed regional economic centers.The average age of women having the episode was (27.87 ± 4.50) years and presented “J” distribution on the prevalence of maternal age.Results from the multivariate regression analysis showed that the following factors were independently at risk for placental abruption:pregnancy the including hypertension (OR=1.65,95％CI:1.09-2.50),mild preeclampsia (OR=3.65,95％CI:2.40-5.56),severe preeclampsia (OR=4.72,95％CI:3.86-5.76) and anemia (OR=2.41,95％CI:2.05-2.83) which were all increased in pregnant women with PA compared with the normal female population without placental abruption.Conclusions Placental abruption seemed to be associated with a moderate increasing risk of age,and was seen higher in those population older than 35 or younger than 20 year-olds.It was suggested that appropriate inoculation programs should be taken in different regions,especially on high-risk groups.Health education on related disease was of great significance for improving the prenatal outcome.

Epidemiological characteristics and related risk factors on placental abruption in Hebei province / 中华流行病学杂志

Objective The aim of this study was to assess the risk factors and epidemiological characteristics of placental abruption (PA) in Hebei province.Methods A cross-sectional survey was conducted to collect data on 218 880 pregnant women who were hospitalized in 22 hospitals which were under a monitoring program,in Hebei province,from January 1,2013 to December 31,2016.Data regarding epidemiological characteristics as time distribution,population distribution and related risk factors of placental abruption were gathered and analyzed.Results In this cohort study,218 880 women were included,with 669 (0.31％) of the pregnant women having PA.The overall prevalence rates were higher in the South than in the north parts of the area and higher in more developed regional economic centers.The average age of women having the episode was (27.87 ± 4.50) years and presented “J” distribution on the prevalence of maternal age.Results from the multivariate regression analysis showed that the following factors were independently at risk for placental abruption:pregnancy the including hypertension (OR=1.65,95％CI:1.09-2.50),mild preeclampsia (OR=3.65,95％CI:2.40-5.56),severe preeclampsia (OR=4.72,95％CI:3.86-5.76) and anemia (OR=2.41,95％CI:2.05-2.83) which were all increased in pregnant women with PA compared with the normal female population without placental abruption.Conclusions Placental abruption seemed to be associated with a moderate increasing risk of age,and was seen higher in those population older than 35 or younger than 20 year-olds.It was suggested that appropriate inoculation programs should be taken in different regions,especially on high-risk groups.Health education on related disease was of great significance for improving the prenatal outcome.

Antophagy inhibition can decrease AR42J cell apoptosis induced by exendin-4 / 中华肝胆外科杂志

Objective To explore whether exendin-4 inhibits AR42J cells and its mechanism.Methods AR42J cells were treated with exendin-4 under multiple concentrations(1,5,10 pmol/L) at 24,48,72,96,120 h to assess its cell viability by MTT assay and got the IC-50 and time points.Then checking whether exendin-4 could induce the AR42Jcells apoptosis by setting normal control (NC) group,exendin-4 (Ex-4) group and Ex-4+ z-VAD-fmk (apoptosis inhibitor) group,and exploring whether 3-MA which is autophagy inhibitor could inhibit the AR42J cells apoptosis induced by exendin-4 by setting NC group,Ex-4 group and Ex-4+3-MA group.Cell viability was analyzed by MTT and the cells apoptosis was detected by flow cytometry and the protein levels of caspase-3,LC3 and p62 were studied by Western blot.Results Concentration of 10 pmol/L exendin-4 and and time point 72 h were selected for the further study.z-VAD-fmk pretreatment can significantly inhibit the cell viability of exendin-4 by (81.2±3.3)％ vs.(49.4±3.0)％ (P＜0.05).Flow cytometry showed that exendin-4 could induce the AR42J cells apoptosis by (28.2± 1.4)％ vs.(3.6±0.8)％,and increased the caspase-3 level by Western blot,which both can be reversed by (79.1 ±2.3) ％ vs.(49.8±2.5)％ (P＜0.05) when the cells were treated for 72 h,as was apoptosis ratio by (14.5±2.1)％ vs.(29.2±3.2)％.Western blot showed that exendin-4 can upregulate protein levels of LC3B-Ⅱ,p62 和 caspase-3 and 3-MA,and pretreatment can inhibit the upregulation of LC3B-Ⅱ and caspase-3 but further increased the upregulation of p62 induced by exendin-4.Conclusions Exendin-4 can induce AR42J cells apoptosis and 3-MA pretreating can inhibit exendin-4 cytotoxicity through downregulating autophagy.So auto phagy inhibitor 3-MA could potentially extenuate the cytotoxicity of exendin-4 in pancreatic acinar cells.

Homogeneity of Different Functional mRNA Indicators for Wound Age Estimation / 法医学杂志

OBJECTIVES@#To explore the homogeneity level of four different functional mRNA （PUM2, TAB2, Cx45 and CHRNA1） expressions in rats with skeletal muscle contusion.@*METHODS@#The relative expressions of PUM2, TAB2, Cx45 and CHRNA1 mRNAs were detected by quantitative real-time reverse transcription-polymerase chain reaction （RT-qPCR）. The coefficient of variation （CV） of the relative expressions for different individuals in each injury group was calculated. The extreme value of CV, cumulative variability, and CVCV were compared.@*RESULTS@#A high CV of PUM2 and TAB2 mRNAs appeared on several different time points. However, the CV of Cx45 and CHRNA1 mRNAs was relatively low. The cumulative variability from high to low was PUM2, CHRNA1, TAB2 and Cx45 mRNAs. The relative expression of PUM2 mRNA was significantly higher than that of TAB2, Cx45 and CHRNA1 mRNAs （ P<0.05）. There was no statistical significance （P>0.05） in the CVCV of the relative expression of TAB2, CHRNA1 and Cx45 mRNAs.@*CONCLUSIONS@#As the mRNAs involving in biological process regulation, PUM2 and CHRNA1 mRNAs show a lowest individual homogeneity of the relative expression followed by TAB2 mRNA. As the mRNAs participating in the composition of cellular structure, Cx45 and CHRNA1 mRNAs show a high individual homogeneity of the relative expressions. The functional classification should be considered for the screening of the mRNA indicators used for wound age estimation.

Correlation analysis of serum cardiac troponin Ⅰ and clinical efficacy observation of Wushen decoction for treatment of patients with sepsis heart failure / 中国中西医结合急救杂志

Objective To investigate the effect of Wushen decoction on levels of serum cardiac troponin Ⅰ (cTnI),cardiac muscle enzyme and clinical parameters in patients with sepsis heart failure,and to analyze the correlations between cTnI and myocardial enzyme level and clinical parameters.Methods Forty-two patients diagnosed as sepsis admitted to Wuhan Hospital of Traditional Chinese Medicine from March 2014 to March 2016 were enrolled,and they were divided into a Wushen decoction treatment group and a control group by principle of single blind complete randomized method,21 cases in each group.The patients in control gToup were treated by conventional western medicine,while the patients in Wushen decoction treatment group,on the basis of conventional western medicine,they were treated additionally by Wushen decoction (composed of ginseng,radix sophorae flavescentis,radix glehniae,radix adenophorae,salvia,astragalus,notoginseng radix,rosewood,etc.),one dose a day,the therapeutic course in both groups being 7 days.The changes of biochemical indicators [cTnI,creatine kinase (CK),CK isoenzyme (CK-MB)],haemodynamics parameters [cardiac index (CI),central venous pressure (CVP),extravascular lung water index (ELWI),global ejection fraction (GEF),mean arterial pressure (MAP),heart rate (HR)],treatment condition and prognostic parameters [vasoactive drug dosage index,acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) score,duration of mechanical ventilation,the length of stay in intensive care unit (ICU) and total hospitalization time] were compared before and after treatment for 7 days in the two groups.The correlations between the level of cTnI on admission before treatment and CK,CK-MB,APACHE Ⅱ,vasoactive drug dosage index,duration of mechanical ventilation,the length of stay in ICU and total hospitalization time were analyzed.Results The levels of cTnI,CK,CK-MB,CVP,ELWI,HR,vasoactive drug dosage index,APACHE Ⅱ score in two groups after treatment were obviously lower than those before treatment,the levels of CI,GEF,MAP were markedly higher than those before treatment,the duration of mechanical ventilation,the length of stay in ICU and total hospitalization time were significantly shorter than those before treatment,and the changes of above indexes were more remarkable in Wushen decoction group than those in control group [cTnI (mg/L):0.94-± 0.29 vs.1.30 ± 0.67,CK (U/L):96.00 ± 24.30 vs.101.38 ± 24.55,CK-MB (U/L):31.14 ± 6.78 vs.36.48 ± 8.17,CI (mL· s-1 · m-2):64.51 ± 5.83 vs.53.34 ± 4.67,CVP (cmH2O,1 cmH2O =0.098 kPa):10.56 ± 1.84 vs.11.94--2.16,ELWI (mL/kg):8.81±1.61 vs.11.66±2.30,GEF:(33.62±3.88)％ vs.(27.14±4.55)％,MAP (mmHg,1 mmHg =0.133 kPa):84.67 ± 5.58 vs.79.52 ± 5.74,HR (bpm):87.86 ± 9.02 vs.82.95 ± 5.26,vasoactive drug dosage index:2.44 ± 0.53 vs.2.89 ± 0.68,APACHE Ⅱ score:10.66 ± 1.66 vs.14.43 ± 1.82,duration of mechanical ventilation (days):1.67 ± 2.11 vs.2.10 ± 2.26,the length of stay in ICU (days):8.86 ± 2.59 vs.10.67 ± 2.96,total hospitalization time (days):13.24 ± 4.53vs.16.76 ± 5.04,all P ＜ 0.05].On admission before treatment,the correlations between the level of cTnI and CK,APACHE Ⅱ score,vasoactive drug dosage index,duration of mechanical ventilation and the length of stay in ICU were all positive (r =0.322,0.335,0.327,0.328,0.338,P =0.038,0.030,0.030,0.034,0.029).Conclusions The elevation of cTnI level may reflect the degree of myocardial damage in patients with sepsis cardiac failure,and it can be used as an indicator to predict the prognosis of the disease;the changes of many biochemical and clinical indexes suggest that the addition of Wushen decoction might elevate the clinical efficacy for treatment of patients with sepsis heart failure.

Expression and significance of autophagy-related genes in acute pancreatitis / 中华胰腺病杂志

Objective To examine the expression and analyze the significance of autophagy-related gene microtubule-associated protein 1 light chain 3 (MAP1-LC3,LC3),p62 and lysosorne-associated membrane protein 2 (LAMP-2) in pancreatic tissues of mice with acute pancreatitis (AP).Methods Twenty mice were randomized into AP group and control group,and the number of mice was equal between two groups.AP group was intra-peritoneally injected by 20％ L-arginine solution (two injections of 4 g/kg body weight,every 1 h) in the dosage of 4 g/l kg twice every 1 hour to establish AP model,while control group was administered with equal volume of normal saline by intra-peritoneal injection.All the mice were euthanized at 24 hour after the last injection.Pancreatic histopathological changes were measured.In addition,the protein expressions of LC3,p62 and LAMP-2 were detected by Western blot.Results No obvious pathological changes were observed in control group.Pancreatic acinar edema,structure destruction,missing,the obvious widening of interlobular septum,small interlobular septum and acinar septum,and the necrosis of acinar cells at different degrees were observed in AP group.The pathological score for tissue edema,hemorrhage,necrosis and inflammation in AP group was 3.13 ± 0.50,2.83 ± 0.32,3.25 ± 0.46 and 3.16 ± 0.47,respectively,which was all 0 in control group.The differences were statistically significant between AP group and control group (P ＜ 0.01).In AP group,the ratio of LC3-Ⅱ/LC3-Ⅰ,p62 and LAMP-2 protein in pancreatic tissue were 1.16 ± 0.08,0.94 ± 0.04 and 0.35 ± 0.04,respectively,which were 0.24 ± 0.02,0.34 ± 0.03 and 0.95 ± 0.03 in control group.The ratio of LC3-Ⅱ/LC3-Ⅰ and p62 protein in pancreatic tissue in AP group were much higher than those in control group,while LAMP-2 in AP group was lower than that in control group,and there was statistically significant difference between two groups (all P ＜0.01).Conclusions Intraperitoneal injection of L-arginine could induce acute pancreatitis,and autophagy is impaired,which was associated with decreased LAMP-2 protein expression.

Regulatory effect of microRNA-141 on synthesis of high mobility group protein B1 in mouse carcinoma cell line hepal-6 / 中南大学学报(医学版)

OBJECTIVE@#To explore the regulatory effect of microRNA-141 (miR-141) on expression of high mobility group protein B1 (HMGB1) in mouse hepatoma carcinoma cell line (hepal-6 cells).
@*METHODS@#The hepal-6 cells were divided into 4 groups: a miR-141 mimic group, a miR-141 mimic control group, a miR-141 inhibitor group and a miR-141 inhibitor control group. The miR-141 was transfected into hepal-6 cells with lipofectamine 2000. The levels of miR-141 and HMGB1 mRNA in the hepal-6 cells were detected by quantitative real-time PCR (qRT-PCR), and then HMGB1 protein was examined by Western blot. The regulatory effect of miR-141 on 3'-UTR of candidate target gene (HMGB1) was determined by dual-luciferase reporter assay.
@*RESULTS@#Compared with the control group, the level of miR-141 was up-regulated in the miR-141 mimic group, while down-regulated in the miR-141 inhibitor group. Moreover, the levels of HMGB1 mRNA and protein decreased in the miR-141 mimic group, while increased in the miR-141 inhibitor group. The dual-luciferase reporter assay showed that miR-141 could target the 3'-UTR of HMGB1 gene.
@*CONCLUSION@#MiR-141 can up-regulate the expression of HMGB1 protein at the post-transcriptional level by targeting to the specific sequence of 3'-UTR of HMGB1 gene, which suggests that HMGB1 gene may be a target gene of miR-141.

Brusatol inhibits the invasion behavior of rheumatoid arthritis fibroblast-like synoviocytes through regulating mechanical properties of cytoskeleton / 医用生物力学

Objective To investigate the effects of brusatol on mechanical properties of the cytoskeleton as well as the invasion behavior of rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS). Methods Cytoskeleton staining method was used to determine the regulatory effects of brusatol on mechanical properties of the RA FLS cytoskeleton. Transwell chamber assay was used to detect the effects of brusatol on the cytoskeleton and invasion behavior of RA FLS. The effects of brusatol on the expression of matrix metalloproteinase-2/3 (MMP-2/3) of RA FLS were measured by zymography and Western blotting methods. Results Cytoskeleton staining and microscope observation showed that brusatol could significantly reduce the formation number of RA FLS pseudopodia, thus inhibited cell movement ability via regulating mechanical properties of cytoskeleton. The invasion behavior of RA FLS was inhibited by brusatol, and brusatol could down-regulate the expression of MMP-2/3. Conclusions Brusatol plays an important role in regulating mechanical properties of cytoskeleton and inhibiting the invasion behavior of RA FLS. Meanwhile, brusatol can inhibit the invasion behavior of RA FLS through down-regulating the expression of MMP-2/3. The research findings provide the corresponding experimental basis for further development of new drugs for RA treatment.

Exenatide induce the impairment of autophagy flux to damage rat pancreatic tissue / 中华内分泌外科杂志

Objective To explore the alteration and effect of autophagy in pancreas tissue of rat injected by exenatide.Methods Diabetes model rats were induced by two-month high-sugar and high-fat diet and streptozotocin injection (35 mg/kg) in normal rats.50 SD male rats were divided into four groups according to the principle of complete random design,namely normal control group (n=10),normal exenatide-injected group (n=10),diabetes-model control group (n=l5) and diabetes-model exenatide-injected group (n=15).Rats in exenatide-injected groups were subcutaneously injected with exenatide respectively in 5 μg/kg dose each time,twice a day,at 8 a.m.and 6 p.m.Animal weights were weighted weekly and the dose of exenatide was adjusted according to current weight.Rats in the two control groups were injected with the corresponding amount of saline.Mter 10 weeks of treatment,all rats were killed and pancreatic tissues were disposed.Immunohistochemistry was used to measure the expression of GLP-1R in pancreatic tissues.Western blot was used to test the expressions of LC3-Ⅰ,LC3-Ⅱ and p62 in pancreatic tissues,and LC3-Ⅱ/Ⅰ ratio and p62 were compared between any two groups.All specimens were stained with hematoxylin-eosin (HE).The data were expressed as means ± standard deviation and were analyzed by unpaired Student t test using SPSS 18.0 statistics software.P value ＜0.05 was considered to be statistically significant for all tests.Results The pancreatic tissues from 13 rats (6 from the normal exenatide-injected group and 7 from the diabetes-model exenatide-injected group) appeared pathological changes such as gland structure damage,pancreatic cells atrophy and cells compartment broadening.The expressions of GLP-1R,LC3-Ⅱ and p62,and LC3B-Ⅱ/Ⅰ ratio in the two exenatide-injected groups were higher than those in the respective control group,and the differences had statistical significance (P＜0.05).Conclusions Long-term subcutaneous injection of exenatide can upregulate the expression of GLP-1R in rat pancreatic acinar cells and may induce the impaiment of autophagy flux in rat pancreatic cell.

Clinical efficacy of pancreaticoduodenectomy and duodenum-preserving pancreatic head resection for the treatment of chronic pancreatitis with mass in the head of the pancreas / 中华消化外科杂志

Objective To investigate the clinical efficacy of pancreaticoduodenectomy (PD) and duodenumpreserving pancreatic head resection (DPPHR,including Beger,Frey and Berne procedures)for the treatment of chronic pancreatitis (CP) with mass in the head of the pancreas.Methods The clinical data of 48 patients with CP who were admitted to the Armed Police Corps Hospital of Hunan province(13) and the Third Xiangya Hospital of Central South University (35) between January 2007 and December 2013 were retrospectively analyzed.The operation methods were selected according to clinical symptoms,imaging findings and intraoperative pathological examinations.Twenty-three patients receiving PD (Whipple procedure or pylorus-preserving PD) were allocated into PD group and 25 receiving DPPHR (Beger,Frey and Berne procedures) were allocated into DPPHR group.The operation time,volume of intraoperative blood loss,rate of postoperative pain relief,changes of pancreatic endocrine and exocrine function,complications,duration of hospital stay and hospital expenses in the 2 groups were analyzed.Patients were followed up by telephone interview and outpatient examination up to September 2014.Measurement data with normal distribution were presented as (x) ± s.Comparison between groups was analyzed using the t test.Count data were analyzed using chi-square test or Fisher exact probability.Results Of the 23 patients in the PD group,15 patients received Whipple procedure and 8 patients received pylorus preserving PD.Of 25 patients in the DPPHR group,8 patients received Beger procedure,13 patients received Frey procedure and 4 patients received Berne procedure.The operation time and volume of intraoperative blood loss were (5.5 ± 0.4) hours,(372 ± 174) mL in the PD group,and (4.2 ± 0.6) hours,(272 ± 114) mL in the DPPHR group,showing significant differences between the 2 groups (t =8.712,2.375,P ＜ 0.05).Three patients had massive hemorrhage in the PD group and 2 patients receiving Beger procedure had massive hemorrhage due to portal vein injury,with no significant difference (x2=0.010,P ＞ 0.05).The intraoperative pathologic examinations of frozen section showed chronic inflammation in all pancreatic tissue samples with fibrous tissue proliferations.Overall pain relief rate was 95.7％ (22/23) in the PD group,including 20 complete remissions and 2 partial remissions,and overall pain relief rate was 92.0％ (23/25) in the PD group,including 18 complete remissions and 5 partial remissions,which were no different in overall pain relief rate (x2 =0.000,P ＞ 0.05).The morbidity of postoperative diabetes mellitus and dyspepsia with fatty diarrhea were 38.9％ (7/18) and 35.7％ (5/14) in the PD group,which were no different from 9.5％ (2/21) and 20.0％ (3/15) in the DPPHR group (x2=3.200,0.281,P ＞0.05).The incidence of postoperative complication was 30.4％ (7/23) in the PD group,including 1 case of intra-abdominal hemorrhage,pancreatic fistula and localized peritonitis,1 case of pancreatic fistula,2 cases of biliary fistula,3 cases of delayed gastric emptying.Patients with pancreatic fistula and biliary fistula recovered after 1-week sufficient drainage.The incidence of postoperative complication was 4.0％ (1/25) in the DPPHR group,including 1 case of pancreatic fistula,showing significant difference in incidence of postoperative complication (x2=4.274,P ＜ 0.05).The duration of postoperative stay and hospital expense were (12.4 ± 2.5) days and (57 751 ± 6 772) yuan in the PD group,which were significantly different from (8.2 ± 1.8) days and (49 109 ± 6 168)yuan in the DPPHR group (t =6.576,4.645,P ＜ 0.05).Forty-eight patients were followed up with a median time of 51.6 months (9.0-92.0 months).Of the 2 patients died,1 patient who underwent Frey procedure died 3 months after diagnosis of pancreatic cancer due to epigastric pain at postoperative month 6,the other died 2 years later due to cardiovascular disease.Among 48 patients with follow-up,1 received biliary-intestine drainage 6 months later and other patients had no recurrence or canceration.Conclusions DPPHR is safe and effective for chronic pancreatitis with mass in the head of the pancreas,having advantages such as shorter duration of operation,less intraoperative hemorrhage,faster postoperative recover,shorter duration of hospital stay and delayed hypofunction of pancreatic endocrine and exocrine function.But DPPHR cannot completely replace PD,It is necessary to master indications for all kinds of operations and choose proper operative approaches based on lesion characteristics.

Study on the regulatory effects of mechano growth factor on soft tissue repair / 生物医学工程学杂志

Mechano growth factor (MGF) is an autocrine/paracrine factor and sensitive to mechanical stimulation. MGF can be highly expressed in various soft tissues under physical stimuli, biochemistry stimuli or in damaged situation. MGF may "compensate" the stress for tissue in the processing of tissue repair. MGF can effectively accelerate the repair of the soft tissue by promoting the proliferation, migration and differentiation of cells. This paper summarizes the MGF expressions in different soft tissues and their functions in soft tissue repair. The paper also discusses current problems and challenges in using MGF to repair the soft tissue.

Analysis of Bayley Scales of Infant Development Test Results of 135 Low Birth Weight Infants / 昆明医科大学学报

Objective To investigate the intelligence development status of the low birth weight infants and its influence factors. Methods The intelligence developments of 135 low birth weight infants aged 6-30 months were investigated using Bayley Scales of Infant Development, and the self-development influential factors were analyzed with questionnaire.Results The average of MDI was 86.76±18.95 in 135 infants,of which the detection rate of MDI<80 points accounted for 17.8%and the detection rate of PDI<80 points accounted for 29.6%;birth weight of infant,age,the degree of parents,culture and feeding way had significant effects on MDI in infants;age and birth weight had significant effects on PDI in infants. Conclusion The development level of infants is influenced by multi-factors. More attention should be paid to reduce premature and low birth weight infants,improve the degree of parents' culture, advocate breastfeeding and conduct early intervention in order to assure the intelligence development of infants.

The experimental study of pancreatic tissue lesion induced by Exenatide / 中华胰腺病杂志

Objective To explore the mechanism of Exenatide-induced rat pancreatic tissue lesion.Methods Thirty SD male rats were divided into three groups according to complete random design,and each group had 10 rats,namely Exenatide group,diabetes-model group and control group.Diabetes-model rats were induced by streptozotocin (STZ,35mg/kg) and high-sugar and high-fat diet.The Exenatide group and diabetes group were subcutaneously administered with Exenatide at a dose of 5 μg/kg twice a day.The control group was treated with same amount of saline.Ten weeks later,all the rats were sacrificed and the pancreatic tissues were harvested for routine pathological examination.Immunohistochemical method was used to detect the expression of α-smooth muscle actin (α-SMA) and type Ⅲ collagen protein in pancreatic tissue,and ELISA was applied to measure the expression of matrix metalloprotei-nase-2 (MMP-2) and MMP-9 in pancreatic tissue.Results In control group,there was no pathological change in pancreatic tissue.In Exenatide group,chronic inflammatory changes were observed; and the degree of inflammatory changes were much severe in diabetes group,and the pathological scores were gradually increased in the 3 groups (P ＜0.05).The expressions of MMP 2 in pancreatic tissue in control group,Exenatide group,diabetes group were (186.98 ± 23.24),(306.07 ± 59.82),(365.08 ± 89.55) μg/L,and the expressions of MMP-9 were (49.37 ± 7.08),(67.24 ±14.73),(87.37 ±13.39)μg/L.The values were significantly higher in Exenatide group and diabetes group than those in control group (P ＜ 0.05),but the difference between the two groups was not statistically significant.The numbers of α-SMA positive cells per high power field were (13.4 ± 5.97),(29.5 ± 8.80),(79.3 ± 27.23) in control group,Exenatide group,diabetes group,and the numbers of type Ⅲ collagen positive cells were (10.6 ± 4.93),(29.3 ± 12.95),(56.0 ± 27.21).The values were significantly higher in Exenatide group than those in control group,and the values were significantly higher in diabetes group than those in Exenatide group (P ＜ 0.05).Conclusions Long-term subcutaneous injection of Exenatide may activate pancreatic stellate cells and cause expression of α-SMA,Ⅲ collagen protein,and MMP-2,MMP-9,then induce chronic inflammatory changes.